Sample records for allograft musculoskeletal tissue

  1. Micro-organisms isolated from cadaveric samples of allograft musculoskeletal tissue.

    PubMed

    Varettas, Kerry

    2013-12-01

    Allograft musculoskeletal tissue is commonly used in orthopaedic surgical procedures. Cadaveric donors of musculoskeletal tissue supply multiple allografts such as tendons, ligaments and bone. The microbiology laboratory of the South Eastern Area Laboratory Services (SEALS, Australia) has cultured cadaveric allograft musculoskeletal tissue samples for bacterial and fungal isolates since 2006. This study will retrospectively review the micro-organisms isolated over a 6-year period, 2006-2011. Swab and tissue samples were received for bioburden testing and were inoculated onto agar and/or broth culture media. Growth was obtained from 25.1 % of cadaveric allograft musculoskeletal tissue samples received. The predominant organisms isolated were coagulase-negative staphylococci and coliforms, with the heaviest bioburden recovered from the hemipelvis. The rate of bacterial and fungal isolates from cadaveric allograft musculoskeletal tissue samples is higher than that from living donors. The type of organism isolated may influence the suitability of the allograft for transplant.

  2. Swab or biopsy samples for bioburden testing of allograft musculoskeletal tissue?

    PubMed

    Varettas, Kerry

    2014-12-01

    Swab and biopsy samples of allograft musculoskeletal tissue are most commonly collected by tissue banks for bacterial and fungal bioburden testing. An in vitro study was performed using the National Committee for Clinical Laboratory Standards standard 'Quality control of microbiological transport systems' (2003) to validate and evaluate the recovery of six challenge organisms from swab and biopsy samples of allograft musculoskeletal tissue. On average, 8.4 to >100 and 7.2 to >100 % of the inoculum was recovered from swab and biopsy samples respectively. A retrospective review of donor episodes was also performed, consisting of paired swab and biopsy samples received in this laboratory during the period 2001-2012. Samples of allograft femoral heads were collected from living donors during hip operations. From the 3,859 donor episodes received, 21 paired swab and biopsy samples each recovered an isolate, 247 swab samples only and 79 biopsy samples only were culture positive. Low numbers of challenge organisms were recovered from inoculated swab and biopsy samples in the in vitro study and validated their use for bioburden testing of allograft musculoskeletal tissue. Skin commensals were the most common group of organisms isolated during a 12-year retrospective review of paired swab and biopsy samples from living donor allograft femoral heads. Paired swab and biopsy samples are a suitable representative sample of allograft musculoskeletal tissue for bioburden testing.

  3. Evaluation of two types of swabs for sampling allograft musculoskeletal tissue.

    PubMed

    Varettas, Kerry

    2015-01-01

    Allograft musculoskeletal tissue is commonly sampled by a swab for bioburden screening. To determine if bioburden recovery could be improved at the pre-analytical stage, two swab systems were evaluated: the Amies gel swab and the ESwab. In vitro studies were performed to determine the recovery of each swab system with <100 colony-forming unit of challenge organisms using inoculated swabs and by sampling inoculated femoral heads. The standard culture protocol used in this laboratory was also evaluated after sampling of inoculated femoral heads. A prospective study was performed with both swab systems used in parallel to sample cadaveric allograft musculoskeletal tissue. The challenge organisms could be recovered from the in vitro inoculated studies. The standard culture protocol in this laboratory recovered all challenge organisms from both swab systems. One hundred and six paired Amies and ESwabs were collected from eight cadaveric donors with skin commensals the predominant isolates. The sampling of an inoculated femoral head was included to reflect routine swab sampling practice as was the inclusion of the standard method used in this laboratory. This appears to be the first study to compare Amies gel swabs with ESwabs to sample allograft femoral heads and in a prospective study with cadaveric allograft musculoskeletal tissue. Other comparative studies of swab systems have used a much higher inoculum to mimic an infection; however, sepsis is an exclusion criterion for allograft donors. It was found that the Amies gel swab and ESwab are both suitable sampling devices for bioburden testing of allograft musculoskeletal tissue. © 2014 Royal Australasian College of Surgeons.

  4. Broth versus solid agar culture of swab samples of cadaveric allograft musculoskeletal tissue.

    PubMed

    Varettas, Kerry

    2013-12-01

    As part of the donor assessment protocol, bioburden assessment must be performed on allograft musculoskeletal tissue samples collected at the time of tissue retrieval. Swab samples of musculoskeletal tissue allografts from cadaveric donors are received at the microbiology department of the South Eastern Area Laboratory Services (Australia) to determine the presence of bacteria and fungi. This study will review the isolation rate of organisms from solid agar and broth culture of swab samples of cadaveric allograft musculoskeletal tissue over a 6-year period, 2006-2011. Swabs were inoculated onto horse blood agar (anaerobic, 35 °C) and chocolate agar (CO2, 35 °C) and then placed into a cooked meat broth (aerobic, 35 °C). A total of 1,912 swabs from 389 donors were received during the study period. 557 (29.1 %) swabs were culture positive with the isolation of 713 organisms, 249 (34.9 %) from solid agar culture and an additional 464 (65.1 %) from broth culture only. This study has shown that the broth culture of cadaveric allograft musculoskeletal swab samples recovered a greater amount of organisms than solid agar culture. Isolates such as Clostridium species and Staphylococcus aureus would not have been isolated from solid agar culture alone. Broth culture is an essential part of the bioburden assessment protocol of swab samples of cadaveric allograft musculoskeletal tissue in this laboratory.

  5. Disinfection of human musculoskeletal allografts in tissue banking: a systematic review.

    PubMed

    Mohr, J; Germain, M; Winters, M; Fraser, S; Duong, A; Garibaldi, A; Simunovic, N; Alsop, D; Dao, D; Bessemer, R; Ayeni, O R

    2016-12-01

    Musculoskeletal allografts are typically disinfected using antibiotics, irradiation or chemical methods but protocols vary significantly between tissue banks. It is likely that different disinfection protocols will not have the same level of microorganism kill; they may also have varying effects on the structural integrity of the tissue, which could lead to significant differences in terms of clinical outcome in recipients. Ideally, a disinfection protocol should achieve the greatest bioburden reduction with the lowest possible impact on tissue integrity. A systematic review of three databases found 68 laboratory and clinical studies that analyzed the microbial bioburden or contamination rates of musculoskeletal allografts. The use of peracetic acid-ethanol or ionizing radiation was found to be most effective for disinfection of tissues. The use of irradiation is the most frequently published method for the terminal sterilization of musculoskeletal allografts; it is widely used and its efficacy is well documented in the literature. However, effective disinfection results were still observed using the BioCleanse™ Tissue Sterilization process, pulsatile lavage with antibiotics, ethylene oxide, and chlorhexidine. The variety of effective methods to reduce contamination rate or bioburden, in conjunction with limited high quality evidence provides little support for the recommendation of a single bioburden reduction method.

  6. Musculoskeletal allograft risks and recalls in the United States.

    PubMed

    Mroz, Thomas E; Joyce, Michael J; Steinmetz, Michael P; Lieberman, Isador H; Wang, Jeffrey C

    2008-10-01

    There have been several improvements to the US tissue banking industry over the past decade. Tissue banks had limited active government regulation until 1993, at which time the US Food and Drug Administration began regulatory oversight because of reports of disease transmission from allograft tissues. Reports in recent years of disease transmission associated with the use of allografts have further raised concerns about the safety of such implants. A retrospective review of allograft recall data was performed to analyze allograft recall by tissue type, reason, and year during the period from January 1994 to June 30, 2007. During the study period, more than 96.5% of all allograft tissues recalled were musculoskeletal. The reasons underlying recent musculoskeletal tissue recalls include insufficient or improper donor evaluation, contamination, recipient infection, and positive serologic tests. Infectious disease transmission following allograft implantation may occur if potential donors are not adequately evaluated or screened serologically during the prerecovery phase and if the implant is not sterilized before implantation.

  7. Bacterial contamination of tissue allografts - experiences of the donor tissue bank of Victoria.

    PubMed

    Ireland, Lyn; Spelman, Denis

    2005-01-01

    The aim of this study is to report the experience of the Donor Tissue Bank of Victoria with bacteria isolated from musculoskeletal, skin and cardiac allografts retrieved from cadaveric donors. The results of all quality control samples for bacterial culture, taken during retrieval and processing of allografts at the DTBV for a 12 month period, were extracted and analysed. It was found that 15.7% of skin, 15.1% of heart valves and 5.8% of musculoskeletal samples had positive culture results. The number and types of organisms isolated varied with tissue type. The most commonly isolated organisms were Staphylococcus species (including S. aureus). The identity of the isolate and the number of positive specimens from the same donor were considerations in the decision concerning the suitability of tissue for subsequent implantation.

  8. Collection and reconstruction after harvesting donor tissues from the musculoskeletal system: Technique specific to the lower limbs.

    PubMed

    Erivan, R; Villatte, G; Lecointe, T; Descamps, S; Boisgard, S

    2018-03-19

    The lack of available musculoskeletal grafts in France forces us to import a very large quantity of these tissues to use in complex reconstruction procedures. The goal of this article is to describe methods for collecting donor tissues from the musculoskeletal system and for reconstructing the harvested areas. We also provide a summary of the collection procedures performed, harvested grafts and available tissues. While tissue collection requires a significant time investment, the emergence of dedicated teams may be a solution for increasing the number and quality of human musculoskeletal allograft tissues. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  9. [Attitude towards organ and tissue donation in Europe : Prerequisite for osteochondral allograft treatment].

    PubMed

    Schmidt, S; Schulte, A; Schwarz, S; Hofmann, N; Tietz, S; Boergel, M; Sixt, S U

    2017-11-01

    The biggest obstacle to overcome for routine treatment of various pathologies with fresh osteochondral allograft is the availability of tissue for transplantation. Large fresh osteochondral allografts are usually harvested from organ donors, but in contrast to organs, tissues can be procured after cardiac arrest. Medical staff as well the general public are much less aware of the possibilities and requirements of tissue donation compared to organ donation. This review aims to highlight the current situation of organ and tissue donation in Europe and to raise this much needed awareness. For this research, PubMed database was scanned using the terms "tissue/organ donation", "bone donation/transplantation", "cartilage transplantation/allografts" and "osteochrondral allografts". Relatives of potential donors are often not approached because physicians and nurses do not feel sufficiently prepared for this task and, thus, are reluctant to address this topic. Different options could alleviate the pressure medical staff is feeling. Furthermore, there are different factors influencing consent that can be addressed to increase donation rates. Currently, a lot of potential concerning musculoskeletal tissue grafts remains unused. Most importantly, families should be encouraged to speak about their potenzial will to donate and educational programs should be established to increase trust in organ and tissue donation and the allocation system and to increase knowledge about the importance of transplantation medicine. But joined efforts of different parts of the medical systems and different organizations involved in tissue transplantation should improve the situation for patients waiting for much needed transplants.

  10. Allograft replacement for absent native tissue.

    PubMed

    Chaudhury, Salma; Wanivenhaus, Florian; Fox, Alice J; Warren, Russell F; Doyle, Maureen; Rodeo, Scott A

    2013-03-01

    Structural instability due to poor soft tissue quality often requires augmentation. Allografts are important biological substitutes that are used for the symptomatic patient in the reconstruction of deficient ligaments, tendons, menisci, and osteochondral defects. Interest in the clinical application of allografts has arisen from the demand to obtain stable anatomy with restoration of function and protection against additional injury, particularly for high-demand patients who participate in sports. Traditionally, allografts were employed to reinforce weakened tissue. However, they can also be employed to substitute deficient or functionally absent tissue, particularly in the sports medicine setting. This article presents a series of 6 cases that utilized allografts to restore functionally deficient anatomic architecture, rather than just simply augmenting the degenerated or damaged native tissue. Detailed discussions are presented of the use of allografts as a successful treatment strategy to replace functionally weakened tissue, often after failed primary repairs.

  11. Allograft Replacement for Absent Native Tissue

    PubMed Central

    Chaudhury, Salma; Wanivenhaus, Florian; Fox, Alice J.; Warren, Russell F.; Doyle, Maureen; Rodeo, Scott A.

    2013-01-01

    Context: Structural instability due to poor soft tissue quality often requires augmentation. Allografts are important biological substitutes that are used for the symptomatic patient in the reconstruction of deficient ligaments, tendons, menisci, and osteochondral defects. Interest in the clinical application of allografts has arisen from the demand to obtain stable anatomy with restoration of function and protection against additional injury, particularly for high-demand patients who participate in sports. Traditionally, allografts were employed to reinforce weakened tissue. However, they can also be employed to substitute deficient or functionally absent tissue, particularly in the sports medicine setting. Objective: This article presents a series of 6 cases that utilized allografts to restore functionally deficient anatomic architecture, rather than just simply augmenting the degenerated or damaged native tissue. Detailed discussions are presented of the use of allografts as a successful treatment strategy to replace functionally weakened tissue, often after failed primary repairs. PMID:24427387

  12. Revitalization of biostatic tissue allografts: new perspectives in tissue transplantology.

    PubMed

    Olender, E; Uhrynowska-Tyszkiewicz, I; Kaminski, A

    2011-10-01

    Biostatic (nonvital) tissue allografts have been used for temporary replacement as well as to trigger, stimulate, and ensure space for the regeneration of a recipient's own tissues. Examples of biostatic allografts routinely used in clinic are bone, tendons, skin, and amniotic membrane. A characteristic feature of biostatic allografts is the lack of living cells. In the recipient's body, biostatic allografts function as scaffolds as well as sources of growth, differentiation, and chemotactic factors. After implantation, recipient cells migrate onto the graft, colonize it, and initiate synthesis of extracellular matrix, thereby regenerating the structure of the lost or damaged tissue. The allograft gradually degrades before being remodeled and substituted by the recipient's new tissue. However, this process is not always effective due to a lack of reaction by recipient cells. New concepts have proposed seeding recipient cells onto the allograft prior to implantation, that is, biostatic allografts that are revitalized ex vivo. The aim of this presentation was to review scientific publications to provide essential information on the revitalization of biostatic allografts, as a rising trend in tissue transplantology. Biostatic allografts show the following advantages: they are human-derived, nontoxic, biocompatible, and, in some cases, already display the desired shape. The process of introducing cells into the biostatic graft is described as "revitalization." The cells used in the process are recipient autologous elements that are either differentiated or progenitor elements. Cells are seeded onto the graft directly after retrieval or after propagation in culture. Revitalized biostatic allografts can be used orthotopically for the regeneration of the same tissue they have been retrieved from or heterotopically wherein the graft retrieved from a different tissue is used as a carrier for cells typical for the tissue to be regenerated. Examples of orthotopic use include

  13. Radiation sterilization of tissue allografts: A review.

    PubMed

    Singh, Rita; Singh, Durgeshwer; Singh, Antaryami

    2016-04-28

    Tissue substitutes are required in a number of clinical conditions for treatment of injured and diseased tissues. Tissues like bone, skin, amniotic membrane and soft tissues obtained from human donor can be used for repair or reconstruction of the injured part of the body. Allograft tissues from human donor provide an excellent alternative to autografts. However, major concern with the use of allografts is the risk of infectious disease transmission. Therefore, tissue allografts should be sterilized to make them safe for clinical use. Gamma radiation has several advantages and is the most suitable method for sterilization of biological tissues. This review summarizes the use of gamma irradiation technology as an effective method for sterilization of biological tissues and ensuring safety of tissue allografts.

  14. Radiation sterilization of tissue allografts: A review

    PubMed Central

    Singh, Rita; Singh, Durgeshwer; Singh, Antaryami

    2016-01-01

    Tissue substitutes are required in a number of clinical conditions for treatment of injured and diseased tissues. Tissues like bone, skin, amniotic membrane and soft tissues obtained from human donor can be used for repair or reconstruction of the injured part of the body. Allograft tissues from human donor provide an excellent alternative to autografts. However, major concern with the use of allografts is the risk of infectious disease transmission. Therefore, tissue allografts should be sterilized to make them safe for clinical use. Gamma radiation has several advantages and is the most suitable method for sterilization of biological tissues. This review summarizes the use of gamma irradiation technology as an effective method for sterilization of biological tissues and ensuring safety of tissue allografts. PMID:27158422

  15. Evaluation of allograft contamination and decontamination at the Treviso Tissue Bank Foundation: A retrospective study of 11,129 tissues.

    PubMed

    Paolin, Adolfo; Trojan, Diletta; Petit, Pieter; Coato, Paola; Rigoli, Roberto

    2017-01-01

    Microbiological contamination of retrieved tissues has become a very important topic and a critical aspect in the safety of allografts. We have analysed contamination in 11,129 tissues with a longitudinal contamination profile for each individual tissue. More specifically, 10,035 musculoskeletal tissues and 1,094 cardiovascular tissues were retrieved from a total of 763 multi-tissue donors, of whom 105 were heart-beating donors as well as organ donors, while the remaining 658 were non-heart beating donors and tissue donors only. All tissues were decontaminated twice, the first time immediately after retrieval and the second time after processing. Each tissue was submitted to microbiological culture three times, i.e., upon retrieval (Time 1), after the first decontamination (Time 2) and after the second decontamination (Time 3). The contamination rate for musculoskeletal tissues was 52%, 16.2% and 0.5% at Time 1, 2 and 3, respectively. The contamination rate for cardiovascular tissues was 84%, 42% and 6%. More than one strain was simultaneously present in 10.8% of musculoskeletal tissues and 44.6% of cardiovascular tissues. Out of 8,560 non-heart-beating donor musculoskeletal tissues, 4,689 (54.8%), 1,383 (16.2%) and 42 (0.5%) were contaminated at Time 1, Time 2 and Time 3, respectively. Out of 1,475 heart-beating donor musculoskeletal tissues, 522 (35.4%) 113 (7.7%) and 2 (0.1%) tissues were found to be contaminated at Time 1, 2 and 3, respectively. Out of 984 non-heart beating donor cardiovascular tissues, 869 (88.3%), 449 (45.6%) and 69 (7%) proved positive at Time 1, 2 and 3 respectively, while 50 (45.5%) and 10 (9.1%) heart-beating donor cardiovascular tissues were contaminated at Time 1 and 2. No tissue was contaminated at Time 3. Based on our methods, the two-step decontamination approach is mandatory in order to drastically reduce the number of tissues found to be positive at the end of the process.

  16. Evaluation of allograft contamination and decontamination at the Treviso Tissue Bank Foundation: A retrospective study of 11,129 tissues

    PubMed Central

    Paolin, Adolfo; Trojan, Diletta; Petit, Pieter; Coato, Paola; Rigoli, Roberto

    2017-01-01

    Microbiological contamination of retrieved tissues has become a very important topic and a critical aspect in the safety of allografts. We have analysed contamination in 11,129 tissues with a longitudinal contamination profile for each individual tissue. More specifically, 10,035 musculoskeletal tissues and 1,094 cardiovascular tissues were retrieved from a total of 763 multi-tissue donors, of whom 105 were heart-beating donors as well as organ donors, while the remaining 658 were non-heart beating donors and tissue donors only. All tissues were decontaminated twice, the first time immediately after retrieval and the second time after processing. Each tissue was submitted to microbiological culture three times, i.e., upon retrieval (Time 1), after the first decontamination (Time 2) and after the second decontamination (Time 3). The contamination rate for musculoskeletal tissues was 52%, 16.2% and 0.5% at Time 1, 2 and 3, respectively. The contamination rate for cardiovascular tissues was 84%, 42% and 6%. More than one strain was simultaneously present in 10.8% of musculoskeletal tissues and 44.6% of cardiovascular tissues. Out of 8,560 non-heart-beating donor musculoskeletal tissues, 4,689 (54.8%), 1,383 (16.2%) and 42 (0.5%) were contaminated at Time 1, Time 2 and Time 3, respectively. Out of 1,475 heart-beating donor musculoskeletal tissues, 522 (35.4%) 113 (7.7%) and 2 (0.1%) tissues were found to be contaminated at Time 1, 2 and 3, respectively. Out of 984 non-heart beating donor cardiovascular tissues, 869 (88.3%), 449 (45.6%) and 69 (7%) proved positive at Time 1, 2 and 3 respectively, while 50 (45.5%) and 10 (9.1%) heart-beating donor cardiovascular tissues were contaminated at Time 1 and 2. No tissue was contaminated at Time 3. Based on our methods, the two-step decontamination approach is mandatory in order to drastically reduce the number of tissues found to be positive at the end of the process. PMID:28267776

  17. Allografts for Ligament Reconstruction: Where Are We Now?

    PubMed

    Wydra, Frank B; York, Philip J; Johnson, Christopher R; Silvestri, Lorenzo

    The use of musculoskeletal allografts by orthopedic surgeons continues to rise. The process of procuring and sterilizing allografts is evolving with much consideration to limiting the spread of infectious diseases and preserving tissue integrity. Research involving the application of allografts, particularly for ligament repair, is quite active, necessitating an update for the practicing orthopedist. Avoiding donor site morbidities is one of the most commonly cited advantages of allografts over autografts. There is controversy amongst studies for allografts in terms of their biological incorporation and clinical outcomes compared to autografts. This article focuses on reviewing the most current literature and usage of allograft tissue for ligamentous reconstruction amongst orthopedic surgeons today. It includes an in-depth analysis of the current processing, handling, and safety standards employed today, in addition to the advantages and disadvantages of allograft use.

  18. Supply of human allograft tissue in Canada.

    PubMed

    Lakey, Jonathan R T; Mirbolooki, Mohammadreza; Rogers, Christina; Mohr, Jim

    2007-01-01

    There is relatively little known about the supply for allograft tissues in Canada. The major aim of this study is to quantify the current or "Known Supply" of human allograft tissue (bone, tendons, soft tissue, cardiovascular, ocular and skin) from known tissue banks in Canada, to estimate the "Unknown Supply" of human allograft tissue available to Canadian users from other sources, and to investigate the nature and source of these tissue products. Two surveys were developed; one for tissue banks processing one or more tissue types and the other specific to eye banks. Thirty nine sites were initially identified as potential tissue bank respondent sites. Of the 39 sites, 29 sites indicated that they were interested in participating or would consider completing the survey. A survey package and a self-addressed courier envelope were couriered to each of 29 sites. A three week response time was indicated. The project consultants conducted telephone and email follow-up for incomplete data. Unknown supply was estimated by 5 methods. Twenty-eight of 29 sites (97%) completed and returned surveys. Over the past year, respondents reported a total of 5,691 donors (1,550 living and 4,141 cadaveric donors). Including cancellous ground bone, there were 10,729 tissue products produced by the respondent banks. Of these, 71% were produced by accredited banks and 32% were ocular tissues. Total predicted shortfall of allograft tissues was 31,860-66,481 grafts. Through estimating Current supply, and compiling additional qualitative information, this study has provided a snapshot of the current Canadian supply and shortfall of allograft tissue grafts.

  19. Effect of low dose and moderate dose gamma irradiation on the mechanical properties of bone and soft tissue allografts.

    PubMed

    Balsly, Colleen R; Cotter, Andrew T; Williams, Lisa A; Gaskins, Barton D; Moore, Mark A; Wolfinbarger, Lloyd

    2008-12-01

    The increased use of allograft tissue for musculoskeletal repair has brought more focus to the safety of allogenic tissue and the efficacy of various sterilization techniques. Gamma irradiation is an effective method for providing terminal sterilization to biological tissue, but it is also reported to have deleterious effects on tissue mechanics in a dose-dependent manner. At irradiation ranges up to 25 kGy, a clear relationship between mechanical strength and dose has yet to be established. The aim of this study was to investigate the mechanical properties of bone and soft tissue allografts, irradiated on dry ice at a low absorbed dose (18.3-21.8 kGy) and a moderate absorbed dose (24.0-28.5 kGy), using conventional compressive and tensile testing, respectively. Bone grafts consisted of Cloward dowels and iliac crest wedges, while soft tissue grafts consisted of patellar tendons, anterior tibialis tendons, semitendinosus tendons, and fascia lata. There were no statistical differences in mechanical strength or modulus of elasticity for any graft irradiated at a low absorbed dose, compared to control groups. Also, bone allografts and two soft tissue allografts (anterior tibialis and semitendinosus tendon) that were irradiated at a moderate dose demonstrated similar strength and modulus of elasticity values to control groups. The results of this study support the use of low dose and moderate dose gamma irradiation of bone grafts. For soft tissue grafts, the results support the use of low dose irradiation.

  20. Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction.

    PubMed

    Yan, Qiang; Wang, Baoyao; Sui, Weiguo; Zou, Guimian; Chen, Huaizhou; Xie, Shenping; Zou, Hequn

    2012-01-13

    To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β) in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction. Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5) years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0) were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls. The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue. There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue. The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/9924478946162998.

  1. Allograft update: the current status of tissue regulation, procurement, processing, and sterilization.

    PubMed

    McAllister, David R; Joyce, Michael J; Mann, Barton J; Vangsness, C Thomas

    2007-12-01

    Allografts are commonly used during sports medicine surgical procedures in the United States, and their frequency of use is increasing. Based on surgeon reports, it is estimated that more than 60 000 allografts were used in knee surgeries by members of the American Orthopaedic Society for Sports Medicine in 2005. In the United States, there are governmental agencies and other regulatory bodies involved in the oversight of tissue banks. In 2005, the Food and Drug Administration finalized its requirements for current good tissue practice and has mandated new rules regarding the "manufacture" of allogenic tissue. In response to well-publicized infections associated with the implantation of allograft tissue, some tissue banks have developed methods to sterilize allograft tissue. Although many surgeons have significant concerns about the safety of allografts, the majority believe that sterilized allografts are safe but that the sterilization process negatively affects tissue biology and biomechanics. However, most know very little about the principles of sterilization and the proprietary processes currently used in tissue banking. This article will review the current status of allograft tissue regulation, procurement, processing, and sterilization in the United States.

  2. Incidence of bacterial contamination and predisposing factors during bone and tendon allograft procurement.

    PubMed

    Terzaghi, Clara; Longo, Alessia; Legnani, Claudio; Bernasconi, Davide Paolo; Faré, Maristella

    2015-03-01

    The aim of this study was to analyze factors contributing to bacteriological contamination of bone and tendon allograft. Between 2008 and 2011, 2,778 bone and tendon allografts obtained from 196 organ and tissue donors or tissue donors only were retrospectively analysed. Several variables were taken into account: donor type (organ and tissue donors vs. tissue donor), cause of death, time interval between death and tissue procurement, duration of the procurement procedure, type of allografts, number of team members, number of trainees members, associated surgical procedures, positivity to haemoculture, type of procurement. The overall incidence of graft contamination was 23 %. The cause of death, the procurement time, the duration of procurement, the associated surgical procedures were not associated with increased risk of contamination. Significant effect on contamination incidence was observed for the number of staff members performing the procurement. In addition, our study substantiated significantly higher contamination rate among bone allografts than from tendon grafts. According to these observations, in order to minimize the contamination rate of procured musculoskeletal allografts, we recommend appropriate donor selection, use of standard sterile techniques, immediate packaging of each allograft to reduce graft exposure. Allograft procurement should be performed by a small surgical team.

  3. In vivo tissue engineering of musculoskeletal tissues.

    PubMed

    McCullen, Seth D; Chow, Andre G Y; Stevens, Molly M

    2011-10-01

    Tissue engineering of musculoskeletal tissues often involves the in vitro manipulation and culture of progenitor cells, growth factors and biomaterial scaffolds. Though in vitro tissue engineering has greatly increased our understanding of cellular behavior and cell-material interactions, this methodology is often unable to recreate tissue with the hierarchical organization and vascularization found within native tissues. Accordingly, investigators have focused on alternative in vivo tissue engineering strategies, whereby the traditional triad (cells, growth factors, scaffolds) or a combination thereof are directly implanted at the damaged tissue site or within ectopic sites capable of supporting neo-tissue formation. In vivo tissue engineering may offer a preferential route for regeneration of musculoskeletal and other tissues with distinct advantages over in vitro methods based on the specific location of endogenous cultivation, recruitment of autologous cells, and patient-specific regenerated tissues. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Molecular testing of Klebsiella pneumoniae contaminating tissue allografts recovered from deceased donors.

    PubMed

    Ghalavand, Zohreh; Heidary Rouchi, Alireza; Bahraminasab, Hassan; Ravanasa, Elham; Mirsamadi, Elnaz Sadat; Nodeh Farahani, Narges; Nikmanesh, Bahram

    2018-02-03

    Microbiological screening of tissue allografts is crucial to prevent the transmission of bacterial and fungal infections to transplant recipients. Klebsiella was the most prevalent and resistant contaminating microorganism observed in our setting in the Iranian Tissue Bank. This study was conducted to determine the presence of extended-spectrum β-lactamase (ESBL) genes, antimicrobial resistance patterns of Klebsiella pneumoniae isolates, and their clonal relationships in allograft materials. K. pneumoniae contaminating bone and other tissue allografts recovered from deceased donors were identified and ESBL isolates were detected using a phenotypic confirmatory method. Antimicrobial susceptibility testing was carried out using the disk diffusion method. Distribution of ESBL genes and molecular typing were performed using polymerase chain reaction (PCR) and Repetitive-element (rep-PCR) methods. Of 3828 donated tissues, 51 (1.3%) were found contaminated by K. pneumoniae isolates. Compared to tissue allografts from brain-dead, heart-beating tissue donors, allografts from donors with circulatory cessation were associated with a higher risk of K. pneumoniae contamination [odds ratio (OR), 1.2 (CI 95% 0.9-2.3) (P value < 0.001)]. Half of the isolates produced ESBL, and the rate of susceptibility to cephalosporins was 51%. Among isolates, 22 (43.1%) harbored CTX-M, 31 (60.8%) SHV, and 9 (17.6%) harbored TEM types. The rep-dendrogram indicated that clones having identical or related strains with a similar antibiotype were isolated in the same period. This study provides evidence that a single clone of K. pneumoniae contaminated tissue allografts recovered from many different donors. A single clone found on tissues from several donors suggests contamination of tissues from a single source such as the tissue recovery process and environment. Genomic DNA testing and clonality of contaminating bacteria using molecular methods can focus the epidemiologic investigation on the

  5. What Factors Influence the Biomechanical Properties of Allograft Tissue for ACL Reconstruction? A Systematic Review.

    PubMed

    Lansdown, Drew A; Riff, Andrew J; Meadows, Molly; Yanke, Adam B; Bach, Bernard R

    2017-10-01

    Allograft tissue is used in 22% to 42% of anterior cruciate ligament (ACL) reconstructions. Clinical outcomes have been inconsistent with allograft tissue, with some series reporting no differences in outcomes and others reporting increased risk of failure. There are numerous variations in processing and preparation that may influence the eventual performance of allograft tissue in ACL reconstruction. We sought to perform a systematic review to summarize the factors that affect the biomechanical properties of allograft tissue for use in ACL reconstruction. Many factors might impact the biomechanical properties of allograft tissue, and these should be understood when considering using allograft tissue or when reporting outcomes from allograft reconstruction. What factors affect the biomechanical properties of allograft tissue used for ACL reconstruction? We performed a systematic review to identify studies on factors that influence the biomechanical properties of allograft tissue through PubMed and SCOPUS databases. We included cadaveric and animal studies that reported on results of biomechanical testing, whereas studies on fixation, histologic evaluation, and clinical outcomes were excluded. There were 319 unique publications identified through the search with 48 identified as relevant to answering the study question. For each study, we recorded the type of tissue tested, parameters investigated, and the effects on biomechanical behavior, including load to failure and stiffness. Primary factors identified to influence allograft tissue properties were graft tissue type, sterilization methods (irradiation and chemical processing), graft preparation, donor parameters, and biologic adjuncts. Load to failure and graft stiffness varied across different tissue types, with nonlooped tibialis grafts exhibiting the lowest values. Studies on low-dose irradiation showed variable effects, whereas high-dose irradiation consistently produced decreased load to failure and

  6. Tissue banking in India: gamma-irradiated allografts.

    PubMed

    Lobo Gajiwala, A

    2003-01-01

    In India, the procurement of tissues for transplantation is governed by the Transplantation of Human Organs Act, 1994. Although this law exists, it is primarily applied to organ transplantation and rules and regulations that are specific to tissue banking which have yet to be developed. The Tata Memorial Hospital (TMH) Tissue Bank was started in 1988 as part of an International Atomic Energy Agency (IAEA) programme to promote the use of ionising radiation for the sterilisation of biological tissues. It represents the Government of India within this project and was the first facility in the country to use radiation for the sterilisation of allografts. It is registered with the Health Services Maharashtra State and provides freeze-dried, gamma irradiated amnion, dura mater, skin and bone. The tissues are obtained either from cadavers or live donors. To date the TMH Tissue Bank has provided 6328 allografts which have found use as biological dressings and in various reconstructive procedures. The TMH Tissue Bank has helped initiate a Tissue Bank at the Defence Laboratory (DL), Jodhpur. At present these are the only two Banks in the country using radiation for the terminal sterilisation of preserved tissues. The availability of safe, clinically useful and cost effective grafts has stimulated innovative approaches to surgery. There is an increased demand for banked tissues and a heightened interest in the development of tissue banks. Inadequate infrastructure for donor referral programmes and the lack of support for tissue transplant co-ordinators however, continue to limit the availability of donor tissue.

  7. An Overview of Recent Patents on Musculoskeletal Interface Tissue Engineering

    PubMed Central

    Rao, Rohit T.; Browe, Daniel P.; Lowe, Christopher J.; Freeman, Joseph W.

    2018-01-01

    Interface tissue engineering involves the development of engineered grafts that promote integration between multiple tissue types. Musculoskeletal tissue interfaces are critical to the safe and efficient transmission of mechanical forces between multiple musculoskeletal tissues e.g. between ligament and bone tissue. However, these interfaces often do not physiologically regenerate upon injury, resulting in impaired tissue function. Therefore, interface tissue engineering approaches are considered to be particularly relevant for the structural restoration of musculoskeletal tissues interfaces. In this article we provide an overview of the various strategies used for engineering musculoskeletal tissue interfaces with a specific focus on the recent important patents that have been issued for inventions that were specifically designed for engineering musculoskeletal interfaces as well as those that show promise to be adapted for this purpose. PMID:26577344

  8. Allograft integration in a rabbit transgenic model for anterior cruciate ligament reconstruction.

    PubMed

    Bachy, M; Sherifi, I; Zadegan, F; Petite, H; Vialle, R; Hannouche, D

    2016-04-01

    Tissue engineering strategies include both cell-based and cell homing therapies. Ligamentous tissues are highly specialized and constitute vital components of the musculoskeletal system. Their damage causes significant morbidity and loss in function. The aim of this study is to analyze tendinous graft integration, cell repopulation and ligamentization by using GFP+/- allografts in GFP+/- transgenic New Zealand white (NZW) rabbits. Graft implantation was designed to closely mimic anterior cruciate ligament (ACL) repair surgery. Allografts were implanted in 8 NZW rabbits and assessed at 5 days, 3 weeks and 6 weeks through: (1) arthroCT imaging, (2) morphological analysis of the transplanted allograft, (3) histological analysis, (4) collagen type I immunochemistry, and (5) GFP cell tracking. Collagen remodeling was appreciated at 3 and 6 weeks. Graft repopulation with host cells, chondrocyte-like cells at the tendon-bone interface and graft corticalization in the bone tunnels were noticed at 3 weeks. By contrast we noticed a central necrosis aspect in the allografts intra-articularly at 6 weeks with a cell migration towards the graft edge near the synovium. Our study has served to gain a better understanding of tendinous allograft bone integration, ligamentization and allograft repopulation. We believe that both cell-based therapies and cell homing therapies are beneficial in ligament tissue engineering. Future studies may elucidate whether cell repopulation occurs with pre-differentiated or progenitor cells. We believe that both cell-based therapies and cell homing therapies are beneficial in ligament tissue engineering. Level V (animal study). Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Evaluation of new antibiotic cocktails against contaminating bacteria found in allograft tissues.

    PubMed

    Serafini, Agnese; Riello, Erika; Trojan, Diletta; Cogliati, Elisa; Palù, Giorgio; Manganelli, Riccardo; Paolin, Adolfo

    2016-12-01

    Contamination of retrieved tissues is a major problem for allograft safety. Consequently, tissue banks have implemented decontamination protocols to eliminate microorganisms from tissues. Despite the widespread adoption of these protocols, few comprehensive studies validating such methods have been published. In this manuscript we compare the bactericidal activity of different antibiotic cocktails at different temperatures against a panel of bacterial species frequently isolated in allograft tissues collected at the Treviso Tissue Bank Foundation, a reference organization of the Veneto Region in Italy that was instituted to select, recover, process, store and distribute human tissues. We were able to identify at least two different formulations capable of killing most of the bacteria during prolonged incubation at 4 °C.

  10. Allograft Fascia Lata as an Augmentation Device for Musculoskeletal Repairs

    DTIC Science & Technology

    2008-12-01

    TissueMend® ( fetal bovine dermis), Restore® (porcine small intestine submucosa), CuffPatch™ (crosslinked porcine small intestine submucosa) and...transfers, grafting lacerated muscles, periosteal coverage and wound healing. Providing an effective treatment for musculoskeletal conditions such

  11. Assessment of tissue allograft safety monitoring with administrative healthcare databases: a pilot project using Medicare data.

    PubMed

    Dhakal, Sanjaya; Burwen, Dale R; Polakowski, Laura L; Zinderman, Craig E; Wise, Robert P

    2014-03-01

    Assess whether Medicare data are useful for monitoring tissue allograft safety and utilization. We used health care claims (billing) data from 2007 for 35 million fee-for-service Medicare beneficiaries, a predominantly elderly population. Using search terms for transplant-related procedures, we generated lists of ICD-9-CM and CPT(®) codes and assessed the frequency of selected allograft procedures. Step 1 used inpatient data and ICD-9-CM procedure codes. Step 2 added non-institutional provider (e.g., physician) claims, outpatient institutional claims, and CPT codes. We assembled preliminary lists of diagnosis codes for infections after selected allograft procedures. Many ICD-9-CM codes were ambiguous as to whether the procedure involved an allograft. Among 1.3 million persons with a procedure ascertained using the list of ICD-9-CM codes, only 1,886 claims clearly involved an allograft. CPT codes enabled better ascertainment of some allograft procedures (over 17,000 persons had corneal transplants and over 2,700 had allograft skin transplants). For spinal fusion procedures, CPT codes improved specificity for allografts; of nearly 100,000 patients with ICD-9-CM codes for spinal fusions, more than 34,000 had CPT codes indicating allograft use. Monitoring infrequent events (infections) after infrequent exposures (tissue allografts) requires large study populations. A strength of the large Medicare databases is the substantial number of certain allograft procedures. Limitations include lack of clinical detail and donor information. Medicare data can potentially augment passive reporting systems and may be useful for monitoring tissue allograft safety and utilization where codes clearly identify allograft use and coding algorithms can effectively screen for infections.

  12. The effect of sterilization on mechanical properties of soft tissue allografts.

    PubMed

    Conrad, Bryan P; Rappé, Matthew; Horodyski, MaryBeth; Farmer, Kevin W; Indelicato, Peter A

    2013-09-01

    One major concern regarding soft tissue allograft use in surgical procedures is the risk of disease transmission. Current techniques of tissue sterilization, such as irradiation have been shown to adversely affect the mechanical properties of soft tissues. Grafts processed using Biocleanse processing (a proprietary technique developed by Regeneration Technologies to sterilize human tissues) will have better biomechanical characteristics than tissues that have been irradiated. Fifteen pairs of cadaveric Achilles tendon allografts were obtained and separated into three groups of 10 each. Three treatment groups were: Biocleanse, Irradiated, and Control (untreated). Each specimen was tested to determine the biomechanical properties of the tissue. Specimens were cyclically preloaded and then loaded to failure in tension. During testing, load, displacement, and optical strain data were captured. Following testing, the cross sectional area of the tendons was determined. Tendons in the control group were found to have a higher extrinsic stiffness (slope of the load-deformation curve, p = .005), have a higher ultimate stress (force/cross sectional area, p = .006) and higher ultimate failure load (p = .003) than irradiated grafts. Biocleanse grafts were also found to be stiffer than irradiated grafts (p = .014) yet were not found to be statistically different from either irradiated or non-irradiated grafts in terms of load to failure. Biocleanse processing seems to be a viable alternative to irradiation for Achilles tendon allografts sterilization in terms of their biomechanical properties.

  13. Advanced Hemophilic Arthropathy: Sensitivity of Soft Tissue Discrimination With Musculoskeletal Ultrasound.

    PubMed

    von Drygalski, Annette; Moore, Randy E; Nguyen, Sonha; Barnes, Richard F W; Volland, Lena M; Hughes, Tudor H; Du, Jiang; Chang, Eric Y

    2018-01-24

    Point-of-care musculoskeletal ultrasound (US) is increasingly used by hemophilia providers to guide management; however, pathologic tissue differentiation with US is uncertain. We sought to determine the extent to which point-of-care musculoskeletal US can identify and discriminate pathologic soft tissue changes in hemophilic arthropathy. Thirty-six adult patients with hemophilia A/B were prospectively enrolled. Point-of-care musculoskeletal US examinations were performed on arthropathic joints (16 knees, 10 ankles, and 10 elbows) using standard views by a musculoskeletal US-trained and certified hematologist, who recorded abnormal intra-articular soft tissue accumulation. Within 3 days, magnetic resonance imaging was performed using conventional and multiecho ultrashort echo time sequences. Soft tissue identification (synovial proliferation with or without hemosiderin, fat, and/or blood products) was performed by a musculoskeletal radiologist. Findings obtained with both imaging modalities were compared and correlated in a blinded fashion. There was perfect agreement between the modalities on the presence of abnormal soft tissue (34 of 36 cases). However, musculoskeletal US was unable to discriminate between coagulated blood, synovium, intrasynovial or extrasynovial fat tissue, or hemosiderin deposits because of wide variations in echogenicity. Musculoskeletal US is valuable for point-of-care imaging to determine the presence of soft tissue accumulation in discrete areas. However, because of limitations of musculoskeletal US in discriminating the nature of pathologic soft tissues and detecting hemosiderin, magnetic resonance imaging will be required if such discrimination is clinically important. © 2018 by the American Institute of Ultrasound in Medicine.

  14. Autograft versus nonirradiated allograft tissue for anterior cruciate ligament reconstruction: a systematic review.

    PubMed

    Mariscalco, Michael W; Magnussen, Robert A; Mehta, Divyesh; Hewett, Timothy E; Flanigan, David C; Kaeding, Christopher C

    2014-02-01

    An autograft has traditionally been the gold standard for anterior cruciate ligament reconstruction (ACLR), but the use of allograft tissue has increased in recent years. While numerous studies have demonstrated that irradiated allografts are associated with increased failure rates, some report excellent results after ACLR with nonirradiated allografts. The purpose of this systematic review was to determine whether the use of nonirradiated allograft tissue is associated with poorer outcomes when compared with autografts. Patients undergoing ACLR with autografts versus nonirradiated allografts will demonstrate no significant differences in graft failure risk, laxity on postoperative physical examination, or differences in patient-oriented outcome scores. Systematic review. A systematic review was performed to identify prospective or retrospective comparative studies (evidence level 1, 2, or 3) of autografts versus nonirradiated allografts for ACLR. Outcome data included graft failure based on clinical findings and instrumented laxity, postoperative laxity on physical examination, and patient-reported outcome scores. Studies were excluded if they did not specify whether the allograft had been irradiated. Quality assessment and data extraction were performed by 2 examiners. Nine studies comparing autografts and nonirradiated allografts were included. Six of the 9 studies compared bone-patellar tendon-bone (BPTB) autografts with BPTB allografts. Two studies compared hamstring tendon autografts to hamstring tendon allografts, and 1 study compared hamstring tendon autografts to tibialis anterior allografts. The mean patient age in 7 of 9 studies ranged from 24.5 to 32 years, with 1 study including only patients older than 40 years and another not reporting patient age. The mean follow-up duration was 24 to 94 months. Six of 9 studies reported clinical graft failure rates, 8 of 9 reported postoperative instrumented laxity measurements, 7 of 9 reported postoperative

  15. Common Soft Tissue Musculoskeletal Pain Disorders.

    PubMed

    Hubbard, Matthew J; Hildebrand, Bernard A; Battafarano, Monica M; Battafarano, Daniel F

    2018-06-01

    Soft tissue musculoskeletal pain disorders are common in the primary care setting. Early recognition and diagnosis of these syndromes minimizes patient pain and disability. This article gives a brief overview of the most common soft tissue musculoskeletal pain syndromes. The authors used a regional approach to organize the material, as providers will encounter these syndromes with complaints of pain referring to an anatomic location. The covered disorders include myofascial pain syndrome, rotator cuff tendinopathy, bicipital tendinopathy, subacromial bursitis, olecranon bursitis, epicondylitis, De Quervain disease, trigger finger, trochanteric bursitis, knee bursitis, pes anserine bursitis, Baker cyst, plantar fasciitis, and Achilles tendinopathy. Published by Elsevier Inc.

  16. Fresh osteochondral allografts-procurement and tissue donation in Europe.

    PubMed

    Schmidt, S; Schulte, A; Schwarz, S; Hofmann, N; Tietz, S; Boergel, M; Sixt, S U

    2017-07-01

    Fresh osteochondral allografts are a well-established treatment for large, full-thickness cartilage defects. The clinical outcome for carefully selected patients is very favorable, especially for the young and active and graft survival up to 25 years has been described in the literature. Furthermore, a high patient satisfaction rate has been reported, but the biggest obstacle to overcome is the availability of tissue for transplantation. Large fresh bone allografts for cartilage damage repair only can be harvested from organ donors following organ removal or cadaveric donors, preferably in the setting of an operation room to minimize possible contamination of the tissue. Apart from the logistic challenges this entails, an experienced recovery team is needed. Furthermore, the public as well as medical staff is much less aware of the possibility and requirements of tissue donation than organ donation and families of deceased are rarely approached for bone and cartilage donation. This review aims to highlight the current situation of organ and tissue donation in Europe with special focus on the processing of bones and possible safety and quality concerns. We analyze what may prevent consent and what might be done to improve the situation of tissue donation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. What tissue bankers should know about the use of allograft meniscus in orthopaedics.

    PubMed

    McDermott, Ian D

    2010-02-01

    The menisci of the knee are two crescent shaped cartilage shock absorbers sitting between the femur and the tibia, which act as load sharers and shock absorbers. Loss of a meniscus leads to a significant increase in the risk of developing arthritis in the knee. Replacement of a missing meniscus with allograft tissue can reduce symptoms and may potentially reduce the risk of future arthritis. Meniscal allograft transplantation is a complex surgical procedure with many outstanding issues, including 'what techniques should be used for processing and storing grafts?', 'how should the allografts be sized?' and 'what surgical implantation techniques might be most appropriate?' Further clinical research is needed and close collaboration between the users (surgeons) and the suppliers (tissue banks) is essential. This review explores the above subject in detail.

  18. Emergence of Scaffold-free Approaches for Tissue Engineering Musculoskeletal Cartilages

    PubMed Central

    DuRaine, Grayson D.; Brown, Wendy E.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2014-01-01

    This review explores scaffold-free methods as an additional paradigm for tissue engineering. Musculoskeletal cartilages –for example articular cartilage, meniscus, temporomandibular joint disc, and intervertebral disc – are characterized by low vascularity and cellularity, and are amenable to scaffold-free tissue engineering approaches. Scaffold-free approaches, particularly the self-assembling process, mimic elements of developmental processes underlying these tissues. Discussed are various scaffold-free approaches for musculoskeletal cartilage tissue engineering, such as cell sheet engineering, aggregation, and the self-assembling process, as well as the availability and variety of cells used. Immunological considerations are of particular importance as engineered tissues are frequently of allogeneic, if not xenogeneic, origin. Factors that enhance the matrix production and mechanical properties of these engineered cartilages are also reviewed, as the fabrication of biomimetically suitable tissues is necessary to replicate function and ensure graft survival in vivo. The concept of combining scaffold-free and scaffold-based tissue engineering methods to address clinical needs is also discussed. Inasmuch as scaffold-based musculoskeletal tissue engineering approaches have been employed as a paradigm to generate engineered cartilages with appropriate functional properties, scaffold-free approaches are emerging as promising elements of a translational pathway not only for musculoskeletal cartilages but for other tissues as well. PMID:25331099

  19. Bone-Patellar Tendon-Bone Versus Soft-Tissue Allograft for Anterior Cruciate Ligament Reconstruction: A Systematic Review.

    PubMed

    Joyce, Christopher D; Randall, Kyle L; Mariscalco, Michael W; Magnussen, Robert A; Flanigan, David C

    2016-02-01

    To describe the outcomes of bone-patellar tendon-bone (BPTB) and soft-tissue allografts in anterior cruciate ligament (ACL) reconstruction with respect to graft failure risk, physical examination findings, instrumented laxity, and patient-reported outcomes. A search of the PubMed, Scopus, CINAHL (Cumulative Index to Nursing and Allied Health Literature) Complete, Cochrane Collaboration, and SPORTDiscus databases was performed. English-language studies with outcome data on primary ACL reconstruction with nonirradiated BPTB and soft-tissue allografts were identified. Outcome data included failure risk, physical examination findings, instrumented laxity measurements, and patient-reported outcome scores. Seventeen studies met the inclusion criteria. Of these studies, 11 reported on BPTB allografts exclusively, 5 reported on soft-tissue allografts exclusively, and 1 compared both types. The comparative study showed no difference in failure risk, Lachman grade, pivot-shift grade, instrumented laxity, or overall International Knee Documentation Committee score between the 2 allograft types. Data from all studies yielded a failure risk of 10.3% (95% confidence interval [CI], 4.5% to 18.1%) in the soft-tissue group and 15.2% (95% CI, 11.3% to 19.6%) in the BPTB group. The risk of a Lachman grade greater than 5 mm was 6.4% (95% CI, 1.7% to 13.7%) in the soft-tissue group and 8.6% (95% CI, 6.3% to 11.2%) in the BPTB group. The risk of a grade 2 or 3 pivot shift was 1.4% (95% CI, 0.3% to 3.3%) in the soft-tissue group and 4.1% (95% CI, 1.9% to 7.2%) in the BPTB group. One comparative study showed no difference in results after ACL reconstruction with nonirradiated BPTB and soft-tissue allografts. Inclusion of case series in the analysis showed qualitatively similar outcomes with the 2 graft types. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  20. Effect of a novel sterilization method on biomechanical properties of soft tissue allografts.

    PubMed

    Baldini, T; Caperton, K; Hawkins, M; McCarty, E

    2016-12-01

    Evaluate allograft tissue commonly used in soft tissue reconstruction to determine whether stiffness and strength were significantly altered after grafts were treated with different sterilization methods. Unprocessed, irradiated, and grafts treated with supercritical CO 2 were compared. Thirty-eight anterior or posterior tibialis tendons were obtained from a tissue bank (Allograft Innovations, Gainesville, FL). Group I was unprocessed, group II was sterilized with gamma irradiation (20-28 kGy), and group III was sterilized with supercritical CO 2 . The grafts were pretensioned to 89 N for 300 s. Specimens were then loaded from 50 to 300 N at 0.5 Hz for 250 cycles before being loaded to failure at 50 mm/min. Dependent variables were compared between sterilization groups with one-way ANOVA (P < 0.05) and equivalence trial. There was no significant difference in load to failure or failure stress among groups I, II, and III. Group III resulted in 27-36 % lower stiffness than group I and II. This difference was significant at 1, 10, 50, 100, and 250 cycles. There was no significant difference in stiffness between group I and group II. The two sterilization methods tested in this study do not affect allograft strength. The supercritical CO 2 sterilization method resulted in significantly lower stiffness than unprocessed and irradiated allografts. However, the stiffness and strength of all groups tested were greater than that of published values of the native intact anterior cruciate ligament (ACL). This study provides previously unpublished mechanical test data on a new sterilization technique that will assist surgeons to decide which allograft to use in ACL reconstruction surgery. III.

  1. Emulating Native Periosteum Cell Population and Subsequent Paracrine Factor Production To Promote Tissue Engineered Periosteum-Mediated Allograft Healing

    PubMed Central

    Hoffman, Michael D.

    2015-01-01

    Emulating autograft healing within the context of decellularized bone allografts has immediate clinical applications in the treatment of critical-sized bone defects. The periosteum, a thin, osteogenic tissue that surrounds bone, houses a heterogeneous population of stem cells and osteoprogenitors. There is evidence that periosteum-cell derived paracrine factors, specifically vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2), orchestrate autograft healing through host cell recruitment and subsequent tissue elaboration. In previous work, we demonstrated that the use of poly(ethylene glycol) (PEG) hydrogels as a tissue engineered (T.E.) periosteum to localize mesenchymal stem cells (MSCs) to the surface of decellularized bone enhances allograft healing and integration. Herein, we utilize a mixed population of 50:50 MSCs and osteoprogenitor cells to better mimic native periosteum cell population and paracrine factor production to further promote allograft healing. This mixed cell population was localized to the surface of decellularized allografts within degradable hydrogels and shown to expedite allograft healing. Specifically, bone callus formation and biomechanical graft-host integration are increased as compared to unmodified allografts. These results demonstrate the dual importance of periosteum-mediated paracrine factors orchestrating host cell recruitment as well as new bone formation while developing clinically translatable strategies for allograft healing and integration. PMID:25818449

  2. Radioprotection provides functional mechanics but delays healing of irradiated tendon allografts after ACL reconstruction in sheep.

    PubMed

    Seto, Aaron U; Culp, Brian M; Gatt, Charles J; Dunn, Michael

    2013-12-01

    Successful protection of tissue properties against ionizing radiation effects could allow its use for terminal sterilization of musculoskeletal allografts. In this study we functionally evaluate Achilles tendon allografts processed with a previously developed radioprotective treatment based on (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) crosslinking and free radical scavenging using ascorbate and riboflavin, for ovine anterior cruciate ligament reconstruction. Arthroscopic anterior cruciate ligament (ACL) reconstruction was performed using double looped allografts, while comparing radioprotected irradiated and fresh frozen allografts after 12 and 24 weeks post-implantation, and to control irradiated grafts after 12 weeks. Radioprotection was successful at preserving early subfailure mechanical properties comparable to fresh frozen allografts. Twelve week graft stiffness and anterior-tibial (A-T) translation for radioprotected and fresh frozen allografts were comparable at 30 % of native stiffness, and 4.6 and 5 times native A-T translation, respectively. Fresh frozen allograft possessed the greatest 24 week peak load at 840 N and stiffness at 177 N/mm. Histological evidence suggested a delay in tendon to bone healing for radioprotected allografts, which was reflected in mechanical properties. There was no evidence that radioprotective treatment inhibited intra-articular graft healing. This specific radioprotective method cannot be recommended for ACL reconstruction allografts, and data suggest that future efforts to improve allograft sterilization procedures should focus on modifying or eliminating the pre-crosslinking procedure.

  3. Amnion allografts prepared in the Central Tissue Bank in Warsaw.

    PubMed

    Tyszkiewicz, J T; Uhrynowska-Tyszkiewicz, I A; Kaminski, A; Dziedzic-Goclawska, A

    1999-01-01

    Applications of allogenic amnion grafts range from wound dressing of severe burns, dermabrasions and lower extremity ulcer treatments to plastic surgery, laryngology and ophthalmology. The aim of the present study was to elaborate the method of processing, preservation and sterilization of human amnion allografts prepared as wound dressing used mainly for burned patients. During the amniotic sac processing (after separation of chorion) special attention was paid to ensure that the epithelial side of amnion is placed directly on polyester net used as a support. After application on the wound, the epithelial side with the basement membrane is facing outwards; this will promote migration, attachment and spreading of the host cells encouraging epithelialization. Human amnion allografts were preserved by lyophilization or deep-freezing and subsequently radiation-sterilized with a dose of 35 kGy. It has been observed, however, that lyophilized irradiated allografts are resorbed within a few days, while frozen irradiated ones better adhere to wound and persist even 3 weeks after grafting, therefore, it has been decided to preserve amnion by deep-freezing. Since the beginning of 1998 over 400 preserved radiation-sterilized amnion allografts (with a total surface area over 40,000 cm2) have been prepared at the Central Tissue Bank in Warsaw and distributed to clinics and hospitals throughout the country.

  4. Risk of Infection After Allograft Anterior Cruciate Ligament Reconstruction: Are Nonprocessed Allografts More Likely to Get Infected? A Cohort Study of Over 10,000 Allografts.

    PubMed

    Yu, Anthony; Prentice, Heather A; Burfeind, William E; Funahashi, Tadashi; Maletis, Gregory B

    2018-03-01

    Allograft tissue is frequently used in anterior cruciate ligament reconstruction (ACLR). It is often irradiated and/or chemically processed to decrease the risk of disease transmission, but some tissue is aseptically harvested without further processing. Irradiated and chemically processed allograft tissue appears to have a higher risk of revision, but whether this processing decreases the risk of infection is not clear. To determine the incidence of deep surgical site infection after ACLR with allograft in a large community-based sample and to evaluate the association of allograft processing and the risk of deep infection. Cohort study; Level of evidence, 3. The authors conducted a cohort study using the Kaiser Permanente Anterior Cruciate Ligament Reconstruction Registry. Primary isolated unilateral ACLR with allograft were identified from February 1, 2005 to September 30, 2015. Ninety-day postoperative deep infections were identified via an electronic screening algorithm and then validated through chart review. Logistic regression was used to evaluate the likelihood of 90-day postoperative deep infection per allograft processing method: processed (graft treated chemically and/or irradiated) or nonprocessed (graft not irradiated or chemically processed). Of 10,190 allograft cases, 8425 (82.7%) received a processed allograft, and 1765 (17.3%) received a nonprocessed allograft. There were 15 (0.15%) deep infections during the study period: 4 (26.7%) coagulase-negative Staphylococcus, 4 (26.7%) methicillin-sensitive Staphylococcus aureus, 1 (6.7%) Peptostreptococcus micros, and 6 (40.0%) with no growth. There was no difference in the likelihood for 90-day deep infection for processed versus nonprocessed allografts (odds ratio = 1.36, 95% CI = 0.31-6.04). The overall incidence of deep infection after ACLR with allograft tissue was very low (0.15%), suggesting that the methods currently employed by tissue banks to minimize the risk of infection are effective. In this

  5. The effect of mesenchymal stem cells delivered via hydrogel-based tissue engineered periosteum on bone allograft healing.

    PubMed

    Hoffman, Michael D; Xie, Chao; Zhang, Xinping; Benoit, Danielle S W

    2013-11-01

    Allografts remain the clinical "gold standard" for treatment of critical sized bone defects despite minimal engraftment and ∼60% long-term failure rates. Therefore, the development of strategies to improve allograft healing and integration are necessary. The periosteum and its associated stem cell population, which are lacking in allografts, coordinate autograft healing. Herein we utilized hydrolytically degradable hydrogels to transplant and localize mesenchymal stem cells (MSCs) to allograft surfaces, creating a periosteum mimetic, termed a 'tissue engineered periosteum'. Our results demonstrated that this tissue engineering approach resulted in increased graft vascularization (∼2.4-fold), endochondral bone formation (∼2.8-fold), and biomechanical strength (1.8-fold), as compared to untreated allografts, over 16 weeks of healing. Despite this enhancement in healing, the process of endochondral ossification was delayed compared to autografts, requiring further modifications for this approach to be clinically acceptable. However, this bottom-up biomaterials approach, the engineered periosteum, can be augmented with alternative cell types, matrix cues, growth factors, and/or other small molecule drugs to expedite the process of ossification. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. The effect of mesenchymal stem cells delivered via hydrogel-based tissue engineered periosteum on bone allograft healing

    PubMed Central

    Hoffman, Michael D.; Xie, Chao; Zhang, Xinping; Benoit, Danielle S.W.

    2013-01-01

    Allografts remain the clinical “gold standard” for treatment of critical sized bone defects despite minimal engraftment and ~60% long-term failure rates. Therefore, the development of strategies to improve allograft healing and integration are necessary. The periosteum and its associated stem cell population, which are lacking in allografts, coordinate autograft healing. Herein we utilized hydrolytically degradable hydrogels to transplant and localize mesenchymal stem cells (MSCs) to allograft surfaces, creating a periosteum mimetic, termed a ‘tissue engineered periosteum’. Our results demonstrated that this tissue engineering approach resulted in increased graft vascularization (~2.4-fold), endochondral bone formation (~2.8-fold), and biomechanical strength (1.8-fold), as compared to untreated allografts, over 16 weeks of healing. Despite this enhancement in healing, the process of endochondral ossification was delayed compared to autografts, requiring further modifications for this approach to be clinically acceptable. However, this bottom-up biomaterials approach, the engineered periosteum, can be augmented with alternative cell types, matrix cues, growth factors, and/or other small molecule drugs to expedite the process of ossification. PMID:23958029

  7. Seeing through Musculoskeletal Tissues: Improving In Situ Imaging of Bone and the Lacunar Canalicular System through Optical Clearing

    PubMed Central

    Berke, Ian M.; Miola, Joseph P.; David, Michael A.; Smith, Melanie K.; Price, Christopher

    2016-01-01

    In situ, cells of the musculoskeletal system reside within complex and often interconnected 3-D environments. Key to better understanding how 3-D tissue and cellular environments regulate musculoskeletal physiology, homeostasis, and health is the use of robust methodologies for directly visualizing cell-cell and cell-matrix architecture in situ. However, the use of standard optical imaging techniques is often of limited utility in deep imaging of intact musculoskeletal tissues due to the highly scattering nature of biological tissues. Drawing inspiration from recent developments in the deep-tissue imaging field, we describe the application of immersion based optical clearing techniques, which utilize the principle of refractive index (RI) matching between the clearing/mounting media and tissue under observation, to improve the deep, in situ imaging of musculoskeletal tissues. To date, few optical clearing techniques have been applied specifically to musculoskeletal tissues, and a systematic comparison of the clearing ability of optical clearing agents in musculoskeletal tissues has yet to be fully demonstrated. In this study we tested the ability of eight different aqueous and non-aqueous clearing agents, with RIs ranging from 1.45 to 1.56, to optically clear murine knee joints and cortical bone. We demonstrated and quantified the ability of these optical clearing agents to clear musculoskeletal tissues and improve both macro- and micro-scale imaging of musculoskeletal tissue across several imaging modalities (stereomicroscopy, spectroscopy, and one-, and two-photon confocal microscopy) and investigational techniques (dynamic bone labeling and en bloc tissue staining). Based upon these findings we believe that optical clearing, in combination with advanced imaging techniques, has the potential to complement classical musculoskeletal analysis techniques; opening the door for improved in situ investigation and quantification of musculoskeletal tissues. PMID:26930293

  8. Seeing through Musculoskeletal Tissues: Improving In Situ Imaging of Bone and the Lacunar Canalicular System through Optical Clearing.

    PubMed

    Berke, Ian M; Miola, Joseph P; David, Michael A; Smith, Melanie K; Price, Christopher

    2016-01-01

    In situ, cells of the musculoskeletal system reside within complex and often interconnected 3-D environments. Key to better understanding how 3-D tissue and cellular environments regulate musculoskeletal physiology, homeostasis, and health is the use of robust methodologies for directly visualizing cell-cell and cell-matrix architecture in situ. However, the use of standard optical imaging techniques is often of limited utility in deep imaging of intact musculoskeletal tissues due to the highly scattering nature of biological tissues. Drawing inspiration from recent developments in the deep-tissue imaging field, we describe the application of immersion based optical clearing techniques, which utilize the principle of refractive index (RI) matching between the clearing/mounting media and tissue under observation, to improve the deep, in situ imaging of musculoskeletal tissues. To date, few optical clearing techniques have been applied specifically to musculoskeletal tissues, and a systematic comparison of the clearing ability of optical clearing agents in musculoskeletal tissues has yet to be fully demonstrated. In this study we tested the ability of eight different aqueous and non-aqueous clearing agents, with RIs ranging from 1.45 to 1.56, to optically clear murine knee joints and cortical bone. We demonstrated and quantified the ability of these optical clearing agents to clear musculoskeletal tissues and improve both macro- and micro-scale imaging of musculoskeletal tissue across several imaging modalities (stereomicroscopy, spectroscopy, and one-, and two-photon confocal microscopy) and investigational techniques (dynamic bone labeling and en bloc tissue staining). Based upon these findings we believe that optical clearing, in combination with advanced imaging techniques, has the potential to complement classical musculoskeletal analysis techniques; opening the door for improved in situ investigation and quantification of musculoskeletal tissues.

  9. Increased Risk of Revision After Anterior Cruciate Ligament Reconstruction With Soft Tissue Allografts Compared With Autografts: Graft Processing and Time Make a Difference.

    PubMed

    Maletis, Gregory B; Chen, Jason; Inacio, Maria C S; Love, Rebecca M; Funahashi, Tadashi T

    2017-07-01

    The optimal graft for anterior cruciate ligament reconstruction (ACLR) remains controversial. To compare the risk of aseptic revision between bone-patellar tendon-bone (BPTB) autografts, hamstring autografts, and soft tissue allografts. Cohort study; Level of evidence, 2. Prospectively collected ACLR cases reconstructed with BPTB autografts, hamstring autografts, and soft tissue allografts were identified using the Kaiser Permanente ACLR Registry. Aseptic revision was the endpoint. The type of graft and allograft processing method (nonprocessed, <1.8-Mrad irradiation with and without chemical processing [Allowash or AlloTrue], ≥1.8-Mrad irradiation with and without chemical processing, and chemical processing alone [BioCleanse]) were the exposures evaluated. Analyses were adjusted for age, sex, and race. Kaplan-Meier curves and Cox proportional hazards models were employed. The cohort included 14,015 cases: there were 8924 (63.7%) male patients, there were 6397 (45.6%) white patients, 4557 (32.5%) ACLRs used BPTB autografts, 3751 ACLRs (26.8%) used soft tissue allografts, and 5707 (40.7%) ACLRs used hamstring autografts. The median age was 34.6 years for soft tissue allografts, 24.3 years for hamstring autografts, and 22.0 years for BPTB autografts. The crude nonadjusted revision rates were 85 (1.9%) in BPTB autograft cases, 132 (2.3%) in hamstring autograft cases, and 83 (2.2%) in soft tissue allograft cases. After adjusting for age, sex, and race, compared with hamstring autografts, a higher risk of revision was found with allografts with ≥1.8 Mrad without chemical processing after 2.5 years (hazard ratio [HR], 3.88; 95% CI, 1.48-10.12) and ≥1.8 Mrad with chemical processing after 1 year (HR, 3.43; 95% CI, 1.58-7.47) and with BioCleanse processed grafts at any time point (HR, 3.02; 95% CI, 1.40-6.50). Nonprocessed allografts and those irradiated with <1.8 Mrad with or without chemical processing were not found to have a different risk of revision compared

  10. Mesenchymal Stem Cells in the Musculoskeletal System: From Animal Models to Human Tissue Regeneration?

    PubMed

    Čamernik, Klemen; Barlič, Ariana; Drobnič, Matej; Marc, Janja; Jeras, Matjaž; Zupan, Janja

    2018-06-01

    The musculoskeletal system includes tissues that have remarkable regenerative capabilities. Bone and muscle sustain micro-damage throughout the lifetime, yet they continue to provide the body with the support that is needed for everyday activities. Our current understanding is that the regenerative capacity of the musculoskeletal system can be attributed to the mesenchymal stem/ stromal cells (MSCs) that reside within its different anatomical compartments. These MSCs can replenish various tissues with progenitor cells to form functional cells, such as osteoblasts, chondrocytes, myocytes, and others. However, with aging and in certain disorders of the musculoskeletal system such as osteoarthritis or osteoporosis, this regenerative capacity of MSCs appears to be lost or diverted for the production of other non-functional cell types, such as adipocytes and fibroblasts. In this review, we shed light on the tissue sources and subpopulations of MSCs in the musculoskeletal system that have been identified in animal models, discuss the mechanisms of their anti-inflammatory action as a prerequisite for their tissue regeneration and their current applications in regenerative medicine. While providing up-to-date evidence of the role of MSCs in different musculoskeletal pathologies, in particular in osteoporosis and osteoarthritis, we share some thoughts on their potential as diagnostic markers in musculoskeletal health and disease.

  11. The visual assessment of broth cultures for tissue bank samples.

    PubMed

    Varettas, Kerry

    2017-09-01

    The bioburden screening process of allograft musculoskeletal tissue samples received at the South Eastern Area Laboratory Services includes the routine use of solid agar and cooked meat (CM) broth media. CM has been routinely sub-cultured onto solid agar plates after aerobic incubation at 35 °C. This study will evaluate whether a visual assessment of CM can replace sub-culture by an in vitro inoculation and a prospective study. Eight challenge organisms were serially diluted and inoculated into CM. The average inoculum of 0.5-5.5 CFU produced visible turbidity of CM after 24-h incubation for 7 of the challenge organisms with one organism producing turbidity after 48-h incubation. The prospective study evaluated 222 CM of which 213 were visually clear and no-growth on sub-culture and 9 turbid CM which were culture positive. Broth cultures are an integral part of the bioburden screening process of allograft musculoskeletal tissue and swab samples and visual assessment of CM can replace sub-culture.

  12. The character of gene expression of human periosteum used to form new tissue in allograft bone.

    PubMed

    Kemppainen, Jessica; Yu, Qing; Alexander, John; Jacquet, Robin; Scharschmidt, Thomas; Landis, William

    2014-08-01

    Of more than 2 million segmental bone defects repaired annually with bone autografts and allografts, 15-40% fail. Improving healing rates may be approached with tissue engineering and use of periosteum overlying an allograft. The present study documents gene expression in human periosteum-allograft constructs compared to allografts alone. Strips of human cadaveric periosteum (26 years, f, distal femur) were sutured about sterilized human femoral cortical strut bone allograft (54 years, m) segments. After construct incubation (M199 supplemented medium) for 8 d, constructs and allografts alone were implanted in nude mice. At 10 and 20 weeks, constructs (N = 4, each group) and allografts (N = 2, each group) were retrieved and placed in RNAlater for quantitative PCR to determine expression of human- and murine-specific genes relevant to remodeling. Specimens were frozen-ground to powders and RNA was extracted, purified, reverse-transcribed, and amplified. Ribosomal protein (P0) was used to normalize sample quantities. Fold change plots were generated following statistical analyses comparing 20- to 10-week gene expression data. Allografts alone yielded no human-specific gene expression. Notable fold changes of human-specific alkaline phosphatase, bone sialoprotein, type I collagen, decorin, RANKL, RANK, cathepsin K, and osteocalcin in 20-week compared to 10-week specimens were found. Murine-specific expression of genes indicative of host mouse vascularization (RANK, type I collagen) was detected in both allograft alone and periosteum-allograft samples. Gene data confirm viable periosteum in constructs after 20 weeks. Relatively higher fold-change values of RANK, RANKL and cathepsin K indicate activities of osteoclast precursors, osteoclasts and osteoblasts involved in allograft remodeling during implantation. All additional genes of interest indicate osteoblast activity in new bone matrix formation. Gene data are directly correlated with previous and present

  13. Soft-tissue allografts terminally sterilized with an electron beam are biomechanically equivalent to aseptic, nonsterilized tendons.

    PubMed

    Elenes, Egleide Y; Hunter, Shawn A

    2014-08-20

    Allograft safety is contingent on effective sterilization. However, current sterilization methods have been associated with decreased biomechanical strength and higher failure rates of soft-tissue allografts. In this study, electron beam (e-beam) sterilization was explored as an alternative sterilization method to preserve biomechanical integrity. We hypothesized that e-beam sterilization would not significantly alter the biomechanical properties of tendon allograft compared with aseptic, nonsterilized controls and gamma-irradiated grafts. Separate sets of forty fresh-frozen tibialis tendon allografts (four from each of ten donors) and forty bisected bone-patellar tendon-bone (BTB) allografts (four from each of ten donors) were randomly assigned to four study groups. One group received a 17.1 to 21.0-kGy gamma radiation dose; two other groups were sterilized with an e-beam at either a high (17.1 to 21.0-kGy) or low (9.2 to 12.2-kGy) dose. A fourth group served as nonsterilized controls. Each graft was cyclically loaded to 200 N of tension for 2000 cycles at a frequency of 2 Hz, allowed to relax for five minutes, and then tested in tension until failure at a 100%/sec strain rate. One-way analysis of variance testing was used to identify significant differences. Tibialis tendons sterilized with both e-beam treatments and with gamma irradiation exhibited values for cyclic tendon elongation, maximum load, maximum displacement, stiffness, maximum stress, maximum strain, and elastic modulus that were not significantly different from those of nonsterilized controls. BTB allografts sterilized with the high e-beam dose and with gamma irradiation were not significantly different in cyclic tendon elongation, maximum load, maximum displacement, stiffness, maximum stress, maximum strain, and elastic modulus from nonsterilized controls. BTB allografts sterilized with the e-beam at the lower dose were significantly less stiff than nonsterilized controls (p = 0.014) but did not

  14. Hand transplantation and vascularized composite tissue allografts in orthopaedics and traumatology.

    PubMed

    Schuind, F

    2010-05-01

    Composite tissue allograft (CTA) is defined as heterologous transplantation of a complex comprising skin and subcutaneous, neurovascular and mesenchymal tissue. Such techniques allow complex reconstruction using matched tissue, without donor site morbidity. The potential indications in orthopaedics-traumatology could in the future be more frequent than the present indications of heart, lung, liver, kidney and pancreas transplantation. International clinical experience clearly demonstrates the feasibility of CTA, both surgically and immunologically. However, immunosuppression remains indispensable, exposing the patient to risks that are not acceptable for purely functional surgery, except in very particular indications. The main hope for the future lies in induction of graft-specific tolerance. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  15. Capillary Thrombosis in the Skin: A Pathologic Hallmark of Severe/Chronic Rejection of Human Vascularized Composite Tissue Allografts?

    PubMed

    Kanitakis, Jean; Petruzzo, Palmina; Gazarian, Aram; Karayannopoulou, Georgia; Buron, Fannie; Dubois, Valérie; Thaunat, Olivier; Badet, Lionel; Morelon, Emmanuel

    2016-04-01

    Vascularized composite tissue allografts (VCA) can undergo rejection, manifesting pathologically with skin changes that form the basis of the Banff 2007 classification of VCA rejection. We have followed 10 human VCA recipients (7 with hand allografts, 3 with face allografts) for pathological signs of rejection. All of them developed episodes of acute rejection. Two patients with hand allografts presented in some of their skin biopsies an as yet unreported pathological finding in human VCA, consisting of capillary thromboses (CT) in the upper dermis. Capillary thrombosis was associated with other typical changes of grade II to III VCA rejection, namely, perivascular T cell infiltrates, but not with vascular C4d deposits (in formalin-fixed tissue). Clinically, the lesions presented as red or violaceous (lichenoid) cutaneous maculopapules. The first patient had several episodes of acute rejection during the 7-year follow-up. The second patient developed donor-specific antibodies; some months after CT were first observed, he developed chronic rejection leading to partial amputation of the allograft. Pathological examination of the skin showed graft vasculopathy and occasional C4d deposits in cutaneous capillaries. Capillary thrombosis seems to be a novel pathologic finding associated with human VCA rejection. Although its mechanism (immunologic vs nonimmunologic) remains unclear, this finding could carry an unfavorable prognostic significance, prompting close monitoring of the patients for severe/chronic rejection.

  16. Skin allograft and vascularized composite allograft: potential for long-term efficacy in the context of lymphatic modulation.

    PubMed

    Rinkinen, Jacob; Selley, Ryan; Agarwal, Shailesh; Loder, Shawn; Levi, Benjamin

    2014-01-01

    Tissue transplantation restores form and function in burn patients. The treatment of burn injuries is influenced by severity, location, and the percentage of total body surface area. There have been a number of different techniques developed to temporize and repair the destroyed tissue. However, in patients with large wound burden, sufficient donor site tissue may not be available for autograft harvesting. Such extensive burns necessitate other temporary and permanent options for wound coverage such as skin or vascularized composite allografts (VCA). Rejection of these tissues presents an ongoing problem which is currently managed using a host of systemic immunosuppressive medications. This article discusses the mechanism behind the innate and adaptive immune systems rejection of the allografts. By understanding these pathways, various techniques using immunomodulatory protocols have led to increased allograft survival. However, our primary interest lies in the initial recognition of the graft. We tailor this article to have a specific emphasis on lymphatic modulation as a potential adjunctive therapy. Reviews of the studies evaluating the effect of lymph node modulation on graft survival are described with future implications to allograft transplant research.

  17. A cost-effective method for femoral head allograft procurement for spinal arthrodesis: an alternative to commercially available allograft.

    PubMed

    Brown, Desmond A; Mallory, Grant W; Higgins, Dominique M; Abdulaziz, Mohammed; Huddleston, Paul M; Nassr, Ahmad; Fogelson, Jeremy L; Clarke, Michelle J

    2014-07-01

    A cost-effective procurement process for harvesting, storing, and using femoral head allografts is described. A brief review of the literature on the use of these allografts and a discussion of costs are provided. To describe a cost-effective method for the harvesting, storage, and use of femoral heads from patients undergoing total hip arthroplasty at our institution as a source of allograft bone. Spine fusion surgery uses a large proportion of commercially available bone grafts and bone substitutes. As the number of such surgical procedures performed in the United States continues to rise, these materials are at a historically high level of demand, which is projected to continue. Iliac crest bone autograft has historically been the standard of care, although this may be losing favor due to potential donor site morbidity. Although many substitutes are effective in promoting arthrodesis, their use is limited because of cost. Femoral heads are harvested under sterile conditions during total hip arthroplasty. The patient is tested per Food and Drug Administration regulations, and the tissue sample is cultured. The tissue is frozen and quarantined for a 6-month minimum pending repeat testing of donors and subsequently released for use. The relative cost-effectiveness of this tissue as a source of allograft bone is discussed. The average femoral head allograft is 54 to 56 mm in diameter and yields 50 cm of bone graft, with an average cost of US $435 for processing of the tissue resulting in a cost of US $8.70 per cm of allograft produced. Average production costs are significantly lower than those for other commonly available commercial bone grafts and substitutes. Femoral head allograft is a cost-effective alternative to commercially available allografts and bone substitutes. The method of procurement, storage, and use described could be adopted by other institutions in an effort to mitigate cost and increase supply. N/A.

  18. Does the Utilization of Allograft Tissue in Medial Patellofemoral Ligament Reconstruction in Pediatric and Adolescent Patients Restore Patellar Stability?

    PubMed

    Hohn, Eric; Pandya, Nirav K

    2017-06-01

    Medial patellofemoral ligament (MPFL) reconstruction is one of several surgical procedures used to treat patellofemoral instability. Use of allograft tissue can preserve autogenous tissue and may be preferable in patients with connective tissue disorders or ligamentous laxity. Although there are successful reports in adults, it is unclear if the use of allograft tissue in MPFL reconstruction can restore patellofemoral stability in children and adolescents. (1) Does allograft tissue in MPFL reconstruction in pediatric and adolescent patients restore patellar stability? (2) What complications were associated with allograft MPFL reconstructions in children and adolescents? Between June 2012 and August 2015, one surgeon (NKP) performed 26 MPFL reconstructions in 23 patients with gracilis allograft for traumatic patellar instability. Of those, 25 (96%) were available for followup more than 1 year later (mean, 24 months; range, 12-44 months). During this time, the surgeon suggested reconstruction to patients who had recurrent dislocation or subluxation after 6 weeks of bracing, physical therapy, and activity modification if they were noted to have a torn or attenuated MPFL on MRI. During that period, this was the only surgical technique the surgeon used to treat traumatic patellar instability. Patients undergoing concurrent bony procedures were ineligible for inclusion. The mean age of the patients in the series was 16.0 (± 2) years. Age, sex, skeletal maturity, presence of trochlear dysplasia, and additional arthroscopic procedures at the time of reconstruction were collected. Postoperative notes and imaging were reviewed for presence of complications defined as recurrent dislocation, recurrent subluxations, fractures, infection, or arthrofibrosis. These complications were identified by chart review by the senior surgeon (NKP) and study personnel (EH) not involved in clinical care of the patients or by patient-reported complications. Recurrent subluxation or

  19. Hamstring autograft versus soft-tissue allograft in anterior cruciate ligament reconstruction: a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Cvetanovich, Gregory L; Mascarenhas, Randy; Saccomanno, Maristella F; Verma, Nikhil N; Cole, Brian J; Bush-Joseph, Charles A; Bach, Bernard R

    2014-12-01

    To compare outcomes of anterior cruciate ligament (ACL) reconstruction with hamstring autograft versus soft-tissue allograft by systematic review and meta-analysis. A systematic review of randomized controlled studies comparing hamstring autograft with soft-tissue allograft in ACL reconstruction was performed. Studies were identified by strict inclusion and exclusion criteria. Descriptive statistics were reported. Where possible, the data were pooled and a meta-analysis was performed using RevMan software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Dichotomous data were reported as risk ratios, whereas continuous data were reported as standardized mean differences and 95% confidence intervals. Heterogeneity was assessed by use of I(2) for each meta-analysis. Study methodologic quality was analyzed with the Modified Coleman Methodology Score and Jadad scale. Five studies with 504 combined patients (251 autograft and 253 allograft; 374 male and 130 female patients) with a mean age of 29.9 ± 2.2 years were included. The allografts used were fresh-frozen hamstring, irradiated hamstring, mixture of fresh-frozen and cryopreserved hamstring, fresh-frozen tibialis anterior, and fresh-frozen Achilles tendon grafts without bone blocks. The mean follow-up period was 47.4 ± 26.9 months, with a mean follow-up rate of 83.3% ± 8.6%. Two studies found a longer operative time with autograft than with allograft (77.1 ± 2.0 minutes v 59.9 ± 0.9 minutes, P = .008). Meta-analysis showed no statistically significant differences between autografts and allografts for any outcome measures (P > .05 for all tests). One study found significantly greater laxity for irradiated allograft than for autograft. The methodologic quality of the 5 studies was poor, with a mean Modified Coleman Methodology Score of 54.4 ± 6.9 and mean Jadad score of 1.6 ± 1.5. On the basis of this systematic review and meta-analysis of 5 randomized controlled trials, there is

  20. Cytokines in single layer amnion allografts compared to multilayer amnion/chorion allografts for wound healing.

    PubMed

    Koob, Thomas J; Lim, Jeremy J; Zabek, Nicole; Massee, Michelle

    2015-07-01

    Human amniotic membrane allografts have proven effective at improving healing of cutaneous wounds. The mechanism of action for these therapeutic effects is poorly understood but is thought to involve the resident growth factors present in near term amniotic tissue. To determine the relative cytokine contribution of the amnion and chorion in amniotic allografts, the content of 18 cytokines involved in wound healing were measured in samples of PURION® Processed dehydrated amnion, chorion, and amnion/chorion membrane (dHACM) grafts by multiplex enzyme-linked immunosorbent assay array. Both amnion and chorion contained similar amounts of each factor when normalized per dry weight; however, when calculated per surface area of tissue applied to a wound, amnion contained on average only 25% as much of each factor as the chorion. Therefore, an allograft containing both amnion and chorion would contain four to five times more cytokine than a single layer amnion allograft alone. Both single layer amnion and multilayer allografts containing amnion and chorion are currently marketed for wound repair. To examine the role of tissue processing technique in cytokine retention, cytokine contents in representative dehydrated single layer wound care products were measured. The results demonstrated that cytokine content varied significantly among the allografts tested, and that PURION® Processed single layer amnion grafts contained more cytokines than other single layer products. These results suggest that PURION® Processed dHACM contains substantially more cytokines than single layer amnion products, and therefore dHACM may be more effective at delivering growth factors to a healing wound than amnion alone. © 2014 Wiley Periodicals, Inc.

  1. Studying tumor growth in Drosophila using the tissue allograft method.

    PubMed

    Rossi, Fabrizio; Gonzalez, Cayetano

    2015-10-01

    This protocol describes a method to allograft Drosophila larval tissue into adult fly hosts that can be used to assay the tumorigenic potential of mutant tissues. The tissue of interest is dissected, loaded into a fine glass needle and implanted into a host. Upon implantation, nontransformed tissues do not overgrow beyond their normal size, but malignant tumors grow without limit, are invasive and kill the host. By using this method, Drosophila malignant tumors can be transplanted repeatedly, for years, and therefore they can be aged beyond the short life span of flies. Because several hosts can be implanted using different pieces from a single tumor, the method also allows the tumor mass to be increased to facilitate further studies that may require large amounts of tissue (i.e., genomics, proteomics and so on). This method also provides an operational definition of hyperplastic, benign and malignant growth. The injection procedure itself requires only ∼1 d. Tumor development can then be monitored until the death of the implanted hosts.

  2. Allograft tissue irradiation and failure rate after anterior cruciate ligament reconstruction: A systematic review.

    PubMed

    Dashe, Jesse; Parisien, Robert L; Cusano, Antonio; Curry, Emily J; Bedi, Asheesh; Li, Xinning

    2016-06-18

    To evaluate whether anterior cruciate ligament (ACL) allograft irradiation is effective for sterility without compromising graft integrity and increasing failure rate. A literature search was conducted using PubMed, Cochrane, and Google. The following search terms were used: "Gamma irradiation AND anterior cruciate ligament AND allograft" with a return of 30 items. Filters used included: English language, years 1990-2015. There were 6 hits that were not reviewed, as there were only abstracts available. Another 5 hits were discarded, as they did not pertain to the topic of interest. There were 9 more articles that were excluded: Three studies were performed on animals and 6 studies were meta-analyses. Therefore, a total of 10 articles were applicable to review. There is a delicate dosing crossover where gamma irradiation is both effective for sterility without catastrophically compromising the structural integrity of the graft. Of note, low dose irradiation is considered less than 2.0 Mrad, moderate dose is between 2.1-2.4 Mrad, and high dose is greater than or equal to 2.5 Mrad. Based upon the results of the literature search, the optimal threshold for sterilization was found to be sterilization at less than 2.2 Mrad of gamma irradiation with the important caveat of being performed at low temperatures. The graft selection process also must include thorough donor screening and testing as well as harvesting the tissue in a sterile fashion. Utilization of higher dose (≥ 2.5 Mrad) of irradiation causes greater allograft tissue laxity that results in greater graft failure rate clinically in patients after ACL reconstruction. Allograft ACL graft gamma irradiated with less than 2.2 Mrad appears to be a reasonable alternative to autograft for patients above 25 years of age.

  3. ANTIBACTERIAL ACTIVITY OF BONE ALLOGRAFTS: COMPARISON OF A NEW VANCOMYCIN-TETHERED ALLOGRAFT WITH ALLOGRAFT LOADED WITH ADSORBED VANCOMYCIN

    PubMed Central

    Ketonis, Constantinos; Barr, Stephanie; Shapiro, Irving M.; Parvizi, Javad; Adams, Christopher S.; Hickok, Noreen J.

    2010-01-01

    Bacterial contamination of bone allograft is a significant complication of orthopaedic surgery. To address this issue, we have engineered a method for covalently modifying bone allograft tissue with the antibiotic vancomycin. The goal of this investigation was to compare the biocidal properties of this new allograft material with those of vancomycin physisorbed onto graft material. The duration of antibiotic release from the vancomycin-modified allograft matrix was determined and no elution was observed. In contrast, the adsorbed antibiotic showed a peak elution at 24 h that then decreased over several days. We next used an S. aureus disk diffusion assay to measure the activity of the eluted vancomycin. Again we found that no active antibiotic was eluted from the covalently–modified allograft. Similarly, when the vancomycin-modified allograft morsel was used in the assay, no measurable elution was observed; amounts of antibiotic released from the adsorbed samples inhibited S. aureus growth for 4-7 days. Probably the most telling property of the allograft was that after two weeks, the tethered-allograft was able to resist bacterial colonization. Unlike the elution system in which vancomycin was depleted over the course of days-weeks, the antibiotic on the allograft was stably bound even after 300 days, while its biocidal activity remained undiminished for 60 days. This finding was in stark contrast to the antibiotic impregnated allograft which was readily colonized by bacteria. Finally we chose to evaluate three indicators of cell function: expression of a key transcription factor, expression of selected transcripts, and assessment of cell morphology. Since the tethered antibiotic appeared to have little or no effect on any of these activities, it was concluded that the stable, tethered antibiotic prevented bacterial infection while not modifying bone cell function. PMID:21035576

  4. Soft Tissue Structure Modelling for Use in Orthopaedic Applications and Musculoskeletal Biomechanics

    NASA Astrophysics Data System (ADS)

    Audenaert, E. A.; Mahieu, P.; van Hoof, T.; Pattyn, C.

    2009-12-01

    We present our methodology for the three-dimensional anatomical and geometrical description of soft tissues, relevant for orthopaedic surgical applications and musculoskeletal biomechanics. The technique involves the segmentation and geometrical description of muscles and neurovascular structures from high-resolution computer tomography scanning for the reconstruction of generic anatomical models. These models can be used for quantitative interpretation of anatomical and biomechanical aspects of different soft tissue structures. This approach should allow the use of these data in other application fields, such as musculoskeletal modelling, simulations for radiation therapy, and databases for use in minimally invasive, navigated and robotic surgery.

  5. CMV allograft pancreatitis: diagnosis, treatment, and histological features.

    PubMed

    Klassen, D K; Drachenberg, C B; Papadimitriou, J C; Cangro, C B; Fink, J C; Bartlett, S T; Weir, M R

    2000-05-15

    Cytomegalovirus (CMV) infection is a common problem in solid organ transplant recipients. CMV infection of pancreas allografts is not, however, well described. We report the clinical presentation, histologic findings, treatment, and outcome in four patients with CMV allograft pancreatitis. These patients presented 18 weeks to 44 months after transplantation with elevated serum amylase and lipase and were suspected to have acute rejection. Percutaneous pancreas allograft biopsy specimens showed evidence of tissue invasive CMV infection. One patient had simultaneous CMV infection and acute rejection. Prolonged treatment with ganciclovir resulted in clinical and histologic resolution of the CMV disease. Rejection was successfully treated. Primary CMV infection in seronegative recipients seemed to be a risk factor. Three patients maintain normal allograft function; one patient lost function due to chronic rejection. The histology of tissue-invasive CMV pancreas allograft infection and its differentiation from acute rejection is described. Prompt diagnosis and prolonged therapy with antiviral agents can result in maintenance of allograft function.

  6. Structural allograft reconstruction of the foot and ankle after tumor resections.

    PubMed

    Ayerza, M A; Piuzzi, N S; Aponte-Tinao, L A; Farfalli, G L; Muscolo, D L

    2016-08-01

    Structural allografts have been used to correct deformities or to fill bone defects secondary to tumor excisions, trauma, osteochondral lesions, or intercalary arthrodesis. However, the quality of published evidence supporting the use of allograft transplantation in foot and ankle surgery has been reported as fair. The purpose of this study was to report the overall survival of structural allograft in the foot and ankle after tumor resection, and the survival according to the type of allograft and the complication rates in the medium to long term. From January 1989 to June 2011, 44 structural allograft reconstructions of the foot and ankle were performed in 42 patients (28 men and 14 women) due to musculoskeletal tumor resections. Mean age at presentation was 27 years. Mean follow-up was 53 months. Demographic data, diagnosis, site of the neoplasm, operations performed, operative complications, outcomes after surgery, date of last follow-up evaluation, and local recurrences were reviewed for all patients. Regarding the type of 44 allograft reconstructions, 16 were hemicylindrical allografts (HA), 12 intercalary allografts (IA), 10 osteoarticular allografts (OA), and 6 were total calcaneal allograft (CA). The overall allograft survival rate, as calculated with the Kaplan-Meier method, at 5 and 10 years was 79 % (95 % CI 64-93 %). When allocated by type of allograft reconstruction the specific allograft survival at 5 and 10 years was: 83 % for CA, 80 % for HA, 77 % for OA, and 75 % for IA. The complications rate for this series was 36 % including: articular failure, local recurrence, infection, fracture and nonunion. This study showed that structural allograft reconstruction in the foot and ankle after tumor resection may be durable with a 79 % survival rate at 5 and 10 years. The two types of allografts that showed better survival rate were hemicylindrical allografts (80 %) and calcaneus allografts (83 %). The highest complication rates occurred

  7. Allograft reconstruction after resection of malignant tumors of the scapula.

    PubMed

    Mnaymneh, Walid A; Temple, H Thomas; Malinin, Theodore I

    2002-12-01

    The oncologic and functional outcomes of six patients who had scapular allograft reconstruction after scapulectomy for malignant tumors were reviewed. Five patients had Stage IIB and one patient had Stage IB tumors. Total scapulectomy was done in five patients, and partial scapulectomy (glenoid and neck) was done in one patient. Frozen glycerolized scapular allografts were implanted and fixed with plates and screws. The scapular muscles were reattached to the allograft. Tendon reconstruction to replace the excised muscles was done in two patients. The patients were followed up for an average of 3.8 years (range, 2-6 years). Cosmesis, elbow, and hand function were good in all patients. There were no infections, nonunions, or shoulder dislocations. One patient fractured the body of the allograft after a fall. One patient had local recurrence and had scapulectomy 5 years postoperatively. Two patients died 3 and 5 years postoperatively with lung metastases but with functioning grafts. The mean functional result using the Musculoskeletal Tumor Society functional score was 82 (range, 77-87). In this series, scapular allograft reconstruction restored cosmesis, shoulder stability, and function. Preservation or reconstruction of rotator cuff muscles is recommended.

  8. [Skin and tissue bank: Operational model for the recovery and preservation of tissues and skin allografts].

    PubMed

    Martínez-Flores, Francisco; Sandoval-Zamora, Hugo; Machuca-Rodriguez, Catalina; Barrera-López, Araceli; García-Cavazos, Ricardo; Madinaveitia-Villanueva, Juan Antonio

    2016-01-01

    Tissue storage is a medical process that is in the regulation and homogenisation phase in the scientific world. The international standards require the need to ensure safety and efficacy of human allografts such as skin and other tissues. The activities of skin and tissues banks currently involve their recovery, processing, storage and distribution, which are positively correlated with technological and scientific advances present in current biomedical sciences. A description is presented of the operational model of Skin and Tissue Bank at INR as successful case for procurement, recovery and preservation of skin and tissues for therapeutic uses, with high safety and biological quality. The essential and standard guidelines are presented as keystones for a tissue recovery program based on scientific evidence, and within an ethical and legal framework, as well as to propose a model for complete overview of the donation of tissues and organ programs in Mexico. Finally, it concludes with essential proposals for improving the efficacy of transplantation of organs and tissue programs. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  9. Orthotopic Transplantation of Achilles Tendon Allograft in Rats

    PubMed Central

    Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun

    2018-01-01

    The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at −80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully

  10. Effect of Adipose Tissue-Derived Osteogenic and Endothelial Cells on Bone Allograft Osteogenesis and Vascularization in Critical-Sized Calvarial Defects

    DTIC Science & Technology

    2012-05-10

    1% peni - cillin/streptomycin, and 50 ng/mL recombinant rat VEGF-C (Promocell, Heidelberg, Germany). The media were changed every other day for 8...various animal models that have demonstrated an enhanced osteogenic effect after treating bone allografts with adipose tissue or bone marrow-derived... enhanced 1560 CORNEJO ET AL. performance of bone allografts using osteogenic differentiated adipose derived mesenchymal stem cells. Biomaterials 32, 8880

  11. Disinfection of human cardiac valve allografts in tissue banking: systematic review report.

    PubMed

    Germain, M; Strong, D M; Dowling, G; Mohr, J; Duong, A; Garibaldi, A; Simunovic, N; Ayeni, O R

    2016-12-01

    Cardiovascular allografts are usually disinfected using antibiotics, but protocols vary significantly between tissue banks. It is likely that different disinfection protocols will not have the same level of efficacy; they may also have varying effects on the structural integrity of the tissue, which could lead to significant differences in terms of clinical outcome in recipients. Ideally, a disinfection protocol should achieve the greatest bioburden reduction with the lowest possible impact on tissue integrity. We conducted a systematic review of methods applied to disinfect cardiovascular tissues. The use of multiple broad spectrum antibiotics in conjunction with an antifungal agent resulted in the greatest reduction in bioburden. Antibiotic incubation periods were limited to less than 24 h, and most protocols incubated tissues at 4 °C, however one study demonstrated a greater reduction of microbial load at 37 °C. None of the reviewed studies looked at the impact of these disinfection protocols on the risk of infection or any other clinical outcome in recipients.

  12. The risk of HIV, HBV, HCV and HTLV infection among musculoskeletal tissue donors in Australia.

    PubMed

    Yao, F; Seed, C; Farrugia, A; Morgan, D; Cordner, S; Wood, D; Zheng, M H

    2007-12-01

    In Australia, there are no current national estimates of the risks of transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or human T-lymphotrophic virus (HTLV) by musculoskeletal tissue transplantation. We determined the prevalence rates of antibodies against HIV (anti-HIV), HCV (anti-HCV) and HTLV (anti-HTLV) and Hepatitis B surface antigen (HBsAg) for 12,415 musculoskeletal tissue donors from three major bone tissue banks across Australia for the period 1993-2004. The prevalence (per 100,000 persons) was 64.44 for anti-HIV, 407.13 for HBsAg, 534.63 for anti-HCV and 121.88 for anti-HTLV. The estimated probability of viremia at the time of donation was 1 in 128,000, 1 in 189,000, 1 in 55,000 and 1 in 118,000, respectively. With the addition of nucleic acid amplification testing (NAT), the probability of donor viremia would be reduced to 1 in 315,000 for HIV, 1 in 385,000 for HBV and 1 in 500,000 for HCV. The prevalence of HIV, HBV, HCV and HTLV although low, are higher among musculoskeletal tissue donors than among first-time blood donors. The risks associated with musculoskeletal donation will be reduced with NAT, though further cost analysis is required prior to its implementation.

  13. Allograft tissue irradiation and failure rate after anterior cruciate ligament reconstruction: A systematic review

    PubMed Central

    Dashe, Jesse; Parisien, Robert L; Cusano, Antonio; Curry, Emily J; Bedi, Asheesh; Li, Xinning

    2016-01-01

    AIM: To evaluate whether anterior cruciate ligament (ACL) allograft irradiation is effective for sterility without compromising graft integrity and increasing failure rate. METHODS: A literature search was conducted using PubMed, Cochrane, and Google. The following search terms were used: “Gamma irradiation AND anterior cruciate ligament AND allograft” with a return of 30 items. Filters used included: English language, years 1990-2015. There were 6 hits that were not reviewed, as there were only abstracts available. Another 5 hits were discarded, as they did not pertain to the topic of interest. There were 9 more articles that were excluded: Three studies were performed on animals and 6 studies were meta-analyses. Therefore, a total of 10 articles were applicable to review. RESULTS: There is a delicate dosing crossover where gamma irradiation is both effective for sterility without catastrophically compromising the structural integrity of the graft. Of note, low dose irradiation is considered less than 2.0 Mrad, moderate dose is between 2.1-2.4 Mrad, and high dose is greater than or equal to 2.5 Mrad. Based upon the results of the literature search, the optimal threshold for sterilization was found to be sterilization at less than 2.2 Mrad of gamma irradiation with the important caveat of being performed at low temperatures. The graft selection process also must include thorough donor screening and testing as well as harvesting the tissue in a sterile fashion. Utilization of higher dose (≥ 2.5 Mrad) of irradiation causes greater allograft tissue laxity that results in greater graft failure rate clinically in patients after ACL reconstruction. CONCLUSION: Allograft ACL graft gamma irradiated with less than 2.2 Mrad appears to be a reasonable alternative to autograft for patients above 25 years of age. PMID:27335815

  14. Three-dimensional virtual bone bank system for selecting massive bone allograft in orthopaedic oncology.

    PubMed

    Wu, Zhigang; Fu, Jun; Wang, Zhen; Li, Xiangdong; Li, Jing; Pei, Yanjun; Pei, Guoxian; Li, Dan; Guo, Zheng; Fan, Hongbin

    2015-06-01

    Although structural bone allografts have been used for years to treat large defects caused by tumour or trauma, selecting the most appropriate allograft is still challenging. The objectives of this study were to: (1) describe the establishment of a visual bone bank system and workflow of allograft selection, and (2) show mid-term follow-up results of patients after allograft implantation. Allografts were scanned and stored in Digital Imaging and Communications in Medicine (DICOM) files. Then, image segmentation was conducted and 3D model reconstructed to establish a visual bone bank system. Based on the volume registration method, allografts were selected after a careful matching process. From November 2010 to June 2013, with the help of the Computer-assisted Orthopaedic Surgery (CAOS) navigation system, the allografts were implanted in 14 patients to fill defects after tumour resection. By combining the virtual bone bank and CAOS, selection time was reduced and matching accuracy was increased. After 27.5 months of follow-up, the mean Musculoskeletal Tumor Society (MSTS) 93 functional score was 25.7 ± 1.1 points. Except for two patients with pulmonary metastases, 12 patents were alive without evidence of disease at the time this report was written. The virtual bone bank system was helpful for allograft selection, tumour excision and bone reconstruction, thereby improving the safety and effectiveness of limb-salvage surgery.

  15. [The clinical use of cryopreserved human skin allografts for transplantation].

    PubMed

    Martínez-Flores, Francisco; Chacón-Gómez, María; Madinaveitia-Villanueva, Juan Antonio; Barrera-Lopez, Araceli; Aguirre-Cruz, Lucinda; Querevalu-Murillo, Walter

    2015-01-01

    The biological recovery of human skin allografts is the gold standard for preservation in Skin Banks. However, there is no worldwide consensus about specific allocation criteria for preserved human skin allografts with living cells. A report is presented on the results of 5 years of experience of using human skin allografts in burned patient in the Skin and Tissue Bank at the "Instituto Nacional de Rehabilitacion" The human skin allografts were obtained from multi-organ donors. processed and preserved at -80 °C for 12 months. Allocation criteria were performed according to blood type match, clinical history, and burned body surface. Up to now, the Skin and Tissue Bank at 'Instituto Nacional de Rehabilitacion" has processed and recovered 125,000 cm(2) of human skin allografts. It has performed 34 surgical implants on 21 burned patients. The average of burn body surface was 59.2%. More than two-thirds (67.7%) of recipients of skin allografts were matched of the same to type blood of the donor, and 66.6% survived after 126 days hospital stay. It is proposed to consider recipient's blood group as allocation criteria to assign tissue; and use human skin allografts on patiens affected with burns over 30% of body surface (according the "rule of the 9"). Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  16. Fresh-frozen Complete Extensor Mechanism Allograft versus Autograft Reconstruction in Rabbits

    PubMed Central

    Chen, Guanyin; Zhang, Hongtao; Ma, Qiong; Zhao, Jian; Zhang, Yinglong; Fan, Qingyu; Ma, Baoan

    2016-01-01

    Different clinical results have been reported in the repair of extensor mechanism disruption using fresh-frozen complete extensor mechanism (CEM) allograft, creating a need for a better understanding of fresh-frozen CME allograft reconstruction. Here, we perform histological and biomechanical analyses of fresh-frozen CEM allograft or autograft reconstruction in an in vivo rabbit model. Our histological results show complete incorporation of the quadriceps tendon into the host tissues, patellar survival and total integration of the allograft tibia, with relatively fewer osteocytes, into the host tibia. Vascularity and cellularity are reduced and delayed in the allograft but exhibit similar distributions to those in the autograft. The infrapatellar fat pad provides the main blood supply, and the lowest cellularity is observed in the patellar tendon close to the tibia in both the allograft and autograft. The biomechanical properties of the junction of quadriceps tendon and host tissues and those of the allograft patellar tendon are completely and considerably restored, respectively. Therefore, fresh-frozen CEM allograft reconstruction is viable, but the distal patellar tendon and the tibial block may be the weak links of the reconstruction. These findings provide new insight into the use of allograft in repairing disruption of the extensor mechanism. PMID:26911538

  17. Fresh-frozen Complete Extensor Mechanism Allograft versus Autograft Reconstruction in Rabbits.

    PubMed

    Chen, Guanyin; Zhang, Hongtao; Ma, Qiong; Zhao, Jian; Zhang, Yinglong; Fan, Qingyu; Ma, Baoan

    2016-02-25

    Different clinical results have been reported in the repair of extensor mechanism disruption using fresh-frozen complete extensor mechanism (CEM) allograft, creating a need for a better understanding of fresh-frozen CME allograft reconstruction. Here, we perform histological and biomechanical analyses of fresh-frozen CEM allograft or autograft reconstruction in an in vivo rabbit model. Our histological results show complete incorporation of the quadriceps tendon into the host tissues, patellar survival and total integration of the allograft tibia, with relatively fewer osteocytes, into the host tibia. Vascularity and cellularity are reduced and delayed in the allograft but exhibit similar distributions to those in the autograft. The infrapatellar fat pad provides the main blood supply, and the lowest cellularity is observed in the patellar tendon close to the tibia in both the allograft and autograft. The biomechanical properties of the junction of quadriceps tendon and host tissues and those of the allograft patellar tendon are completely and considerably restored, respectively. Therefore, fresh-frozen CEM allograft reconstruction is viable, but the distal patellar tendon and the tibial block may be the weak links of the reconstruction. These findings provide new insight into the use of allograft in repairing disruption of the extensor mechanism.

  18. Inability to determine tissue health is main indication of allograft use in intermediate extent burns.

    PubMed

    Fletcher, John L; Cancio, Leopoldo C; Sinha, Indranil; Leung, Kai P; Renz, Evan M; Chan, Rodney K

    2015-12-01

    Cutaneous allograft is commonly used in the early coverage of excised burns when autograft is unavailable. However, allograft is also applied in intermediate-extent burns (25-50%), during cases in which it is possible to autograft. In this population, there is a paucity of data on the indications for allograft use. This study explores the indications for allograft usage in moderate size burns. Under an IRB-approved protocol, patients admitted to our burn unit between March 2003 and December 2010 were identified through a review of the burn registry. Data on allograft use, total burn surface area, operation performed, operative intent, number of operations, intensive care unit length of stay, and overall length of stay were collected and analyzed. Data are presented as means±standard deviations, except where noted. In the study period, 146 patients received allograft during their acute hospitalization. Twenty-five percent of allograft recipients sustained intermediate-extent burns. Patients with intermediate-extent burns received allograft later in their hospitalization than those with large-extent (50-75% TBSA) burns (6.8 days vs. 3.4 days, p=0.01). Allografted patients with intermediate-extent burns underwent more operations (10.8 vs. 6.1, p=0.002) and had longer hospitalizations (78.3 days vs. 40.9 days, p<0.001) than non-allografted patients, when controlled for TBSA. Clinical rationale for placement of allograft in this population included autograft failure, uncertain depth of excision, lack of autograft donor site, and wound complexity. When uncertain depth of excision was the indication, allograft was universally applied onto the face. In half of allografted intermediate-extent burn patients the inability to identify a viable recipient bed was the ultimate reason for allograft use. Unlike large body surface area burns, allograft skin use in intermediate-extent injury occurs later in the hospitalization and is driven by the inability to determine wound bed

  19. The interaction of force and repetition on musculoskeletal and neural tissue responses and sensorimotor behavior in a rat model of work-related musculoskeletal disorders

    PubMed Central

    2013-01-01

    Background We examined the relationship of musculoskeletal risk factors underlying force and repetition on tissue responses in an operant rat model of repetitive reaching and pulling, and if force x repetition interactions were present, indicative of a fatigue failure process. We examined exposure-dependent changes in biochemical, morphological and sensorimotor responses occurring with repeated performance of a handle-pulling task for 12 weeks at one of four repetition and force levels: 1) low repetition with low force, 2) high repetition with low force, 3) low repetition with high force, and 4) high repetition with high force (HRHF). Methods Rats underwent initial training for 4–6 weeks, and then performed one of the tasks for 12 weeks, 2 hours/day, 3 days/week. Reflexive grip strength and sensitivity to touch were assayed as functional outcomes. Flexor digitorum muscles and tendons, forelimb bones, and serum were assayed using ELISA for indicators of inflammation, tissue stress and repair, and bone turnover. Histomorphometry was used to assay macrophage infiltration of tissues, spinal cord substance P changes, and tissue adaptative or degradative changes. MicroCT was used to assay bones for changes in bone quality. Results Several force x repetition interactions were observed for: muscle IL-1alpha and bone IL-1beta; serum TNFalpha, IL-1alpha, and IL-1beta; muscle HSP72, a tissue stress and repair protein; histomorphological evidence of tendon and cartilage degradation; serum biomarkers of bone degradation (CTXI) and bone formation (osteocalcin); and morphological evidence of bone adaptation versus resorption. In most cases, performance of the HRHF task induced the greatest tissue degenerative changes, while performance of moderate level tasks induced bone adaptation and a suggestion of muscle adaptation. Both high force tasks induced median nerve macrophage infiltration, spinal cord sensitization (increased substance P), grip strength declines and forepaw

  20. The interaction of force and repetition on musculoskeletal and neural tissue responses and sensorimotor behavior in a rat model of work-related musculoskeletal disorders.

    PubMed

    Barbe, Mary F; Gallagher, Sean; Massicotte, Vicky S; Tytell, Michael; Popoff, Steven N; Barr-Gillespie, Ann E

    2013-10-25

    We examined the relationship of musculoskeletal risk factors underlying force and repetition on tissue responses in an operant rat model of repetitive reaching and pulling, and if force x repetition interactions were present, indicative of a fatigue failure process. We examined exposure-dependent changes in biochemical, morphological and sensorimotor responses occurring with repeated performance of a handle-pulling task for 12 weeks at one of four repetition and force levels: 1) low repetition with low force, 2) high repetition with low force, 3) low repetition with high force, and 4) high repetition with high force (HRHF). Rats underwent initial training for 4-6 weeks, and then performed one of the tasks for 12 weeks, 2 hours/day, 3 days/week. Reflexive grip strength and sensitivity to touch were assayed as functional outcomes. Flexor digitorum muscles and tendons, forelimb bones, and serum were assayed using ELISA for indicators of inflammation, tissue stress and repair, and bone turnover. Histomorphometry was used to assay macrophage infiltration of tissues, spinal cord substance P changes, and tissue adaptative or degradative changes. MicroCT was used to assay bones for changes in bone quality. Several force x repetition interactions were observed for: muscle IL-1alpha and bone IL-1beta; serum TNFalpha, IL-1alpha, and IL-1beta; muscle HSP72, a tissue stress and repair protein; histomorphological evidence of tendon and cartilage degradation; serum biomarkers of bone degradation (CTXI) and bone formation (osteocalcin); and morphological evidence of bone adaptation versus resorption. In most cases, performance of the HRHF task induced the greatest tissue degenerative changes, while performance of moderate level tasks induced bone adaptation and a suggestion of muscle adaptation. Both high force tasks induced median nerve macrophage infiltration, spinal cord sensitization (increased substance P), grip strength declines and forepaw mechanical allodynia by task week

  1. Small Molecule based Musculoskeletal Regenerative Engineering

    PubMed Central

    Lo, Kevin W.-H.; Jiang, Tao; Gagnon, Keith A.; Nelson, Clarke; Laurencin, Cato T.

    2014-01-01

    Clinicians and scientists working in the field of regenerative engineering are actively investigating a wide range of methods to promote musculoskeletal tissue regeneration. Small molecule-mediated tissue regeneration is emerging as a promising strategy for regenerating various musculoskeletal tissues and a large number of small molecule compounds have been recently discovered as potential bioactive molecules for musculoskeletal tissue repair and regeneration. In this review, we summarize the recent literature encompassing the past four years in the area of small bioactive molecule for promoting repair and regeneration of various musculoskeletal tissues including bone, muscle, cartilage, tendon, and nerve. PMID:24405851

  2. Disinfection of human skin allografts in tissue banking: a systematic review report.

    PubMed

    Johnston, C; Callum, J; Mohr, J; Duong, A; Garibaldi, A; Simunovic, N; Ayeni, O R

    2016-12-01

    The use of skin allografts to temporarily replace lost or damaged skin is practiced worldwide. Naturally occurring contamination can be present on skin or can be introduced at recovery or during processing. This contamination can pose a threat to allograft recipients. Bacterial culture and disinfection of allografts are mandated, but the specific practices and methodologies are not dictated by standards. A systematic review of literature from three databases found 12 research articles that evaluated bioburden reduction processes of skin grafts. The use of broad spectrum antibiotics and antifungal agents was the most frequently identified disinfection method reported demonstrating reductions in contamination rates. It was determined that the greatest reduction in the skin allograft contamination rates utilized 0.1 % peracetic acid or 25 kGy of gamma irradiation at lower temperatures.

  3. Non-invasive evaluation of stable renal allograft function using point shear-wave elastography.

    PubMed

    Kim, Bom Jun; Kim, Chan Kyo; Park, Jung Jae

    2018-01-01

    To investigate the feasibility of point shear-wave elastography (SWE) in evaluating patients with stable renal allograft function who underwent protocol biopsies. 95 patients with stable renal allograft function that underwent ultrasound-guided biopsies at predefined time points (10 days or 1 year after transplantation) were enrolled. Ultrasound and point SWE examinations were performed immediately before protocol biopsies. Patients were categorized into two groups: subclinical rejection (SCR) and non-SCR. Tissue elasticity (kPa) on SWE was measured in the cortex of all renal allografts. SCR was pathologically confirmed in 34 patients. Tissue elasticity of the SCR group (31.0 kPa) was significantly greater than that of the non-SCR group (24.5 kPa) (=0.016), while resistive index value did not show a significant difference between the two groups (p = 0.112). Tissue elasticity in renal allografts demonstrated significantly moderate negative correlation with estimated glomerular filtration rate (correlation coefficient = -0.604, p < 0.001). Tissue elasticity was not independent factor for SCR prediction on multivariate analysis. As a non-invasive tool, point SWE appears feasible in distinguishing between patients with SCR and without SCR in stable functioning renal allografts. Moreover, it may demonstrate the functional state of renal allografts. Advances in knowledge: On point SWE, SCR has greater tissue elasticity than non-SCR.

  4. Prolonged Allograft Survival in a Patient With Chronic Immunosuppression: A Case Report and Systematic Review.

    PubMed

    Vyas, Krishna S; Burns, Chase; Ryan, Dylan T; Wong, Lesley

    2017-06-01

    A 41-year-old man with past medical history of kidney-liver transplantation requiring chronic immunosuppression presented 2 years posttransplant with a necrotizing soft tissue infection of his right thigh. Serial debridement to remove necrotic tissue was performed, and a Matrix HD Allograft Fenestrated (RTI Surgical, Alachua, FL) was applied. At 5-months post grafting, the patient demonstrated fully vascularized and intact skin. Under normal circumstances, a cadaveric allograft sloughs over several weeks and is not usually considered a permanent solution for wound closure. A systematic review of transplant patients on chronic immunosuppression with skin allografts demonstrates the potential for the indefinite survival of an allograft. Necrotizing soft tissue infections can definitively be treated using serial debridement and allograft transplantation in the chronically immunosuppressed.

  5. Fresh Osteochondral Allograft Versus Autograft: Twelve-Month Results in Isolated Canine Knee Defects.

    PubMed

    McCarty, Eric C; Fader, Ryan R; Mitchell, Justin J; Glenn, R Edward; Potter, Hollis G; Spindler, Kurt P

    2016-09-01

    Osteochondral autografts and allografts have been widely used in the treatment of isolated grade 4 articular cartilage lesions of the knee. However, there is a paucity of literature regarding the basic science investigating the direct comparison between fresh osteochondral allografts to autografts. At 12 months, fresh osteochondral allografts are equal to autografts with respect to function, bony incorporation into host bone, and chondrocyte viability. Controlled laboratory study. Eight adult mongrel dogs underwent bilateral hindlimb osteochondral graft implantation in the knee after creation of an acute Outerbridge grade 4 cartilage defect. One hindlimb of each dog knee received an autograft, and the contralateral knee received an allograft. All dogs were sacrificed at 12 months. Graft analysis included gross examination, radiographs, magnetic resonance imaging (MRI), biomechanical testing, and histology. MRI demonstrated excellent bony incorporation of both autografts and allografts, except for 1 allograft that revealed partial incorporation. Histologic examination of cartilage showed intact hyaline appearance for both autografts and allografts, with fibrocartilage at the host-graft interface of both. Biomechanical testing demonstrated no significant difference between allografts and autografts (P = .76). Furthermore, no significant difference was observed between allografts and the native cartilage with biomechanical testing (P = .84). After 12 months from time of implantation, fresh osteochondral allograft tissue and autograft tissue in this study were not statistically different with respect to biomechanical properties, gross morphology, bony incorporation, or overall histologic characteristics. When compared with the previously reported 6-month incorporation rates, there was improved allograft and autograft incorporation at 12 months. With no significant differences in gross examination, radiographs, MRI, biomechanical testing, or histology in the canine

  6. Ankle bipolar fresh osteochondral allograft survivorship and integration: transplanted tissue genetic typing and phenotypic characteristics.

    PubMed

    Neri, Simona; Vannini, Francesca; Desando, Giovanna; Grigolo, Brunella; Ruffilli, Alberto; Buda, Roberto; Facchini, Andrea; Giannini, Sandro

    2013-10-16

    Fresh osteochondral allografts represent a treatment option for early ankle posttraumatic arthritis. Transplanted cartilage survivorship, integration, and colonization by recipient cells have not been fully investigated. The aim of this study was to evaluate the ability of recipient cells to colonize the allograft cartilage and to assess allograft cell phenotype. Seventeen ankle allograft samples were studied. Retrieved allograft cartilage DNA from fifteen cases was compared with recipient and donor constitutional DNA by genotyping. In addition, gene expression was evaluated on six allograft cartilage samples by means of real-time reverse transcription-polymerase chain reaction. Histology and immunohistochemistry were performed to support molecular observations. Of fifteen genotyped allografts, ten completely matched to the host, three matched to the donor, and two showed a mixed profile. Gene expression analysis showed that grafted cartilage expressed cartilage-specific markers. The rare persistence of donor cells and the prevailing presence of host DNA in retrieved ankle allografts suggest the ingrowth of recipient cells into the allograft cartilage, presumably migrating from the subchondral bone, in accordance with morphological findings. The expression of chondrogenic markers in some of the samples argues for the acquisition of a chondrocyte-like phenotype by these cells. To our knowledge, this is the first report describing the colonization of ankle allograft cartilage by host cells showing the acquisition of a chondrocyte-like phenotype.

  7. Recent tissue engineering-based advances for effective rAAV-mediated gene transfer in the musculoskeletal system.

    PubMed

    Rey-Rico, Ana; Cucchiarini, Magali

    2016-04-01

    Musculoskeletal tissues are diverse and significantly different in their ability to repair upon injury. Current treatments often fail to reproduce the natural functions of the native tissue, leading to an imperfect healing. Gene therapy might improve the repair of tissues by providing a temporarily and spatially defined expression of the therapeutic gene(s) at the site of the injury. Several gene transfer vehicles have been developed to modify various human cells and tissues from musculoskeletal system among which the non-pathogenic, effective, and relatively safe recombinant adeno-associated viral (rAAV) vectors that have emerged as the preferred gene delivery system to treat human disorders. Adapting tissue engineering platforms to gene transfer approaches mediated by rAAV vectors is an attractive tool to circumvent both the limitations of the current therapeutic options to promote an effective healing of the tissue and the natural obstacles from these clinically adapted vectors to achieve an efficient and durable gene expression of the therapeutic sequences within the lesions.

  8. Tissue-associated self-antigens containing exosomes: Role in allograft rejection.

    PubMed

    Sharma, Monal; Ravichandran, Ranjithkumar; Bansal, Sandhya; Bremner, Ross M; Smith, Michael A; Mohanakumar, T

    2018-06-15

    Exosomes are extracellular vesicles that express self-antigens (SAgs) and donor human leukocyte antigens. Tissue-specific exosomes can be detected in the circulation following lung, heart, kidney and islet cell transplantations. We collected serum samples from patients who had undergone lung (n = 30), heart (n = 8), or kidney (n = 15) transplantations to isolate circulating exosomes. Exosome purity was analyzed by Western blot, using CD9 exosome-specific markers. Tissue-associated lung SAgs, collagen V (Col-V) and K-alpha 1 tubulin (Kα1T), heart SAgs, myosin and vimentin, and kidney SAgs, fibronectin and collagen IV (Col-IV), were identified using western blot. Lung transplant recipients diagnosed with bronchiolitis obliterans syndrome had exosomes with higher expression of Col-V (4.2-fold) and Kα1T (37.1-fold) than stable. Exosomes isolated from heart transplant recipients diagnosed with coronary artery vasculopathy had a 3.9-fold increase in myosin and a 4.7-fold increase in vimentin compared with stable. Further, Kidney transplant recipients diagnosed with transplant glomerulopathy had circulating exosomes with a 2-fold increased expression of fibronectin and 2.5-fold increase in Col-IV compared with stable. We conclude that circulating exosomes with tissue associated SAgs have the potential to be a noninvasive biomarker for allograft rejection. Copyright © 2018. Published by Elsevier Inc.

  9. Tolerance to Vascularized Composite Allografts in Canine Mixed Hematopoietic Chimeras

    PubMed Central

    Mathes, David W.; Hwang, Billanna; Graves, Scott S.; Edwards, James; Chang, Jeff; Storer, Barry E.; Butts-Miwongtum, Tiffany; Sale, George E.; Nash, Richard A.; Storb, Rainer.

    2012-01-01

    Background Mixed donor-host chimerism, established through hematopoietic cell transplantation (HCT), is a highly reproducible strategy for the induction of tolerance towards solid organs. Here, we ask whether a nonmyeloablative conditioning regimen establishing mixed donor-host chimerism leads to tolerance of highly antigenic vascularized composite allografts. Methods Stable mixed chimerism was established in dogs given a sublethal dose (1–2 Gy) total body irradiation before and a short course of immunosuppression after dog leukocyte antigen-identical marrow transplantation. Vascularized composite allografts from marrow donors were performed after a median of 36 (range 4-54) months after HCT. Results All marrow recipients maintained mixed donor-host hematopoietic chimerism and accepted composite tissue grafts for periods ranging between 52 and 90 weeks; in turn, marrow donors rejected vascularized composite allografts from their respective marrow recipients within 18–29 days. Biopsies of muscle and skin of vascularized composite allografts from mixed chimeras showed few infiltrating cells compared to extensive infiltrates in biopsies of vascularized composite allografts from marrow donors. Elevated levels of CD3+ FoxP3+ T-regulatory cells were found in skin and muscle of vascularized composite allografts of mixed chimeras compared to normal tissues. In mixed chimeras, increased numbers of T-regulatory cells were found in draining compared to non-draining lymph nodes of vascularized composite allografts. Conclusion These data suggest that nonmyeloablative HCT may form the basis for future clinical applications of solid organ transplantation and that T-regulatory cells may function towards maintenance of the vascularized composite allograft. PMID:22082819

  10. Adipose tissue as a stem cell source for musculo-skeletal regeneration

    PubMed Central

    Gimble, Jeffrey M.; Grayson, Warren; Guilak, Farshid; Lopez, Mandi J.; Vunjak-Novakovic, Gordana

    2013-01-01

    Adipose tissue is an abundant, easily accessible, and reproducible cell source for musculo-skeletal regenerative medicine applications. Initial derivation steps yield a heterogeneous population of cells collectively termed the stromal vascular fraction (SVF), which consist of endothelial cells, immune cells, pericytes, and pre-adipocytes. Subsequent selection of an adherent cell subset from the SVF results in a relatively homogeneous population of adipose-derived stromal/stem cells (ASCs). Mammalian ASCs exhibit the ability to selectively differentiate into chondrogenic, myogenic, and osteogenic lineages in response to inductive stimuli in vitro (when cultured on scaffolds in bioreactors) and in vivo (when implanted in pre-clinical animal models). Unlike hematopoietic cells, ASCs do not elicit a robust lymphocyte reaction and instead generate and release immunosuppressive factors, such as prostaglandin E2. These unique immunomodulatory features suggest that both allogeneic and autologous ASCs will engraft successfully following application for tissue regeneration purposes. The differentiation and expansion potential of ASCs can be modified by growth factors like bone morphogenetic protein 6, bio-inductive scaffolds, and bioreactors providing environmental control and biophysical stimulation. Gene therapy approaches using lentiviral transduction can also be used to direct differentiation of ASCs along particular lineage pathways. We discuss here the utility of ASCs for musculo-skeletal tissue repair and some of the technologies that can be implemented to unlock the full regenerative potential of these highly valuable cells. PMID:21196358

  11. Severe adult burn survivors. What information about skin allografts?

    PubMed Central

    Gaucher, Sonia; Duchange, Nathalie; Jarraya, Mohamed; Magne, Jocelyne; Rochet, Jean-Michel; Stéphanazzi, Jean; Hervé, Christian; Moutel, Grégoire

    2013-01-01

    Background and objective During the acute phase of a severe burn, surgery is an emergency. In this situation, human skin allografts constitute an effective temporary skin substitute. However, information about the use of human tissue can not be given to the patients because most of the allografted patients are unconscious due to their injury. Objective This study explored the restitution of information on skin donation to patients who have been skin allografted and who have survived their injury. Method A qualitative study was conducted due to the limited number of patients in ability to be interviewed according to our medical and psychological criteria. Results and discussion Twelve patients who had been treated between 2002 and 2008 were interviewed. Our results show that 10 of them ignored that they had received skin allografts. One of the two patients who knew that they had received allografts knew that skin had been harvested from deceased donor. All patients expressed that there is no information that should not be delivered. They also expressed their relief to have had the opportunity to discuss their case and at being informed during their interview. Their own experience impacted their view in favor of organ and tissue donation. PMID:23229877

  12. Quality control processes in allografting: A twenty-year retrospective review of a hospital-based bone bank in Taiwan.

    PubMed

    Fu, Shau-Huai; Liu, Jyh-You; Huang, Chuan-Ching; Lin, Feng-Ling; Yang, Rong-Sen; Hou, Chun-Han

    2017-01-01

    Musculoskeletal allografts are now commonly used. To decrease the potential risks of transmission of pathogenic bacteria, fungi, or viruses to the transplant recipients, certain issues regarding the management of patients who receive contaminated allografts need to be addressed. We aimed to clarify the incidence and extent of disease transmission from allografts by analyzing the allografting procedures performed in the bone bank of our hospital over the past 20 years. We retrospectively reviewed the data from our allograft registry center on 3979 allografts that were implanted in 3193 recipients throughout a period of two decades, from July 1991 to June 2011. The source of the allografts, results of all screening tests, dates of harvesting and implantation, and recipients of all allografts were checked. With the help of the Center for Infection Control of our hospital, a strict prospective, hospital-wide, on-site surveillance was conducted, and every patient with healthcare-associated infection was identified. Fisher's exact test was used to compare the infection rate between recipients with sterile allografts and those with contaminated allografts. The overall discard and infection rates were, respectively, 23% and 1.3% in the first decade (1991-2001); and 18.4% and 1.25% in the second decade (2001-2011). The infection rate of contaminated allograft recipients was significantly higher than that of sterile allograft recipients (10% vs. 1.15%, P < 0.01) in the second decade. Both infection and discard rates of our bone bank are comparable with those of international bone banks. Strict allograft processing and adequate prophylactic use of antibiotics are critical to prevent infection and disease transmission in such cases.

  13. Quality control processes in allografting: A twenty-year retrospective review of a hospital-based bone bank in Taiwan

    PubMed Central

    Fu, Shau-Huai; Liu, Jyh-You; Huang, Chuan-Ching; Lin, Feng-ling; Yang, Rong-Sen; Hou, Chun-han

    2017-01-01

    Musculoskeletal allografts are now commonly used. To decrease the potential risks of transmission of pathogenic bacteria, fungi, or viruses to the transplant recipients, certain issues regarding the management of patients who receive contaminated allografts need to be addressed. We aimed to clarify the incidence and extent of disease transmission from allografts by analyzing the allografting procedures performed in the bone bank of our hospital over the past 20 years. We retrospectively reviewed the data from our allograft registry center on 3979 allografts that were implanted in 3193 recipients throughout a period of two decades, from July 1991 to June 2011. The source of the allografts, results of all screening tests, dates of harvesting and implantation, and recipients of all allografts were checked. With the help of the Center for Infection Control of our hospital, a strict prospective, hospital-wide, on-site surveillance was conducted, and every patient with healthcare-associated infection was identified. Fisher’s exact test was used to compare the infection rate between recipients with sterile allografts and those with contaminated allografts. The overall discard and infection rates were, respectively, 23% and 1.3% in the first decade (1991–2001); and 18.4% and 1.25% in the second decade (2001–2011). The infection rate of contaminated allograft recipients was significantly higher than that of sterile allograft recipients (10% vs. 1.15%, P < 0.01) in the second decade. Both infection and discard rates of our bone bank are comparable with those of international bone banks. Strict allograft processing and adequate prophylactic use of antibiotics are critical to prevent infection and disease transmission in such cases. PMID:29049290

  14. Determination of residual dimethylsulfoxide in cryopreserved cardiovascular allografts.

    PubMed

    Díaz Rodríguez, R; Van Hoeck, B; De Gelas, S; Blancke, F; Ngakam, R; Bogaerts, K; Jashari, R

    2017-06-01

    Dimethylsulfoxide (DMSO) is a solvent which protects the structure of allografts during the cryopreservation and thawing process. However, several toxic effects of DMSO in patients after transplantation of cryopreserved allografts have been described. The aim of this study is to determine the residual DMSO in the cardiovascular allografts after thawing and preparation of cryopreserved allografts for clinical application following guidelines of the European Pharmacopoeia for DMSO detection. Four types of EHB allografts (aortic valve-AV, pulmonary valve-PV, descending thoracic aorta-DA, and femoral artery-FA) are cryopreserved using as cryoprotecting solution a 10% of DMSO in medium 199. Sampling is carried out after thawing, after DMSO dilution and after delay of 30 min from final dilution (estimated delay until allograft implantation). After progressive thawing in sterile water bath at 37-42 °C (duration of about 20 min), DMSO dilution is carried out by adding consecutively 33, 66 and 200 mL of saline. Finally, tissues are transferred into 200 mL of a new physiologic solution. Allograft samples are analysed for determination of the residual DSMO concentration using a validated Gas Chromatography analysis. Femoral arteries showed the most important DMSO reduction after the estimated delay: 92.97% of decrease in the cryoprotectant final amount while a final reduction of 72.30, 72.04 and 76.29% in DMSO content for AV, PV and DA, was found, respectively. The residual DMSO in the allografts at the moment of implantation represents a final dose of 1.95, 1.06, 1.74 and 0.26 mg kg -1 in AV, PV, DA and FA, respectively, for men, and 2.43, 1.33, 2.17 and 0.33 mg kg -1 for same tissues for women (average weight of 75 kg in men, and 60 kg in women). These results are seriously below the maximum recommended dose of 1 g DMSO kg -1 (Regan et al. in Transfusion 50:2670-2675, 2010) of weight of the patient guaranteeing the safety and quality of allografts.

  15. [Oral mucosa analog allografts in non-consanguineous rats].

    PubMed

    González, Luis; Padrón, Karla; Salmen, Siham; Jerez, Elsy; Dávila, Lorena; Solórzano, Eduvigis

    2017-01-24

    Although there are therapeutic options for the treatment of oral mucosa defects, the need for functional, anatomical and aesthetically similar substitutes persists, as well as for solutions to reduce autologous grafts morbidity. To determine clinical and histological compatibility of equivalent oral mucosa allografts generated through tissue engineering in non-consanguineous rats. We used a sample of oral mucosa from Sprague Dawley rats to obtain a fibroblast culture and a keratinocytes and fibroblasts co-culture. In both cases, we used a commercial collagen membrane as "scaffold". After ten weeks of culture, we grafted the resulting membranes into four Wistar rats. The first phase of the study was the development of the oral mucosa equivalents generated by tissue engineering. Then, we implanted them in immunocompetent Wistar rats, and finallywe evaluated the clinical and histological features of the allografts. In vivo evaluation of mucosal substitutes showed a correct integration of artificial oral mucosa in immunocompetent hosts, with an increase in periodontal biotype and the creation of a zone with increased keratinization. Histologically, the tissue was similar to the control oral mucosa sample with no inflammatory reaction nor clinical or histological rejection signs. The equivalent oral mucosa allografts generated by tissue engineering showed clinical and histological compatibility.

  16. Hepatitis B transmission by cell and tissue allografts: How safe is safe enough?

    PubMed Central

    Solves, Pilar; Mirabet, Vicente; Alvarez, Manuel

    2014-01-01

    More than 2 million human tissue transplants (bone, tendon, cartilage, skin, cornea, amniotic membrane, stem cells, heart valve, blood vessel, etc.), are performed worldwide every year. Cells and tissues are shared between countries which have different regulations and laboratory equipment and represent a risk of hepatitis B virus (HBV) transmission that has become a global safety concern. While the risk of transfusion-transmitted HBV infection from blood donations has been estimated, the rate of HBV transmission from donors to recipients of allografts is unknown and varies between different tissues. There are various important ways of reducing the transmission risk, but donor screening and donor testing are still the main factors for preventing HBV transmission. HBV detection is included in the routine screening tests for cell and tissue donors. The standard test for preventing transplant-transmitted hepatitis B is the hepatitis B surface antigen. The implementation of methods involving nucleic acid amplification and the new generation of reactives to detect viral antibodies or antigens with an immunoassay, has increased the sensitivity and the specificity of the screening tests. The objective of our research was to review the literature and critically analyse the different steps for avoiding HBV transmission in cell and tissue donors, focusing on the screening tests performed. PMID:24966613

  17. Musculoskeletal tissue engineering with human umbilical cord mesenchymal stromal cells

    PubMed Central

    Wang, Limin; Ott, Lindsey; Seshareddy, Kiran; Weiss, Mark L; Detamore, Michael S

    2011-01-01

    Multipotent mesenchymal stromal cells (MSCs) hold tremendous promise for tissue engineering and regenerative medicine, yet with so many sources of MSCs, what are the primary criteria for selecting leading candidates? Ideally, the cells will be multipotent, inexpensive, lack donor site morbidity, donor materials should be readily available in large numbers, immunocompatible, politically benign and expandable in vitro for several passages. Bone marrow MSCs do not meet all of these criteria and neither do embryonic stem cells. However, a promising new cell source is emerging in tissue engineering that appears to meet these criteria: MSCs derived from Wharton’s jelly of umbilical cord MSCs. Exposed to appropriate conditions, umbilical cord MSCs can differentiate in vitro along several cell lineages such as the chondrocyte, osteoblast, adipocyte, myocyte, neuronal, pancreatic or hepatocyte lineages. In animal models, umbilical cord MSCs have demonstrated in vivo differentiation ability and promising immunocompatibility with host organs/tissues, even in xenotransplantation. In this article, we address their cellular characteristics, multipotent differentiation ability and potential for tissue engineering with an emphasis on musculoskeletal tissue engineering. PMID:21175290

  18. The extent of soft tissue and musculoskeletal injuries after earthquakes; describing a role for reconstructive surgeons in an emergency response.

    PubMed

    Clover, A J P; Jemec, B; Redmond, A D

    2014-10-01

    Earthquakes are the leading cause of natural disaster-related mortality and morbidity. Soft tissue and musculoskeletal injuries are the predominant type of injury seen after these events and a major reason for admission to hospital. Open fractures are relatively common; however, they are resource-intense to manage. Appropriate management is important in minimising amputation rates and preserving function. This review describes the pattern of musculoskeletal and soft-tissue injuries seen after earthquakes and explores the manpower and resource implications involved in their management. A Medline search was performed, including terms "injury pattern" and "earthquake," "epidemiology injuries" and "earthquakes," "plastic surgery," "reconstructive surgery," "limb salvage" and "earthquake." Papers published between December 1992 and December 2012 were included, with no initial language restriction. Limb injuries are the commonest injuries seen accounting for 60 % of all injuries, with fractures in more than 50 % of those admitted to hospital, with between 8 and 13 % of these fractures open. After the first few days and once the immediate lifesaving phase is over, the management of these musculoskeletal and soft-tissue injuries are the commonest procedures required. Due to the predominance of soft-tissue and musculoskeletal injuries, plastic surgeons as specialists in soft-tissue reconstruction should be mobilised in the early stages of a disaster response as part of a multidisciplinary team with a focus on limb salvage.

  19. The safety of bone allografts used in dentistry: a review.

    PubMed

    Holtzclaw, Dan; Toscano, Nicholas; Eisenlohr, Lisa; Callan, Don

    2008-09-01

    Recent media reports concerning "stolen body parts" have shaken the public's trust in the safety of and the use of ethical practices involving human allografts. The authors provide a comprehensive review of the safety aspects of human bone allografts. The authors reviewed U.S. government regulations, industry standards, independent industry association guidelines, company guidelines and scientific articles related to the use of human bone allografts in the practice of dentistry published in the English language. The use of human bone allografts in the practice of dentistry involves the steps of procurement, processing, use and tracking. Rigorous donor screening and aseptic proprietary processing programs have rendered the use of human bone allografts safe and effective as a treatment option. When purchasing human bone allografts for the practice of dentistry, one should choose products accredited by the American Association of Tissue Banks for meeting uniformly high safety and quality control measures. Knowledge of human bone allograft procurement, processing, use and tracking procedures may allow dental clinicians to better educate their patients and address concerns about this valuable treatment option.

  20. Deep convolutional neural network and 3D deformable approach for tissue segmentation in musculoskeletal magnetic resonance imaging.

    PubMed

    Liu, Fang; Zhou, Zhaoye; Jang, Hyungseok; Samsonov, Alexey; Zhao, Gengyan; Kijowski, Richard

    2018-04-01

    To describe and evaluate a new fully automated musculoskeletal tissue segmentation method using deep convolutional neural network (CNN) and three-dimensional (3D) simplex deformable modeling to improve the accuracy and efficiency of cartilage and bone segmentation within the knee joint. A fully automated segmentation pipeline was built by combining a semantic segmentation CNN and 3D simplex deformable modeling. A CNN technique called SegNet was applied as the core of the segmentation method to perform high resolution pixel-wise multi-class tissue classification. The 3D simplex deformable modeling refined the output from SegNet to preserve the overall shape and maintain a desirable smooth surface for musculoskeletal structure. The fully automated segmentation method was tested using a publicly available knee image data set to compare with currently used state-of-the-art segmentation methods. The fully automated method was also evaluated on two different data sets, which include morphological and quantitative MR images with different tissue contrasts. The proposed fully automated segmentation method provided good segmentation performance with segmentation accuracy superior to most of state-of-the-art methods in the publicly available knee image data set. The method also demonstrated versatile segmentation performance on both morphological and quantitative musculoskeletal MR images with different tissue contrasts and spatial resolutions. The study demonstrates that the combined CNN and 3D deformable modeling approach is useful for performing rapid and accurate cartilage and bone segmentation within the knee joint. The CNN has promising potential applications in musculoskeletal imaging. Magn Reson Med 79:2379-2391, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  1. Evaluation of the autopsy report before releasing musculoskeletal tissue donors; what is the benefit? EATB International Conference, October 17-20, Budapest, Hungary.

    PubMed

    Van Wijk, Marja J; Visser, Laura; Bokhorst, Arlinke G

    2008-12-01

    EU directive 2006/17/EC requires that all available medical information, including the autopsy report, is evaluated before releasing tissues for transplantation. The study objective was to investigate whether evaluation of autopsy results of musculoskeletal tissue donors contributes to safety and availability of transplantable tissues. The files of all donors of whom musculoskeletal tissues were retrieved by BIS in 2006 were reviewed for death cause and autopsy results. Of 84 donors musculoskeletal tissues were retrieved. In 47 donors autopsy was performed (56.0%). The groups with and without autopsy were similar in sex, age, length, and weight. In one donor no autopsy results were evaluated, since the donor was already rejected because of positive blood tests. In 13 donors (28.1%) death causes before autopsy were unknown. In 12 of these donors a death cause could be established after autopsy. In nine of the donors with a clear suspected death cause (27.3%), the death cause after autopsy differed from the suspected death cause. Four donors with autopsy (8.7%) had a general contraindication for donation, a (possible) sepsis in three and a persisting unknown death cause in one. Eight donors (17.4%) had musculoskeletal-specific contraindications, i.e. local infections. In conclusion, in 26.1% of the donors with autopsy, general or musculoskeletal-specific contraindications for donation were found. Furthermore, performance of autopsies enlarges the potential donor pool, since death causes can be established in almost all autopsies done in case of an unknown death cause. Therefore, evaluation of autopsy results improves the safety and quantity of tissues for transplantation.

  2. Gamma Radiation Sterilization Reduces the High-cycle Fatigue Life of Allograft Bone.

    PubMed

    Islam, Anowarul; Chapin, Katherine; Moore, Emily; Ford, Joel; Rimnac, Clare; Akkus, Ozan

    2016-03-01

    Sterilization by gamma radiation impairs the mechanical properties of bone allografts. Previous work related to radiation-induced embrittlement of bone tissue has been limited mostly to monotonic testing which does not necessarily predict the high-cycle fatigue life of allografts in vivo. We designed a custom rotating-bending fatigue device to answer the following questions: (1) Does gamma radiation sterilization affect the high-cycle fatigue behavior of cortical bone; and (2) how does the fatigue life change with cyclic stress level? The high-cycle fatigue behavior of human cortical bone specimens was examined at stress levels related to physiologic levels using a custom-designed rotating-bending fatigue device. Test specimens were distributed among two treatment groups (n = 6/group); control and irradiated. Samples were tested until failure at stress levels of 25, 35, and 45 MPa. At 25 MPa, 83% of control samples survived 30 million cycles (run-out) whereas 83% of irradiated samples survived only 0.5 million cycles. At 35 MPa, irradiated samples showed an approximately 19-fold reduction in fatigue life compared with control samples (12.2 × 10(6) ± 12.3 × 10(6) versus 6.38 × 10(5) ± 6.81 × 10(5); p = 0.046), and in the case of 45 MPa, this reduction was approximately 17.5-fold (7.31 × 10(5) ± 6.39 × 10(5) versus 4.17 × 10(4) ± 1.91 × 10(4); p = 0.025). Equations to estimate high-cycle fatigue life of irradiated and control cortical bone allograft at a certain stress level were derived. Gamma radiation sterilization severely impairs the high cycle fatigue life of structural allograft bone tissues, more so than the decline that has been reported for monotonic mechanical properties. Therefore, clinicians need to be conservative in the expectation of the fatigue life of structural allograft bone tissues. Methods to preserve the fatigue strength of nonirradiated allograft bone tissue are needed. As opposed to what monotonic tests might suggest, the cyclic

  3. PTH promotes allograft integration in a calvarial bone defect

    PubMed Central

    Sheyn, Dmitriy; Yakubovich, Doron Cohn; Kallai, Ilan; Su, Susan; Da, Xiaoyu; Pelled, Gadi; Tawackoli, Wafa; Cook-Weins, Galen; Schwarz, Edward M.; Gazit, Dan; Gazit, Zulma

    2013-01-01

    Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting in allograft osseointegration in cranial membranous bones. Calvarial bone defects were created in transgenic mice, in which luciferase is expressed under the control of the osteocalcin promoter. The mice were given implants of allografts with or without daily PTH treatment. Bioluminescence imaging (BLI) was performed to monitor host osteprogenitor differentiation at the implantation site. Bone formation was evaluated with the aid of fluorescence imaging (FLI) and micro–computed tomography (μCT) as well as histological analyses. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the expression of key osteogenic and angiogenic genes. Osteoprogenitor differentiation, as detected by BLI, in mice treated with an allograft implant and PTH was over 2-fold higher than those in mice treated with an allograft implant without PTH. FLI also demonstrated that the bone mineralization process in PTH-treated allografts was significantly higher than that in untreated allografts. The μCT scans revealed a significant increase in bone formation in Allograft + PTH–treated mice comparing to Allograft + PBS treated mice. The osteogenic genes osteocalcin (Oc/Bglap) and integrin binding sialoprotein (Ibsp) were upregulated in the Allograft + PTH–treated animals. In summary, PTH treatment enhances osteoprogenitor differentiation and augments bone formation around structural allografts. The precise mechanism is not clear, but we show that infiltration pattern of mast cells, associated with the formation of fibrotic tissue, in the defect site is significantly affected by the PTH treatment. PMID:24131143

  4. PTH promotes allograft integration in a calvarial bone defect.

    PubMed

    Sheyn, Dmitriy; Cohn Yakubovich, Doron; Kallai, Ilan; Su, Susan; Da, Xiaoyu; Pelled, Gadi; Tawackoli, Wafa; Cook-Weins, Galen; Schwarz, Edward M; Gazit, Dan; Gazit, Zulma

    2013-12-02

    Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting in allograft osseointegration in cranial membranous bones. Calvarial bone defects were created in transgenic mice, in which luciferase is expressed under the control of the osteocalcin promoter. The mice were given implants of allografts with or without daily PTH treatment. Bioluminescence imaging (BLI) was performed to monitor host osteprogenitor differentiation at the implantation site. Bone formation was evaluated with the aid of fluorescence imaging (FLI) and microcomputed tomography (μCT) as well as histological analyses. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the expression of key osteogenic and angiogenic genes. Osteoprogenitor differentiation, as detected by BLI, in mice treated with an allograft implant and PTH was over 2-fold higher than those in mice treated with an allograft implant without PTH. FLI also demonstrated that the bone mineralization process in PTH-treated allografts was significantly higher than that in untreated allografts. The μCT scans revealed a significant increase in bone formation in allograft + PTH treated mice comparing to allograft + PBS treated mice. The osteogenic genes osteocalcin (Oc/Bglap) and integrin binding sialoprotein (Ibsp) were upregulated in the allograft + PTH treated animals. In summary, PTH treatment enhances osteoprogenitor differentiation and augments bone formation around structural allografts. The precise mechanism is not clear, but we show that infiltration pattern of mast cells, associated with the formation of fibrotic tissue, in the defect site is significantly affected by the PTH treatment.

  5. X-ray microtomography-based measurements of meniscal allografts.

    PubMed

    Mickiewicz, P; Binkowski, M; Bursig, H; Wróbel, Z

    2015-05-01

    X-ray microcomputed tomography (XMT) is a technique widely used to image hard and soft tissues. Meniscal allografts as collagen structures can be imaged and analyzed using XMT. The aim of this study was to present an XMT scanning protocol that can be used to obtain the 3D geometry of menisci. It was further applied to compare two methods of meniscal allograft measurement: traditional (based on manual measurement) and novel (based on digital measurement of 3D models of menisci obtained with use of XMT scanner). The XMT-based menisci measurement is a reliable method for assessing the geometry of a meniscal allograft by measuring the basic meniscal dimensions known from traditional protocol. Thirteen dissected menisci were measured according the same principles traditionally applied in a tissue bank. Next, the same specimens were scanned by a laboratory scanner in the XMT Lab. The images were processed to obtain a 3D mesh. 3D models of allograft geometry were then measured using a novel protocol enhanced by computer software. Then, both measurements were compared using statistical tests. The results showed significant differences (P<0.05) between the lengths of the medial and lateral menisci measured in the tissue bank and the XMT Lab. Also, medial meniscal widths were significantly different (P<0.05). Differences in meniscal lengths may result from difficulties in dissected meniscus measurements in tissue banks, and may be related to the elastic structure of the dissected meniscus. Errors may also be caused by the lack of highlighted landmarks on the meniscal surface in this study. The XMT may be a good technique for assessing meniscal dimensions without actually touching the specimen. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. [Tongue, trachea, abdominal wall, uterus, and penis allografts. More details on some other clinical applications of vascularized composite tissue allotransplantation].

    PubMed

    Petit, F

    2007-10-01

    The first hand and face allografts opened a new era in medicine history: a time when allotransplantation and reconstructive surgery coupled their principles. Their success and their development made composite tissue allotransplantation (CTA) a clinical reality for our speciality. Although still recent and limited, experience from this new surgical practice will widen with feedback from the first clinical cases and with experience gained from more clinical cases, more anatomical areas, more type of allografts, more surgical techniques, more immunosuppressive regimens. Tongue, trachea, abdominal wall, uterus, penis allotransplantations have been performed, contemporarily. Whatever the future and the benefits for the selected patients might have been, reports from these - un- and misknown - cases contribute to a better knowledge of CTA, its therapeutic potential, its limits, its challenges.

  7. Decellularized Versus Fresh-Frozen Allografts in Anterior Cruciate Ligament Reconstruction: An In Vitro Study in a Rabbit Model.

    PubMed

    Dong, Shikui; Huangfu, Xiaoqiao; Xie, Guoming; Zhang, Yang; Shen, Peng; Li, Xiaoxi; Qi, Jin; Zhao, Jinzhong

    2015-08-01

    The common fresh-frozen allografts that are used for anterior cruciate ligament (ACL) reconstructions behave slower during the remodeling process and produce weaker tendon-bone integrations than do autografts. Decellularization of allogenic tendons results in a clean and porous collagen scaffold with low antigenicity and high compatibility, which may be more suitable for ACL reconstructions. Allograft decellularization will result in a tissue structure with suitable mechanical characteristics for ACL reconstruction, thereby promoting graft remodeling and enhancing tendon-bone healing. Controlled laboratory study. Decellularized allograft tissues were prepared with a pH-modified decellularization process and evaluated for their biocompatibility and biomechanical character in vitro. Eighty New Zealand White rabbits were divided into 2 groups, with 40 in each group, to receive ACL reconstruction with either fresh-frozen (common) allografts or decellularized allografts on both knees. At 2, 4, 8, and 12 weeks postoperatively, the rabbits were euthanized for biomechanical testing, micro-computed tomography analysis, and histologic analysis. The pH-modified decellularized allograft tissues kept excellent biocompatibility and biomechanical character during the in vitro study. Biomechanical testing indicated that the decellularized allograft had significantly higher ultimate load (P = .02) and stiffness (P = .01) levels than the common allograft at 12 weeks, and there was no significant difference between the 2 groups at any other time point. The micro-CT evaluation determined significantly higher bone mineral density (P < .01) in the decellularized allograft group than that in the common allograft group at 12 weeks, but no difference between the 2 groups was observed at any other time point. Regarding bone volume/total volume, there was no difference between the 2 groups at any time point. Fibroblast ingrowths, vascular formation, and connective tissue formation in the

  8. Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats.

    PubMed

    Mikesh, Michelle; Ghergherehchi, Cameron L; Rahesh, Sina; Jagannath, Karthik; Ali, Amir; Sengelaub, Dale R; Trevino, Richard C; Jackson, David M; Tucker, Haley O; Bittner, George D

    2018-07-01

    Many publications report that ablations of segments of peripheral nerves produce the following unfortunate results: (1) Immediate loss of sensory signaling and motor control; (2) rapid Wallerian degeneration of severed distal axons within days; (3) muscle atrophy within weeks; (4) poor behavioral (functional) recovery after many months, if ever, by slowly-regenerating (∼1mm/d) axon outgrowths from surviving proximal nerve stumps; and (5) Nerve allografts to repair gap injuries are rejected, often even if tissue matched and immunosuppressed. In contrast, using a female rat sciatic nerve model system, we report that neurorrhaphy of allografts plus a well-specified-sequence of solutions (one containing polyethylene glycol: PEG) successfully addresses each of these problems by: (a) Reestablishing axonal continuity/signaling within minutes by nonspecific ally PEG-fusing (connecting) severed motor and sensory axons across each anastomosis; (b) preventing Wallerian degeneration by maintaining many distal segments of inappropriately-reconnected, PEG-fused axons that continuously activate nerve-muscle junctions; (c) maintaining innervation of muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; (d) inducing remarkable behavioral recovery to near-unoperated levels within days to weeks, almost certainly by CNS and PNS plasticities well-beyond what most neuroscientists currently imagine; and (e) preventing rejection of PEG-fused donor nerve allografts with no tissue matching or immunosuppression. Similar behavioral results are produced by PEG-fused autografts. All results for Negative Control allografts agree with current neuroscience data 1-5 given above. Hence, PEG-fusion of allografts for repair of ablated peripheral nerve segments expand on previous observations in single-cut injuries, provoke reconsideration of some current neuroscience dogma, and further extend the potential of PEG-fusion in clinical practice. © 2018 Wiley Periodicals

  9. Bone tissue engineering by way of allograft revitalization: mechanistic and mechanical investigations using a porcine model.

    PubMed

    Runyan, Christopher M; Ali, Samantha T; Chen, Wendy; Calder, Bennet W; Rumburg, Aaron E; Billmire, David A; Taylor, Jesse A

    2014-05-01

    "Allograft revitalization" is a process in which cadaveric bone is used to generate well-vascularized living bone. We had previously found that porcine allograft hemimandibles filled with autologous adipose-derived stem cells (ASCs) and recombinant human bone morphogenetic protein-2-soaked absorbable collagen sponge (rhBMP-2/ACS) were completely replaced by vascularized bone, provided the construct had been incubated within a periosteal envelope. The present study sought to deepen our understanding of allograft revitalization by investigating the individual contributions of ASCs and rhBMP-2 in the process and the mechanical properties of the revitalized allograft. Porcine allograft hemimandible constructs were implanted bilaterally into rib periosteal envelopes in 8 pigs. To examine the contributions of ASCs and rhBMP-2, the following groups were assessed: group 1, periosteum alone; group 2, periosteum+ASCs; group 3, periosteum+rhBMP-2/ACS; and group 4, periosteum+ASCs+rhBMP-2/ACS. After 8 weeks, the allograft constructs were harvested for micro-computed tomography (CT) and histologic analyses and 3-point bending to assess the strength. On harvesting, the constructs receiving rhBMP-2/ACS had significantly greater bone shown by micro-CT than those receiving periosteum only (51,463 vs. 34,310 mm3; P = .031). The constructs receiving ASCs had increased bone compared to group 1 (periosteum only), although not significantly (P = .087). The combination of rhBMP-2/ACS with ASCs produced bone (50,399 mm3) equivalent to that of the constructs containing rhBMP-2/ACS only. The 3-point bending tests showed no differences between the 4 groups and a nonimplanted allograft or native mandible (P = .586), suggesting the absence of decreased strength of the allograft bone when revitalized. These data have shown that rhBMP-2/ACS significantly stimulates new bone formation by way of allograft revitalization and that the revitalized allograft has equivalent mechanical strength to

  10. The biophysical characteristics of human composite flexor tendon allograft for upper extremity reconstruction.

    PubMed

    DeGeorge, Brent R; Rodeheaver, George T; Drake, David B

    2014-01-01

    Devastating volar hand injuries with significant damage to the skin and soft tissues, pulley structures and fibro-osseous sheath, flexor tendons, and volar plates pose a major problem to the reconstructive hand surgeon. Despite advances in tendon handling, operative technique, and postoperative hand rehabilitation, patients who have undergone flexor tendon reconstruction are often plagued by chronic pain, stiffness, and decreased range of motion with resultant decreased ability to work and poor quality of life. In this article, we expand the technique of human composite flexor tendon allografts (CFTAs), pioneered by Dr E.E. Peacock, Jr, which consist of both the intrasynovial and extrasynovial flexor digitorum superficialis and flexor digitorum profundus tendons and their respective fibro-osseous sheath consisting of the digital pulley structures, periosteum, and volar plates procured from cadaveric donors with the use of modern tissue processing techniques. Human cadaveric CFTAs were procured and divided into 2 groups-unprocessed CFTAs and processed CFTAs, which are cleansed and sterilized to a sterility assurance level of 10(-6). Physical length and width relationships as well as tensile strength and gliding resistance assessments were recorded pre-tissue and post-tissue processing. The histologic properties of the composite allografts were assessed before and after tissue processing. There was no significant difference with respect to physical properties of the composite allografts before or after tissue processing. The processed composite allografts demonstrated equivalent maximum load to failure and elastic modulus compared to unprocessed tendons. The gliding resistance of the composite tendon allografts was not significantly different between the 2 groups. The use of CFTAs addresses the issues of adhesion formation and lack of suitable donor material by providing a source of intrasynovial tendon in its unaltered fibro-osseous sheath without donor morbidity

  11. Treatment of Labial Soft Tissue Recession Around Dental Implants in the Esthetic Zone Using Guided Bone Regeneration With Mineralized Allograft: A Retrospective Clinical Case Series.

    PubMed

    Le, Bach; Borzabadi-Farahani, Ali; Nielsen, Brady

    2016-08-01

    Soft tissue augmentation procedures are often performed to correct gingival recession on the facial aspects of implants in the esthetic zone. This retrospective clinical case series reports on the use of guided bone regeneration (GBR) and a coronal advancement flap with a resorbable membrane and allograft. We analyzed the records of 14 patients (7 men and 7 women) with a mean age of 36.78 years (SD, 13.9 years) who were treated for soft tissue recessions around implant-supported restorations in the maxillary central or lateral incisor location. Implant diameters ranged from 3.3 to 4.7 mm. All patients had bone loss confined to the labial surface of the implant. A solvent-dehydrated particulate mineralized allograft (Puros Cancellous Bone Allograft; Zimmer Biomet Dental, Palm Beach Gardens, FL) and a resorbable membrane (CopiOs Pericardium; Zimmer Biomet Dental) were used in a GBR surgical procedure in combination with a roughened titanium tenting screw placed 3 to 4 mm below the implant platform to restore unesthetic defects in the anterior maxilla. All postoperative tissue changes from their preoperative states were statistically significant (P < .05, Wilcoxon signed rank test). Mean preoperative crestal bone thickness (measured 2 mm from crest) and mid-implant buccal bone thickness increased by 1.84 mm (SD, 0.89 mm; 95% confidence interval [CI], 1.32 to 2.35 mm) and 2.07 mm (SD, 0.81 mm; 95% CI, 1.60 to 2.53 mm), respectively, approximately 1 year after treatment (P < .001). Significant mean increases of 1.28 mm (SD, 0.53 mm; 95% CI, 0.97 to 1.58 mm), 1.29 mm (SD, 0.81 mm; 95% CI, 0.82 to 1.75 mm) and 1.23 mm (SD, 0.53 mm; 95% CI, 0.92 to 1.53 mm) also were noted in soft tissue thickness, keratinized tissue width, and gingival height, respectively (P < .001). Use of the allograft and xenogeneic membrane effectively increased alveolar hard and soft tissue dimensions in the esthetic zone of the anterior maxilla. Future prospective clinical

  12. Bone allografting in children

    NASA Astrophysics Data System (ADS)

    Sadovoy, M. A.; Kirilova, I. A.; Podorognaya, V. T.; Matsuk, S. A.; Novoselov, V. P.; Moskalev, A. V.; Bondarenko, A. V.; Afanasev, L. M.; Gubina, E. V.

    2017-09-01

    A total of 522 patients with benign and intermediate bone tumors of various locations, aged 1 to 15 years, were operated in the period from 1996 to 2016. To diagnose skeleton tumors, we used clinical observation, X-ray, and, if indicated, tomography and tumor site biopsy. In the extensive bone resection, we performed bone reconstruction with the replacement of a defect with an allograft (bone strips, deproteinized and spongy grafts), sometimes in the combination with bone autografting. After segmental resection, the defects were filled with bone strips in the form of matchstick grafts; the allografts were received from the Laboratory for Tissue Preparation and Preservation of the Novosibirsk Research Institute of Traumatology and Orthopedics. According to the X-ray data, a complete reorganization of bone grafts occurred within 1.5 to 3 years. The long-term result was assessed as good.

  13. Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration

    PubMed Central

    Brown, Patrick T.; Handorf, Andrew M.; Jeon, Won Bae; Li, Wan-Ju

    2014-01-01

    The field of regenerative medicine and tissue engineering is an ever evolving field that holds promise in treating numerous musculoskeletal diseases and injuries. An important impetus in the development of the field was the discovery and implementation of stem cells. The utilization of mesenchymal stem cells, and later embryonic and induced pluripotent stem cells, opens new arenas for tissue engineering and presents the potential of developing stem cell-based therapies for disease treatment. Multipotent and pluripotent stem cells can produce various lineage tissues, and allow for derivation of a tissue that may be comprised of multiple cell types. As the field grows, the combination of biomaterial scaffolds and bioreactors provides methods to create an environment for stem cells that better represent their microenvironment for new tissue formation. As technologies for the fabrication of biomaterial scaffolds advance, the ability of scaffolds to modulate stem cell behavior advances as well. The composition of scaffolds could be of natural or synthetic materials and could be tailored to enhance cell self-renewal and/or direct cell fates. In addition to biomaterial scaffolds, studies of tissue development and cellular microenvironments have determined other factors, such as growth factors and oxygen tension, that are crucial to the regulation of stem cell activity. The overarching goal of stem cell-based tissue engineering research is to precisely control differentiation of stem cells in culture. In this article, we review current developments in tissue engineering, focusing on several stem cell sources, induction factors including growth factors, oxygen tension, biomaterials, and mechanical stimulation, and the internal and external regulatory mechanisms that govern proliferation and differentiation. PMID:23432679

  14. Editorial Commentary: The Acellular Osteochondral Allograft, the Emperor Has New Clothes.

    PubMed

    Mandelbaum, Bert R; Chahla, Jorge

    2017-12-01

    For larger lesions (>2.5-cm 2 ), clinical evidence and practice have shown that fresh osteochondral allograft have good durability, with 88% return to sport and greater than 75% 10-year survival rates for treatment of large femoral condyle lesions. That said, the use of fresh osteochondral allografts in clinical practice is limited by the availability of acceptable donor tissues for eligible patients in a timely fashion. Significant diminution of chondrocyte viability and density occurs during the preservation and storage period. All osteochondral allografts are not equal in performance and outcome. Chondrocyte density and viability are critical for successful transplantation and outcome in the short and long term. This commentary highlights the high failure rates of tissue when it is acellular. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  15. Electrospun nanofibres to mimic natural hierarchical structure of tissues: application in musculoskeletal regeneration.

    PubMed

    Sankar, Sharanya; Sharma, Chandra S; Rath, Subha N; Ramakrishna, Seeram

    2018-01-01

    Biomimetic scaffolds mimicking the natural hierarchical structure of tissues have recently attracted the interest of researchers and provide a promising strategy to resemble the nonhomogeneous property of tissues. This review provides an overview of the various hierarchical length scales in the native tissues of the musculoskeletal system. It further focuses on electrospinning as a technique to mimic the tissue structures with specific emphasis on bone. The effect of cellular alignment, infiltration, vascularisation, and differentiation in these nanostructures has also been discussed. An outline of the various additive manufacturing techniques in combination with electrospinning has been elaborated. The review concludes with the challenges and future directions to understand the intricacies of bottom-up approach to engineer the systems at a macroscale. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Rapid development of tissue bank achieved by International Atomic Energy Agency (IAEA) Tissue Banking Programme in China.

    PubMed

    Zhang, Yu-Min; Wang, Jian-Ru; Zhang, Nai-Li; Liu, Xiao-Ming; Zhou, Mo; Ma, Shao-Ying; Yang, Ting; Li, Bao-Xing

    2014-09-01

    Before 1986, the development of tissue banking in China has been slow and relatively uncoordinated. Under the support of International Atomic Energy Agency (IAEA), Tissue Banking in China experienced rapid development. In this period, China Institute for Radiation Protection tissue bank mastered systematic and modern tissue banking technique by IAEA training course and gradually developed the first regional tissue bank (Shanxi Provincial Tissue Bank, SPTB) to provide tissue allograft. Benefit from training course, SPTB promoted the development of tissue transplantation by ways of training, brochure, advertisement and meeting. Tissue allograft transplantation acquired recognition from clinic and supervision and administration from government. Quality system gradually is developing and perfecting. Tissue allograft transplantation and tissue bank are developing rapidly and healthy.

  17. Postoperative ultrasonography of the musculoskeletal system.

    PubMed

    Chun, Kyung Ah; Cho, Kil-Ho

    2015-07-01

    Ultrasonography of the postoperative musculoskeletal system plays an important role in the accurate diagnosis of abnormal lesions in the bone and soft tissues. Ultrasonography is a fast and reliable method with no harmful irradiation for the evaluation of postoperative musculoskeletal complications. In particular, it is not affected by the excessive metal artifacts that appear on computed tomography or magnetic resonance imaging. Another benefit of ultrasonography is its capability to dynamically assess the pathologic movement in joints, muscles, or tendons. This article discusses the frequent applications of musculoskeletal ultrasonography in various postoperative situations including those involving the soft tissues around the metal hardware, arthroplasty, postoperative tendons, recurrent soft tissue tumors, bone unions, and amputation surgery.

  18. Re-do aortic root replacement after an allograft aortic root replacement.

    PubMed

    Vrtik, Marian; Tesar, Peter J

    2009-10-01

    Structural degeneration of allograft aortic root is a global process. In addition to valvular degeneration, the allograft wall calcification poses a risk of systemic calcific embolization and late phase anastomotic aneurysm formation and rupture (anecdotal). Furthermore, the valve annulus is often small, and the tissues are rigid making the implantation of an adequately sized prosthesis within the allograft wall difficult. To avoid these issues, we routinely perform re-do aortic root replacement with either a mechanical valve conduit or bio-root composite graft. The technique has been successfully used in 22 consecutive patients with no operative mortality and minimal morbidity.

  19. Orthotopic Transplantation of Achilles Tendon Allograft in Rats: With or without Incorporation of Autologous Mesenchymal Stem Cells.

    PubMed

    Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun

    2018-02-01

    The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at -80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully

  20. Mechanical regulation of musculoskeletal system development.

    PubMed

    Felsenthal, Neta; Zelzer, Elazar

    2017-12-01

    During embryogenesis, the musculoskeletal system develops while containing within itself a force generator in the form of the musculature. This generator becomes functional relatively early in development, exerting an increasing mechanical load on neighboring tissues as development proceeds. A growing body of evidence indicates that such mechanical forces can be translated into signals that combine with the genetic program of organogenesis. This unique situation presents both a major challenge and an opportunity to the other tissues of the musculoskeletal system, namely bones, joints, tendons, ligaments and the tissues connecting them. Here, we summarize the involvement of muscle-induced mechanical forces in the development of various vertebrate musculoskeletal components and their integration into one functional unit. © 2017. Published by The Company of Biologists Ltd.

  1. A radiopaque electrospun scaffold for engineering fibrous musculoskeletal tissues: Scaffold characterization and in vivo applications.

    PubMed

    Martin, John T; Milby, Andrew H; Ikuta, Kensuke; Poudel, Subash; Pfeifer, Christian G; Elliott, Dawn M; Smith, Harvey E; Mauck, Robert L

    2015-10-01

    Tissue engineering strategies have emerged in response to the growing prevalence of chronic musculoskeletal conditions, with many of these regenerative methods currently being evaluated in translational animal models. Engineered replacements for fibrous tissues such as the meniscus, annulus fibrosus, tendons, and ligaments are subjected to challenging physiologic loads, and are difficult to track in vivo using standard techniques. The diagnosis and treatment of musculoskeletal conditions depends heavily on radiographic assessment, and a number of currently available implants utilize radiopaque markers to facilitate in vivo imaging. In this study, we developed a nanofibrous scaffold in which individual fibers included radiopaque nanoparticles. Inclusion of radiopaque particles increased the tensile modulus of the scaffold and imparted radiation attenuation within the range of cortical bone. When scaffolds were seeded with bovine mesenchymal stem cells in vitro, there was no change in cell proliferation and no evidence of promiscuous conversion to an osteogenic phenotype. Scaffolds were implanted ex vivo in a model of a meniscal tear in a bovine joint and in vivo in a model of total disc replacement in the rat coccygeal spine (tail), and were visualized via fluoroscopy and microcomputed tomography. In the disc replacement model, histological analysis at 4 weeks showed that the scaffold was biocompatible and supported the deposition of fibrous tissue in vivo. Nanofibrous scaffolds that include radiopaque nanoparticles provide a biocompatible template with sufficient radiopacity for in vivo visualization in both small and large animal models. This radiopacity may facilitate image-guided implantation and non-invasive long-term evaluation of scaffold location and performance. The healing capacity of fibrous musculoskeletal tissues is limited, and injury or degeneration of these tissues compromises the standard of living of millions in the US. Tissue engineering repair

  2. Intraoperative culture positive allograft bone and subsequent postoperative infections: a retrospective review.

    PubMed

    Sims, Laura; Kulyk, Paul; Woo, Allan

    2017-04-01

    Obtaining intraoperative cultures of allograft bone just before use in orthopedic procedures is standard practice in many centres; however, the association between positive cultures and subsequent surgical infections is unknown. Our study had 3 goals: to determine the prevalence of positive intraoperative allograft culture and subsequent infection; to determine if, in cases of subsequent infection, organisms isolated at reoperation were the same as those cultured from the allograft at the time of the index procedure; and to assess the costs associated with performing intraoperative allograft cultures. In this retrospective case series, we obtained data on patients receiving allograft bone between 2009 and 2012. Patients receiving allograft with positive cultures were reviewed to identify cases of significant infection. Organisms isolated at reoperation were compared with the allograft culture taken at the time of implantation, and we performed a cost assessment. Of the 996 allograft bone grafts used, 43 (4.3%) had positive intraoperative cultures and significant postoperative infections developed in 2, requiring reoperation. Antibiotics based on culture results were prescribed in 24% of cases. Organisms cultured at the time of reoperation differed from those isolated initially. The cost of performing 996 allograft cultures was $169 320. This series suggests that rates of positive intraoperative bone allograft culture are low, and subsequent infection is rare. In cases of postoperative infection, primary allograft culture and secondary tissue cultures isolated different organisms. Costs associated with performing cultures are high. Eliminating initial culture testing could save $42 500 per year in our health region.

  3. Intraoperative culture positive allograft bone and subsequent postoperative infections: a retrospective review

    PubMed Central

    Sims, Laura; Kulyk, Paul; Woo, Allan

    2017-01-01

    Background Obtaining intraoperative cultures of allograft bone just before use in orthopedic procedures is standard practice in many centres; however, the association between positive cultures and subsequent surgical infections is unknown. Our study had 3 goals: to determine the prevalence of positive intraoperative allograft culture and subsequent infection; to determine if, in cases of subsequent infection, organisms isolated at reoperation were the same as those cultured from the allograft at the time of the index procedure; and to assess the costs associated with performing intraoperative allograft cultures. Methods In this retrospective case series, we obtained data on patients receiving allograft bone between 2009 and 2012. Patients receiving allograft with positive cultures were reviewed to identify cases of significant infection. Organisms isolated at reoperation were compared with the allograft culture taken at the time of implantation, and we performed a cost assessment. Results Of the 996 allograft bone grafts used, 43 (4.3%) had positive intraoperative cultures and significant postoperative infections developed in 2, requiring reoperation. Antibiotics based on culture results were prescribed in 24% of cases. Organisms cultured at the time of reoperation differed from those isolated initially. The cost of performing 996 allograft cultures was $169 320. Conclusion This series suggests that rates of positive intraoperative bone allograft culture are low, and subsequent infection is rare. In cases of postoperative infection, primary allograft culture and secondary tissue cultures isolated different organisms. Costs associated with performing cultures are high. Eliminating initial culture testing could save $42 500 per year in our health region. PMID:28234217

  4. Inflammation reduces physiological tissue tolerance in the development of work-related musculoskeletal disorders.

    PubMed

    Barr, Ann E; Barbe, Mary F

    2004-02-01

    Work-related musculoskeletal disorders (MSDs) cause substantial worker discomfort, disability and loss of productivity. Due to the difficulty in analyzing the tissues of patients in the early stages of work-related MSD, there is controversy concerning the pathomechanisms of the development of these disorders. The pathophysiology of work-related MSD can be studied more easily in animal models. The purpose of this review is to relate theories of the development of tissue injury due to repeated motion to findings of recent investigations in animals that address the role of the inflammatory response in propagating tissue injury and contributing to chronic or recurring tissue injury. These tissue effects are related to behavioral indicators of discomfort and movement dysfunction with the aim of clarifying key time points for specific intervention approaches. The results from animal models of MSD are discussed in the light of findings in patients, whose tissues are examined at a much later phase of MSD development. Finally, a conceptual model of the potentially negative impact of inflammation on tissue tolerance is proposed along with suggestions for future research directions.

  5. Aneuploidy in benign tumors and nonneoplastic lesions of musculoskeletal tissues.

    PubMed

    Alho, A; Skjeldal, S; Pettersen, E O; Melvik, J E; Larsen, T E

    1994-02-15

    Aneuploidy in DNA flow cytometry (FCM) of musculoskeletal tumors is generally considered to be a sign of malignancy. Previously, giant cell tumor of the bone has been reported to contain aneuploid (near-diploid) DNA stemlines. Otherwise, only spordic cases have been reported. The authors wanted to study the relationships among DNA FCM, histology, and clinical course of nonmalignant musculoskeletal lesions. Twenty-eight histologically benign tumors and seven nonneoplastic lesions were subjected to DNA FCM: After tissue preparation mechanically and with ribonuclease and trypsin, the isolated nuclei were stained with propidium iodine using chicken and rainbow trout erythrocytes as controls. In the DNA FCM histograms, ploidy and cell cycle fractions were determined using a computerized mathematical model. The histologic diagnoses were made without knowledge of the DNA FCM results. Aneuploidy was found in eight lesions. A shoulder in the diploid peak, suggesting a diploid and a near-diploid population, was found in DNA histograms of a condensing osteitis of the clavicle (a benign inflammatory process) and of a giant cell tumor of bone. The latter lesion also had a tetraploid population. Six benign tumors--two enchondromas, one osteochondroma, one subcutaneous and one intramuscular lipoma, and a calcifying aponeurotic fibroma--showed clear aneuploidy with separate peaks. The S-phase fraction was less than 10% in all cases. The highest aneuploid population, DNA index = 1.70, in a subcutaneous lipoma, was small, with an undetectable S phase. Despite nonradical operations in seven lesions, no recurrences were observed during a median follow-up of 49 months (range, 28-73 months). Small aneuploid populations with low DNA synthetic activity may be compatible with a benign histologic picture and uneventful clinical course of the musculoskeletal lesion.

  6. Multiplexed color-coded probe-based gene expression assessment for clinical molecular diagnostics in formalin-fixed paraffin-embedded human renal allograft tissue.

    PubMed

    Adam, Benjamin; Afzali, Bahman; Dominy, Katherine M; Chapman, Erin; Gill, Reeda; Hidalgo, Luis G; Roufosse, Candice; Sis, Banu; Mengel, Michael

    2016-03-01

    Histopathologic diagnoses in transplantation can be improved with molecular testing. Preferably, molecular diagnostics should fit into standard-of-care workflows for transplant biopsies, that is, formalin-fixed paraffin-embedded (FFPE) processing. The NanoString(®) gene expression platform has recently been shown to work with FFPE samples. We aimed to evaluate its methodological robustness and feasibility for gene expression studies in human FFPE renal allograft samples. A literature-derived antibody-mediated rejection (ABMR) 34-gene set, comprised of endothelial, NK cell, and inflammation transcripts, was analyzed in different retrospective biopsy cohorts and showed potential to molecularly discriminate ABMR cases, including FFPE samples. NanoString(®) results were reproducible across a range of RNA input quantities (r = 0.998), with different operators (r = 0.998), and between different reagent lots (r = 0.983). There was moderate correlation between NanoString(®) with FFPE tissue and quantitative reverse transcription polymerase chain reaction (qRT-PCR) with corresponding dedicated fresh-stabilized tissue (r = 0.487). Better overall correlation with histology was observed with NanoString(®) (r = 0.354) than with qRT-PCR (r = 0.146). Our results demonstrate the feasibility of multiplexed gene expression quantification from FFPE renal allograft tissue. This represents a method for prospective and retrospective validation of molecular diagnostics and its adoption in clinical transplantation pathology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Clinical application and viability of cryopreserved cadaveric skin allografts in severe burn: a retrospective analysis.

    PubMed

    Cleland, Heather; Wasiak, Jason; Dobson, Hannah; Paul, Michelle; Pratt, George; Paul, Eldho; Herson, Marisa; Akbarzadeh, Shiva

    2014-02-01

    Cadaveric cutaneous allografts are used in burns surgery both as a temporary bio-dressing and occasionally as definitive management of partial thickness burns. Nonetheless, limitations in the understanding of the biology of these grafts have meant that their role in burns surgery continues to be controversial. A review of all patients suffering 20% or greater total body surface area (TBSA) burns over an eight year period that received cadaveric allografts were identified. To investigate whether tissue viability plays a role in engraftment success, five samples of cryopreserved cadaveric cutaneous allograft processed at the Donor Tissue Bank of Victoria (DTBV) were submitted to our laboratory for viability analysis using two methods of Trypan Blue Exclusion and tetrazolium salt (MTT) assays. During the study period, 36 patients received cadaveric allograft at our institution. The average total burn surface area (TBSA) for this group of patients was 40% and all patients received cadaveric skin as a temporizing measure prior to definitive grafting. Cadaveric allograft was used in complicated cases such as wound contamination, where synthetic dressings had failed. Viability tests showed fewer than 30% viability in processed allografts when compared to fresh skin following the thawing process. However, the skin structure in the frozen allografts was histologically well preserved. Cryopreserved cutaneous cadaveric allograft has a positive and definite role as an adjunct to conventional dressing and grafting where available, particularly in patients with large TBSA burns. The low viability of cryopreserved specimens processed at DTBV suggests that cell viability in cadaveric allograft may not be essential for its clinical function as a wound dressing or even as permanent dermal substitute. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

  8. Revision of anterior cruciate ligament reconstruction with allografts in patients younger than 40 years old: a 2 to 4 year results.

    PubMed

    Pascual-Garrido, Cecilia; Carbo, L; Makino, A

    2014-05-01

    The purpose of this study is first to report the outcomes, at 4 years follow-up, in revision ACL surgery using allografts in patients younger than 40 years old, and then compared soft tissue allografts to bone tendon allografts. This retrospective study included 47 patients who underwent ACL revision surgery with fresh-frozen allografts. Patellar tendon allograft or tibialis anterior allograft was used. Twenty-seven patients undergoing ACL revision with patellar tendon allograft were compared retrospectively with twenty-two patients undergoing the same procedure with soft tissue tibialis anterior allograft. Lysholm, IKDC, and KT-1000 values were obtained preoperatively and postoperatively. The average patient follow-up was 4.6 years (±2.5). The mean age at time of the revision was 34 years old (±6.3). Overall, patients reported the overall condition of their knee as excellent or good in 85% of the patients (10 excellent, 33 good). Based on their experience, 85% would have the surgery again if they had the same problem in the other knee. Both subgroups experienced significant improvement in Lysholm, IKDC, and KT-1000 values, with no difference found between groups at final follow-up. Revision ACL with allografts has excellent and good results in 85% of patients younger than 40 years old. No statistical difference was seen between soft tissue (tibialis anterior) and patellar tendon allograft. IV.

  9. Remodeling of ACL Allografts is Inhibited by Peracetic Acid Sterilization

    PubMed Central

    Gonnermann, Johannes; Kamp, Julia; Przybilla, Dorothea; Pruss, Axel

    2008-01-01

    Sterilization of allografts for anterior cruciate ligament (ACL) reconstruction has become an important prerequisite to prevent disease transmission. However, current sterilization techniques impair the biological or mechanical properties of such treated grafts. Peracetic acid (PAA) has been successfully used to sterilize bone allografts without these disadvantages and does not impair the mechanical properties of soft tissue grafts in vitro. We asked whether PAA sterilization would influence recellularization, restoration of crimp length and pattern, and revascularization of ACL grafts during early healing. We used an in vivo sheep model for open ACL reconstruction. We also correlated the histologic findings with the restoration of anteroposterior stability and structural properties during load-to-failure testing. PAA slowed remodeling activity at 6 and 12 weeks compared to nonsterilized allografts and autografts. The mechanical properties of PAA grafts were also reduced compared to these control groups at both time points. We conclude PAA sterilization currently should not be used to sterilize soft tissue grafts typically used in ACL reconstruction. PMID:18491201

  10. Experiences using IAEA Code of practice for radiation sterilization of tissue allografts: Validation and routine control

    NASA Astrophysics Data System (ADS)

    Hilmy, N.; Febrida, A.; Basril, A.

    2007-11-01

    Problems of tissue allografts in using International Standard (ISO) 11137 for validation of radiation sterilization dose (RSD) are limited and low numbers of uniform samples per production batch, those are products obtained from one donor. Allograft is a graft transplanted between two different individuals of the same species. The minimum number of uniform samples needed for verification dose (VD) experiment at the selected sterility assurance level (SAL) per production batch according to the IAEA Code is 20, i.e., 10 for bio-burden determination and the remaining 10 for sterilization test. Three methods of the IAEA Code have been used for validation of RSD, i.e., method A1 that is a modification of method 1 of ISO 11137:1995, method B (ISO 13409:1996), and method C (AAMI TIR 27:2001). This paper describes VD experiments using uniform products obtained from one cadaver donor, i.e., cancellous bones, demineralized bone powders and amnion grafts from one life donor. Results of the verification dose experiments show that RSD is 15.4 kGy for cancellous and demineralized bone grafts and 19.2 kGy for amnion grafts according to method A1 and 25 kGy according to methods B and C.

  11. A Biomechanical Comparison of Allograft Tendons for Ligament Reconstruction.

    PubMed

    Palmer, Jeremiah E; Russell, Joseph P; Grieshober, Jason; Iacangelo, Abigail; Ellison, Benjamin A; Lease, T Dylan; Kim, Hyunchul; Henn, R Frank; Hsieh, Adam H

    2017-03-01

    Allograft tendons are frequently used for ligament reconstruction about the knee, but they entail availability and cost challenges. The identification of other tissues that demonstrate equivalent performance to preferred tendons would improve limitations. Hypothesis/Purpose: We compared the biomechanical properties of 4 soft tissue allograft tendons: tibialis anterior (TA), tibialis posterior (TP), peroneus longus (PL), and semitendinosus (ST). We hypothesized that allograft properties would be similar when standardized by the looped diameter. Controlled laboratory study. This study consisted of 2 arms evaluating large and small looped-diameter grafts: experiment A consisted of TA, TP, and PL tendons (n = 47 each) with larger looped diameters of 9.0 to 9.5 mm, and experiment B consisted of TA, TP, PL, and ST tendons (n = 53 each) with smaller looped diameters of 7.0 to 7.5 mm. Each specimen underwent mechanical testing to measure the modulus of elasticity (E), ultimate tensile force (UTF), maximal elongation at failure, ultimate tensile stress (UTS), and ultimate tensile strain (UTε). Experiment A: No significant differences were noted among tendons for UTF, maximal elongation at failure, and UTϵ. UTS was significantly higher for the PL (54 MPa) compared with the TA (44 MPa) and TP (43 MPa) tendons. E was significantly higher for the PL (501 MPa) compared with the TP (416 MPa) tendons. Equivalence testing showed that the TP and PL tendon properties were equivalent or superior to those of the TA tendons for all outcomes. Experiment B: All groups exhibited a similar E. UTF was again highest in the PL tendons (2294 N) but was significantly different from only the ST tendons (1915 N). UTϵ was significantly higher for the ST (0.22) compared with the TA (0.19) and TP (0.19) tendons. Equivalence testing showed that the TA, TP, and PL tendon properties were equivalent or superior to those of the ST tendons. Compared with TA tendons, TP and PL tendons of a given looped

  12. Mechanical Stimulation of Adipose-Derived Stem Cells for Functional Tissue Engineering of the Musculoskeletal System via Cyclic Hydrostatic Pressure, Simulated Microgravity, and Cyclic Tensile Strain.

    PubMed

    Nordberg, Rachel C; Bodle, Josie C; Loboa, Elizabeth G

    2018-01-01

    It is critical that human adipose stem cell (hASC) tissue-engineering therapies possess appropriate mechanical properties in order to restore function of the load bearing tissues of the musculoskeletal system. In an effort to elucidate the hASC response to mechanical stimulation and develop mechanically robust tissue engineered constructs, recent research has utilized a variety of mechanical loading paradigms including cyclic tensile strain, cyclic hydrostatic pressure, and mechanical unloading in simulated microgravity. This chapter describes methods for applying these mechanical stimuli to hASC to direct differentiation for functional tissue engineering of the musculoskeletal system.

  13. Platelet-rich therapies for musculoskeletal soft tissue injuries.

    PubMed

    Moraes, Vinícius Y; Lenza, Mário; Tamaoki, Marcel Jun; Faloppa, Flávio; Belloti, João Carlos

    2014-04-29

    Platelet-rich therapies are being used increasingly in the treatment of musculoskeletal soft tissue injuries such as ligament, muscle and tendon tears and tendinopathies. These therapies can be used as the principal treatment or as an augmentation procedure (application after surgical repair or reconstruction). Platelet-rich therapies are produced by centrifuging a quantity of the patient's own blood and extracting the active, platelet-rich, fraction. The platelet-rich fraction is applied to the injured tissue; for example, by injection. Platelets have the ability to produce several growth factors, so these therapies should enhance tissue healing. There is a need to assess whether this translates into clinical benefit. To assess the effects (benefits and harms) of platelet-rich therapies for treating musculoskeletal soft tissue injuries. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (25 March 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013 Issue 2), MEDLINE (1946 to March 2013), EMBASE (1980 to 2013 Week 12) and LILACS (1982 to March 2012). We also searched trial registers (to Week 2 2013) and conference abstracts (2005 to March 2012). No language or publication restrictions were applied. We included randomised and quasi-randomised controlled trials that compared platelet-rich therapy with either placebo, autologous whole blood, dry needling or no platelet-rich therapy for people with acute or chronic musculoskeletal soft tissue injuries. Primary outcomes were functional status, pain and adverse effects. Two review authors independently extracted data and assessed each study's risk of bias. Disagreement was resolved by discussion or by arbitration by a third author. We contacted trial authors for clarification of methods or missing data. Treatment effects were assessed using risk ratios for dichotomous data and mean differences (MD) or standardised mean differences (SMD) for continuous data, together with

  14. Histomorphometric analysis following augmentation of the posterior mandible using cancellous bone-block allograft.

    PubMed

    Nissan, Joseph; Marilena, Vered; Gross, Ora; Mardinger, Ofer; Chaushu, Gavriel

    2011-06-15

    The present study was conducted to histologically and histomorphometrically evaluate the application of cancellous bone-block allografts for the augmentation of the posterior atrophic mandible. Twenty-four consecutive patients underwent augmentation with cancellous bone-block allografts in the posterior mandible. A bony deficiency of at least 3 mm horizontally and/or vertically according to CT para-axial reconstruction served as inclusion criteria. Following 6 months, 85 implants were placed and a cylindrical sample core was collected. All specimens were prepared for histological and histomorphometrical examination. Implant survival rate was 95.3%. Follow-up ranged 12-66 months (mean 43 ± 19 months). The mean newly formed bone was 44 ± 28%, that of the residual cancellous bone-block allograft 29 ± 24%, and of the marrow and connective tissue 27 ± 21%. Statistically significant histomorphometric differences regarding newly formed bone (69% vs. 31%, p = 0.05) were found between younger (< 45 years) and older (> 45 years) patients, respectively. Histomorphometric differences regarding residual cancellous bone-block allograft (17% vs. 35%) and of the marrow and connective tissue (14% vs. 34%) were not statistically significant. Cancellous bone-block allograft is biocompatible and osteoconductive, permitting new bone formation following augmentation of extremely atrophic posterior mandible with a two-stage implant placement procedure. New bone formation was age-dependent. Copyright © 2011 Wiley Periodicals, Inc.

  15. Lacertus Fibrosus Versus Achilles Allograft Reconstruction for Distal Biceps Tears: A Biomechanical Study.

    PubMed

    Murthi, Anand M; Ramirez, Miguel A; Parks, Brent G; Carpenter, Shannon R

    2017-12-01

    The bicipital aponeurosis, or lacertus fibrosus, can potentially be used as a reconstruction graft in chronic distal biceps tendon tears. To evaluate construct stiffness, load to failure, and failure mechanism with lacertus fibrosus versus Achilles allograft for distal biceps tendon reconstruction. Controlled laboratory study. Ten fresh-frozen matched cadaveric pairs of elbows were used. Three centimeters of the distal biceps tendon was resected. Specimens were randomized to the lacertus fibrosus or Achilles tendon group. In one group, the lacertus fibrosus was released from its distal attachment and then tubularized and repaired intraosseously to the radius. In the other group, an Achilles tendon graft was sutured to the biceps muscle and repaired to the ulna. The prepared radii were rigidly mounted at a 45° angle on a load frame. The proximal biceps muscle was secured in a custom-fabricated cryogenic grip. Displacement was measured using a differential variable reluctance transducer mounted at the radius-soft tissue junction and in the muscle- or muscle allograft-tissue junction proximal to the repair. Specimens were loaded at 20 mm/min until failure, defined as a 3-mm displacement at the radius-soft tissue junction. No significant difference was found in mean load to failure between the lacertus fibrosus and Achilles tendon group (mean ± SD, 20.2 ± 5.5 N vs 16.89 ± 4.54 N; P = .18). Stiffness also did not differ significantly between the lacertus fibrosus and Achilles tendon group (12.3 ± 7.1 kPa vs 10.5 ± 5.7 kPa; P = .34). The primary mode of failure in the lacertus fibrosus group was suture pullout from the tissue at the musculotendinous junction (7 of 10). In the Achilles group, failures were observed at the muscle-allograft interface (3) and the allograft-bone (radial tuberosity) interface (3), and 3 suture failures were observed. The button fixation did not fail in any specimens. The mean stiffness and load-to-failure values were not significantly

  16. Prevalence of microbiological markers in bone tissue from live and cadaver donors in the musculoskeletal tissue bank of Passo Fundo.

    PubMed

    Dutra Roos, Bruno; Valdomiro Roos, Milton; Camisa Júnior, Antero; Moreno Ungaretti Lima, Ezequiel; Noshang Pereira, Rafael; Luciano Zangirolami, Maurício; Machado de Albuquerque, Gisela

    2014-01-01

    To conduct an epidemiological analysis on the main microbiological markers in bone tissue that was processed at the musculoskeletal tissue bank of Hospital São Vicente de Paulo, in Passo Fundo, between August 2007 and October 2011. Between August 2007 and October 2011, 202 musculoskeletal tissue samples were collected for the tissue bank. Among these, 159 samples were from living donor patients and 43 were from cadaver donors. The following serological tests were requested: hepatitis B, hepatitis C, syphilis, cytomegalovirus, Chagas disease, toxoplasmosis, HIV and HTLV. Among the 159 living donors, 103 (64.75%) were men and 56 (35.25%) were women. The patients' mean age was 59.35 ± 8.87 years. Out of this total, 76 tissue samples (47.8%) from donors were rejected. There was no difference in the number of rejections in relation to sex (p = 0.135) or age (p = 0.523). The main cause of rejection was serologically positive findings for the hepatitis B virus, which was responsible for 48 rejections (63.15%). Among the 43 cadaver donors, the mean age was 37.84 ± 10.32 years. Of these, 27 (62.8%) were men and 16 (37.2%) were women. Six of the samples collected from cadaver donors were rejected (13.9%), and the main cause of rejection was serologically positive findings for the hepatitis C virus, which was responsible for three cases (50%). There was no significant difference in the number of rejections in relation to sex (p = 0.21) or age (p = 0.252). There were a greater number of rejections of tissues from living donors (47.8%) than from cadaver donors (13.9%). Among the living donors, the main cause of rejection was the presence of serologically positive findings of the hepatitis B virus, while among the cadaver donors, it was due to the hepatitis C virus.

  17. Von Willebrand Factor Deposition and ADAMTS-13 Consumption in Allograft Tissue of Thrombotic Microangiopathy-like Disorder After Living Donor Liver Transplantation: A Case Report.

    PubMed

    Nakanuma, S; Miyashita, T; Hayashi, H; Ohbatake, Y; Takamura, H; Okazaki, M; Yamaguchi, T; Sakai, S; Makino, I; Oyama, K; Tajima, H; Ninomiya, I; Fushida, S; Ohta, T

    2017-09-01

    Thrombotic microangiopathy (TMA) pathogenesis after living donor liver transplantation (LDLT) is thought to be caused by release of unusually large von Willebrand factor multimers (UL-vWFMs) resulting from sinusoidal endothelial cell damage and induction of platelet adhesion and aggregation. A decrease in a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs-13 (ADAMTS-13) that cleave UL-vWFMs might cause excessive UL-vWFMs activity and result in platelet thrombus formation. However, this phenomenon has not undergone a full pathologic assessment. A 60-year-old man was diagnosed with hepatitis C-related end-stage cirrhosis. His son was the donor, and he underwent LDLT. On postoperative day 44, his laboratory findings met most TMA diagnostic criteria, and he was diagnosed with TMA-like disorder (TMALD). Localization of CD42b as a platelet marker, vWF, and ADAMTS-13 in allograft tissue of this patient were evaluated using immunohistochemistry. CD42b expression was observed as platelet aggregates attached to hepatocytes or within the hepatocyte cytoplasm, a morphology called extravasated platelet aggregation (EPA). vWF expression was observed mainly as deposited compact clusters, and ADAMTS-13 expression resembled distinct dots throughout the liver tissue. These findings suggest that EPA indicated sinusoidal endothelial cell damage followed by detachment, and vWF deposition resulted from UL-vWFM oversynthesis. ADAMTS-13 might be consumed in the allograft tissue to cleave UL-vWFMs, but ADAMTS-13 levels might be insufficient to cleave all the deposited UL-vWFMs. We present the case of an LDLT recipient diagnosed with TMALD using blood tests, which showed the presence of TMA pathogenesis in the allograft. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Revision Risk After Allograft Anterior Cruciate Ligament Reconstruction: Association With Graft Processing Techniques, Patient Characteristics, and Graft Type.

    PubMed

    Tejwani, Samir G; Chen, Jason; Funahashi, Tadashi T; Love, Rebecca; Maletis, Gregory B

    2015-11-01

    Allograft tissue is a common graft choice for anterior cruciate ligament reconstruction (ACLR). Allograft sterilization methods vary widely across numerous commercial tissue vendors. Multiple studies, despite being limited in sample size, have suggested a higher rate of clinical failure associated with the use of allograft tissue in ACLR when compared with autograft. To examine the association of graft processing techniques, patient characteristics, and graft type with risk of revision surgery after allograft ACLR. Cohort study; Level of evidence, 3. A retrospective cohort study was conducted that used an integrated United States health care system's ACLR registry to identify primary unilateral cases in which allografts were used. Aseptic revision was the endpoint of the study. Allograft type, processing methods (irradiation dose, AlloWash, AlloTrue, BioCleanse), and graft donor age were assessed as potential risk factors for revision, with adjustment for patient age, sex, and body mass index (BMI) by use of survival analysis. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated. A total of 5968 primary ACLR cases with allograft were included in the study, of which 3688 (61.8%) were male patients. The median age of the cohort at the time of surgery was 34.1 years (interquartile range, 24.1-42.9 years). The mean time to follow-up (±SD) was 2.1 ± 1.5 years. There were 3751 (62.9%) allograft ACLRs using soft tissue, 1188 (19.9%) with Achilles tendon, and 1029 (17.2%) with bone-patellar tendon-bone (BPTB). Graft processing groups included BioCleanse (n = 367), AlloTrue or AlloWash (n = 2278), irradiation greater than 1.8 Mrad (n = 1146), irradiation up to 1.8 Mrad (n = 3637), and no irradiation (n = 1185). There were 156 (2.6%) aseptic revisions. After adjustment for patient age, sex, and BMI, the use of BioCleanse (HR = 2.45; 95% CI, 1.36-4.40) and irradiation greater than 1.8 Mrad (HR = 1.64; 95% CI, 1.08-2.49) were associated with a higher risk of

  19. [Secondary orthopaedic complications after childhood tumors of the musculoskeletal system].

    PubMed

    Mary, Pierre; Bachy, Manon; Mascard, Éric; Gouin, François

    2015-01-01

    Multidisciplinary care, modern care management, and medical progress have brought significant gains in modern survival rates for children and adolescents with tumors of the musculoskeletal system. The surgical approach must rest on the consideration of the long-term orthopedic sequelae likely to be caused by the elected treatment (limb amputation versus limb conservation - reconstruction choices), as well as by adjuvant therapies, such as chemotherapy or radiotherapy. Complications due to allograft reconstructions (infections, fractures, pseudoarthritis) occur within the range of 0 to 36 months. After 36 months, allograft longevity is fair, but 10 years later, 60% of grafts are likely to have failed and been removed. Joint prostheses have overall survival rates of 75% over 10 years, and 52% over 20 years. As for allografts, infectious complications occur within the first few years, while later prosthetic replacements are mostly due to mechanical causes. Assessing the long-term evolution of biological reconstructions proves a lot more challenging, due to the lack of hindsight and available information, except for vascularized fibula grafts, which show good long-term results. Numerous medical reviews have been published that address the quality of life of children treated for malignant tumors of the musculoskeletal system. They mostly consist in comparative studies between limb conservation and limb amputation, and point to similar results overall. Such data must be taken into account when deciding on a treatment for a child or an adolescent: quality of life, the function of the affected limb, the probable need for re-operation all encourage to favor reconstructions whenever they are possible, as they come closest to normal anatomy. Too frequently, medical knowledge remains fragmented among multiple disciplines, because of the difficulty of organizing follow-up over the very long-term. Progress can only be achieved by setting-up multidisciplinary care pathways

  20. Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection

    PubMed Central

    Cui, Ye; Liu, Kaifeng; Monzon-Medina, Maria E.; Padera, Robert F.; Wang, Hao; George, Gautam; Toprak, Demet; Abdelnour, Elie; D’Agostino, Emmanuel; Goldberg, Hilary J.; Perrella, Mark A.; Forteza, Rosanna Malbran; Rosas, Ivan O.; Visner, Gary; El-Chemaly, Souheil

    2015-01-01

    Lung transplantation is the only viable option for patients suffering from otherwise incurable end-stage pulmonary diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Despite aggressive immunosuppression, acute rejection of the lung allograft occurs in over half of transplant recipients, and the factors that promote lung acceptance are poorly understood. The contribution of lymphatic vessels to transplant pathophysiology remains controversial, and data that directly address the exact roles of lymphatic vessels in lung allograft function and survival are limited. Here, we have shown that there is a marked decline in the density of lymphatic vessels, accompanied by accumulation of low-MW hyaluronan (HA) in mouse orthotopic allografts undergoing rejection. We found that stimulation of lymphangiogenesis with VEGF-C156S, a mutant form of VEGF-C with selective VEGFR-3 binding, alleviates an established rejection response and improves clearance of HA from the lung allograft. Longitudinal analysis of transbronchial biopsies from human lung transplant recipients demonstrated an association between resolution of acute lung rejection and decreased HA in the graft tissue. Taken together, these results indicate that lymphatic vessel formation after lung transplantation mediates HA drainage and suggest that treatments to stimulate lymphangiogenesis have promise for improving graft outcomes. PMID:26485284

  1. Liver Transplantation in the Mouse: Insights Into Liver Immunobiology, Tissue Injury and Allograft Tolerance

    PubMed Central

    Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A.; Thomson, Angus W.

    2016-01-01

    The surgically-demanding mouse orthotopic liver transplant model was first described in 1991. It has proved a powerful research tool for investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, since the mouse genome is well-characterized and there is much greater availability of both genetically-modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice has provided valuable mechanistic insights into the immuno- and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/ immune-mediated events in the hepatic environment and systemically. Conclusion: Orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology and allograft tolerance that may result in therapeutic innovation in liver and other diseases. PMID:26709949

  2. Increased Risk of Revision After Anterior Cruciate Ligament Reconstruction With Bone-Patellar Tendon-Bone Allografts Compared With Autografts.

    PubMed

    Maletis, Gregory B; Chen, Jason; Inacio, Maria C S; Love, Rebecca M; Funahashi, Tadashi T

    2017-05-01

    The use of allograft tissue for anterior cruciate ligament reconstruction (ACLR) remains controversial. To compare the risk of aseptic revision between bone-patellar tendon-bone (BPTB) autografts and BPTB allografts. Cohort study; Level of evidence, 2. A retrospective cohort study of prospectively collected data was conducted using the Kaiser Permanente ACLR Registry. A cohort of patients who underwent primary unilateral ACLR with BPTB autografts and BPTB allografts was identified. Aseptic revision was the endpoint. The type of graft and allograft processing method (nonprocessed, <1.8-Mrad, and ≥1.8-Mrad irradiation) were the exposures of interest evaluated. Age (≤21 and ≥22 years) was evaluated as an effect modifier. Analyses were adjusted for age, sex, and race. Kaplan-Meier curves and Cox proportional hazards models were employed. Hazard ratios (HRs) and 95% CIs are provided. The BPTB cohort consisted of 5586 patients: 3783 (67.7%) were male, 2359 (42.2%) were white, 1029 (18.4%) had allografts (nonprocessed: 155; <1.8 Mrad: 525; ≥1.8 Mrad: 288), and 4557 (81.6%) had autografts. The median age was 34.9 years (interquartile range [IQR], 25.4-44.0) for allograft cases and 22.0 years (IQR, 17.6-30.0) for autograft cases. The estimated cumulative revision rate at 2 years was 4.1% (95% CI, 2.9%-5.9%) for allografts and 1.7% (95% CI, 1.3%-2.2%) for autografts. BPTB allografts had a significantly higher adjusted risk of revision than BPTB autografts (HR, 4.54; 95% CI, 3.03-6.79; P < .001). This higher risk of revision was consistent with all allograft processing methods when compared with autografts and was also consistently higher in patients with allografts regardless of age. When BPTB allograft tissue was used for ACLR, an overall 4.54 times adjusted higher risk of revision was observed compared with surgery performed with a BPTB autograft. Whether the tissue was irradiated with either high- or low-dose radiation, chemically processed, or not processed at

  3. Long-term outcome of free fibula osteocutaneous flap and massive allograft in the reconstruction of long bone defect.

    PubMed

    Halim, Ahmad Sukari; Chai, Siew Cheng; Wan Ismail, Wan Faisham; Wan Azman, Wan Sulaiman; Mat Saad, Arman Zaharil; Wan, Zulmi

    2015-12-01

    Reconstruction of massive bone defects in bone tumors with allografts has been shown to have significant complications including infection, delayed or nonunion of allograft, and allograft fracture. Resection compounded with soft tissue defects requires skin coverage. A composite osteocutaneous free fibula offers an optimal solution where the allografts can be augmented mechanically and achieve biological incorporation. Following resection, the cutaneous component of the free osteocutaneous fibula flaps covers the massive soft tissue defect. In this retrospective study, the long-term outcome of 12 patients, who underwent single-stage limb reconstruction with massive allograft and free fibula osteocutaneous flaps instead of free fibula osteal flaps only, was evaluated. This study included 12 consecutive patients who had primary bone tumors and had follow-up for a minimum of 24 months. The mean age at the time of surgery was 19.8 years. A total of eight patients had primary malignant bone tumors (five osteosarcomas, two chondrosarcomas and one synovial sarcoma), and four patients had benign bone tumors (two giant-cell tumors, one aneurysmal bone cyst, and one neurofibromatosis). The mean follow-up for the 12 patients was 63 months (range 24-124 months). Out of the 10 patients, nine underwent lower-limb reconstruction and ambulated with partial weight bearing and full weight bearing at an average of 4.2 months and 8.2 months, respectively. In conclusion, augmentation of a massive allograft with free fibula osteocutaneous flap is an excellent alternative for reducing the long-term complication of massive allograft and concurrently addresses the soft tissue coverage. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  4. Can Skin Allograft Occasionally Act as a Permanent Coverage in Deep Burns? A Pilot Study.

    PubMed

    Rezaei, Ezzatollah; Beiraghi-Toosi, Arash; Ahmadabadi, Ali; Tavousi, Seyed Hassan; Alipour Tabrizi, Arash; Fotuhi, Kazem; Jabbari Nooghabi, Mehdi; Manafi, Amir; Ahmadi Moghadam, Shokoofeh

    2017-01-01

    Skin allograft is the gold standard of wound coverage in patients with extensive burns; however, it is considered as a temporary wound coverage and rejection of the skin allograft is considered inevitable. In our study, skin allograft as a permanent coverage in deep burns is evaluated. Skin allograft survival was assessed in 38 patients from March 2009 to March 2014, retrospectively. Because of the lack of tissue specimen from the skin donors, patients with long skin allograft survival in whom the gender of donor and recipient of allograft was the same were excluded. Seven cases with skin allograft longevity and opposite gender in donor and recipient were finally enrolled. A polymerase chain reaction (PCR) test on the biopsy specimen from recipients and donors were undertaken. PCR on the biopsy specimen from recipients confirmed those specimens belong to the donors. All patients received allograft from the opposite sex. Two (28.57%) patients received allograft from their first-degree blood relatives, and in one (14.29%) case, the allograft was harvested from an alive individual with no blood relation. The rest were harvested from multiorgan donors. In eight months of follow up, no clinical evidence of graft rejection was noted. Long term persistence of skin allograft in patients is worthy of more attention. Further studies An increase in knowledge of factors influencing this longevity could realize the dream of burn surgeons to achieve a permanent coverage other than autograft for major burn patients.

  5. Scabies in a bilateral hand allograft recipient: An additional mimicker of acute skin rejection in vascularized composite allotransplantation.

    PubMed

    Kanitakis, Jean; Morelon, Emmanuel

    2017-06-01

    Vascularized composite tissue allografts include skin, which frequently undergoes, in the early post-graft period, acute rejections. The diagnosis of acute rejection may be difficult as it can be mimicked by several dermatoses. We present a bilateral hand allograft recipient who developed, 16.5 years post-graft, cutaneous lesions raising suspicion about rejection. Physical examination and skin biopsy were diagnostic of scabies. This ectoparasitosis should be added in the list of dermatoses that can mimic allograft rejection in vascular composite allografts. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. The effect of mesenchymal stem cell sheets on structural allograft healing of critical-sized femoral defects in mice

    PubMed Central

    Long, Teng; Zhu, Zhenan; Awad, Hani A.; Schwarz, Edward M.; Hilton, Matthew J.; Dong, Yufeng

    2014-01-01

    Structural bone allografts are widely used in the clinic to treat critical sized bone defects, despite lacking the osteoinductive characteristics of live autografts. To address this, we generated revitalized structural allografts wrapped with mesenchymal stem/progenitor cell (MSC) sheets, which were produced by expanding primary syngenic bone marrow derived cells on temperature-responsive plates, as a tissue engineered periosteum. In vitro assays demonstrated maintenance of the MSC phenotype in the sheets, suggesting that short-term culturing of MSC sheets is not detrimental. To test their efficacy in vivo, allografts wrapped with MSC sheets were transplanted into 4-mm murine femoral defects and compared to allografts with direct seeding of MSCs and allografts without cells. Evaluations consisted of x-ray plain radiography, 3D microCT, histology, and biomechanical testing at 4- and 6-weeks post-surgery. Our findings demonstrate that MSC sheets induce prolonged cartilage formation at the graft-host junction and enhanced bone callus formation, as well as graft-host osteointegration. Moreover, a large periosteal callus was observed spanning the allografts with MSC sheets, which partially mimics live autograft healing. Finally, biomechanical testing showed a significant increase in the structural and functional properties of MSC sheet grafted femurs. Taken together, MSC sheets exhibit enhanced osteogenicity during critical sized bone defect repair, demonstrating the feasibility of this tissue engineering solution for massive allograft healing. PMID:24393269

  7. Platelet-rich therapies for musculoskeletal soft tissue injuries.

    PubMed

    Moraes, Vinícius Y; Lenza, Mário; Tamaoki, Marcel Jun; Faloppa, Flávio; Belloti, João Carlos

    2013-12-23

    Platelet-rich therapies are being used increasingly in the treatment of musculoskeletal soft tissue injuries such as ligament, muscle and tendon tears and tendinopathies. These therapies can be used as the principal treatment or as an augmentation procedure (application after surgical repair or reconstruction). Platelet-rich therapies are produced by centrifuging a quantity of the patient's own blood and extracting the active, platelet-rich, fraction. The platelet-rich fraction is applied to the injured tissue; for example, by injection. Platelets have the ability to produce several growth factors, so these therapies should enhance tissue healing. There is a need to assess whether this translates into clinical benefit. To assess the effects (benefits and harms) of platelet-rich therapies for treating musculoskeletal soft tissue injuries. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (25 March 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013 Issue 2), MEDLINE (1946 to March 2013), EMBASE (1980 to 2013 Week 12) and LILACS (1982 to March 2012). We also searched trial registers (to Week 2 2013) and conference abstracts (2005 to March 2012). No language or publication restrictions were applied. We included randomised and quasi-randomised controlled trials that compared platelet-rich therapy with either placebo, autologous whole blood, dry needling or no platelet-rich therapy for people with acute or chronic musculoskeletal soft tissue injuries. Primary outcomes were functional status, pain and adverse effects. Two review authors independently extracted data and assessed each study's risk of bias. Disagreement was resolved by discussion or by arbitration by a third author. We contacted trial authors for clarification of methods or missing data. Treatment effects were assessed using risk ratios for dichotomous data and mean differences (MD) or standardised mean differences (SMD) for continuous data, together with

  8. The Lymphatic Phenotype of Lung Allografts in Patients With Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome.

    PubMed

    Traxler, Denise; Schweiger, Thomas; Schwarz, Stefan; Schuster, Magdalena Maria; Jaksch, Peter; Lang, Gyoergy; Birner, Peter; Klepetko, Walter; Ankersmit, Hendrik Jan; Hoetzenecker, Konrad

    2017-02-01

    Chronic lung allograft dysfunction (CLAD), presenting as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) is the major limiting factor of long-term survival in lung transplantation. Its pathogenesis is still obscure. In BOS, persistent alloimmune injury and chronic airway inflammation are suggested. One of the main tasks of the lymphatic vessel (LV) system is the promotion of immune cell trafficking. The formation of new LVs has been shown to trigger chronic allograft rejection in kidney transplants. We therefore sought to address the role of lymphangiogenesis in CLAD. Formalin-fixed paraffin-embedded tissue samples of 22 patients receiving a lung retransplantation due to BOS or RAS were collected. Lymphatic vessel density (LVD) was determined by immunohistochemical staining for podoplanin. Lung tissue obtained from 13 non-CLAD patients served as control. The impact of LVD on graft survival was assessed. Lymphatic vessel density in CLAD patients did not differ from those in control subjects (median number of LVs per bronchiole: 4.75 (BOS), 6.47 (RAS), 4.25 (control), P = 0.97). Moreover, the number of LVs was not associated with regions of cellular infiltrates (median number of LVs per bronchiole: with infiltrates, 5.00 (BOS), 9.00 (RAS), 4.00 (control), P = 0.62; without infiltrates, 4.5 (BOS), 0.00 (RAS), 4.56 (control), P = 0.74). Lymphatic vessel density did not impact the time to development of BOS or RAS in lung transplantation (low vs high LVD: 38.5 vs 86.0 months, P = 0.15 [BOS]; 60.5 vs 69.5 months, P = 0.80 [RAS]). Unlike chronic organ failure in kidney transplantation, lymphangiogenesis is not altered in CLAD patients. Our findings highlight unique immunological processes leading to BOS and RAS.

  9. Allografts with autogenous platelet-rich plasma for tibial defect reconstruction: a rabbit study.

    PubMed

    Nather, Aziz; Wong, Keng Lin; David, Vikram; Pereira, Barry P

    2012-12-01

    To evaluate the effect of autogenous platelet-rich plasma (PRP) for fresh-frozen allografts in tibial defect reconstruction in rabbits. 40 adult New Zealand white rabbits underwent tibial defect reconstruction with autografts (n=12), allografts without PRP (n=12), or allografts with PRP (n=12) and were observed for 12, 16, and 24 weeks (4 for each period). Tibias of the remaining 4 rabbits were used as donor allografts, and the remaining allografts were procured from recipient rabbits. A 1.5- cm cortical segment of the tibia was osteotomised, and then fixed with a 9-hole mini-compression plate and 2 cerclage wires. Allografts were stripped off the periosteum and soft tissues and medullary contents, and then stored in a freezer at -80 ºC. All allografts were deep frozen for at least 4 weeks before transplantation. 7 ml of whole blood was drawn to prepare 1 ml of PRP. The PRP was then mixed with 1.0 ml of human thrombin to form a platelet gel. The PRP gel was then packed into the medullary canal of the allograft and applied on the cortical surface before tibial defect reconstruction. Rabbits were sacrificed at 12, 16, and 24 weeks. The specimens were assessed for bone union at host-graft junctions and for bone resorption, new bone formation, callus encasement, and viable osteocyte counts. There were 4 specimens in each group at each observation period. Osteoid bridging the gap at host-graft junctions was noted in all specimens in the autograft and allograft-with-PRP groups at week 12 and in the allograft-without-PRP group at week 24. Bone union in allografts without PRP was delayed. All indices for biological incorporation (resorption index, new bone formation index, callus encasement index, and viable osteocyte count) were significantly greater in the autograft than allograft-without-PRP groups, except for the resorption index at week 24, whereas the differences were not significant between the autograft and allograft-with-PRP groups. The differences between the 2

  10. Expression of bone morphogenetic proteins 4, 6 and 7 is downregulated in kidney allografts with interstitial fibrosis and tubular atrophy.

    PubMed

    Furic-Cunko, Vesna; Kes, Petar; Coric, Marijana; Hudolin, Tvrtko; Kastelan, Zeljko; Basic-Jukic, Nikolina

    2015-07-01

    Bone morphogenetic proteins (BMPs) are pleiotropic growth factors. This paper investigates the connection between the expression pattern of BMPs in kidney allograft tissue versus the cause of allograft dysfunction. The expression pattern of BMP2, BMP4, BMP6 and BMP7 in 50 kidney allografts obtained by transplant nephrectomy is investigated. Immunohistochemical staining is semiquantitatively evaluated for intensity to identify the expression pattern of BMPs in normal and allograft kidney tissues. The expression of BMP4 is unique between different tubular cell types in grafts without signs of fibrosis. This effect is not found in specimens with high grades of interstitial fibrosis and tubular atrophy (IFTA). In samples with IFTA grades II and III, the BMP7 expression is reduced in a significant fraction of specimens relative to those without signs of IFTA. The expression pattern of BMP6 indicates that its activation may be triggered by the act of transplantation and subsequent reperfusion injury. The expression of BMP2 is strong in all types of tubular epithelial cells and does not differ between the compared allografts and control kidney specimens. The intensity and expression pattern of BMP4, BMP6 and BMP7 in transplanted kidney tissue are found to be dependent upon the length of the transplanted period, the clinical indication for transplant nephrectomy and signs of IFTA in kidney tissue.

  11. Improved osteochondral allograft preservation using serum-free media at body temperature.

    PubMed

    Garrity, Joseph T; Stoker, Aaron M; Sims, Hannah J; Cook, James L

    2012-11-01

    Osteochondral allografts (OCAs) are currently preserved at 4°C and used within 28 days of donor harvest. The window of opportunity for implantation is limited to 14 days due to a 2-week disease testing protocol. Osteochondral allograft tissues stored at 37°C will have significantly higher chondrocyte viability, as well as superior biochemical and biomechanical properties, than those stored at 4°C. Controlled laboratory study. Osteochondral allografts from 15 adult canine cadavers were aseptically harvested within 4 hours of death. Medial and lateral femoral condyles were stored in Media 1, similar to the current standard, or Media 2, an anti-inflammatory and chondrogenic media containing dexamethasone and transforming growth factor-β3, at 4°C or 37°C for up to 56 days. Chondrocyte viability, glycosaminoglycan (GAG) and collagen (hydroxyproline [HP]) content, biomechanical properties, and collagen II and aggrecan content were assessed at days 28 and 56. Five femoral condyles were stored overnight and assessed the next day to serve as controls. Storage in Media 1 at 37°C maintained chondrocyte viability at significantly higher levels than in any other media-temperature combination and at levels not significantly different from controls. Osteochondral allografts stored in either media at 4°C showed a significant decrease in chondrocyte viability throughout storage. Glycosaminoglycan and HP content were maintained through 56 days of storage in OCAs in Media 1 at 37°C. There were no significant differences in elastic or dynamic moduli among groups at day 56. Qualitative immunohistochemistry demonstrated the presence of collagen II and aggrecan throughout all layers of cartilage. Osteochondral allograft viability, matrix content and composition, and biomechanical properties were maintained at "fresh" levels through 56 days of storage in Media 1 at 37°C. Osteochondral allografts stored at 4°C were unable to maintain viability or matrix integrity through 28 days

  12. Graft-Derived CCL2 Increases Graft Injury During Antibody-Mediated Rejection of Cardiac Allografts

    PubMed Central

    Abe, Toyofumi; Su, Charles A.; Iida, Shoichi; Baldwin, William M.; Nonomura, Norio; Takahara, Shiro; Fairchild, Robert L.

    2015-01-01

    The pathogenic role of macrophages in antibody-mediated rejection (AMR) remains unclear. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a potent chemotactic factor for monocytes and macrophages. The current studies used a murine model of AMR to investigate the role of graft-derived CCL2 in AMR and how macrophages may participate in antibody-mediated allograft injury. B6.CCR5−/−/CD8−/− recipients rejected MHC-mismatched wild type A/J allografts with high donor-reactive antibody titers and diffuse C4d deposition in the large vessels and myocardial capillaries, features consistent with AMR. In contrast, A/J.CCL2−/− allografts induced low donor-reactive antibody titers and C4d deposition at day 7 post-transplant. Decreased donor-reactive CD4 T cells producing IFN-γ were induced in response to A/J.CCL2−/− vs. wild type allografts. Consequently, A/J.CCL2−/− allograft survival was modestly but significantly longer than A/J allografts. Macrophages purified from wild type allografts expressed high levels of IL-1β and IL-12p40 and this expression and the numbers of classically activated macrophages were markedly reduced in CCL2-deficient allografts on day 7. The results indicate that allograft-derived CCL2 plays an important role in directing classically activated macrophages into allografts during AMR and that macrophages are important contributors to the inflammatory environment mediating graft tissue injury in this pathology, suggesting CCL2 as a therapeutic target for AMR. PMID:25040187

  13. The use of a novel bone allograft wash process to generate a biocompatible, mechanically stable and osteoinductive biological scaffold for use in bone tissue engineering.

    PubMed

    Smith, C A; Richardson, S M; Eagle, M J; Rooney, P; Board, T; Hoyland, J A

    2015-05-01

    Fresh-frozen biological allograft remains the most effective substitute for the 'gold standard' autograft, sharing many of its osteogenic properties but, conversely, lacking viable osteogenic cells. Tissue engineering offers the opportunity to improve the osseointegration of this material through the addition of mesenchymal stem cells (MSCs). However, the presence of dead, immunogenic and potentially harmful bone marrow could hinder cell adhesion and differentiation, graft augmentation and incorporation, and wash procedures are therefore being utilized to remove the marrow, thereby improving the material's safety. To this end, we assessed the efficiency of a novel wash technique to produce a biocompatible, biological scaffold void of cellular material that was mechanically stable and had osteoinductive potential. The outcomes of our investigations demonstrated the efficient removal of marrow components (~99.6%), resulting in a biocompatible material with conserved biomechanical stability. Additionally, the scaffold was able to induce osteogenic differentiation of MSCs, with increases in osteogenic gene expression observed following extended culture. This study demonstrates the efficiency of the novel wash process and the potential of the resultant biological material to serve as a scaffold in bone allograft tissue engineering. © 2014 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd.

  14. Skin donors and human skin allografts: evaluation of an 11-year practice and discard in a referral tissue bank.

    PubMed

    Gaucher, Sonia; Khaznadar, Zena; Gourevitch, Jean-Claude; Jarraya, Mohamed

    2016-03-01

    The Saint Louis hospital tissue bank provides skin allografts to pediatric and adult burn units in the Paris area. The aim of this study was to analyze our activity during the last 11 years focusing on the reasons for skin discard. Skin is procured solely from the back of the body, which is divided into 10 zones that are harvested and processed separately. This retrospective study included all skin donors harvested between June 2002 and June 2013, representing a total of 336 donors and 2770 zones. The donors were multiorgan heart-beating donors in 91 % of cases (n = 307). The main reason for discarding harvested skin was microbial contamination, detected in 99 donors (29 %). Most contaminants were of low pathogenicity. Other reasons for discard included positive serologic tests for 2 donors [17 zones (0.61 %)], unsuitable physical skin characteristics for 3 zones (0.11 %), the donor's medical history for 53 zones (1.91 %), and technical issues with processing or distribution for 61 zones (2.2 %). In our experience, microbial contamination continues to be the main reason for discarding potential skin allografts. However, discards are limited by separate harvesting and processing of multiple zones in each donor.

  15. Ultrasound Imaging of the Musculoskeletal System.

    PubMed

    Cook, Cristi R

    2016-05-01

    Musculoskeletal ultrasound is a rapidly growing field within veterinary medicine. Ultrasound for musculoskeletal disorders has been commonly used in equine and human medicine and is becoming more commonly performed in small animal patients due to the increase in the recognition of soft tissue injuries. Ultrasound is widely available, cost-effective, but technically difficult to learn. Advantages of musculoskeletal ultrasound are the opposite limb is commonly used for comparison to evaluate symmetry of the tendinous structures and the ease of repeat examinations to assess healing. The article discusses the major areas of shoulder, stifle, iliopsoas, gastrocnemius, and musculoskeletal basics. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Polyglutamate directed coupling of bioactive peptides for the delivery of osteoinductive signals on allograft bone

    PubMed Central

    Culpepper, Bonnie K.; Bonvallet, Paul P.; Reddy, Michael S.; Ponnazhagan, Selvarangan; Bellis, Susan L.

    2012-01-01

    Allograft bone is commonly used as an alternative to autograft, however allograft lacks many osteoinductive factors present in autologous bone due to processing. In this study, we investigated a method to reconstitute allograft with osteoregenerative factors. Specifically, an osteoinductive peptide from collagen I, DGEA, was engineered to express a heptaglutamate (E7) domain, which binds the hydroxyapatite within bone mineral. Addition of E7 to DGEA resulted in 9× greater peptide loading on allograft, and significantly greater retention after a 5-day interval with extensive washing. When factoring together greater initial loading and retention, the E7 domain directed a 45-fold enhancement of peptide density on the allograft surface. Peptide-coated allograft was also implanted subcutaneously into rats and it was found that E7DGEA was retained in vivo for at least 3 months. Interestingly, E7DGEA peptides injected intravenously accumulated within bone tissue, implicating a potential role for E7 domains in drug delivery to bone. Finally, we determined that, as with DGEA, the E7 modification enhanced coupling of a bioactive BMP2-derived peptide on allograft. These results suggest that E7 domains are useful for coupling many types of bone-regenerative molecules to the surface of allograft to reintroduce osteoinductive signals and potentially advance allograft treatments. PMID:23182349

  17. A retrospective study on annual evaluation of radiation processing for frozen bone allografts complying to quality system requirements.

    PubMed

    Ramalingam, Saravana; Mohd, Suhaili; Samsuddin, Sharifah Mazni; Min, N G Wuey; Yusof, Norimah; Mansor, Azura

    2015-12-01

    Bone allografts have been used widely to fill up essential void in orthopaedic surgeries. The benefit of using allografts to replace and reconstruct musculoskeletal injuries, fractures or disease has obtained overwhelming acceptance from orthopaedic surgeons worldwide. However, bacterial infection and disease transmission through bone allograft transplantation have always been a significant issue. Sterilization by radiation is an effective method to eliminate unwanted microorganisms thus assist in preventing life threatening allograft associated infections. Femoral heads procured from living donors and long bones (femur and tibia) procured from cadaveric donors were sterilized at 25 kGy in compliance with international standard ISO 11137. According to quality requirements, all records of bone banking were evaluated annually. This retrospective study was carried out on annual evaluation of radiation records from 1998 until 2012. The minimum doses absorbed by the bones were ranging from 25.3 to 38.2 kGy while the absorbed maximum doses were from 25.4 to 42.3 kGy. All the bones supplied by our UMMC Bone Bank were sterile at the required minimum dose of 25 kGy. Our analysis on dose variation showed that the dose uniformity ratios in 37 irradiated boxes of 31 radiation batches were in the range of 1.003-1.251, which indicated the doses were well distributed.

  18. Sterilization of allograft bone: is 25 kGy the gold standard for gamma irradiation?

    PubMed

    Nguyen, Huynh; Morgan, David A F; Forwood, Mark R

    2007-01-01

    For several decades, a dose of 25 kGy of gamma irradiation has been recommended for terminal sterilization of medical products, including bone allografts. Practically, the application of a given gamma dose varies from tissue bank to tissue bank. While many banks use 25 kGy, some have adopted a higher dose, while some choose lower doses, and others do not use irradiation for terminal sterilization. A revolution in quality control in the tissue banking industry has occurred in line with development of quality assurance standards. These have resulted in significant reductions in the risk of contamination by microorganisms of final graft products. In light of these developments, there is sufficient rationale to re-establish a new standard dose, sufficient enough to sterilize allograft bone, while minimizing the adverse effects of gamma radiation on tissue properties. Using valid modifications, several authors have applied ISO standards to establish a radiation dose for bone allografts that is specific to systems employed in bone banking. These standards, and their verification, suggest that the actual dose could be significantly reduced from 25 kGy, while maintaining a valid sterility assurance level (SAL) of 10(-6). The current paper reviews the methods that have been used to develop radiation doses for terminal sterilization of medical products, and the current trend for selection of a specific dose for tissue banks.

  19. Allograft dendritic cell p40 homodimers activate donor-reactive memory CD8+ T cells

    PubMed Central

    Tsuda, Hidetoshi; Su, Charles A.; Tanaka, Toshiaki; Ayasoufi, Katayoun; Min, Booki; Valujskikh, Anna; Fairchild, Robert L.

    2018-01-01

    Recipient endogenous memory T cells with donor reactivity pose an important barrier to successful transplantation and costimulatory blockade–induced graft tolerance. Longer ischemic storage times prior to organ transplantation increase early posttransplant inflammation and negatively impact early graft function and long-term graft outcome. Little is known about the mechanisms enhancing endogenous memory T cell activation to mediate tissue injury within the increased inflammatory environment of allografts subjected to prolonged cold ischemic storage (CIS). Endogenous memory CD4+ and CD8+ T cell activation is markedly increased within complete MHC-mismatched cardiac allografts subjected to prolonged versus minimal CIS, and the memory CD8+ T cells directly mediate CTLA-4Ig–resistant allograft rejection. Memory CD8+ T cell activation within allografts subjected to prolonged CIS requires memory CD4+ T cell stimulation of graft DCs to produce p40 homodimers, but not IL-12 p40/p35 heterodimers. Targeting p40 abrogates memory CD8+ T cell proliferation within the allografts and their ability to mediate CTLA-4Ig–resistant allograft rejection. These findings indicate a critical role for memory CD4+ T cell–graft DC interactions to increase the intensity of endogenous memory CD8+ T cell activation needed to mediate rejection of higher-risk allografts subjected to increased CIS. PMID:29467328

  20. Allografts about the Knee in Young Patients with High-Grade Sarcoma.

    PubMed

    Brigman, Brian E; Hornicek, Francis J; Gebhardt, Mark C; Mankin, Henry J

    2004-04-01

    Reconstruction after resections for high-grade sarcomas about the knee in children and adolescents is a challenging problem because of the large soft tissue and skeletal defects, the effects of adjuvant therapy, and the potential for long-term use of the limb. One hundred sixteen patients, all 18 years or younger, with osteosarcoma or Ewing's sarcoma located between the middle femur and middle tibia, were treated with chemotherapy, resection, and allograft reconstruction. One hundred three patients with osteosarcoma and 13 patients with Ewing's sarcoma had 105 Stage II and 11 Stage III tumors. There were 72 osteoarticular grafts (39 femur, 33 tibia), 28 intercalary grafts (19 femur), seven allograft-prosthetic composites (all femur,) and nine allograft-arthrodeses (seven femur, two tibia). At latest followup, 49% of all of the allograft reconstructions were rated good or excellent, 14% were rated as fair, and 37% were failures. Sixteen percent had an infection develop. Twenty-seven percent of patients had a fracture, 34% had a nonunion, and 14 patients eventually required amputation. Reconstruction of large bone defects about the knee in young patients who are being treated with chemotherapy is difficult. Although complications significantly affect outcome, allografts are a viable option for reconstruction in children with high-grade sarcomas about the knee.

  1. Can Skin Allograft Occasionally Act as a Permanent Coverage in Deep Burns? A Pilot Study 

    PubMed Central

    Rezaei, Ezzatollah; Beiraghi-Toosi, Arash; Ahmadabadi, Ali; Tavousi, Seyed Hassan; Alipour Tabrizi, Arash; Fotuhi, Kazem; Jabbari Nooghabi, Mehdi; Manafi, Amir; Ahmadi Moghadam, Shokoofeh

    2017-01-01

    BACKGROUND Skin allograft is the gold standard of wound coverage in patients with extensive burns; however, it is considered as a temporary wound coverage and rejection of the skin allograft is considered inevitable. In our study, skin allograft as a permanent coverage in deep burns is evaluated. METHODS Skin allograft survival was assessed in 38 patients from March 2009 to March 2014, retrospectively. Because of the lack of tissue specimen from the skin donors, patients with long skin allograft survival in whom the gender of donor and recipient of allograft was the same were excluded. Seven cases with skin allograft longevity and opposite gender in donor and recipient were finally enrolled. A polymerase chain reaction (PCR) test on the biopsy specimen from recipients and donors were undertaken. RESULTS PCR on the biopsy specimen from recipients confirmed those specimens belong to the donors. All patients received allograft from the opposite sex. Two (28.57%) patients received allograft from their first-degree blood relatives, and in one (14.29%) case, the allograft was harvested from an alive individual with no blood relation. The rest were harvested from multiorgan donors. In eight months of follow up, no clinical evidence of graft rejection was noted. CONCLUSION Long term persistence of skin allograft in patients is worthy of more attention. Further studies An increase in knowledge of factors influencing this longevity could realize the dream of burn surgeons to achieve a permanent coverage other than autograft for major burn patients. PMID:28289620

  2. HEMATOPOIETIC STEM CELL INFUSION/TRANSPLANTATION FOR INDUCTION OF ALLOGRAFT TOLERANCE

    PubMed Central

    Granados, Jose M. Marino; Benichou, Gilles; Kawai, Tatsuo

    2015-01-01

    Purpose of review This review updates the current status of basic, preclinical, and clinical research on donor hematopoietic stem cell infusion for allograft tolerance induction. Recent findings Recent basic studies in mice provide evidence of significant involvement of both central deletional and peripheral regulatory mechanisms in induction and maintenance of allograft tolerance effected through a mixed chimerism approach with donor hematopoietic stem cell infusion. The presence of heterologous memory T cells in primates hampers the induction of persistent chimerism. Durable mixed chimerism, however, now has been recently induced in inbred major histocompatibility complex-mismatched swine, resulting in tolerance of vascularized composite tissue allografts. In clinical transplantation, allograft tolerance has been achieved in human leukocyte antigen-mismatched kidney transplantation after the induction of transient mixed chimerism or persistent full donor chimerism. Summary Tolerance induction in clinical kidney transplantation has been achieved by donor hematopoietic stem cell infusion. Improving the consistency and safety of tolerance induction and extending successful protocols to other organs, as well as to organs from deceased donors, are critical next steps to bringing tolerance to a wider range of clinical applications. PMID:25563992

  3. Histomorphometric analysis following augmentation of the anterior atrophic maxilla with cancellous bone block allograft.

    PubMed

    Nissan, Joseph; Marilena, Vered; Gross, Ora; Mardinger, Ofer; Chaushu, Gavriel

    2012-01-01

    Grafting with bone blocks may be required to restore the alveolar process in extremely atrophic maxillae prior to implant placement to ensure both function and esthetics. The present study was conducted to histologically and histomorphometrically evaluate the application of allograft cancellous bone blocks for the augmentation of the anterior atrophic maxilla. Consecutive patients with severe atrophy in the anterior maxilla underwent augmentation with cancellous bone block allografts. Bony deficiencies of at least 3 mm horizontally and up to 3 mm vertically according to computed tomographic para-axial reconstructions served as inclusion criteria. After 6 months, implants were placed and a cylindric sample core from the graft area was collected. All specimens were prepared for histologic and histomorphometric examination. Forty patients were included in the study. Eighty-three implants were placed in bone that was augmented with 60 cancellous freeze-dried bone block allografts. The implant survival rate was 98.8%. Mean follow-up was 48 ± 22 months (range, 14 to 82 months). The mean percentage of newly formed bone was 33% ± 18%, that of the residual cancellous block allograft was 26% ± 17%, and marrow and connective tissue comprised 41% ± 2%. Statistically significant histomorphometric differences regarding newly formed bone and residual cancellous block allograft were found between younger (< 40 years) and older (≥ 40 years) patients, respectively. Age did not appear to influence the percentage of marrow and connective tissue. Cancellous bone block allograft is biocompatible and osteoconductive, permitting new bone formation following augmentation of extremely atrophic anterior maxillae in a two-stage implant placement procedure. New bone formation was age-dependent.

  4. RNA-seq Analysis of Clinical-Grade Osteochondral Allografts Reveals Activation of Early Response Genes

    PubMed Central

    Lin, Yang; Lewallen, Eric A.; Camilleri, Emily T.; Bonin, Carolina A.; Jones, Dakota L.; Dudakovic, Amel; Galeano-Garces, Catalina; Wang, Wei; Karperien, Marcel J.; Larson, Annalise N.; Dahm, Diane L.; Stuart, Michael J.; Levy, Bruce A.; Smith, Jay; Ryssman, Daniel B.; Westendorf, Jennifer J.; Im, Hee-Jeong; van Wijnen, Andre J.; Riester, Scott M.; Krych, Aaron J.

    2016-01-01

    Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA-seq) and real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess genome-wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of “early response genes” that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of “early response genes” and reduced levels of ECM-related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. PMID:26909883

  5. The effect of mesenchymal stem cell sheets on structural allograft healing of critical sized femoral defects in mice.

    PubMed

    Long, Teng; Zhu, Zhenan; Awad, Hani A; Schwarz, Edward M; Hilton, Matthew J; Dong, Yufeng

    2014-03-01

    Structural bone allografts are widely used in the clinic to treat critical sized bone defects, despite lacking the osteoinductive characteristics of live autografts. To address this, we generated revitalized structural allografts wrapped with mesenchymal stem/progenitor cell (MSC) sheets, which were produced by expanding primary syngenic bone marrow derived cells on temperature-responsive plates, as a tissue-engineered periosteum. In vitro assays demonstrated maintenance of the MSC phenotype in the sheets, suggesting that short-term culturing of MSC sheets is not detrimental. To test their efficacy in vivo, allografts wrapped with MSC sheets were transplanted into 4-mm murine femoral defects and compared to allografts with direct seeding of MSCs and allografts without cells. Evaluations consisted of X-ray plain radiography, 3D microCT, histology, and biomechanical testing at 4- and 6-weeks post-surgery. Our findings demonstrate that MSC sheets induce prolonged cartilage formation at the graft-host junction and enhanced bone callus formation, as well as graft-host osteointegration. Moreover, a large periosteal callus was observed spanning the allografts with MSC sheets, which partially mimics live autograft healing. Finally, biomechanical testing showed a significant increase in the structural and functional properties of MSC sheet grafted femurs. Taken together, MSC sheets exhibit enhanced osteogenicity during critical sized bone defect repair, demonstrating the feasibility of this tissue engineering solution for massive allograft healing. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Sonoelastography in the musculoskeletal system: Current role and future directions.

    PubMed

    Winn, Naomi; Lalam, Radhesh; Cassar-Pullicino, Victor

    2016-11-28

    Ultrasound is an essential modality within musculoskeletal imaging, with the recent addition of elastography. The elastic properties of tissues are different from the acoustic impedance used to create B mode imaging and the flow properties used within Doppler imaging, hence elastography provides a different form of tissue assessment. The current role of ultrasound elastography in the musculoskeletal system will be reviewed, in particular with reference to muscles, tendons, ligaments, joints and soft tissue tumours. The different ultrasound elastography methods currently available will be described, in particular strain elastography and shear wave elastography. Future directions of ultrasound elastography in the musculoskeletal system will also be discussed.

  7. Analysis of complications following augmentation with cancellous block allografts.

    PubMed

    Chaushu, Gavriel; Mardinger, Ofer; Peleg, Michael; Ghelfan, Oded; Nissan, Joseph

    2010-12-01

    Bone grafting may be associated with soft and hard tissue complications. Recipient site complications encountered using cancellous block allografts for ridge augmentation are analyzed. A total of 101 consecutive patients (62 females and 39 males; mean age 44 ± 17 years) were treated with implant-supported restoration of 137 severe atrophic alveolar ridges augmented with cancellous bone-block allografts. Alveolar ridge deficiency locations were classified as anterior maxilla (n = 58); posterior maxilla (n = 32 sinuses); posterior mandible (n = 32); and anterior mandible (n = 15). A total of 271 rough-surface implants were placed. Recipient site complications associated with block grafting (infection, membrane exposure, incision line opening, perforation of mucosa over the grafted bone, partial graft failure, total graft failure, and implant failure) were recorded. Partial and total bone-block graft failure occurred in 10 (7%) and 11 (8%) of 137 augmented sites, respectively. Implant failure rate was 12 (4.4%) of 271. Soft tissue complications included membrane exposure (42 [30.7%] of 137); incision line opening (41 [30%] of 137); and perforation of the mucosa over the grafted bone (19 [14%] of 137). Infection of the grafted site occurred in 18 (13%) of 137 bone blocks. Alveolar ridge deficiency location had a statistically significant effect on the outcome of recipient site complications. More complications were noted in the mandible compared to the maxilla. Age and gender had no statistically significant effect. Failures caused by complications were rarely noted in association with cancellous block grafting. The incidence of complications in the mandible was significantly higher. Soft tissue complications do not necessarily result in total loss of cancellous block allograft.

  8. Osteochondral allograft.

    PubMed

    Torrie, Arissa M; Kesler, William W; Elkin, Joshua; Gallo, Robert A

    2015-12-01

    Over the past decade, osteochondral allograft transplantation has soared in popularity. Advances in storage techniques have demonstrated improved chondrocyte viability at longer intervals and allowed for potential of increased graft availability. Recent studies have stratified outcomes according to location and etiology of the chondral or osteochondral defect. Unipolar lesions generally have favorable outcomes with promising 10-year survival rates. Though those undergoing osteochondral allograft transplantation often require reoperation, patient satisfaction remains high.

  9. Immunomodulation to Optimize Vascularized Composite Allograft Integration in Limb Loss Therapy

    DTIC Science & Technology

    2015-10-01

    2 AWARD  NUMBER:        W81XWH-­12-­2-­0058   TITLE:      Immunomodulation to Optimize Vascularized Composite Allograft Integration in Limb Loss...NUMBER   Immunomodulation to Optimize Vascularized Composite Allograft Integration in Limb Loss Therapy 5b.  GRANT  NUMBER   W81XWH-­12-­2-­0058...transplanted   tissues  are  now  available   that  may  greatly   reduce   the   risks  associated   with  limb  transplantation.       The  proposal

  10. Radiation sterilization of skin allograft

    NASA Astrophysics Data System (ADS)

    Kairiyama, E.; Horak, C.; Spinosa, M.; Pachado, J.; Schwint, O.

    2009-07-01

    In the treatment of burns or accidental loss of skin, cadaveric skin allografts provide an alternative to temporarily cover a wounded area. The skin bank facility is indispensable for burn care. The first human skin bank was established in Argentina in 1989; later, 3 more banks were established. A careful donor selection is carried out according to the national regulation in order to prevent transmissible diseases. As cadaveric human skin is naturally highly contaminated, a final sterilization is necessary to reach a sterility assurance level (SAL) of 10 -6. The sterilization dose for 106 batches of processed human skin was determined on the basis of the Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control (2004) and ISO 11137-2 (2006). They ranged from 17.6 to 33.4 kGy for bioburdens of >10-162.700 CFU/100 cm 2. The presence of Gram negative bacteria was checked for each produced batch. From the analysis of the experimental results, it was observed that the bioburden range was very wide and consequently the estimated sterilization doses too. If this is the case, the determination of a tissue-specific dose per production batch is necessary to achieve a specified requirement of SAL. Otherwise if the dose of 25 kGy is preselected, a standardized method for substantiation of this dose should be done to confirm the radiation sterilization process.

  11. Case Series With Histopathologic and Radiographic Analyses Following Failure of Fresh Osteochondral Allografts of the Talus.

    PubMed

    Pomajzl, Ryan Joseph; Baker, Erin Ann; Baker, Kevin Charles; Fleischer, Mackenzie Marie; Salisbury, Meagan R; Phillips, Dylan M; Fortin, Paul Thomas

    2016-09-01

    Fresh osteochondral allografting of the talus is one treatment option for large chondral defects. Following positive early term results, failure rates of up to 35% have been reported. A retrieval study was performed to characterize failed talar allografts. Failed fresh osteochondral allografts of the talus were retrieved on revision. Cases of deep infection were excluded. After tissue fixation, samples were decalcified, embedded, and stained with Safranin-O/Fast Green, osteocalcin, tumor necrosis factor alpha (TNF-α), CD4, CD8, and CD68. Slides were graded according to the modified Mankin scoring system or severity scale. Medical record review was performed. Eight allografts (7 patients) were retrieved from patients, following an average term of implantation of 31 months (range, 12-58). There were 3 types of allografts in this series (hemidome, n=5; segmental, n=2; bipolar, n=1). Reasons for transplantation were post-traumatic arthritis or osteonecrosis; reasons for revision were graft failure/collapse, nonunion, progressive arthritis, and/or pain. Prior to revision, all grafts exhibited collapse and subchondral lucencies. At the graft host interface, Safranin-O staining demonstrated substantial loss of sulfated glycosaminoglycans, Osteocalcin immunostaning was nearly absent, CD68 (indicating osteoclast activity) was predominantly exhibited, and CD4+ helper T cells as well as CD8+ cytotoxic T cells and NK cells-cell types commonly implicated in allogeneic organ transplant rejection-were found in high concentrations. TNF-α was present throughout the graft. A histopathologic analysis of 8 retrieved, failed talar allografts was performed. Graft failure appeared to be primarily biologic, with an extensive loss of viable cartilaginous and osseous tissue at the graft-host interface. This study provides the first evidence of a potential CD4+ and CD8+ lymphocyte-mediated failure mechanism in fresh osteochondral allografts that were revised following collapse. Level IV

  12. Rapid Raman spectroscopy of musculoskeletal tissue using a visible laser and an electron-multiplying CCD (EMCCD) detector

    NASA Astrophysics Data System (ADS)

    Golcuk, Kurtulus; Mandair, Gurjit S.; Callender, Andrew F.; Finney, William F.; Sahar, Nadder; Kohn, David H.; Morris, Michael D.

    2006-02-01

    Background fluorescence can often complicate the use of Raman microspectroscopy in the study of musculoskeletal tissues. Such fluorescence interferences are undesirable as the Raman spectra of matrix and mineral phases can be used to differentiate between normal and pathological or microdamaged bone. Photobleaching with the excitation laser provides a non-invasive method for reducing background fluorescence, enabling 532 nm Raman hyperspectral imaging of bone tissue. The signal acquisition time for a 400 point Raman line image is reduced to 1-4 seconds using electronmultiplying CCD (EMCCD) detector, enabling acquisition of Raman images in less than 10 minutes. Rapid photobleaching depends upon multiple scattering effects in the tissue specimen and is applicable to some, but not all experimental situations.

  13. Erythropoietin, but not the correction of anemia alone, protects from chronic kidney allograft injury.

    PubMed

    Cassis, Paola; Gallon, Lorenzo; Benigni, Ariela; Mister, Marilena; Pezzotta, Anna; Solini, Samantha; Gagliardini, Elena; Cugini, Daniela; Abbate, Mauro; Aiello, Sistiana; Rocchetta, Federica; Scudeletti, Pierangela; Perico, Norberto; Noris, Marina; Remuzzi, Giuseppe

    2012-05-01

    Anemia can contribute to chronic allograft injury by limiting oxygen delivery to tissues, particularly in the tubulointerstitium. To determine mechanisms by which erythropoietin (EPO) prevents chronic allograft injury we utilized a rat model of full MHC-mismatched kidney transplantation (Wistar Furth donor and Lewis recipients) with removal of the native kidneys. EPO treatment entirely corrected post-transplant anemia. Control rats developed progressive proteinuria and graft dysfunction, tubulointerstitial damage, inflammatory cell infiltration, and glomerulosclerosis, all prevented by EPO. Normalization of post-transplant hemoglobin levels by blood transfusions, however, had no impact on chronic allograft injury, indicating that EPO-mediated graft protection went beyond the correction of anemia. Compared to syngeneic grafts, control allografts had loss of peritubular capillaries, higher tubular apoptosis, tubular and glomerular oxidative injury, and reduced expression of podocyte nephrin; all prevented by EPO treatment. The effects of EPO were associated with preservation of intragraft expression of angiogenic factors, upregulation of the anti-apoptotic factor p-Akt in tubuli, and increased expression of Bcl-2. Inhibition of p-Akt by Wortmannin partially antagonized the effect of EPO on allograft injury and tubular apoptosis, and prevented EPO-induced Bcl-2 upregulation. Thus non-erythropoietic derivatives of EPO may be useful to prevent chronic renal allograft injury.

  14. Acellular dermal matrix allograft. The results of controlled randomized clinical studies.

    PubMed

    Novaes, Arthur Belém; de Barros, Raquel Rezende Martins

    2008-10-01

    The aim of this presentation was to discuss the effectiveness of the acellular dermal matrix in root coverage therapy and in alveolar ridge augmentation, based on three controlled randomized clinical trials conducted by our research team (Novaes Jr et al., 2001; Barros et al., 2005; Luczyszyn et al., 2005). The first and second studies highlight the allograft's performance in the treatment of gingival recession. In both studies, clinical parameters were assessed prior to surgery and 6 or 12 months post-surgery. The first one compared the use of the acellular dermal matrix with the subepithelial connective tissue graft and showed 1.83 and 2.10 mm of recession reduction, respectively. Because no statistically significant differences between the groups were observed, it was concluded that the allograft can be used as a substitute for the autograft. In the second study, a new surgical approach was compared to a conventional surgical procedure described by Langer and Langer in 1985. A statistically significant greater recession reduction favoring the test procedure was achieved. The percentage of root coverage was 82.5% and 62.3% for test and control groups. Thus the new technique was considered more suitable for the treatment of gingival recessions with the allograft. Finally, the third study evaluated the allograft as a membrane, associated or not with a resorbable hydroxyapatite in bone regeneration to prevent ridge deformities. In one group the extraction sockets were covered only by the allograft and in the other, the alveoli were also filled with the resorbable hydroxyapatite. After six months, both treatments were able to preserve ridge thickness, considering the pre-operative values. In conclusion, no adverse healing events were noted with the use of allograft in site preservation procedures, and sites treated with the combination of allograft plus resorbable hydroxyapatite showed significantly greater ridge thickness preservation at six months when compared to

  15. Root coverage of advanced gingival recession: a comparative study between acellular dermal matrix allograft and subepithelial connective tissue grafts.

    PubMed

    Tal, Haim; Moses, Ofer; Zohar, Ron; Meir, Haya; Nemcovsky, Carlos

    2002-12-01

    Acellular dermal matrix allograft (ADMA) has successfully been applied as a substitute for free connective tissue grafts (CTG) in various periodontal procedures, including root coverage. The purpose of this study was to clinically compare the efficiency of ADMA and CTG in the treatment of gingival recessions > or = 4 mm. Seven patients with bilateral recession lesions participated. Fourteen teeth presenting gingival recessions > or = 4 mm were randomly treated with ADMA or CTG covered by coronally advanced flaps. Recession, probing depth, and width of keratinized tissue were measured preoperatively and 12 months postoperatively. Changes in these clinical parameters were calculated within and compared between groups and analyzed statistically. Baseline recession, probing depth, and keratinized tissue width were similar for both groups. At 12 months, root coverage gain was 4.57 mm (89.1%) versus 4.29 mm (88.7%) (P = NS), and keratinized tissue gain was 0.86 mm (36%) versus 2.14 mm (107%) (P < 0.05) for ADMA and CTG, respectively. Probing depth remained unchanged (0.22 mm/0 mm), with no difference between the groups. Recession defects may be covered using ADMA or CTG, with no practical difference. However, CTG results in significantly greater gain of keratinized gingiva.

  16. Should fractures in massive intercalary bone allografts of the lower limb be treated with ORIF or with a new allograft?

    PubMed

    Aponte-Tinao, Luis A; Ayerza, Miguel A; Muscolo, D Luis; Farfalli, Germán L

    2015-03-01

    Massive bone allografts have been used for limb salvage of bone tumor resections as an alternative to endoprostheses, although they have different outcomes and risks. There is no general consensus about when to use these alternatives, but when it is possible to save the native joints after the resection of a long bone tumor, intercalary allografts offer some advantages despite complications, such as fracture. The management and outcomes of this complication deserve more study. The purposes of this study were to (1) analyze the fracture frequency in a group of patients treated with massive intercalary bone allografts of the femur and tibia; (2) compare the results of allografts treated with open reduction and internal fixation (ORIF) with those treated with resection and repeat allograft reconstruction; and (3) determine the likelihood that treatment of a fracture resulted in a healed intercalary reconstruction. We reviewed patients treated with intercalary bone allografts between 1991 and 2011. During this period, patients were generally treated with intercalary allografts when after tumor resection at least 1 cm of residual epiphysis remained to allow fixation of the osteotomy junction. To obtain a homogeneous group of patients, we excluded allograft-prosthesis composites and osteoarticular and hemicylindrical intercalary allografts from this study. We analyzed the fracture rate of 135 patients reconstructed with segmental intercalary bone allografts of the lower extremities (98 femurs and 37 tibias). In patients whose grafts fractured were treated either by internal fixation or a second allograft, ORIF generally was attempted but after early failures in femur fractures, these fractures were treated with a second allograft. Using a chart review, we ascertained the frequency of osseous union, complications, and reoperations after the treatment of fractured intercalary allografts. Followup was at a mean of 101 months (range, 24-260 months); of the original 135

  17. Replacement of the anterior cruciate ligament with a bone-ligament-bone anterior cruciate ligament allograft in dogs.

    PubMed

    Vasseur, P B; Rodrigo, J J; Stevenson, S; Clark, G; Sharkey, N

    1987-06-01

    Acute replacement of the canine anterior cruciate ligament (ACL) with a frozen, bone-ligament-bone anterior cruciate ligament preparation was studied using biochemical, immunologic, and biomechanical testing methods. Nine dogs were used for the study, six dogs received allografts and three received autografts. No tissue antigen matching was performed. All nine dogs were killed nine months after surgery. Necropsy examination revealed that the ACL was not present in three joints (one autograft, two allografts). The two autograft and four allograft ligaments available for mechanical testing sustained mean maximum loads that were 10% and 14%, respectively, of the mean maximum loads sustained by the contralateral ACL. Autoradiography indicated that cellular activity was more pronounced in the autograft specimens. Hydroxyproline uptake was 200% and 45% of normal in the autograft and allograft ligaments, respectively. Both autograft and allograft specimens were producing Type I collagen at the time of killing. Antidonor dog leukocyte antigen (DLA) antibody was detected in the synovial fluid taken at the time of killing from six of six dogs that received allografts and in zero of three dogs that received autografts.

  18. Bioinspired Technologies to Connect Musculoskeletal Mechanobiology to the Person for Training and Rehabilitation

    PubMed Central

    Pizzolato, Claudio; Lloyd, David G.; Barrett, Rod S.; Cook, Jill L.; Zheng, Ming H.; Besier, Thor F.; Saxby, David J.

    2017-01-01

    Musculoskeletal tissues respond to optimal mechanical signals (e.g., strains) through anabolic adaptations, while mechanical signals above and below optimal levels cause tissue catabolism. If an individual's physical behavior could be altered to generate optimal mechanical signaling to musculoskeletal tissues, then targeted strengthening and/or repair would be possible. We propose new bioinspired technologies to provide real-time biofeedback of relevant mechanical signals to guide training and rehabilitation. In this review we provide a description of how wearable devices may be used in conjunction with computational rigid-body and continuum models of musculoskeletal tissues to produce real-time estimates of localized tissue stresses and strains. It is proposed that these bioinspired technologies will facilitate a new approach to physical training that promotes tissue strengthening and/or repair through optimal tissue loading. PMID:29093676

  19. Micropuncture and pressure assisted Schwann cell seeding of nerve allograft.

    PubMed

    Isaacs, Jonathan; Richards, Nathan; McMurtry, John; Mallu, Satya; Patel, Gaurangkumar; Thompson, Matthew; Yager, Dorne

    2017-08-01

    Tissue processing to create immunotolerant nerve allograft removes neurosupportive cells. Few strategies have been described for implanting new cells into the graft to support axonal regeneration. Micropuncture of the nerve allograft surface combined with immersion into a pressurized cell-rich solution to potentiate the introduction of viable Schwann cells (SC) into processed nerve allograft. Allografts were used to repair rodent sciatic nerve defects. At 3, 7, and 21days, grafts were harvested, stained for SCs, and analyzed using total cross sectional area (CSA) occupied by SCs to quantify SC presence. At days 3 and 7, SC CSA was significantly greater for the injection group compared to all other groups. At day 21, SC CSA for the injection group (0.2252%±0.2730) was significantly greater compared to following groups: pressurized-punctured (0.0653%±0.0934), nonpressurized-nonpunctured (0.0607%±0.0709), punctured-control (0.0246%±0.0398), and nonpunctured-control (0.0126%±0.0151). A significant decrease in percent CSA occupied by SCs from day 3 to day 21 was noted in nonpressurized-punctured group (p=0.0106), pressurized-nonpunctured group (p=0.0477), and injection group (p=0.0010). Most studies have used small caliber hypodermic needles to inject the cells into grafts. Despite a presumed decrease in cell viability over the three weeks of the study, the large initial inoculum achieved by injection technique results in higher levels of final SC seeding in acellular nerve allograft compared with bathing techniques with or without micropuncture or pressurization. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Infrared fiber optic probes for evaluation of musculoskeletal tissue pathology

    NASA Astrophysics Data System (ADS)

    Padalkar, Mugdha; McGoverin, Cushla; Onigbanjo, Quam; Spencer, Richard; Barbash, Scott; Kropf, Eric; Pleshko, Nancy

    2014-03-01

    Musculoskeletal pathology of the knee commonly occurs with aging and as a result of injury. The incidence of anterior cruciate ligament (ACL) injuries continues to increase annually, and may precede the eventual onset of osteoarthritis (OA), a debilitating and prevalent disease characterized by cartilage degeneration. Early detection of OA remains elusive, with current imaging methods lacking adequate sensitivity to detect early pathologic cartilage changes. We used mid- and near- infrared (IR) spectroscopy through arthroscopic-based fiber-optic devices to assess cartilage damage and differentiate tendon from ligament. Mid-IR spectroscopy is characterized by distinct bands and low penetration depth (< 10 μm) and near-IR spectroscopy is characterized by complex overlapping bands and greater penetration depths (< 1 cm). We have found that combined mid- and near-IR analysis greatly extends the information available through either in the analysis of soft tissues, including cartilage, ligaments and tendons. We discuss here basic science studies and the potential for translation to clinical research with novel arthroscopic probes.

  1. Allograft-prosthetic composite reverse total shoulder arthroplasty for reconstruction of proximal humerus tumor resections.

    PubMed

    King, Joseph J; Nystrom, Lukas M; Reimer, Nickolas B; Gibbs, C Parker; Scarborough, Mark T; Wright, Thomas W

    2016-01-01

    Proximal humerus reconstructions after resection of tumors are challenging. Early success of the reverse shoulder arthroplasty for reconstructions has recently been reported. The reverse allograft-prosthetic composite offers the advantage of improved glenohumeral stability compared with hemiarthroplasty for proximal humeral reconstructions as it uses the deltoid for stability. This article describes the technique for treating proximal humeral tumors, including preoperative planning, biopsy principles, resection pearls, soft tissue tensioning, and specifics about reconstruction using the reverse allograft-prosthetic composite. Two cases are presented along with the functional outcomes with use of this technique. Biomechanical considerations during reconstruction are reviewed, including techniques to improve the deltoid compression force. Reported instability rates are less with reverse shoulder arthroplasty reconstruction as opposed to hemiarthroplasty or total shoulder arthroplasty reconstructions of tumor resections. Reported functional outcomes are promising for the reverse allograft-prosthetic composite reconstructions, although complications are reported. Reverse allograft-prosthetic composites are a promising option for proximal humeral reconstructions, although nonunion of the allograft-host bone junction continues to be a challenge for this technique. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  2. Recent Advances in Allograft Vasculopathy

    PubMed Central

    Merola, Jonathan; Jane-Wit, Daniel D.; Pober, Jordan S.

    2017-01-01

    Purpose of review Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy (AV). This review discusses recently reported mechanistic insights of AV pathogenesis as well recent clinical evaluations of new therapeutic approaches. Recent findings Although adaptive immunity is the major driver of AV, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA). However, NK cells may also dampen chronic inflammatory responses by killing donor-derived tissue-resident CD4 T cells that provide help to host B cells, the source of DSA. DSA may directly contribute to vascular inflammation by inducing intracellular signaling cascades that upregulate leukocyte adhesion molecules, facilitating recruitment of neutrophils and monocytes. DSA-mediated complement activation additionally enhances endothelial alloimmunogenicity through activation of non-canonical NF-κB signaling. New clinical studies evaluating mTOR and proteasome inhibitors to target these pathways have been reported. Summary AV is a pathology resultant from several innate and adaptive alloimmune responses. Mechanistic insights from preclinical studies have identified agents that are currently being investigated in clinical trials. PMID:27898462

  3. RNA-seq analysis of clinical-grade osteochondral allografts reveals activation of early response genes.

    PubMed

    Lin, Yang; Lewallen, Eric A; Camilleri, Emily T; Bonin, Carolina A; Jones, Dakota L; Dudakovic, Amel; Galeano-Garces, Catalina; Wang, Wei; Karperien, Marcel J; Larson, Annalise N; Dahm, Diane L; Stuart, Michael J; Levy, Bruce A; Smith, Jay; Ryssman, Daniel B; Westendorf, Jennifer J; Im, Hee-Jeong; van Wijnen, Andre J; Riester, Scott M; Krych, Aaron J

    2016-11-01

    Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA-seq) and real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess genome-wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of "early response genes" that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of "early response genes" and reduced levels of ECM-related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1950-1959, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  4. Superagonistic CD28 antibody induces donor-specific tolerance in rat renal allografts.

    PubMed

    Azuma, H; Isaka, Y; Li, X; Hünig, T; Sakamoto, T; Nohmi, H; Takabatake, Y; Mizui, M; Kitazawa, Y; Ichimaru, N; Ibuki, N; Ubai, T; Inamoto, T; Katsuoka, Y; Takahara, S

    2008-10-01

    The ultimate goal of organ transplantation is to establish graft tolerance where CD4+CD25+FOXP3+ regulatory T (Treg) cells play an important role. We examined whether a superagonistic monoclonal antibody specific for CD28 (CD28 SA), which expands Treg cells in vivo, would prevent acute rejection and induce tolerance using our established rat acute renal allograft model (Wistar to Lewis). In the untreated or mouse IgG-treated recipients, graft function significantly deteriorated with marked destruction of renal tissue, and all rats died by 13 days with severe azotemia. In contrast, 90% of recipients treated with CD28 SA survived over 100 days, and 70% survived with well-preserved graft function until graft recovery at 180 days. Analysis by flow cytometry and immunohistochemistry demonstrated that CD28 SA induced marked infiltration of FOXP3+ Treg cells into the allografts. Furthermore, these long-surviving recipients showed donor-specific tolerance, accepting secondary (donor-matched) Wistar cardiac allografts, but acutely rejecting third-party BN allografts. We further demonstrated that adoptive transfer of CD4+CD25+ Treg cells, purified from CD28 SA-treated Lewis rats, significantly prolonged allograft survival and succeeded in inducing donor-specific tolerance. In conclusion, CD28 SA treatment successfully induces donor-specific tolerance with the involvement of Treg cells, and thus the therapeutic value of this approach warrants further investigation and preclinical studies.

  5. Role of Magnetic Resonance Elastography as a Noninvasive Measurement Tool of Fibrosis in a Renal Allograft: A Case Report.

    PubMed

    Kim, J K; Yuen, D A; Leung, G; Jothy, S; Zaltzman, J; Ramesh Prasad, G V; Prabhudesai, V; Mnatzakanian, G; Kirpalani, A

    2017-09-01

    A major reason for poor long-term kidney transplant outcomes is the development of chronic allograft injury, characterized by interstitial fibrosis and tubular atrophy. Currently, an invasive biopsy that samples only <1% of the kidney is the gold standard for detecting kidney allograft fibrosis. We report the use of magnetic resonance elastography (MRE) to quantify tissue stiffness as a noninvasive and whole-kidney measurement tool of allograft fibrosis in a kidney transplant patient at 2 time points. The MRE whole-kidney stiffness values reflected the changes in fibrosis of the kidney allograft as assessed by histologic examination. To our knowledge, this technique is the first observation of change over time in MRE-derived whole-kidney stiffness in an allograft that is consistent with changes in histology-derived fibrosis scores in a single patient. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Shear-Wave Elastography: Basic Physics and Musculoskeletal Applications.

    PubMed

    Taljanovic, Mihra S; Gimber, Lana H; Becker, Giles W; Latt, L Daniel; Klauser, Andrea S; Melville, David M; Gao, Liang; Witte, Russell S

    2017-01-01

    In the past 2 decades, sonoelastography has been progressively used as a tool to help evaluate soft-tissue elasticity and add to information obtained with conventional gray-scale and Doppler ultrasonographic techniques. Recently introduced on clinical scanners, shear-wave elastography (SWE) is considered to be more objective, quantitative, and reproducible than compression sonoelastography with increasing applications to the musculoskeletal system. SWE uses an acoustic radiation force pulse sequence to generate shear waves, which propagate perpendicular to the ultrasound beam, causing transient displacements. The distribution of shear-wave velocities at each pixel is directly related to the shear modulus, an absolute measure of the tissue's elastic properties. Shear-wave images are automatically coregistered with standard B-mode images to provide quantitative color elastograms with anatomic specificity. Shear waves propagate faster through stiffer contracted tissue, as well as along the long axis of tendon and muscle. SWE has a promising role in determining the severity of disease and treatment follow-up of various musculoskeletal tissues including tendons, muscles, nerves, and ligaments. This article describes the basic ultrasound physics of SWE and its applications in the evaluation of various traumatic and pathologic conditions of the musculoskeletal system. © RSNA, 2017.

  7. "Proprietary Processed" Allografts: Clinical Outcomes and Biomechanical Properties in Anterior Cruciate Ligament Reconstruction.

    PubMed

    Roberson, Troy A; Abildgaard, Jeffrey T; Wyland, Douglas J; Siffri, Paul C; Geary, Stephen P; Hawkins, Richard J; Tokish, John M

    2017-11-01

    The processing of allograft tissues in anterior cruciate ligament (ACL) reconstruction continues to be controversial. While high-dose irradiation of grafts has received scrutiny for high failure rates, lower dose irradiation and "proprietary-based" nonirradiated sterilization techniques have become increasingly popular, with little in the literature to evaluate their outcomes. Recent studies have suggested that the specifics of allograft processing techniques may be a risk factor for higher failure rates. To assess these proprietary processes and their clinical outcomes and biomechanical properties. Systematic review. A systematic review was performed using searches of PubMed, EMBASE, Google Scholar, and Cochrane databases. English-language studies were identified with the following search terms: "allograft ACL reconstruction" (title/abstract), "novel allograft processing" (title/abstract), "allograft anterior cruciate ligament" (title/abstract), "anterior cruciate ligament allograft processing" (title/abstract), or "biomechanical properties anterior cruciate ligament allograft" (title/abstract). Duplicate studies, studies not providing the allograft processing technique, and those not containing the outcomes of interest were excluded. Outcomes of interest included outcome scores, complication and failure rates, and biomechanical properties of the processed allografts. Twenty-four studies (13 clinical, 11 biomechanical) met inclusion criteria for review. No demonstrable difference in patient-reported outcomes was appreciated between the processing techniques, with the exception of the Tutoplast process. The clinical failure rate of the Tutoplast process was unacceptably high (45% at 6 years), but no other difference was found between other processing techniques (BioCleanse: 5.4%; AlloTrue: 5.7%; MTF: 6.7%). Several studies did show an increased failure rate, but these studies either combined processing techniques or failed to delineate enough detail to allow a

  8. Enhanced cellular infiltration of human adipose-derived stem cells in allograft menisci using a needle-punch method.

    PubMed

    Nordberg, Rachel C; Charoenpanich, Adisri; Vaughn, Christopher E; Griffith, Emily H; Fisher, Matthew B; Cole, Jacqueline H; Spang, Jeffrey T; Loboa, Elizabeth G

    2016-10-28

    The meniscus plays a crucial role in knee joint stability, load transmission, and stress distribution. Meniscal tears are the most common reported knee injuries, and the current standard treatment for meniscal deficiency is meniscal allograft transplantation. A major limitation of this approach is that meniscal allografts do not have the capacity to remodel and maintain tissue homeostasis due to a lack of cellular infiltration. The purpose of this study was to provide a new method for enhanced cellular infiltration in meniscal allografts. Twenty medial menisci were collected from cadaveric human sources and split into five experimental groups: (1) control native menisci, (2) decellularized menisci, (3) decellularized menisci seeded with human adipose-derived stem cells (hASC), (4) decellularized needle-punched menisci, and (5) decellularized needle-punched menisci seeded with hASC. All experimental allografts were decellularized using a combined method with trypsin EDTA and peracetic acid. Needle punching (1-mm spacing, 28 G microneedle) was utilized to improve porosity of the allograft. Samples were recellularized with hASC at a density of 250 k/g of tissue. After 28 days of in vitro culture, menisci were analyzed for mechanical, biochemical, and histological characteristics. Menisci maintained structural integrity and material properties (compressive equilibrium and dynamic moduli) throughout preparations. Increased DNA content was observed in the needle-punched menisci but not in the samples without needle punching. Histology confirmed these results, showing enhanced cellular infiltration in needle-punched samples. The enhanced infiltration achieved in this study could help meniscal allografts better remodel post-surgery. The integration of autologous adipose-derived stem cells could improve long-term efficacy of meniscal transplantation procedures by helping to maintain the meniscus in vivo.

  9. [Pedal bypass using venous allograft].

    PubMed

    Pluháčková, H; Staffa, R; Konečný, Z; Kříž, Z; Vlachovský, R

    Pedal or distal crural bypass surgery for limb salvage is a method with very good long-term results. For patients in whom a suitable autologous venous graft is not available, the use of a venous allograft is an alternative procedure. A 68 years old man with ischaemic disease of lower extremities and gangrene of the left foot was admitted to our Centre in August 2014. He underwent percutaneous transluminal angioplasty of crural arteries of his left lower extremity. This, however, failed to improve peripheral circulation. The patient was then indicated for pedal or distal crural vascular reconstruction. Since no suitable autologous vein was available, distal bypass surgery using a donor graft remained the only option for limb salvage. Amputation of the toes on the left foot due to gangrene was necessary. Subsequently, femoro-pedal bypass to the left common plantar artery was performed using a great saphenous vein allograft. The post-operative course was without complications, the pedal bypass was patent and toe amputation was with good healing. The patient remained in follow-up care. A good outcome of vascular reconstruction with an allograft depends on the availability of a suitable allograft and good patient compliance with post-operative care. In the case presented here, the pedal bypass grafting by means of an allograft helped to save the patients limb. pedal bypass venous allograft limb salvage.

  10. Characterization of skin allograft use in thermal injury.

    PubMed

    Fletcher, John L; Caterson, E J; Hale, Robert G; Cancio, Leopoldo C; Renz, Evan M; Chan, Rodney K

    2013-01-01

    This study provides objective data on the practice of allograft usage in severely burned patients. Furthermore, gaps in our knowledge are identified, and areas for further research are delineated. Using an institutional review board-approved protocol, active duty military patients injured while deployed in support of overseas contingency operations and treated at our burn center between March 2003 and December 2010 were identified. Their electronic medical records were reviewed for allograft use, TBSA burned, injury severity score, anatomic distribution of burns, operative burden, length of stay, transfusions, and outcome. Among 844 patients, 112 (13.3%) received allograft and 732 (86.7%) did not. The amount of allograft used per patient varied and was not normally distributed (median, 23.5; interquartile range, 69.5). Patients received allograft skin an average of 12.75 times during their admission. Allografted patients sustained severe burns (μ, 53.8% TBSA); most were transfused (71.2%) and grafted frequently, averaging every 7.45 days. Most commonly, allograft was placed on the extremities (66.5%) followed by the trunk (44.2%); however, the vast majority of allografted patients also had concomitant burns of the head (91.1%) and hands (87.5%). All-cause mortality among the allografted patients was 19.1%. In conclusion, allograft is commonly used in the surgical treatment of severe burns. Although there are no anatomic limitations to allograft placement, there are distinct patterns of use. Given the role of allograft in the acute management of large burns, there is need for further investigation of its effect on mortality, morbidity, and antigenicity.

  11. Musculoskeletal discipline science plan

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Life sciences research in the musculoskeletal discipline must identify possible consequences of weightlessness on this system, understand the mechanisms of these effects, and develop effective and operationally practical countermeasures to protect crewmembers. The musculoskeletal system is highly plastic in that is possesses the inherent capability to adapt its structural and functional properties in accordance with the type and degree of stimuli imposed on it. Prolonged space travel is essentially a period of significant unloading of the musculoskeletal system. This results in adaptive responses in the structure and function of this system, placing it on the low end of a continuum from one of complete disuse to one of maximal use. There is a high probability that the musculoskeletal system is functionally impaired with increasing duration of weightlessness. The purpose of this Discipline Science Plan is to provide a conceptual strategy for NASA's Life Sciences division research and development activities in the area of musculoskeletal function. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, identifies science priorities, and defines research opportunities, which encompass critical questions in the subdiscipline areas (e.g., muscle, bone, and other musculoskeletal connective tissues). These science activities include ground-based and flight; basic, applied, and operational; and animal and human research and development. This document contains a general plan that will be used by both NASA Headquarters Program Offices and the field centers to review and plan basic, applied, and operational intramural and extramural research and development activities in this area.

  12. Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking

    PubMed Central

    Makris, Eleftherios A.; Responte, Donald J.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2014-01-01

    The inability to recapitulate native tissue biomechanics, especially tensile properties, hinders progress in regenerative medicine. To address this problem, strategies have focused on enhancing collagen production. However, manipulating collagen cross-links, ubiquitous throughout all tissues and conferring mechanical integrity, has been underinvestigated. A series of studies examined the effects of lysyl oxidase (LOX), the enzyme responsible for the formation of collagen cross-links. Hypoxia-induced endogenous LOX was applied in multiple musculoskeletal tissues (i.e., cartilage, meniscus, tendons, ligaments). Results of these studies showed that both native and engineered tissues are enhanced by invoking a mechanism of hypoxia-induced pyridinoline (PYR) cross-links via intermediaries like LOX. Hypoxia was shown to enhance PYR cross-linking 1.4- to 6.4-fold and, concomitantly, to increase the tensile properties of collagen-rich tissues 1.3- to 2.2-fold. Direct administration of exogenous LOX was applied in native cartilage and neocartilage generated using a scaffold-free, self-assembling process of primary chondrocytes. Exogenous LOX was found to enhance native tissue tensile properties 1.9-fold. LOX concentration- and time-dependent increases in PYR content (∼16-fold compared with controls) and tensile properties (approximately fivefold compared with controls) of neocartilage were also detected, resulting in properties on par with native tissue. Finally, in vivo subcutaneous implantation of LOX-treated neocartilage in nude mice promoted further maturation of the neotissue, enhancing tensile and PYR content approximately threefold and 14-fold, respectively, compared with in vitro controls. Collectively, these results provide the first report, to our knowledge, of endogenous (hypoxia-induced) and exogenous LOX applications for promoting collagen cross-linking and improving the tensile properties of a spectrum of native and engineered tissues both in vitro and in

  13. Magnetic resonance imaging findings of paracoccidioidomycosis in the musculoskeletal system.

    PubMed

    Savarese, Leonor G; Monsignore, Lucas M; de Andrade Hernandes, Mateus; Martinez, Roberto; Nogueira-Barbosa, Marcello H

    2015-10-01

    To describe magnetic resonance imaging (MRI) findings in musculoskeletal paracoccidioidomycosis (PCM). Retrospective case series study after IRB approval. Two musculoskeletal radiologists reviewed in consensus the MRI findings of 11 patients with microbiologically and/or pathologically proven osteoarticular PCM. The MRI evaluation included discrimination of abnormalities in joints, bones and soft tissues. Mean age of patients was 29 years (10-55 years), eight men and three women. Musculoskeletal involvement was the only or the primary presentation of the disease in seven patients (63%). Osteomyelitis was the most common presentation, with seven cases (63%). Primary arthritis was found in one patient (9%). Isolated extra-articular soft tissue PCM was found in three patients: myositis (2) and subcutaneous infection (1). All cases showed regions with signal intensity higher than or similar to the signal of muscle on T1-weighted images. Penumbra sign was present in five cases (45%). T2-weighted images showed reactive soft tissue oedema in eight cases (72%). Post-gadolinium images showed peripheral (8/9) or heterogeneous (1/9) enhancement. Synovial enhancement was present in all cases of joint involvement (6/6). Lipomatosis arborescens was documented in one case of chronic knee involvement. To our knowledge, this is the first case series describing MRI findings of musculoskeletal PCM. Musculoskeletal involvement was the primary presentation of the disease in most cases, and therefore, neoplasms were initially in the differential diagnosis. Osteomyelitis was the most common presentation, often with secondary involvement of joint and or soft tissue. © 2015 John Wiley & Sons Ltd.

  14. To what extent is joint and muscle mechanics predicted by musculoskeletal models sensitive to soft tissue artefacts?

    PubMed

    Lamberto, Giuliano; Martelli, Saulo; Cappozzo, Aurelio; Mazzà, Claudia

    2017-09-06

    Musculoskeletal models are widely used to estimate joint kinematics, intersegmental loads, and muscle and joint contact forces during movement. These estimates can be heavily affected by the soft tissue artefact (STA) when input positional data are obtained using stereophotogrammetry, but this aspect has not yet been fully characterised for muscle and joint forces. This study aims to assess the sensitivity to the STA of three open-source musculoskeletal models, implemented in OpenSim. A baseline dataset of marker trajectories was created for each model from experimental data of one healthy volunteer. Five hundred STA realizations were then statistically generated using a marker-dependent model of the pelvis and lower limb artefact and added to the baseline data. The STA׳s impact on the musculoskeletal model estimates was finally quantified using a Monte Carlo analysis. The modelled STA distributions were in line with the literature. Observed output variations were comparable across the three models, and sensitivity to the STA was evident for most investigated quantities. Shape, magnitude and timing of the joint angle and moment time histories were not significantly affected throughout the entire gait cycle, whereas magnitude variations were observed for muscle and joint forces. Ranges of contact force variations differed between joints, with hip variations up to 1.8 times body weight observed. Variations of more than 30% were observed for some of the muscle forces. In conclusion, musculoskeletal simulations using stereophotogrammetry may be safely run when only interested in overall output patterns. Caution should be paid when more accurate estimated values are needed. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Diagnostic and interventional musculoskeletal ultrasound: part 2. Clinical applications.

    PubMed

    Smith, Jay; Finnoff, Jonathan T

    2009-02-01

    Musculoskeletal ultrasound involves the use of high-frequency sound waves to image soft tissues and bony structures in the body for the purposes of diagnosing pathology or guiding real-time interventional procedures. Recently, an increasing number of physicians have integrated musculoskeletal ultrasound into their practices to facilitate patient care. Technological advancements, improved portability, and reduced costs continue to drive the proliferation of ultrasound in clinical medicine. This increased interest creates a need for education pertaining to all aspects of musculoskeletal ultrasound. The primary purpose of this article is to review diagnostic ultrasound technology and its potential clinical applications in the evaluation and treatment of patients with neurological and musculoskeletal disorders. After reviewing this article, physicians should be able to (1) list the advantages and disadvantages of ultrasound compared to other available imaging modalities; (2) describe how ultrasound machines produce images using sound waves; (3) discuss the steps necessary to acquire and optimize an ultrasound image; (4) understand the difference ultrasound appearances of tendons, nerves, muscles, ligaments, blood vessels, and bones; and (5) identify multiple applications for diagnostic and interventional musculoskeletal ultrasound. Part 2 of this 2-part article will focus on the clinical applications of musculoskeletal ultrasound in clinical practice, including the ultrasonographic appearance of normal and abnormal tissues as well as specific diagnostic and interventional applications in major body regions.

  16. Humeral Head Reconstruction With Osteochondral Allograft Transplantation.

    PubMed

    Saltzman, Bryan M; Riboh, Jonathan C; Cole, Brian J; Yanke, Adam B

    2015-09-01

    setting of large Hill-Sachs lesions due to instability-has shown significant improvements in shoulder motion and American Shoulder and Elbow Surgeons scores as far as 1 year postoperatively. Return-to-work rates and satisfaction levels are high after the intervention. Complication and reoperation rates are substantial, although it is possible that use of fresh allograft tissue may result in less resorption and necrosis. Level V, systematic review of Level IV and V studies. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  17. A biomechanical cadaveric study comparing superior capsule reconstruction using fascia lata allograft with human dermal allograft for irreparable rotator cuff tear.

    PubMed

    Mihata, Teruhisa; Bui, Christopher N H; Akeda, Masaki; Cavagnaro, Matthew A; Kuenzler, Michael; Peterson, Alexander B; McGarry, Michelle H; Itami, Yasuo; Limpisvasti, Orr; Neo, Masashi; Lee, Thay Q

    2017-12-01

    Biomechanical and clinical success of the superior capsule reconstruction (SCR) using fascia lata (FL) grafts has been reported. In the United States, human dermal (HD) allograft has been used successfully for SCRs; however, the biomechanical characteristics have not been reported. Eight cadaveric shoulders were tested in 5 conditions: (1) intact; (2) irreparable supraspinatus tear; (3) SCR using FL allograft with anterior and posterior suturing; (4) SCR using HD allograft with anterior and posterior suturing; and (5) SCR using HD allograft with posterior suturing. Rotational range of motion, superior translation, glenohumeral joint force, and subacromial contact were measured at 0°, 30°, and 60° of glenohumeral abduction in the scapular plane. Graft dimensions before and after testing were also recorded. Biomechanical parameters were compared using a repeated-measures analysis of variance with Tukey post hoc test, and graft dimensions were compared using a Student t-test (P < .05). Irreparable supraspinatus tear significantly increased superior translation, superior glenohumeral joint force, and subacromial contact pressure, which were completely restored with the SCR FL allografts. Both SCR HD allograft repairs partially restored superior translation and completely restored subacromial contact and superior glenohumeral joint force. The HD allografts significantly elongated by 15% during testing, whereas the FL allograft lengths were unchanged. Single-layered HD SCR allografts partially restored superior glenohumeral stability, whereas FL allograft SCR completely restored the superior glenohumeral stability. This may be due to the greater flexibility of the HD allograft, and the SCR procedure used was developed on the basis of FL grafts. Published by Elsevier Inc.

  18. Identification of Regulatory T Cells in Tolerated Allografts

    PubMed Central

    Graca, Luis; Cobbold, Stephen P.; Waldmann, Herman

    2002-01-01

    Induction of transplantation tolerance with certain therapeutic nondepleting monoclonal antibodies can lead to a robust state of peripheral “dominant” tolerance. Regulatory CD4+ T cells, which mediate this form of “dominant” tolerance, can be isolated from spleens of tolerant animals. To determine whether there were any extra-lymphoid sites that might harbor regulatory T cells we sought their presence in tolerated skin allografts and in normal skin. When tolerated skin grafts are retransplanted onto T cell–depleted hosts, graft-infiltrating T cells exit the graft and recolonize the new host. These colonizing T cells can be shown to contain members with regulatory function, as they can prevent nontolerant lymphocytes from rejecting fresh skin allografts, without hindrance of rejection of third party skin. Our results suggest that T cell suppression of graft rejection is an active process that operates beyond secondary lymphoid tissue, and involves the persistent presence of regulatory T cells at the site of the tolerated transplant. PMID:12070291

  19. Dual growth factor delivery from biofunctionalized allografts: Sequential VEGF and BMP-2 release to stimulate allograft remodeling.

    PubMed

    Sharmin, Farzana; McDermott, Casey; Lieberman, Jay; Sanjay, Archana; Khan, Yusuf

    2017-05-01

    Autografts have been shown to stimulate osteogenesis, osteoclastogenesis, and angiogenesis, and subsequent rapid graft incorporation. Large structural allografts, however, suffer from limited new bone formation and remodeling, both of which are directly associated with clinical failure due to non-unions, late graft fractures, and infections, making it a priority to improve large structural allograft healing. We have previously shown the osteogenic ability of a polymer-coated allograft that delivers bone morphogenetic protein-2 both in vitro and in vivo through both burst release and sustained release kinetics. In this study, we have demonstrated largely sequential delivery of bone morphogenetic protein-2 and vascular endothelial growth factor from the same coated allograft. Release data showed that loading both growth factors onto a polymeric coating with two different techniques resulted in short-term (95% release within 2 weeks) and long-term (95% release within 5 weeks) delivery kinetics. We have also demonstrated how released VEGF, traditionally associated with angiogenesis, can also provide a stimulus for allograft remodeling via resorption. Bone marrow derived mononuclear cells were co-cultured with VEGF released from the coated allograft and showed a statistically significant (p < 0.05) and dose dependent increase in the number of tartrate-resistant acid phosphatase-positive multinucleated osteoclasts. Functionality of these osteoclasts was assessed quantitatively and qualitatively by evaluating resorption pit area from both osteo-assay plates and harvested bone. Data indicated a statistically significant higher resorption area from the cells exposed to VEGF released from the allografts over controls (p < 0.05). These results indicate that by using different loading protocols temporal control can be achieved when delivering multiple growth factors from a polymer-coated allograft. Further, released VEGF can also stimulate osteoclastogenesis that may

  20. Opioid receptors and their ligands in the musculoskeletal system and relevance for pain control.

    PubMed

    Spetea, Mariana

    2013-01-01

    Interest in opioid drugs like morphine, as the oldest and most potent pain-killing agents known, has been maintained through the years. One of the most frequent chronic pain sensations people experience is associated with pathological conditions of the musculoskeletal system. Chronic musculoskeletal pain is a major health problem, and an adequate management requires understanding of both peripheral and central components, with more attention drawn to the former. Intense experimental and clinical research activities resulted in important knowledge on the mechanisms and functions of the endogenous opioid system located in the periphery. This review describes the occurrence and distribution of endogenous opioids and their receptors in the musculoskeletal system, and their role in pain control in musculoskeletal disorders, such as rheumatoid arthritis and osteoarthritis. Using different techniques, including immunohistochemistry, electron microscopy or radioimmunoassay, expression of enkephalins, dynorphin, β-endorphin, and endomorphins was demonstrated in musculoskeletal tissues of animals and humans. Localization of opioid peptides was found in synovial membrane, periosteum, bone and bone marrow, loose connective tissue, the paratenon and musculotendinous junction of the achilles tendon. Animal and human studies have also demonstrated expression of µ, δ and κ opioid receptor proteins in musculoskeletal tissues using radioligand binding assays, autoradiography, electrophysiology, immunohistochemistry and Western blotting. Opioid receptor gene expression was reported based on polymerase chain reaction and in situ hybridization techniques. Combining morphological and quantitative approaches, important evidence that the musculoskeletal apparatus is equipped with a peripheral opioid system is provided. Demonstration of the occurrence of an endogenous opioid system in bone and joint tissues represents an essential step for defining novel pharmacological strategies to

  1. Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig.

    PubMed

    De Wolf, Julien; Brieu, Mathias; Zawadzki, Christophe; Ung, Alexandre; Kipnis, Eric; Jashari, Ramadan; Hubert, Thomas; Fayoux, Pierre; Mariette, Christophe; Copin, Marie-Christine; Wurtz, Alain

    2017-08-01

    It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model. Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs. The tracheal segments were surgically denuded of their epithelium, then cryopreserved and stored in a tissue bank for 33 to 232 days. After thawing, tracheal segments stented with a silicone tube were wrapped in the omentum in 2 groups of 5 female recipients. The animals did not receive any immunosuppressive drugs. The animals were euthanized from Day 6 to Day 90 in both groups. An effective revascularization of allografts regardless of length was observed. Lymphocyte infiltrate was shown in the early postoperative period and became non-significant after 30 days. Allografts displayed high levels of neoangiogenesis and viable cartilage rings with islets of calcification. Biomechanical measurements demonstrated strain properties similar to those of a fresh tracheal segment from Day 58. Our results demonstrate the acceptability and satisfactory stiffness of epithelium-denuded cryopreserved tracheal allografts implanted in the omentum, despite the absence of immunosuppressive drugs. Since the omentum has the capability to reach the tracheal region, this approach should be investigated in the setting of orthotopic transplants in a pig model before considering clinical applications. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  2. Revision allograft reconstruction of the lateral collateral ligament complex in elbows with previous failed reconstruction and persistent posterolateral rotatory instability.

    PubMed

    Baghdadi, Yaser M K; Morrey, Bernard F; O'Driscoll, Shawn W; Steinmann, Scott P; Sanchez-Sotelo, Joaquin

    2014-07-01

    Primary reconstruction of the lateral collateral ligament complex (LCLC) using graft tissue restores elbow stability in many, but not all, elbows with acute or chronic posterolateral rotatory instability (PLRI). Revision reconstruction using a tendon allograft is occasionally considered for persistent PLRI, but the outcome of revision ligament reconstruction in this setting is largely unknown. We determined whether revision allograft ligament reconstruction can (1) restore the stability and (2) result in improved elbow scores for patients with persistent PLRI of the elbow after a previous failed primary reconstructive attempt and in the context of the diverse pathology being addressed. Between 2001 and 2011, 160 surgical elbow procedures were performed at our institution for the LCLC reconstruction using allograft tissue. Only patients undergoing revision allograft reconstruction of the LCLC for persistent PLRI with a previous failed primary reconstructive attempt using graft tissue and at least I year of followup were included in the study. Eleven patients (11 elbows) fulfilled our inclusion criteria and formed our study cohort. The cohort consisted of six female patients and five male patients. The mean age at the time of revision surgery was 36 years (range, 14-59 years). The revision allograft reconstruction was carried out after a mean of 3 years (range, 2.5 months to 9 years) from a failed attempted reconstruction of the LCLC. Osseous deficiency to some extent was identified in the preoperative radiographs of eight elbows. Mean followup was 5 years (range, 1-12 years). Revision allograft reconstruction of the LCLC restored elbow stability in eight of the 11 elbows; two of the three elbows with persistent instability were operated on a third time (at 6 and 7 months after allograft revision reconstruction). For elbows with no persistent instability, the mean Mayo Elbow Performance Score at most recent followup was 83 points (range, 60-100 points), and

  3. Does sterilization with fractionated electron beam irradiation prevent ACL tendon allograft from tissue damage?

    PubMed

    Schmidt, T; Grabau, D; Grotewohl, J H; Gohs, U; Pruß, A; Smith, M; Scheffler, S; Hoburg, A

    2017-02-01

    Allografts are frequently used for anterior cruciate ligament (ACL) reconstruction. However, due to the inherent risk of infection, a method that achieves complete sterilization of grafts is warranted without impairing their biomechanical properties. Fractionation of electron beam (FEbeam) irradiation has been shown to maintain similar biomechanical properties compared to fresh-frozen allografts (FFA) in vitro. Therefore, aim of this study was to evaluate the biomechanical properties and early remodelling of grafts that were sterilized with fractionated high-dose electron beam irradiation in an in vivo sheep model. ACL reconstruction was performed in 18 mature merino mix sheep. Sixteen were reconstructed with allografts sterilized with FEbeam irradiation (8 × 3.4 kGy) and two with FFA. Eight FFA from prior studies with identical surgical reconstruction and biomechanical and histological analyzes served as controls. Half of the animals were sacrificed at 6 and 12 weeks, and biomechanical testing was performed. Anterior-posterior laxity (APL) was assessed with an AP drawer test at 60° flexion, and load to failure testing was carried out. Histological evaluation of mid-substance samples was performed for descriptive analysis, cell count, crimp and vessel density. For statistical analysis a Kruskal-Wallis test was used for overall group comparison followed by a Mann-Whitney U test for pairwise comparison of the histological and biomechanical parameters. Biomechanical testing showed significantly decreased stiffness in FEbeam compared to FFA at both time points (p ≤ 0.004). APL was increased in FEbeam compared to FFA, which was significant at 6 weeks (p = 0.004). Median of failure loads was decreased in FEbeam grafts, with 12 reconstructions already failing during cyclic loading. Vessel density was decreased in FEbeam compared to FFA at both time points, with significant differences at 12 weeks (p = 0.015). Crimp length was significantly shorter in

  4. Rabbit Trochlear Model of Osteochondral Allograft Transplantation

    PubMed Central

    To, Nhat; Curtiss, Shane; Neu, Corey P; Salgado, Christopher J; Jamali, Amir A

    2011-01-01

    Allografting and autografting of osteochondral tissues is a promising strategy to treat articular cartilage lesions in damaged joints. We developed a new model of fresh osteochondral allografting using the entire rabbit trochlea. The objective of the current study was to demonstrate that this model would achieve reproducible graft–host healing and maintain normal articular cartilage histologic, immunolocalization, and biochemical characteristics after transplantation under diverse storage and transplantation conditions. New Zealand white (n = 8) and Dutch belted (n = 8) rabbits underwent a 2-stage transplantation operation using osteochondral grafts that had been stored for 2 or 4 wk. Trochlear grafts harvested from the left knee were transplanted to the right knee as either autografts or allografts. Grafts were fixed with 22-gauge steel wire or 3-0 nylon suture. Rabbits were euthanized for evaluation at 1, 2, 4, 6, and 12 wk after transplantation. All grafts that remained in vivo for at least 4 wk demonstrated 100% interface healing by microCT. Trabecular bridging was present at the host–graft interface starting at 2 wk after transplantation, with no significant difference in cartilage histology between the various groups. The combined histology scores indicated minimal evidence of osteoarthritis. Immunostaining revealed that superficial zone protein was localized at the surface of all transplants. The rabbit trochlear model met our criteria for a successful model in regard to the ease of the procedure, low rate of surgical complications, relatively large articular cartilage surface area, and amount of host–graft bone interface available for analysis. PMID:22330350

  5. Evaluation of the Potential Risk of Hepatitis B Virus Transmission in Skin Allografting.

    PubMed

    Wang, D; Xie, W; Chen, T; Dong, C; Zhao, C; Tan, H; Tian, H; Xie, Q

    2015-01-01

    Skin transplantation is associated with potential risk of infectious disease transmission; however, the exclusion of donors owing to hepatitis B virus (HBV) infection will worsen the shortage of allograft skin supply. We report a paired study to evaluate the potential risk of HBV transmission in skin allografting. The presence of HBV DNA in the serum and skin from 37 burn patients with chronic HBV infection (CHB) was monitored by a HBV polymerase chain reaction (PCR) and the positive rates were compared by Fisher's exact probability test. There was a high consistency in the HBV serology profile between HBV DNA PCR (83.78%) and the clinical HBV test. Only 2 patients who were positive for hepatitis B surface antigen, hepatitis B e antigen, and hepatitis B core antibody had detectable HBV DNA in the skin tissue; however, no hepatitis B surface antigen was detected as examined by immunohistochemistry staining. There was a significant difference between the positive rates of HBV DNA in the serum and skin (χc(2) = 27.03; P < .001). The potential risk for HBV transmission by skin allografting is very low. Given that China has a large population of patients with HBV, the acceptance of skin from donors with CHB to the skin bank would increase the number of tissue donations to meet the urgent medical need for skin transplantation. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. The use of a biostatic fascia lata thigh allograft as a scaffold for autologous human culture of fibroblasts--An in vitro study.

    PubMed

    Żurek, Jarek; Dominiak, Marzena; Botzenhart, Ute; Bednarz, Wojciech

    2015-05-01

    The method for covering gingival recession defects and augmenting keratinized gingiva involves the use of autogenuous connective tissue grafts obtained from palatal mucosa in combination with various techniques of flap repositioning or tunnel techniques. In the case of multiple gingival recession defects the amount of connective tissue available for grafting is insufficient. Therefore, the use of substitutes is necessary. The most widely used material in recent years has been the acellular dermal matrix allograft. The disadvantage of its application lies in the absence of cells and blood vessels, which increases incorporation time. Primary cultured human autologic fibroblasts are commonly used to optimize the healing process. The aim of this study was to examine the in vitro biocompatibility of human fascia lata allograft as a new scaffold for primary cultured human autologic fibroblasts. For that, a fibroblast culture obtained from a fragment of gingival tissue taken from the hard palate mucosa of a subject was used. After 14 days the colony cells were inoculated on a fragment of human fascia lata allograft. After a further 7 days of incubation the material was frozen, cut and prepared for histochemical examination. After two weeks of incubation, and 7 days after inoculation on a fragment of fascia lata allograft numerous accumulations of the cultured fibroblast were found that had a typical structure and produced collagen fibres. A human fascia lata allograft can be used as a scaffold for primary cultured human autologic fibroblasts. Further studies should confirm the clinical efficacy of this solution. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. Tissue-engineered collateral ligament composite allografts for scapholunate ligament reconstruction: an experimental study.

    PubMed

    Endress, Ryan; Woon, Colin Y L; Farnebo, Simon J; Behn, Anthony; Bronstein, Joel; Pham, Hung; Yan, Xinrui; Gambhir, Sanjiv S; Chang, James

    2012-08-01

    In patients with chronic scapholunate (SL) dissociation or dynamic instability, ligament repair is often not possible, and surgical reconstruction is indicated. The ideal graft ligament would recreate both anatomical and biomechanical properties of the dorsal scapholunate ligament (dorsal SLIL). The finger proximal interphalangeal joint (PIP joint) collateral ligament could possibly be a substitute ligament. We harvested human PIP joint collateral ligaments and SL ligaments from 15 cadaveric limbs. We recorded ligament length, width, and thickness, and measured the biomechanical properties (ultimate load, stiffness, and displacement to failure) of native dorsal SLIL, untreated collateral ligaments, decellularized collateral ligaments, and SL repairs with bone-collateral ligament-bone composite collateral ligament grafts. As proof of concept, we then reseeded decellularized bone-collateral ligament-bone composite grafts with green fluorescent protein-labeled adipo-derived mesenchymal stem cells and evaluated them histologically. There was no difference in ultimate load, stiffness, and displacement to failure among native dorsal SLIL, untreated and decellularized collateral ligaments, and SL repairs with tissue-engineered collateral ligament grafts. With pair-matched untreated and decellularized scaffolds, there was no difference in ultimate load or stiffness. However, decellularized ligaments revealed lower displacement to failure compared with untreated ligaments. There was no difference in displacement between decellularized ligaments and native dorsal SLIL. We successfully decellularized grafts with recently described techniques, and they could be similarly reseeded. Proximal interphalangeal joint collateral ligament-based bone-collateral ligament-bone composite allografts had biomechanical properties similar to those of native dorsal SLIL. Decellularization did not adversely affect material properties. These tissue-engineered grafts may offer surgeons another

  8. Design and optimization of a tissue-engineered bone graft substitute

    NASA Astrophysics Data System (ADS)

    Shimko, Daniel Andrew

    2004-12-01

    In 2000, 3.1 million surgical procedures on the musculoskeletal system were reported in the United States. For many of these cases, bone grafting was essential for successful fracture stabilization. Current techniques use intact bone obtained either from the patient (autograft) or a cadaver (allograft) to repair large defects, however, neither source is optimal. Allografts suffer integration problems, and for autografts, the tissue supply is limited. Because of these shortcomings, and the high demand for graft tissues, alternatives are being explored. To successfully engineer a bone graft replacement, one must employ a three pronged research approach, addressing (1) the cells that will inhabit the new tissue, (2) the culture environment that these cells will be exposed to, and (3) the scaffold in which these cells will reside. The work herein examines each of these three aspects in great detail. Both adult and embryonic stem cells (ESCs) were considered for the tissue-engineered bone graft. Both exhibited desirable qualities, however, neither were optimal in all categories examined. In the end, the possibility of teratoma formation and ethical issues surrounding ESCs, made the use of adult marrow-derived stem cells in the remaining experiments obligatory. In subsequent experiments, the adult stem cells' ability to form bone was optimized. Basic fibroblast growth factor, fetal bovine serum, and extracellular calcium supplementation studies were all performed. Ultimately, adult stem cells cultured in alpha-MEM supplemented with 10% fetal bovine serum, 10mM beta-glycerophosphate, 10nM dexamethasone, 50mug/ml ascorbic acid, 1%(v/v) antibiotic/antimycotic, and 10.4mM CaCl2 performed the best, producing nearly four times more mineral than any other medium formulation. Several scaffolds were then investigated including those fabricated from poly(alpha-hydroxy esters), tantalum, and poly-methylmethacrylate. In the final study, the most appealing cell type, medium

  9. Potential of PET-MRI for imaging of non-oncologic musculoskeletal disease.

    PubMed

    Kogan, Feliks; Fan, Audrey P; Gold, Garry E

    2016-12-01

    Early detection of musculoskeletal disease leads to improved therapies and patient outcomes, and would benefit greatly from imaging at the cellular and molecular level. As it becomes clear that assessment of multiple tissues and functional processes are often necessary to study the complex pathogenesis of musculoskeletal disorders, the role of multi-modality molecular imaging becomes increasingly important. New positron emission tomography-magnetic resonance imaging (PET-MRI) systems offer to combine high-resolution MRI with simultaneous molecular information from PET to study the multifaceted processes involved in numerous musculoskeletal disorders. In this article, we aim to outline the potential clinical utility of hybrid PET-MRI to these non-oncologic musculoskeletal diseases. We summarize current applications of PET molecular imaging in osteoarthritis (OA), rheumatoid arthritis (RA), metabolic bone diseases and neuropathic peripheral pain. Advanced MRI approaches that reveal biochemical and functional information offer complementary assessment in soft tissues. Additionally, we discuss technical considerations for hybrid PET-MR imaging including MR attenuation correction, workflow, radiation dose, and quantification.

  10. Tissue allograft coding and traceability in USM Tissue Bank, Malaysia.

    PubMed

    Sheikh Ab Hamid, Suzina; Abd Rahman, Muhamad Nor Firdaus

    2010-11-01

    In Malaysia, tissue banking activities began in Universiti Sains Malaysia (USM) Tissue Bank in early 1990s. Since then a few other bone banks have been set up in other government hospitals and institutions. However, these banks are not governed by the national authority. In addition there is no requirement set by the national regulatory authority on coding and traceability for donated human tissues for transplantation. Hence, USM Tissue Bank has taken the initiatives to adopt a system that enables the traceability of tissues between the donor, the processed tissue and the recipient based on other international standards for tissue banks. The traceability trail has been effective and the bank is certified compliance to the international standard ISO 9001:2008.

  11. Chronic Lung Allograft Dysfunction: A Systematic Review of Mechanisms.

    PubMed

    Royer, Pierre-Joseph; Olivera-Botello, Gustavo; Koutsokera, Angela; Aubert, John-David; Bernasconi, Eric; Tissot, Adrien; Pison, Christophe; Nicod, Laurent; Boissel, Jean-Pierre; Magnan, Antoine

    2016-09-01

    Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction. Because current literature suggests bronchiolitis obliterans syndrome and restrictive allograft syndrome as 2 distinct entities, we focus on the specific factors behind one or the other syndromes. Chronic lung allograft dysfunction is a multifactorial disease that remains irreversible and unpredictable so far. We thus finally discuss the potential of systems-biology approach to predict its occurrence and to better understand its underlying mechanisms.

  12. Allograft materials in phalloplasty: a comparative analysis.

    PubMed

    Solomon, Mark P; Komlo, Caroline; Defrain, Molly

    2013-09-01

    Allograft use has increased recently with the rising use of allograft materials in breast surgery. There are few data that compare the performance of the various allograft materials in this application, despite marketing efforts by the manufacturers to present one allograft material as superior to another. Phalloplasty is a procedure that uses allografts for penis girth augmentation. Preparation of these grafts differs with each manufacturer. We report our experience with 3 different types of allografts for this procedure. This allows for the comparison of these materials in their performance with a single model. Forty-seven patients who underwent penis girth enhancement with allograft material were reviewed. All patients underwent circumferential grafting to the shaft of the penis at the level of Buck's fascia. Graft materials included AlloDerm (n = 9), Belladerm (n = 20), and Repriza (n = 21). Charts were reviewed for material type, presence and type of infection, wound exposure, and graft loss with attention to the type of allograft material that was used. Follow-up ranged from 1 to 120 months with an average of 11.25 months. Infection, defined as an open wound with graft exposure, occurred in 20 (42%) of 47 patients. Of these, graft exposure only occurred in 17 (36%) patients, whereas 3 (6%) patients sustained total graft loss. Graft exposure or loss occurred in 3 patients who had AlloDerm, 9 patients with Belladerm, and 8 patients with Repriza. No patients with AlloDerm sustained graft loss, whereas 2 patients with Belladerm and 1 patient with Repriza sustained graft loss. There were no statistical differences among these graft types with regard to infection or graft loss. Three different brands of allograft material were used in 1 surgical procedure and followed up for their performance with regard to exposure and infection. In this model, there is no difference in the rate of infection in these materials despite their different methods of preparation

  13. Successful liver allografts in mice by combination with allogeneic bone marrow transplantation.

    PubMed Central

    Nakamura, T; Good, R A; Yasumizu, R; Inoue, S; Oo, M M; Hamashima, Y; Ikehara, S

    1986-01-01

    Successful liver allografts were established by combination with allogeneic bone marrow transplantation. When liver tissue of BALB/c (H-2d) or C57BL/6J (H-2b) mice was minced and grafted under the kidney capsules of C3H/HeN (H-2k) mice, it was rejected. However, when C3H/HeN mice were irradiated and reconstituted with T-cell-depleted BALB/c or BALB/c nu/nu bone marrow cells, or with fetal liver cells of BALB/c mice, they accepted both donor (stem-cell)-type (BALB/c) and host (thymus)-type (C3H/HeN) liver tissue. Assays for both mixed-lymphocyte reaction and induction of cytotoxic T lymphocytes revealed that the newly developed T cells were tolerant of both donor (stem-cell)-type and host (thymus)-type major histocompatibility complex determinants. We propose that liver allografts combined with bone marrow transplantation should be considered as a viable therapy for patients with liver disease such as liver cirrhosis and hepatoma. Images PMID:3520575

  14. The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Easterling, K.J.; Trumble, T.E.

    1990-10-01

    Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively).more » Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.« less

  15. Shear-Wave Elastography: Basic Physics and Musculoskeletal Applications

    PubMed Central

    Gimber, Lana H.; Becker, Giles W.; Latt, L. Daniel; Klauser, Andrea S.; Melville, David M.; Gao, Liang; Witte, Russell S.

    2017-01-01

    In the past 2 decades, sonoelastography has been progressively used as a tool to help evaluate soft-tissue elasticity and add to information obtained with conventional gray-scale and Doppler ultrasonographic techniques. Recently introduced on clinical scanners, shear-wave elastography (SWE) is considered to be more objective, quantitative, and reproducible than compression sonoelastography with increasing applications to the musculoskeletal system. SWE uses an acoustic radiation force pulse sequence to generate shear waves, which propagate perpendicular to the ultrasound beam, causing transient displacements. The distribution of shear-wave velocities at each pixel is directly related to the shear modulus, an absolute measure of the tissue’s elastic properties. Shear-wave images are automatically coregistered with standard B-mode images to provide quantitative color elastograms with anatomic specificity. Shear waves propagate faster through stiffer contracted tissue, as well as along the long axis of tendon and muscle. SWE has a promising role in determining the severity of disease and treatment follow-up of various musculoskeletal tissues including tendons, muscles, nerves, and ligaments. This article describes the basic ultrasound physics of SWE and its applications in the evaluation of various traumatic and pathologic conditions of the musculoskeletal system. ©RSNA, 2017 PMID:28493799

  16. Autograft versus Allograft for Cervical Spinal Fusion

    PubMed Central

    Brodke, Darrel S.; Youssef, Jim A.; Meisel, Hans-Jörg; Dettori, Joseph R.; Park, Jong-Beom; Yoon, S. Tim; Wang, Jeffrey C.

    2017-01-01

    Study Design Systematic review. Objective To compare the effectiveness and safety between iliac crest bone graft (ICBG), non-ICBG autologous bone, and allograft in cervical spine fusion. To avoid problems at the donor site, various allograft materials have been used as a substitute for autograft. However, there are still questions as to the comparative effectiveness and safety of cadaver allograft compared with autologous ICBG. Methods A systematic search of multiple major medical reference databases was conducted to identify studies evaluating spinal fusion in patients with cervical degenerative disk disease using ICBG compared with non-ICBG autograft or allograft or non-ICBG autograft compared with allograft in the cervical spine. Radiographic fusion, patient-reported outcomes, and functional outcomes were the primary outcomes of interest. Adverse events were evaluated for safety. Results The search identified 13 comparative studies that met our inclusion criteria: 2 prospective cohort studies and 11 retrospective cohort studies. Twelve cohort studies compared allograft with ICBG autograft during anterior cervical fusion and demonstrated with a low evidence level of support that there are no differences in fusion percentages, pain scores, or functional results. There was insufficient evidence comparing patients receiving allograft with non-ICBG autograft for fusion, pain, revision, and functional and safety outcomes. No publications directly comparing non-ICBG autograft with ICBG were found. Conclusion Although the available literature suggests ICBG and allograft may have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes following anterior cervical fusion, there are too many limitations in the available literature to draw any significant conclusions. No individual study provided greater than class III evidence, and when evaluating the overall body of literature, no conclusion had better than low evidence support. A prospective

  17. The Basics of Renal Allograft Pathology.

    PubMed

    Troxell, Megan L; Houghton, Donald C

    2014-09-01

    Renal allograft biopsy provides critical information in the management of renal transplant patients, and must be analyzed in close collaboration with the clinical team. The histologic correlates of acute T-cell mediated rejection are interstitial inflammation, tubulitis, and endothelialitis; polyomavirus nephropathy is a potential mimic. Evidence of antibody-mediated rejection includes C4d deposition; morphologic acute tissue injury; and donor specific antibodies. Acute tubular injury/necrosis is a reversible cause of impaired graft function, especially in the immediate post-transplant period. Drug toxicity, recurrent disease, chronic injury, and other entities affecting both native and transplant kidneys must also be evaluated. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Reducing the radiation sterilization dose improves mechanical and biological quality while retaining sterility assurance levels of bone allografts.

    PubMed

    Nguyen, Huynh; Cassady, Alan I; Bennett, Michael B; Gineyts, Evelyne; Wu, Andy; Morgan, David A F; Forwood, Mark R

    2013-11-01

    Bone allografts carry a risk of infection, so terminal sterilization by gamma irradiation at 25kGy is recommended; but is deleterious to bone quality. Contemporary bone banking significantly reduces initial allograft bioburden, questioning the need to sterilize at 25kGy. We inoculated allograft bone with Staphylococcus epidermidis and Bacillus pumilus, then exposed them to gamma irradiation at 0, 5, 10, 15, 20 and 25kGy. Mechanical and biological properties of allografts were also assessed. Our aim was to determine an optimal dose that achieves sterility assurance while minimizing deleterious effects on allograft tissue. 20-25kGy eliminated both organisms at concentrations from 10(1) to 10(3)CFU, while 10-15kGy sterilized bone samples to a bioburden concentration of 10(2)CFU. Irradiation did not generate pro-inflammatory bone surfaces, as evidenced by macrophage activation, nor did it affect attachment or proliferation of osteoblasts. At doses ≥10kGy, the toughness of cortical bone was reduced (P<0.05), and attachment and fusion of osteoclasts onto irradiated bone declined at 20 and 25kGy (P<0.05). There was no change in collagen cross-links, but a significant dose-response increase in denatured collagen (P<0.05). Our mechanical and cell biological data converge on 15kGy as a threshold for radiation sterilization of bone allografts. Between 5 and 15kGy, bone banks can undertake validation that provides allografts with an acceptable sterility assurance level, improving their strength and biocompatibility significantly. The application of radiation sterilization doses between 5 and 15kGy will improve bone allograft mechanical performance and promote integration, while retaining sterility assurance levels. Improved quality of allograft bone will promote superior clinical outcomes. © 2013.

  19. Chest wall reconstruction using iliac bone allografts and muscle flaps.

    PubMed

    Garcia-Tutor, Emilio; Yeste, Luis; Murillo, Julio; Aubá, Cristina; Sanjulian, Mikel; Torre, Wenceslao

    2004-01-01

    Technically we can divide full-thickness thoracic reconstruction into 2 parts: providing a rigid support and ensuring well-vascularized coverage. Since 1986, the authors' center has had ample experience with bone banks and the use of cryopreserved bone grafts, which led them to consider the possibility of using these grafts for full-thickness chest wall reconstruction. They describe 3 patients in whom resection of the tumor and reconstruction of the thorax were carried out using iliac bone allografts covered with muscle flaps (1 pectoralis major and 2 rectus abdominis). None of the patients experienced breathing difficulties, pain, or instability after 14 months, 18 months, and 11 years of follow-up. The result of the reconstruction was excellent in all 3 patients in terms of function and aesthetics. The advantage of allografts compared with synthetic materials is their potential integration; they can become part of the host patient's living tissue.

  20. Tanshinol suppresses cardiac allograft rejection in a murine model.

    PubMed

    Lu, Chuanjian; Zeng, Yu-Qun; Liu, Huazhen; Xie, Qingfeng; Xu, Shengmei; Tu, Kangsheng; Dou, Changwei; Dai, Zhenhua

    2017-02-01

    Achieving long-term cardiac allograft survival without continuous immunosuppression is highly desired in organ transplantation. Studies have shown that Salvia miltiorrhiza, an herb also known as danshen, improves microcirculation and is highly effective in treating coronary heart disease. Our objective is to determine whether tanshinol, an ingredient of danshen, improves cardiac allograft survival. Fully vascularized heterotopic heart transplantation was performed using BALB/c mice as donors and C57BL/6 mice as recipients, which were then treated with tanshinol and rapamycin. CD4 + FoxP3 + regulatory T cells (Tregs) were quantified by flow analyses, whereas CCL22 was measured by real-time polymerase chain reaction and Western blotting. We found that tanshinol significantly delayed cardiac allograft rejection. It promoted long-term allograft survival induced by rapamycin, a mammalian target-of-rapamycin (mTOR) inhibitor. Tanshinol increased CD4 + FoxP3 + Treg numbers in cardiac allografts, but not spleens and lymph nodes, of recipient mice by enhancing chemokine CCL22 expression in cardiac allografts, especially cardiac dendritic cells. In contrast, rapamycin increased Treg numbers in both lymphoid organs and allografts, suggesting that it generally expands Tregs. Moreover, Tregs induced by rapamycin plus tanshinol were more potent in suppressing T-cell proliferation in vitro than those from untreated recipients. Neutralizing CCL22 hindered CD4 + FoxP3 + Treg migration to cardiac allografts and reversed long-term allograft survival induced by tanshinol plus rapamycin. Tanshinol suppresses cardiac allograft rejection by recruiting CD4 + FoxP3 + Tregs to the graft, whereas rapamycin does so via expanding the Tregs. Thus, tanshinol cooperates with rapamycin to further extend cardiac allograft survival. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  1. Use of cultured human epidermal keratinocytes for allografting burns and conditions for temporary banking of the cultured allografts.

    PubMed

    Bolívar-Flores, J; Poumian, E; Marsch-Moreno, M; Montes de Oca, G; Kuri-Harcuch, W

    1990-02-01

    Five children who suffered burns clinically regarded as full skin thickness loss were grafted with cultured allogeneic skin from newborn prepuce. The wounds had remained open and infected without healing for about 20 days before the patients were received in the burn unit. To avoid losing surviving deep epidermal cells the wounds were débrided but not deeply excised and, a few days before allografting, they were washed with isodine solution and sterile water, and treated with silvadene cream application. All children received 76 cultured allografts of about 60 cm2 each. After allografting, the wounds were epithelized in 7-10 days and the allogeneic grafted skin began desquamation suggesting that the allograft did not 'take' permanently but was replaced by the newly formed skin. On the other hand, since allografting is an adequate therapy to provide early temporary coverage in extensively burned patients, we developed conditions for banking cultured skin to make it available for immediate use. The conditions described allow banking of the cultured grafts for 15-20 days with retention of clonal growth ability similar to that of unstored epithelia. The results show that cultured epidermal cells obtained from human newborn foreskin, when used as allografts for coverage of full skin or deep partial skin thickness burns, allow rapid epithelization of the burn wounds.

  2. Concurrent musculoskeletal dynamics and finite element analysis predicts altered gait patterns to reduce foot tissue loading.

    PubMed

    Halloran, Jason P; Ackermann, Marko; Erdemir, Ahmet; van den Bogert, Antonie J

    2010-10-19

    Current computational methods for simulating locomotion have primarily used muscle-driven multibody dynamics, in which neuromuscular control is optimized. Such simulations generally represent joints and soft tissue as simple kinematic or elastic elements for computational efficiency. These assumptions limit application in studies such as ligament injury or osteoarthritis, where local tissue loading must be predicted. Conversely, tissue can be simulated using the finite element method with assumed or measured boundary conditions, but this does not represent the effects of whole body dynamics and neuromuscular control. Coupling the two domains would overcome these limitations and allow prediction of movement strategies guided by tissue stresses. Here we demonstrate this concept in a gait simulation where a musculoskeletal model is coupled to a finite element representation of the foot. Predictive simulations incorporated peak plantar tissue deformation into the objective of the movement optimization, as well as terms to track normative gait data and minimize fatigue. Two optimizations were performed, first without the strain minimization term and second with the term. Convergence to realistic gait patterns was achieved with the second optimization realizing a 44% reduction in peak tissue strain energy density. The study demonstrated that it is possible to alter computationally predicted neuromuscular control to minimize tissue strain while including desired kinematic and muscular behavior. Future work should include experimental validation before application of the methodology to patient care. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration

    PubMed Central

    2014-01-01

    Background Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis. Methods Angiogenic growth factors were identified in dHACM tissues using enzyme-linked immunosorbent assays (ELISAs), and the effects of dHACM extract on human microvascular endothelial cell (HMVEC) proliferation and production of angiogenic growth factors was determined in vitro. Chemotactic migration of human umbilical vein endothelial cells (HUVECs) toward pieces of dHACM tissue was determined using a standard in vitro transwell assay. Neovascularization of dHACM in vivo was determined utilizing a murine subcutaneous implant model. Results Quantifiable levels of the angiogenic cytokines angiogenin, angiopoietin-2 (ANG-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), platelet derived growth factor BB (PDGF-BB), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were measured in dHACM. Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro. Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process. Conclusions

  4. Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration.

    PubMed

    Koob, Thomas J; Lim, Jeremy J; Massee, Michelle; Zabek, Nicole; Rennert, Robert; Gurtner, Geoffrey; Li, William W

    2014-01-01

    Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis. Angiogenic growth factors were identified in dHACM tissues using enzyme-linked immunosorbent assays (ELISAs), and the effects of dHACM extract on human microvascular endothelial cell (HMVEC) proliferation and production of angiogenic growth factors was determined in vitro. Chemotactic migration of human umbilical vein endothelial cells (HUVECs) toward pieces of dHACM tissue was determined using a standard in vitro transwell assay. Neovascularization of dHACM in vivo was determined utilizing a murine subcutaneous implant model. Quantifiable levels of the angiogenic cytokines angiogenin, angiopoietin-2 (ANG-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), platelet derived growth factor BB (PDGF-BB), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were measured in dHACM. Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro. Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process. TAKEN TOGETHER, THESE RESULTS

  5. Reliability of a semi-automated 3D-CT measuring method for tunnel diameters after anterior cruciate ligament reconstruction: A comparison between soft-tissue single-bundle allograft vs. autograft.

    PubMed

    Robbrecht, Cedric; Claes, Steven; Cromheecke, Michiel; Mahieu, Peter; Kakavelakis, Kyriakos; Victor, Jan; Bellemans, Johan; Verdonk, Peter

    2014-10-01

    Post-operative widening of tibial and/or femoral bone tunnels is a common observation after ACL reconstruction, especially with soft-tissue grafts. There are no studies comparing tunnel widening in hamstring autografts versus tibialis anterior allografts. The goal of this study was to observe the difference in tunnel widening after the use of allograft vs. autograft for ACL reconstruction, by measuring it with a novel 3-D computed tomography based method. Thirty-five ACL-deficient subjects were included, underwent anatomic single-bundle ACL reconstruction and were evaluated at one year after surgery with the use of 3-D CT imaging. Three independent observers semi-automatically delineated femoral and tibial tunnel outlines, after which a best-fit cylinder was derived and the tunnel diameter was determined. Finally, intra- and inter-observer reliability of this novel measurement protocol was defined. In femoral tunnels, the intra-observer ICC was 0.973 (95% CI: 0.922-0.991) and the inter-observer ICC was 0.992 (95% CI: 0.982-0.996). In tibial tunnels, the intra-observer ICC was 0.955 (95% CI: 0.875-0.985). The combined inter-observer ICC was 0.970 (95% CI: 0.987-0.917). Tunnel widening was significantly higher in allografts compared to autografts, in the tibial tunnels (p=0.013) as well as in the femoral tunnels (p=0.007). To our knowledge, this novel, semi-automated 3D-computed tomography image processing method has shown to yield highly reproducible results for the measurement of bone tunnel diameter and area. This series showed a significantly higher amount of tunnel widening observed in the allograft group at one-year follow-up. Level II, Prospective comparative study. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Ageing, musculoskeletal health and work

    PubMed Central

    Palmer, Keith; Goodson, Nicola

    2016-01-01

    Changing demographics mean that many patients with soft tissue rheumatism, osteoarthritis, inflammatory arthritis, large joint prostheses, and age-related co-morbidities are seeking to work beyond the traditional retirement age. In this chapter we review the evidence on musculoskeletal health and work at older ages. We conclude that musculoskeletal problems are common in older workers and have a substantial impact on their work capacity. Factors that influence their job retention are described, together with approaches that may extend working life. Many gaps in evidence were found, notably on the health risks and benefits of continued work in affected patients and on which interventions work best. The roles of physicians and managers are also considered. PMID:26612237

  7. Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

    PubMed Central

    Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

    2011-01-01

    Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

  8. IL-1 Receptor Signaling on Graft Parenchymal Cells Regulates Memory and De Novo Donor-Reactive CD8 T Cell Responses to Cardiac Allografts.

    PubMed

    Iida, Shoichi; Tsuda, Hidetoshi; Tanaka, Toshiaki; Kish, Danielle D; Abe, Toyofumi; Su, Charles A; Abe, Ryo; Tanabe, Kazunari; Valujskikh, Anna; Baldwin, William M; Fairchild, Robert L

    2016-03-15

    Reperfusion of organ allografts induces a potent inflammatory response that directs rapid memory T cell, neutrophil, and macrophage graft infiltration and their activation to express functions mediating graft tissue injury. The role of cardiac allograft IL-1 receptor (IL-1R) signaling in this early inflammation and the downstream primary alloimmune response was investigated. When compared with complete MHC-mismatched wild-type cardiac allografts, IL-1R(-/-) allografts had marked decreases in endogenous memory CD8 T cell and neutrophil infiltration and expression of proinflammatory mediators at early times after transplant, whereas endogenous memory CD4 T cell and macrophage infiltration was not decreased. IL-1R(-/-) allograft recipients also had marked decreases in de novo donor-reactive CD8, but not CD4, T cell development to IFN-γ-producing cells. CD8 T cell-mediated rejection of IL-1R(-/-) cardiac allografts took 3 wk longer than wild-type allografts. Cardiac allografts from reciprocal bone marrow reconstituted IL-1R(-/-)/wild-type chimeric donors indicated that IL-1R signaling on graft nonhematopoietic-derived, but not bone marrow-derived, cells is required for the potent donor-reactive memory and primary CD8 T cell alloimmune responses observed in response to wild-type allografts. These studies implicate IL-1R-mediated signals by allograft parenchymal cells in generating the stimuli-provoking development and elicitation of optimal alloimmune responses to the grafts. Copyright © 2016 by The American Association of Immunologists, Inc.

  9. 77 FR 51544 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-24

    ... Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the... Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel: Tissue Engineering and Regenerative.... (Catalogue of Federal Domestic Assistance Program Nos. 93.846, Arthritis, Musculoskeletal and Skin Diseases...

  10. Histomorphometric analysis after maxillary sinus floor augmentation using cancellous bone-block allograft.

    PubMed

    Chaushu, Gavriel; Vered, Marilena; Mardinger, Ofer; Nissan, Joseph

    2010-08-01

    Cancellous bone-block allografts may contribute to improved initial implant stability during sinus augmentation in cases with posterior atrophic maxillary ridge height < or =4 mm. The present study histologically and histomorphometrically evaluates the application of cancellous bone-block allografts for maxillary sinus-floor augmentation. Thirty-one consecutive patients, 16 females and 15 males (age range, 25 to 65 years; mean age: 54 +/- 9 years) underwent sinus augmentation with simultaneous implant placement with cancellous bone-block allografts. After 9 months, a second-stage surgery was performed. The previous window location was determined. A cylindrical sample core was collected. All specimens were prepared for histologic and histomorphometric examinations. Seventy-two of 76 implants were clinically osseointegrated (94.7%). All patients received a fixed implant-supported prosthesis. The mean t values of newly formed bone, residual cancellous bone-block allograft, marrow and connective tissue were 26.1% +/- 15% (range: 10% to 58%); 24.7% +/- 19.4% (range: 0.6% to 71%), and 49.2% +/- 20.4% (range: 14.9% to 78.9%), respectively. No statistically significant histomorphometric differences regarding newly formed bone were found between genders (27.02% in males versus 25.68% in females; P = 0.446), ages (29.82% in subjects < or =40 years old versus 24.43% in subjects >40 years old; P = 0.293), presence of membrane perforations (25.5% in non-perforated sinuses versus 27.3% in perforated sinuses; P = 0.427), and residual alveolar bone height (25.85% for residual alveolar bone height <2 mm versus 26.48% for residual alveolar bone height of 2 to 4 mm; P = 0.473). The cancellous bone-block allograft is biocompatible and osteoconductive and permits new bone formation in sinus augmentations with simultaneous implant-placement procedures in extremely atrophic posterior maxillae.

  11. Donation FAQs (Bone and Tissue Allografts)

    MedlinePlus

    ... about organ, tissue and eye donation in your state, visit www.donatelife.net . Is there a difference between tissue and organ donation? In order for a person to become an organ donor (kidney, heart, liver, lung), blood and oxygen must flow through the organs until the time of recovery ...

  12. Diagnostic and interventional musculoskeletal ultrasound: part 1. Fundamentals.

    PubMed

    Smith, Jay; Finnoff, Jonathan T

    2009-01-01

    Musculoskeletal ultrasound involves the use of high-frequency sound waves to image soft tissues and bony structures in the body for the purposes of diagnosing pathology or guiding real-time interventional procedures. Recently, an increasing number of physicians have integrated musculoskeletal ultrasound into their practices to facilitate patient care. Technological advancements, improved portability, and reduced costs continue to drive the proliferation of ultrasound in clinical medicine. This increased interest creates a need for education pertaining to all aspects of musculoskeletal ultrasound. The primary purpose of this article is to review diagnostic ultrasound technology and its potential clinical applications in the evaluation and treatment of patients with neurologic and musculoskeletal disorders. After reviewing this article, physicians should be able to (1) list the advantages and disadvantages of ultrasound compared with other available imaging modalities, (2) describe how ultrasound machines produce images using sound waves, (3) discuss the steps necessary to acquire and optimize an ultrasound image, (4) understand the different ultrasound appearances of tendons, nerves, muscles, ligaments, blood vessels, and bones, and (5) identify multiple applications for diagnostic and interventional musculoskeletal ultrasound in musculoskeletal practice. Part 1 of this 2-part article reviews the fundamentals of clinical ultrasonographic imaging, including relevant physics, equipment, training, image optimization, and scanning principles for diagnostic and interventional purposes.

  13. Long palatal connective tissue rolled pedicle graft with demineralized freeze-dried bone allograft plus platelet-rich fibrin combination: A novel technique for ridge augmentation - Three case reports

    PubMed Central

    Reddy, Pathakota Krishnajaneya; Bolla, Vijayalakshmi; Koppolu, Pradeep; Srujan, Peruka

    2015-01-01

    Replacement of missing maxillary anterior tooth with localized residual alveolar ridge defect is challenging, considering the high esthetic demand. Various soft and hard tissue procedures were proposed to correct alveolar ridge deformities. Novel techniques have evolved in treating these ridge defects to improve function and esthetics. In the present case reports, a novel technique using long palatal connective tissue rolled pedicle graft with demineralized freeze-dried bone allografts (DFDBAs) plus Platelet-rich fibrin (PRF) combination was proposed to correct the Class III localized anterior maxillary anterior alveolar ridge defect. The present technique resulted in predictable ridge augmentation, which can be attributed to the soft and hard tissue augmentation with a connective tissue pedicle and DFDBA plus PRF combination. This technique suggests a variation in roll technique with DFDBA plus PRF and appears to promise in gaining predictable volume in the residual ridge defect and can be considered for the treatment of moderate to severe maxillary anterior ridge defects. PMID:26015679

  14. Allograft-prosthesis composites after bone tumor resection at the proximal tibia.

    PubMed

    Biau, David Jean; Dumaine, Valérie; Babinet, Antoine; Tomeno, Bernard; Anract, Philippe

    2007-03-01

    The survival of irradiated allograft-prosthesis composites at the proximal tibia is mostly unknown. However, allograft-prosthesis composites have proved beneficial at other reconstruction sites. We presumed allograft-prosthesis composites at the proximal tibia would improve survival and facilitate reattachment of the extensor mechanism compared with that of conventional (megaprostheses) reconstructions. We retrospectively reviewed 26 patients who underwent resection of proximal tibia tumors followed by reconstruction with allo-graft-prosthesis composites. Patients received Guepar massive custom-made fully constrained prostheses. Allografts were sterilized with gamma radiation, and the stems were cemented into the allograft and host bone. The minimum followup was 6 months (median, 128 months; range, 6-195 months). Fourteen patients had one or more components removed. The median allograft-prosthesis composite survival was 102 months (95% confidence interval, 64.2-infinity). Of the 26 allografts, seven fractured, six showed signs of partial resorption, and six had infections develop. Seven allografts showed signs of fusion with the host bone. Six extensor mechanism reconstructions failed. Allograft-prosthesis composites sterilized by gamma radiation yielded poor results for proximal tibial reconstruction as complications and failures were common. We do not recommend irradiated allograft-prosthesis composites for proximal tibia reconstruction.

  15. Bacteriology testing of cardiovascular tissues: comparison of transport solution versus tissue testing.

    PubMed

    Díaz Rodríguez, R; Van Hoeck, B; Mujaj, B; Ngakam, R; Fan, Y; Bogaerts, K; Jashari, R

    2016-06-01

    Bacteriology testing is mandatory for quality control of recovered cardiovascular allografts (CVA). In this paper, two different bacteriology examinations (A tests) performed before tissue antibiotic decontamination were compared: transport solution filtration analysis (A1) and tissue fragment direct incubation (A2). For this purpose, 521 CVA (326 heart and 195 artery tissues) from 280 donors were collected and analyzed by the European Homograft Bank (EHB). Transport solution (A1) tested positive in 43.25 % of hearts and in 48.21 % of arteries, whereas the tissue samples (A2) tested positive in 38.34 % of hearts and 33.85 % of arteries. The main species identified in both A1 and A2 were Staphylococcus spp. in 55 and 26 % of cases, and Propionibacterium spp. in 8 and 19 %, respectively. Mismatches in bacteriology results between both initial tests A1 and A2 were found. 18.40 % of the heart valves were identified as positive by A1 whilst 13.50 % were considered positive by A2. For arteries, 20.51 % of cases were positive in A1 and negative in A2, and just 6.15 % of artery allografts presented contamination in the A2 test but were considered negative for the A1 test. Comparison between each A test with the B and C tests after antibiotic treatment of the allograft was also performed. A total decontamination rate of 70.8 % of initial positive A tests was obtained. Due to the described mismatches and different bacteria identification percentage, utilization of both A tests should be implemented in tissue banks in order to avoid false negatives.

  16. The genetic pleiotropy of musculoskeletal aging

    PubMed Central

    Karasik, David; Cohen-Zinder, Miri

    2012-01-01

    Musculoskeletal aging is detrimental to multiple bodily functions and starts early, probably in the fourth decade of an individual's life. Sarcopenia is a health problem that is expected to only increase as a greater portion of the population lives longer; prevalence of the related musculoskeletal diseases is similarly expected to increase. Unraveling the biological and biomechanical associations and molecular mechanisms underlying these diseases represents a formidable challenge. There are two major problems making disentangling the biological complexity of musculoskeletal aging difficult: (a) it is a systemic, rather than “compartmental,” problem, which should be approached accordingly, and (b) the aging per se is neither well defined nor reliably measurable. A unique challenge of studying any age-related condition is a need of distinguishing between the “norm” and “pathology,” which are interwoven throughout the aging organism. We argue that detecting genes with pleiotropic functions in musculoskeletal aging is needed to provide insights into the potential biological mechanisms underlying inter-individual differences insusceptibility to the musculoskeletal diseases. However, exploring pleiotropic relationships among the system's components is challenging both methodologically and conceptually. We aimed to focus on genetic aspects of the cross-talk between muscle and its “neighboring” tissues and organs (tendon, bone, and cartilage), and to explore the role of genetics to find the new molecular links between skeletal muscle and other parts of the “musculoskeleton.” Identification of significant genetic variants underlying the musculoskeletal system's aging is now possible more than ever due to the currently available advanced genomic technologies. In summary, a “holistic” genetic approach is needed to study the systems's normal functioning and the disease predisposition in order to improve musculoskeletal health. PMID:22934054

  17. Survival, recurrence, and function after epiphyseal preservation and allograft reconstruction in osteosarcoma of the knee.

    PubMed

    Aponte-Tinao, Luis; Ayerza, Miguel A; Muscolo, D Luis; Farfalli, Germán L

    2015-05-01

    Bone tumor resections for limb salvage have become the standard treatment. Recently, intercalary tumor resection with epiphyseal sparing has been used as an alternative in patients with osteosarcoma. The procedure maintains normal joint function and obviates some complications associated with osteoarticular allografts or endoprostheses; however, long-term studies analyzing oncologic outcomes are scarce, and to our knowledge, the concern that a higher local recurrence rate may be an issue has not been addressed. We wanted to assess (1) the overall survival in patients treated with this surgical technique; (2) the percentage of local recurrence and limb survival, specifically the incidence of recurrence in the remaining epiphysis; (3) the frequency of orthopaedic complications, and, (4) the functional outcomes in patients who have undergone intercalary tumor resection. We analyzed all 35 patients with osteosarcomas about the knee (distal femur and proximal tibia) treated at our center between 1991 and 2008 who had resection preserving the epiphysis and reconstruction with intercalary allografts. Minimum followup was 5 years, unless death occurred earlier (mean, 9 years; range, 1-16 years), and no patients were lost to followup. During the study period, our indications for this approach included patients without metastases, with clinical and imaging response to neoadjuvant chemotherapy, that a residual epiphysis of at least 1 cm thickness could be available after a surgical margin width in bone of 10 mm was planned, and 16% of patients (35 of 223) meeting these indications were treated using this approach. Using a chart review, we ascertained overall survival of patients, oncologic complications such as local recurrence and tumor progression, limb survival, and orthopaedic complications including infection, fracture, and nonunion. Survival rates were estimated using the Kaplan-Meier method. Patient function was evaluated using the Musculoskeletal Tumor Society (MSTS

  18. Chronic symptoms in construction workers treated for musculoskeletal injuries.

    PubMed

    Welch, L S; Hunting, K L; Nessel-Stephens, L

    1999-11-01

    Soft tissue musculoskeletal injuries make up a high proportion of all work-related injuries in construction. Data from Workers' Compensation claims indicate that strains and sprains are the leading compensable injury for construction workers. This study describes the consequences of soft tissue musculoskeletal injuries for construction workers, and assesses the persistence of symptoms after an injury and the impact of that injury on return to work. Through an Emergency Department surveillance system [Hunting et al., 1994a], we recorded 176 construction worker visits, from 5/01/93 through 2/28/95, for strains, sprains, joint injury or pain, tendinitis, dislocations, hernias, or other musculoskeletal injuries excluding fractures. Telephone interviews were conducted several months after workers had visited the emergency room for a musculoskeletal injury. Seventy individuals were interviewed about the long-term impacts of 72 incidents that had resulted in work-related musculoskeletal injuries. For 46 (62%) of the 74 diagnoses, problems continued beyond two months. The likelihood of problems continuing more than two months varied considerably by body location of injury. Hispanic workers and older workers were more likely to have continuing symptoms. Eleven of the 45 construction workers with symptoms persisting longer than two months were not employed at the time of the interview. Only 11 of the 45 workers with ongoing symptoms told us that modifications had been made to their jobs to accommodate their symptoms. About one-quarter of these 45 subjects reported substantial effects on home or work life. Acute musculoskeletal injuries in construction workers frequently result in chronic symptoms, and those with chronic symptoms report substantial effects of the injury on their quality of life. Job accommodations were made in a minority of these injuries. These findings point to the need for heightened efforts for injury prevention in this industry. Copyright 1999 Wiley

  19. Comparative immunohistologic studies in an adoptive transfer model of acute rat cardiac allograft rejection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Forbes, R.D.; Lowry, R.P.; Gomersall, M.

    1985-07-01

    It has been shown that fulminant acute rejection of rat cardiac allografts across a full haplotype disparity may occur as a direct result of adoptive transfer of sensitized W3/25+ MRC OX8- SIg- T helper/DTH syngeneic spleen cells to sublethally irradiated recipients. In order to establish the immunohistologic parameters of this form of rejection, allografts and recipient lymphoid tissue were analyzed using a panel of monoclonal antibodies of known cellular distribution. These data were compared with those obtained following reconstitution of irradiated allograft recipients with unseparated sensitized spleen cells, with unreconstituted irradiated donor recipient pairs, with unmodified first-set rejection, and withmore » induced myocardial infarction of syngeneic heart grafts transplanted to normal and to sublethally irradiated recipients. Rejecting cardiac allografts transplanted to all reconstituted irradiated recipients were characterized by extensive infiltration with MRC OX8+ (T cytotoxic-suppressor, natural killer) cells even when this subset was virtually excluded from the reconstituting inocula. A similar proportional accumulation of MRC OX8+ cells observed at the infarct margins of syngeneic heart grafts transplanted to irradiated unreconstituted recipients greatly exceeded that present in normal nonirradiated controls. These data provide evidence that under conditions of heavy recipient irradiation, MRC OX8+ cells may be sequestered within heart grafts in response to nonspecific injury unrelated to the rejection process.« less

  20. [Focused musculoskeletal sonography].

    PubMed

    Horn, Rudolf

    2015-09-16

    Even in emergent situations, focused musculoskeletal sonography must not be overlooked. It has a place in traumatology no less valuable than its place in internal medicine. It can be used to identify traumatic joint effusions, occult fractures and fissures, joint inflammation, muscle and tendon rupture; it can differentiate soft tissue swelling, locate a foreign body, or identify the location of fractures. Focused ultrasound should be performed by the attending physician directly at the patient’s bedside, in order to answer these specific questions.

  1. Interleukin (IL)-1 Receptor Signaling on Graft Parenchymal Cells Regulates Memory and De Novo Donor-Reactive CD8 T Cell Responses to Cardiac Allografts1

    PubMed Central

    Iida, Shoichi; Tsuda, Hidetoshi; Tanaka, Toshiaki; Kish, Danielle D.; Abe, Toyofumi; Su, Charles A.; Abe, Ryo; Tanabe, Kazunari; Valujskikh, Anna; Baldwin, William M.; Fairchild, Robert L.

    2016-01-01

    Reperfusion of organ allografts induces a potent inflammatory response that directs rapid memory T cell, neutrophil and macrophage graft infiltration and their activation to express functions mediating graft tissue injury. The role of cardiac allograft IL-1 receptor signaling in this early inflammation and the downstream primary alloimmune response was investigated. When compared to complete MHC-mismatched wild type cardiac allografts, IL-1R−/− allografts had marked decreases in endogenous memory CD8 T cell and neutrophil infiltration and expression of proinflammatory mediators at early times after transplant whereas endogenous memory CD4 T cell and macrophage infiltration was not decreased. IL-1R−/− allograft recipients also had marked decreases in de novo donor-reactive CD8, but not CD4, T cell development to IFN-γ-producing cells. CD8 T cell-mediated rejection of IL-1R−/− cardiac allografts took 3 weeks longer than wild type allografts. Cardiac allografts from reciprocal bone marrow reconstituted IL-1R−/−/wild type chimeric donors indicated that IL-1R signaling on graft non-hematopoietic-derived, but not bone marrow-derived, cells is required for the potent donor-reactive memory and primary CD8 T cell alloimmune responses observed in response to wild type allografts. These studies implicate IL-1R-mediated signals by allograft parenchymal cells in generating the stimuli provoking development and elicitation of optimal alloimmune responses to the grafts. PMID:26856697

  2. Choosing the right diagnostic imaging modality in musculoskeletal diagnosis.

    PubMed

    Aagesen, Andrea L; Melek, Maged

    2013-12-01

    Radiological studies can confirm or rule out competing diagnoses for musculoskeletal injuries and pain. Obtaining a detailed history and physical examination is pivotal for localizing the pain generator and choosing the most appropriate imaging studies, based on the suspected injured tissue. Judicious use of imaging is important to avoid unnecessary radiation exposure, minimize cost, and avoid therapy targeting asymptomatic imaging abnormalities. This article compares and contrasts the diagnostic imaging commonly used for detecting musculoskeletal injuries. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes

    PubMed Central

    Naesens, Maarten; Khatri, Purvesh; Li, Li; Sigdel, Tara K.; Vitalone, Matthew J.; Chen, Rong; Butte, Atul J.; Salvatierra, Oscar; Sarwal, Minnie M.

    2015-01-01

    The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy. PMID:21881554

  4. Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes.

    PubMed

    Naesens, Maarten; Khatri, Purvesh; Li, Li; Sigdel, Tara K; Vitalone, Matthew J; Chen, Rong; Butte, Atul J; Salvatierra, Oscar; Sarwal, Minnie M

    2011-12-01

    The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy.

  5. Photochemical tissue bonding

    DOEpatents

    Redmond, Robert W [Brookline, MA; Kochevar, Irene E [Charlestown, MA

    2012-01-10

    Photochemical tissue bonding methods include the application of a photosensitizer to a tissue and/or tissue graft, followed by irradiation with electromagnetic energy to produce a tissue seal. The methods are useful for tissue adhesion, such as in wound closure, tissue grafting, skin grafting, musculoskeletal tissue repair, ligament or tendon repair and corneal repair.

  6. Effects of mechanical ventilation on gene expression profiles in renal allografts from brain dead rats.

    PubMed

    Hottenrott, Maximilia C; Krebs, Joerg; Pelosi, Paolo; Luecke, Thomas; Rocco, Patricia R M; Sticht, Carsten; Breedijk, Annette; Yard, Benito; Tsagogiorgas, Charalambos

    2017-12-01

    Pathophysiological changes of brain death (BD) are impairing distal organ function and harming potential renal allografts. Whether ventilation strategies influence the quality of renal allografts from BD donors has not been thoroughly studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no brain death (NBD) with low tidal volume/low positive endexpiratory pressure (PEEP) titrated to minimal static elastance of the respiratory system (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. We hypothesized that HVT/LPEEP in BD leads to increased interleukin 6 (IL-6) gene expression and impairs potential renal allografts after six hours of mechanical ventilation. We assessed inflammatory cytokines in serum, genome wide gene expression profiles and quantitative PCR (qPCR) in kidney tissue. The influence of BD on renal gene-expression profiles was greater than the influence of the ventilation strategy. In BD, LVT ventilation did not influence the inflammatory parameters or kidney function in our experimental model. Copyright © 2017. Published by Elsevier B.V.

  7. Bone allograft banking in South Australia.

    PubMed

    Campbell, D G; Oakeshott, R D

    1995-12-01

    The South Australian Bone Bank had expanded to meet an increased demand for allograft bone. During a 5 year period from 1988 to 1992, 2361 allografts were harvested from 2146 living donors and 30 cadaveric donors. The allografts were screened by contemporary banking techniques which include a social history, donor serum tests for HIV-1, HIV-2, hepatitis B and C, syphilis serology, graft microbiology and histology. Grafts were irradiated with 25 kGy. The majority of grafts were used for arthroplasty or spinal surgery and 99 were used for tumour reconstruction. Of the donated grafts 336 were rejected by the bank. One donor was HIV-positive and two had false positive screens. There were seven donors with positive serology for hepatitis B, eight for hepatitis C and nine for syphilis. Twenty-seven grafts had positive cultures. Bone transplantation is the most frequent non-haematogenous allograft in South Australia and probably nationally. The low incidence of infectious viral disease in the donor population combined with an aggressive discard policy has ensured relative safety of the grafts. The frequency of graft rejection was similar to other bone banks but the incidence of HIV was lower.

  8. Anterior cruciate ligament allograft transplantation in dogs.

    PubMed

    Vasseur, P B; Stevenson, S; Gregory, C R; Rodrigo, J J; Pauli, S; Heitter, D; Sharkey, N

    1991-08-01

    The biomechanical and clinical performance of bone-ligament-bone anterior cruciate ligament (ACL) allografts was studied in eight dogs. Allografts were collected from skeletally mature, healthy dogs using aseptic technique, and stored at -70 degrees for three to five weeks before implantation. The allografts were size-matched to the recipient dogs using ACL length and then rigidly fixed in position with interference screws and Kirschner wires. Three dogs regained a normal gait, and their grafts sustained breaking loads that were 25%, 41%, and 59% of controls. Partial or complete graft failure occurred in the other five dogs at some point in the study. Four had intraligamentous rupture and one had an avulsion fracture of the femoral attachment site. Joint-fluid cytology was normal in all eight dogs. Histologic examination showed persistent lymphoplasmacytic infiltrate. Eventually the allograft cores were incorporated in the host bed. Hyperplasia and fibrosis of the synovial membrane were diffuse and persisted as focal accumulations of mononuclear inflammatory cells.

  9. Surgical technique and clinical results for scapular allograft reconstruction following resection of scapular tumors.

    PubMed

    Zhang, Kaiwei; Duan, Hong; Xiang, Zhou; Tu, Chongqi

    2009-04-01

    Progress in developing effective surgical techniques, such as scapular allograft reconstruction, enhance shoulder stability and extremity function, in patients following scapular tumor resection. Case details from seven patients who underwent scapular allograft reconstruction following scapular tumor resection were reviewed. A wide marginal resection (partial scapulectomy) was performed in all patients and all affected soft tissues were resected to achieve a clean surgical margin. The glenoid-resected and glenoid-saved reconstructions were performed in three and four patients, respectively. The residual host scapula were fixed to the size-matched scapular allografts with plates and screws. The rotator cuff was affected frequently and was mostly resected. The deltoid and articular capsule were infrequently involved, but reconstructed preferentially. The remaining muscles were reattached to the allografts. The median follow-up was 26 months (range, 14-50 months). The average function scores were 24 points (80%) according to the International Society of Limb Salvage criteria. The range of active shoulder abduction and forward flexion motion were 40 degrees -110 degrees and 30 degrees -90 degrees, respectively. There was no difference between the glenoid-saved and glenoid-resected reconstructions in the total scores (mean, 24.5 points/81% versus 24 points/79%), but the glenoid-saved procedure was superior to the later in terms of abduction/flexion motion (mean, 72 degrees /61 degrees versus 55 degrees /43 degrees). During the study follow-up period, one patient died following a relapse, one patient lived despite of local recurrence, and five patients survived with no evidence of recurrence of the original cancer. Post-surgical complications such as shoulder dislocations, non-unions, and articular degeneration were not noted during this study period. Scapular allograft reconstruction had a satisfactory functional, cosmetic, and oncological outcome in this case series

  10. Surgical technique and clinical results for scapular allograft reconstruction following resection of scapular tumors

    PubMed Central

    Zhang, Kaiwei; Duan, Hong; Xiang, Zhou; Tu, Chongqi

    2009-01-01

    Background Progress in developing effective surgical techniques, such as scapular allograft reconstruction, enhance shoulder stability and extremity function, in patients following scapular tumor resection. Methods Case details from seven patients who underwent scapular allograft reconstruction following scapular tumor resection were reviewed. A wide marginal resection (partial scapulectomy) was performed in all patients and all affected soft tissues were resected to achieve a clean surgical margin. The glenoid-resected and glenoid-saved reconstructions were performed in three and four patients, respectively. The residual host scapula were fixed to the size-matched scapular allografts with plates and screws. The rotator cuff was affected frequently and was mostly resected. The deltoid and articular capsule were infrequently involved, but reconstructed preferentially. The remaining muscles were reattached to the allografts. Results The median follow-up was 26 months (range, 14–50 months). The average function scores were 24 points (80%) according to the International Society of Limb Salvage criteria. The range of active shoulder abduction and forward flexion motion were 40°–110° and 30°–90°, respectively. There was no difference between the glenoid-saved and glenoid-resected reconstructions in the total scores (mean, 24.5 points/81% versus 24 points/79%), but the glenoid-saved procedure was superior to the later in terms of abduction/flexion motion (mean, 72°/61° versus 55°/43°). During the study follow-up period, one patient died following a relapse, one patient lived despite of local recurrence, and five patients survived with no evidence of recurrence of the original cancer. Post-surgical complications such as shoulder dislocations, non-unions, and articular degeneration were not noted during this study period. Conclusion Scapular allograft reconstruction had a satisfactory functional, cosmetic, and oncological outcome in this case series

  11. Unique molecular changes in kidney allografts after simultaneous liver-kidney compared with solitary kidney transplantation.

    PubMed

    Taner, Timucin; Park, Walter D; Stegall, Mark D

    2017-05-01

    Kidney allografts transplanted simultaneously with liver allografts from the same donor are known to be immunologically privileged. This is especially evident in recipients with high levels of donor-specific anti-HLA antibodies. Here we investigated the mechanisms of liver's protective impact using gene expression in the kidney allograft. Select solitary kidney transplant or simultaneous liver-kidney transplant recipients were retrospectively reviewed and separated into four groups: 16 cross-match negative kidney transplants, 15 cross-match positive kidney transplants, 12 cross-match negative simultaneous liver-kidney transplants, and nine cross-match-positive simultaneous liver-kidney transplants. Surveillance biopsies of cross-match-positive kidney transplants had increased expression of genes associated with donor-specific antigens, inflammation, and endothelial cell activation compared to cross-match-negative kidney transplants. These changes were not found in cross-match-positive simultaneous liver-kidney transplant biopsies when compared to cross-match-negative simultaneous liver-kidney transplants. In addition, simultaneously transplanting a liver markedly increased renal expression of genes associated with tissue integrity/metabolism, regardless of the cross-match status. While the expression of inflammatory gene sets in cross-match-positive simultaneous liver-kidney transplants was not completely reduced to the level of cross-match-negative kidney transplants, the downstream effects of donor-specific anti-HLA antibodies were blocked. Thus, simultaneous liver-kidney transplants can have a profound impact on the kidney allograft, not only by decreasing inflammation and avoiding endothelial cell activation in cross-match-positive recipients, but also by increasing processes associated with tissue integrity/metabolism by unknown mechanisms. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  12. Tendon allograft sterilized by peracetic acid/ethanol combined with gamma irradiation.

    PubMed

    Zhou, Mo; Zhang, Naili; Liu, Xiaoming; Li, Youchen; Zhang, Yumin; Wang, Xusheng; Li, Baoming; Li, Baoxing

    2014-07-01

    Research and clinical applications have demonstrated that the effects of tendon allografts are comparable to those of autografts when reconstructing injured tendons or ligaments, but allograft safety remains problematic. Sterilisation could eliminate or decrease the possibility of disease transmission, but current methods seldom achieve satisfactory sterilisation without affecting the mechanical properties of the tendon. Peracetic acid-ethanol in combination with low-dose gamma irradiation (PE-R) would inactivate potential deleterious microorganisms without affecting mechanical and biocompatible properties of tendon allograft. Controlled laboratory design. HIV, PPV, PRV and BVDV inactivation was evaluated. After verifying viral inactivation, the treated tendon allografts were characterised by optical microscopy, scanning electron microscopy and tensile testing, and the cytocompatibility was assessed with an MTT assay and by subcutaneous implantation. Effective and efficient inactivation of HIV, PPV, PRV and BVDV was observed. Histological structure and ultrastructure were unchanged in the treated tendon allograft, which also exhibited comparable biomechanical properties and good biocompatibility. The preliminary results confirmed our hypothesis and demonstrated that the PE-R tendon allograft has significant potential as an alternative to ligament/tendon reconstruction. Tendon allografts have been extensively used in ligament reconstruction and tendon repair. However, current sterilisation methods have various shortcomings, so PE-R has been proposed. This study suggests that PE-R tendon allograft has great potential as an alternative for ligament/tendon reconstruction. Sterilisation has been a great concern for tendon allografts. However, most sterilisation methods cannot inactivate viruses and bacteria without impairing the mechanical properties of the tendon allograft. Peracetic acid/ethanol with gamma irradiation can effectively inactivate viruses and bacteria

  13. Clinical and biometrical evaluation of socket preservation using demineralized freeze-dried bone allograft with and without the palatal connective tissue as a biologic membrane.

    PubMed

    Moghaddas, Hamid; Amjadi, Mohammad Reza; Naghsh, Narges

    2012-11-01

    Alveolar ridge preservation following tooth extraction has the ability to maintain the ridge dimensions and allow the implant placement in an ideal position fulfilling both functional and aesthetic results. The aim of this study was to evaluate the efficacy of the palatal connective tissue as a biological membrane for socket preservation with demineralized freeze-dried bone allograft (DFDBA). Twelve extraction sites were treated with DFDBA with (case group) and without (control group) using autogenous palatal connective tissue membrane before placement of implants. Alveolar width and height, amount of keratinized tissue, and gingival level were measured at pre-determined points using a surgical stent at two times, the time of socket preservation surgery. In both groups a decrease in all socket dimensions was found. The average decrease in socket width, height, keratinized tissue, and gingival level in case group was 1.16, 0.72, 3.58, and 1.27 mm, and in control group was 2.08, 0.86, 4.52, and 1.58 mm respectively. Statistical analysis showed that decrease in socket width (P = 0.012), keratinized tissue (P ≤ 0.001), and gingival level (P = 0.031) in case group was significantly lower than that of the control group. Results showed no meaningful difference in socket height changes when compared with case and control groups (P = 0.148). Under the limits of this study, connective tissue membrane could preserve socket width, amount of keratinized tissue, and the gingival level more effectively than DFDBA alone.

  14. The influence of vascularization of transplanted processed allograft nerve on return of motor function in rats.

    PubMed

    Giusti, Guilherme; Lee, Joo-Yup; Kremer, Thomas; Friedrich, Patricia; Bishop, Allen T; Shin, Alexander Y

    2016-02-01

    Processed nerve allografts have become an alternative to repair segmental nerve defects, with results comparable with autografts regarding sensory recovery; however, they have failed to reproduce comparable motor recovery. The purpose of this study was to determine how revascularizaton of processed nerve allograft would affect motor recovery. Eighty-eight rats were divided in four groups of 22 animals each. A unilateral 10-mm sciatic nerve defect was repaired with allograft (group I), allograft wrapped with silicone conduit (group II), allograft augmented with vascular endothelial growth factor (group III), or autograft (group IV). Eight animals from each group were sacrificed at 3 days, and the remaining animals at 16 weeks. Revascularization was evaluated by measuring the graft capillary density at 3 days and 16 weeks. Measurements of ankle contracture, compound muscle action potential, tibialis anterior muscle weight and force, and nerve histomorphometry were performed at 16 weeks. All results were normalized to the contralateral side. The results of capillary density at 3 days were 0.99% ± 1.3% for group I, 0.33% ± 0.6% for group II, 0.05% ± 0.1% for group III, and 75.6% ± 45.7% for group IV. At 16 weeks, the results were 69.9% ± 22.4% for group I, 37.0% ± 16.6% for group II, 84.6% ± 46.6% for group III, and 108.3% ± 46.8% for group IV. The results of muscle force were 47.5% ± 14.4% for group I, 21.7% ± 13.5% for group II, 47.1% ± 7.9% for group III, and 54.4% ± 10.6% for group IV. The use of vascular endothelial growth factor in the fashion used in this study improved neither the nerve allograft short-term revascularization nor the functional motor recovery after 16 weeks. Blocking allograft vascularization from surrounding tissues was detrimental for motor recovery. The processed nerve allografts used in this study showed similar functional motor recovery compared with that of the autograft. © 2014

  15. Evaluation of Copper and Hydrogen Peroxide Treatments on the Biology, Biomechanics, and Cytotoxicity of Decellularized Dermal Allografts.

    PubMed

    Leow-Dyke, Sophie F; Rooney, Paul; Kearney, John N

    2016-03-01

    Decellularized tissue allografts are paving the way as an alternative to cellular tissue transplantation. Effective sterilization or decontamination of tissue allografts is paramount for the safety of the allograft; however, some of the current sterilization procedures have a detrimental effect on the tissue scaffold. The bactericidal and virucidal activity of copper (II) ions and hydrogen peroxide (H2O2) have been widely reported, however, their effect on the biology, biochemistry, and biocompatibility of decellularized tissue have yet to be elucidated. In this study, decellularized human dermis (dCELL human dermis) was treated with copper (II) chloride (CuCl2) and H2O2; both singly and in combination, and parameters, including concentration, pH, and synergy between CuCl2 and H2O2, were evaluated to identify conditions where any detrimental effects on the tissue scaffold were observed. Skin from 13 human donors was retrieved with appropriate consent and processed into dCELL human dermis. The dCELL human dermis was then treated for 3 h with 0.1 mg/L-1 g/L (w/v) CuCl2 and 0.01-7.5% (v/v) H2O2 and combinations of both of these in the same concentration range. dCELL human dermis treated with solutions of 0.1 mg/L-1 g/L CuCl2 or 0.01-7.5% H2O2 caused no detrimental effects on gross histology, collagen denaturation, collagen orientation, and biomechanical properties of the tissue or cytotoxicity. The highest combined concentration of CuCl2 and H2O2 demonstrated an increase in ultimate tensile strength, loss of collagen type IV immunostaining at the dermal-epidermal junction, and in vitro cytotoxicity. Combinations within the range of up to 10 mg/L CuCl2 with up to 0.5% H2O2 had no effect. The data identify the concentrations of CuCl2 and H2O2 solutions that have no effect on the biological, biomechanical, and biochemical properties of dCELL human dermis, while retaining biocompatibility. These treatments may be suitable for use as sterilization

  16. A Small Molecule β2 Integrin Agonist Improves Chronic Kidney Allograft Survival by Reducing Leukocyte Recruitment and Accompanying Vasculopathy

    PubMed Central

    Khan, Samia Q.; Guo, Lingling; Cimbaluk, David J.; Elshabrawy, Hatem; Faridi, Mohd Hafeez; Jolly, Meenakshi; George, James F.; Agarwal, Anupam; Gupta, Vineet

    2014-01-01

    Kidney allograft rejection is associated with infiltration of inflammatory CD11b+ leukocytes. A CD11b agonist leukadherin-1 (LA1) increases leukocyte adhesion, preventing their transmigration and tissue recruitment in vivo. Here, we test the extent to which LA1-mediated activation of CD11b/CD18 enhances kidney allograft survival in a mouse model of fully MHC-mismatched orthotopic kidney transplantation, where C57BL/6J (H-2b) recipients received kidney allografts from Balb/c mice (H-2d). Isograft control recipients received a kidney from a littermate. Control isograft and allograft recipients were treated daily with cyclosporine (CsA) for 2 weeks, while the test group received CsA therapy and daily LA1 injections during week 1 and alternate days during weeks 2–8. LA1 treatment reduced interstitial leukocyte infiltration in the allograft, reduced neointimal hyperplasia and glomerular damage, and prolonged graft survival from 48.5% (CsA only) to 100% (CsA and LA1) on day 60. Serum creatinine levels showed significantly improved kidney function in LA1-treated mice compared to CsA-treated allograft controls [0.52 ± 0.18 mg/dL vs 0.24 ± 0.07 mg/dL (n = 5), respectively]. Furthermore, combination therapy reduced macrophage infiltration and increased the frequency of FoxP3 + Tregs in the allograft. These findings indicate a crucial role for CD11b/CD18 in the control of leukocyte migration to the transplanted kidney and identify integrin agonist LA1 as a novel potential therapeutic agent for kidney transplantation. PMID:25593918

  17. Physiology of ageing of the musculoskeletal system.

    PubMed

    Boros, Katalin; Freemont, Tony

    2017-04-01

    This review aims to provide a summary of current concepts of ageing in relation to the musculoskeletal system, highlighting recent advances in the understanding of the mechanisms involved in the development of age-related changes in bone, skeletal muscle, chondroid and fibrous tissues. The key components of the musculoskeletal system and their functions are introduced together with a general overview of the molecular hallmarks of ageing. A brief description of the normal architecture of each of these tissue types is followed by a summary of established and developing concepts of mechanisms contributing to the age-related alterations in each. Extensive detailed description of these changes is beyond the scope of this review; instead, we aim to highlight some of the most significant processes and, where possible, the molecular changes underlying these and refer the reader to in-depth, subspecialist reviews of the individual components for further details. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  18. Cryopreserved Cadaveric Arterial Allograft for Arterial Reconstruction in Patients with Prosthetic Infection.

    PubMed

    Lejay, Anne; Delay, Charline; Girsowicz, Elie; Chenesseau, Bettina; Bonnin, Emilie; Ghariani, Mohamed-Zied; Thaveau, Fabien; Georg, Yannick; Geny, Bernard; Chakfe, Nabil

    2017-11-01

    The aim of this study was to report outcomes of cryopreserved arterial allografts used as a vascular substitute in the setting of prosthetic material infection. A retrospective analysis of prospectively collected data was conducted including all consecutive interventions performed with cryopreserved arterial allografts used for vascular reconstruction in the setting of prosthetic material infection between January 2005 and December 2014. Five year outcomes included allograft related re-interventions, survival, primary patency, and limb salvage rates. Fifty-three procedures were performed using cryopreserved allografts for vascular prosthetic infection: 25 procedures (47%) were performed at aorto-iliac level (Group 1) and 28 procedures (53%) at peripheral level (Group 2). The mean follow-up was 52 months. Five year allograft related re-intervention was 55% in Group 1 (6 allograft ruptures and 5 allograft aneurysm degenerations) and 33% in Group 2 (2 allograft ruptures and 7 allograft aneurysm degenerations). Five year survival was 40% and 68%, primary patency was 89% and 59% and limb salvage was 100% and 89% for Group 1 and 2 respectively. Use of cryopreserved arterial allografts provides acceptable results but is tempered by suboptimal 5 year outcomes with high re-intervention rates. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  19. Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation.

    PubMed

    Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy; Botchwey, Edward

    2012-03-01

    Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm(3), respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

  20. Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation

    PubMed Central

    Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy

    2012-01-01

    Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 µg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm3, respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls. PMID:21863314

  1. Serum Uromodulin: A Biomarker of Long-Term Kidney Allograft Failure.

    PubMed

    Bostom, Andrew; Steubl, Dominik; Garimella, Pranav S; Franceschini, Nora; Roberts, Mary B; Pasch, Andreas; Ix, Joachim H; Tuttle, Katherine R; Ivanova, Anastasia; Shireman, Theresa; Kim, S Joseph; Gohh, Reginald; Weiner, Daniel E; Levey, Andrew S; Hsu, Chi-Yuan; Kusek, John W; Eaton, Charles B

    2018-01-01

    Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center -European study involving 91 kidney transplant recipients (KTRs). The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, n = 433), and all individuals who developed kidney allograft failure (cases, n = 226) during follow-up. Serum uromodulin was determined in this total of n = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome. The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05-5.01]). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06-3.77). Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs. © 2018 S. Karger AG, Basel.

  2. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras

    PubMed Central

    Das, Anusuya; Segar, Claire E.; Chu, Yihsuan; Wang, Tiffany W.; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C.; Cui, Quanjun; Botchwey, Edward A.

    2015-01-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. PMID:26125501

  3. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

    PubMed

    Das, Anusuya; Segar, Claire E; Chu, Yihsuan; Wang, Tiffany W; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C; Cui, Quanjun; Botchwey, Edward A

    2015-09-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Immunological and inflammatory mapping of vascularized composite allograft rejection processes in a rat model

    PubMed Central

    Friedman, Or; Carmel, Narin; Sela, Meirav; Abu Jabal, Ameen; Inbal, Amir; Ben Hamou, Moshe; Krelin, Yakov; Gur, Eyal

    2017-01-01

    Background Hand and face vascularized composite allotransplantation (VCA) is an evolving and challenging field with great opportunities. During VCA, massive surgical damage is inflicted on both donor and recipient tissues, which may contribute to the high VCA rejection rates. To segregate between the damage-induced and rejection phase of post-VCA responses, we compared responses occurring up to 5 days following syngeneic versus allogeneic vascularized groin flap transplantations, culminating in transplant acceptance or rejection, respectively. Methods The immune response elicited upon transplantation of a syngeneic versus allogeneic vascularized groin flap was compared at Post-operative days 2 or 5 by histology, immunohistochemistry and by broad-scope gene and protein analyses using quantitative real-time PCR and Multiplex respectively. Results Immune cell infiltration began at the donor-recipient interface and paralleled expression of a large group of wound healing-associated genes in both allografts and syngrafts. By day 5 post-transplantation, cell infiltration spread over the entire allograft but remained confined to the wound site in the syngraft. This shift correlated with upregulation of IL-18, INFg, CXCL9, 10 and 11, CCL2, CCL5, CX3CL1 and IL-10 in the allograft only, suggesting their role in the induction of the anti-alloantigen adaptive immune response. Conclusions High resemblance between the cues governing VCA and solid organ rejection was observed. Despite this high resemblance we describe also, for the first time, a damage induced inflammatory component in VCA rejection as immune cell infiltration into the graft initiated at the surgical damage site spreading to the entire allograft only at late stage rejection. We speculate that the highly inflammatory setting created by the unique surgical damage during VCA may enhance acute allograft rejection. PMID:28746417

  5. A target field design of open multi-purpose RF coil for musculoskeletal MR imaging at 3T.

    PubMed

    Gao, Fei; Zhang, Rui; Zhou, Diange; Wang, Xiaoying; Huang, Kefu; Zhang, Jue

    2016-10-01

    Musculoskeletal MR imaging under multi-angle situations plays an increasingly important role in assessing joint and muscle tissues system. However, there are still limitations due to the closed structures of most conventional RF coils. In this study, a time-harmonic target-field method was employed to design open multi-purpose coil (OMC) for multi-angle musculoskeletal MR imaging. The phantom imaging results suggested that the proposed OMC could achieve homogeneously distributed magnetic field and high signal-to-noise ratio (SNR) of 239.04±0.83 in the region of interest (ROI). The maximum temperature in the heating hazard test was 16°C lower than the standard regulation, which indicated the security of the designed OMC. Furthermore, to demonstrate the effectiveness of the proposed OMC for musculoskeletal MR imaging, especially for multi-angle imaging, a healthy volunteer was examined for MR imaging of elbow, ankle and knee using OMC. The in vivo imaging results showed that the proposed OMC is effective for MR imaging of musculoskeletal tissues at different body parts, with satisfied B1 field homogeneity and SNR. Moreover, the open structure of the OMC could provide a large joint movement region. The proposed open multi-purpose coil is feasible for musculoskeletal MR imaging, and potentially, it is more suitable for the evaluation of musculoskeletal tissues under multi-angle conditions. Copyright © 2016. Published by Elsevier Inc.

  6. Host-Pathogen Interactions and Chronic Lung Allograft Dysfunction.

    PubMed

    Belperio, John; Palmer, Scott M; Weigt, S Sam

    2017-09-01

    Lung transplantation is now considered to be a therapeutic option for patients with advanced-stage lung diseases. Unfortunately, due to post-transplant complications, both infectious and noninfectious, it is only a treatment and not a cure. Infections (e.g., bacterial, viral, and fungal) in the immunosuppressed lung transplant recipient are a common cause of mortality post transplant. Infections have more recently been explored as factors contributing to the risk of chronic lung allograft dysfunction (CLAD). Each major class of infection-(1) bacterial (Staphylococcus aureus and Pseudomonas aeruginosa); (2) viral (cytomegalovirus and community-acquired respiratory viruses); and (3) fungal (Aspergillus)-has been associated with the development of CLAD. Mechanistically, the microbe seems to be interacting with the allograft cells, stimulating the induction of chemokines, which recruit recipient leukocytes to the graft. The recipient leukocyte interactions with the microbe further up-regulate chemokines, amplifying the influx of allograft-infiltrating mononuclear cells. These events can promote recipient leukocytes to interact with the allograft, triggering an alloresponse and graft dysfunction. Overall, interactions between the microbe-allograft-host immune system alters chemokine production, which, in part, plays a role in the pathobiology of CLAD and mortality due to CLAD.

  7. [The use of structural proximal tibial allografts coated with human albumin in treating extensive periprosthetic knee-joint bone deficiency and averting late complications. Case report].

    PubMed

    Klára, Tamás; Csönge, Lajos; Janositz, Gábor; Pap, Károly; Lacza, Zsombor

    2015-01-11

    The authors report the history of a 74-year-old patient who underwent surgical treatment for segmental knee-joint periprosthetic bone loss using structural proximal tibial allografts coated with serum albumin. Successful treatment of late complications which occurred in the postoperative period is also described. The authors emphasize that bone replacement with allografts is a physiological process that enables the stable positioning of the implant and the reconstruction of the soft tissues, the replacement of extensive bone loss, and also it is a less expensive operation. It has been already confirmed that treatment of lyophilised allografts with albumin improves the ability of bone marrow-derived mesenchymal stem cells to adhere and proliferate the surface of the allografts, penetrate the pores and reach deeper layers of the graft. Earlier studies have shown osteoblast activity on the surface and interior of the graft.

  8. Multiparity activates interferon pathways in peritoneal adipose tissue and decreases susceptibility to ovarian cancer metastasis in a murine allograft model.

    PubMed

    Loughran, Elizabeth A; Phan, Ryan C; Leonard, Annemarie K; Tarwater, Laura; Asem, Marwa; Liu, Yueying; Yang, Jing; Klymenko, Yuliya; Johnson, Jeff; Shi, Zonggao; Hilliard, Tyvette S; Blumenthaler, Marielle; Leevy, Matthew; Ravosa, Matthew J; Stack, M Sharon

    2017-12-28

    Ovarian cancer is the fifth leading cause of cancer deaths in U.S. women and the deadliest gynecologic malignancy. This lethality is largely due to the fact that most cases are diagnosed at metastatic stages of the disease when the prognosis is poor. Epidemiologic studies consistently demonstrate that parous women have a reduced risk of developing ovarian cancer, with a greater number of births affording greater protection; however little is known about the impact of parity on ovarian cancer metastasis. Here we report that multiparous mice are less susceptible to ovarian cancer metastasis in an age-matched syngeneic murine allograft model. Interferon pathways were found to be upregulated in healthy adipose tissue of multiparous mice, suggesting a possible mechanism for the multiparous-related protective effect against metastasis. This protective effect was found to be lost with age. Based on this work, future studies exploring therapeutic strategies which harness the multiparity-associated protective effect demonstrated here are warranted. Copyright © 2017. Published by Elsevier B.V.

  9. Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease

    ClinicalTrials.gov

    2017-09-14

    Lumbar Degenerative Disc Disease; Spinal Stenosis; Spondylolisthesis; Spondylosis; Intervertebral Disk Displacement; Intervertebral Disk Degeneration; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Spondylolysis

  10. In vivo outcomes of tissue-engineered osteochondral grafts.

    PubMed

    Bal, B Sonny; Rahaman, Mohamed N; Jayabalan, Prakash; Kuroki, Keiichi; Cockrell, Mary K; Yao, Jian Q; Cook, James L

    2010-04-01

    Tissue-engineered osteochondral grafts have been synthesized from a variety of materials, with some success at repairing chondral defects in animal models. We hypothesized that in tissue-engineered osteochondral grafts synthesized by bonding mesenchymal stem cell-loaded hydrogels to a porous material, the choice of the porous scaffold would affect graft healing to host bone, and the quality of cell restoration at the hyaline cartilage surface. Bone marrow-derived allogeneic mesenchymal stem cells were suspended in hydrogels that were attached to cylinders of porous tantalum metal, allograft bone, or a bioactive glass. The tissue-engineered osteochondral grafts, thus created were implanted into experimental defects in rabbit knees. Subchondral bone restoration, defect fill, bone ingrowth-implant integration, and articular tissue quality were compared between the three subchondral materials at 6 and 12 weeks. Bioactive glass and porous tantalum were superior to bone allograft in integrating to adjacent host bone, regenerating hyaline-like tissue at the graft surface, and expressing type II collagen in the articular cartilage.

  11. [Homeostasis and Disorder of Musculoskeletal System.Pathogenesis of musculoskeletal diseases and strategies for their treatment.

    PubMed

    Miyamoto, Takeshi

    Decline of homeostasis in musculoskeletal locomotive organs such as bone and muscle with age leads to age-related diseases such as osteoporosis and muscle atrophy. To date, various findings underlying the pathogenesis of these tissues were accumulated. In this review, we discuss regarding the recent advances in the findings in the treatment for osteoporosis and the strategy for muscle atrophy, and our recent findings on the mechanisms underlying these diseases.

  12. Coding and traceability: cells and tissues in North America.

    PubMed

    Brubaker, Scott A; Wilson, Diane

    2010-11-01

    Cell and tissue banking professionals in North America have long understood the value of labeling their allografts with descriptive names that make them easily recognized. They have also understood that advantages exist in possessing the capability to track them internally and externally to better understand tissue handling from donation through distribution. An added insight that can assist with strategic planning is to know who uses them, how many, and for what purpose or application. Uniquely coding allografts naturally aids tracking in event of recall or the rare need to link them if implicated in an adverse outcome report. These values relate to an ability or inability to sufficiently track specific cell/tissue types throughout the allograft's lifetime. These concepts easily fit into the functions of a Quality Program and promote recipient safety. It is management oversight that drives the direction taken and either optimizes this knowledge or limits it. How concepts related to coding and tracing human cells and tissues for transplantation have evolved in North America, and where they may be headed, are described in this manuscript. Many protocols are in place but they exist in numerous operational silos. Quality Management System concepts should drive decision-making and include considerations for future planning beyond our own professional lifetimes.

  13. Factors Predicting Meniscal Allograft Transplantation Failure

    PubMed Central

    Parkinson, Ben; Smith, Nicholas; Asplin, Laura; Thompson, Peter; Spalding, Tim

    2016-01-01

    Background: Meniscal allograft transplantation (MAT) is performed to improve symptoms and function in patients with a meniscal-deficient compartment of the knee. Numerous studies have shown a consistent improvement in patient-reported outcomes, but high failure rates have been reported by some studies. The typical patients undergoing MAT often have multiple other pathologies that require treatment at the time of surgery. The factors that predict failure of a meniscal allograft within this complex patient group are not clearly defined. Purpose: To determine predictors of MAT failure in a large series to refine the indications for surgery and better inform future patients. Study Design: Cohort study; Level of evidence, 3. Methods: All patients undergoing MAT at a single institution between May 2005 and May 2014 with a minimum of 1-year follow-up were prospectively evaluated and included in this study. Failure was defined as removal of the allograft, revision transplantation, or conversion to a joint replacement. Patients were grouped according to the articular cartilage status at the time of the index surgery: group 1, intact or partial-thickness chondral loss; group 2, full-thickness chondral loss 1 condyle; and group 3, full-thickness chondral loss both condyles. The Cox proportional hazards model was used to determine significant predictors of failure, independently of other factors. Kaplan-Meier survival curves were produced for overall survival and significant predictors of failure in the Cox proportional hazards model. Results: There were 125 consecutive MATs performed, with 1 patient lost to follow-up. The median follow-up was 3 years (range, 1-10 years). The 5-year graft survival for the entire cohort was 82% (group 1, 97%; group 2, 82%; group 3, 62%). The probability of failure in group 1 was 85% lower (95% CI, 13%-97%) than in group 3 at any time. The probability of failure with lateral allografts was 76% lower (95% CI, 16%-89%) than medial allografts at

  14. Urine biomarkers informative of human kidney allograft rejection and tolerance.

    PubMed

    Nissaisorakarn, Voravech; Lee, John Richard; Lubetzky, Michelle; Suthanthiran, Manikkam

    2018-05-01

    We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report. Copyright © 2018. Published by Elsevier Inc.

  15. Targeting Sirtuin-1 prolongs murine renal allograft survival and function

    PubMed Central

    Levine, Matthew H.; Wang, Zhonglin; Xiao, Haiyan; Jiao, Jing; Wang, Liqing; Bhatti, Tricia R.; Hancock, Wayne W.; Beier, Ulf H.

    2016-01-01

    Current immunosuppressive medications used after transplantation have significant toxicities. Foxp3+ T-regulatory (Treg) cells can prevent allograft rejection without compromising protective host immunity. Interestingly, inhibiting the class III histone/protein deacetylase Sirtuin-1 can augment Foxp3+ Treg suppressive function through increasing Foxp3 acetylation. Here we determined whether Sirtuin-1 targeting can stabilize biological allograft function. BALB/c kidney allografts were transplanted into C57BL/6 recipients with a CD4-conditional deletion of Sirtuin-1 (Sirt1fl/flCD4cre) or mice treated with a Sirtuin-1 specific inhibitor (EX-527), and the native kidneys removed. Blood chemistries and hematocrit were followed weekly. Sirt1fl/flCD4cre recipients showed markedly longer survival and improved kidney function. Sirt1fl/flCD4cre recipients exhibited donor specific tolerance, accepted BALB/c, but rejected third-party C3H cardiac allografts. C57BL/6 recipients of BALB/c renal allografts that were treated with EX-527 showed improved survival and renal function at 1, but not 10 mg/kg/day. Pharmacologic inhibition of Sirtuin-1 also improved renal allograft survival and function with dosing effects having relevance to outcome. Thus, inhibiting Sirtuin-1 can be a useful asset in controlling T-cell mediated rejection. However, effects on non-T cells that could adversely affect allograft survival and function merit consideration. PMID:27083279

  16. [Homeostasis and Disorder of Musculoskeletal System.Cellular dynamics in musculoskeletal system visualized by intravital imaging techniques.

    PubMed

    Kikuta, Junichi; Ishii, Masaru

    Bone is continually remodeled by bone-resorbing osteoclasts and bone-forming osteoblasts. Although it has long been believed that bone homeostasis is tightly regulated by communication between osteoclasts and osteoblasts, the fundamental process and dynamics have remained elusive. We originally established an advanced imaging system to visualize living bone tissues using intravital two-photon microscopy. By means of this system, we revealed the in vivo behavior of bone-resorbing osteoclasts and bone-forming osteoblasts in bone tissues. This approach facilitates investigation of cellular dynamics in the pathogenesis of musculoskeletal disorders, and would thus be useful for evaluating the efficacy of novel therapeutic agents.

  17. Histologic healing following tooth extraction with ridge preservation using mineralized versus combined mineralized-demineralized freeze-dried bone allograft: a randomized controlled clinical trial.

    PubMed

    Borg, Tyler D; Mealey, Brian L

    2015-03-01

    Mineralized and demineralized freeze-dried bone allografts (FDBAs) are used in alveolar ridge (AR) preservation; however, each material has advantages and disadvantages. Combinations of allografts aimed at capitalizing on the advantages each offers are available. To date, there is no evidence to indicate if a combination allograft is superior in this application. The primary objective of this study is to histologically evaluate and compare healing of non-molar extraction sites grafted with either mineralized FDBA or a 70:30 mineralized:demineralized FDBA combination allograft in AR preservation. The secondary objective is to compare dimensional changes in ridge height and width after grafting with these two materials. Forty-two patients randomized into two equal groups received ridge preservation with either 100% mineralized FDBA (active control group) or the combination 70% mineralized: 30% demineralized allograft (test group). Sites were allowed to heal for 18 to 20 weeks, at which time core biopsies were obtained and dental implants were placed. AR dimensions were evaluated at the time of extraction and at implant placement, including change in ridge width and change in buccal and lingual ridge height. Histomorphometric analysis was performed to determine percentage of vital bone, residual graft, and connective tissue/other non-bone components. There was no significant difference between groups in AR dimensional changes. Combination allograft produced increased vital bone percentage (36.16%) compared to the FDBA group (24.69%; P = 0.0116). The combination allograft also had a significantly lower mean percentage of residual graft particles (18.24%) compared to FDBA (27.04%; P = 0.0350). This study provides the first histologic evidence showing greater new bone formation with a combination mineralized/demineralized allograft compared to 100% mineralized FDBA in AR preservation in humans. Combination allograft results in increased vital bone formation while

  18. Nonexpanded Adipose Stromal Vascular Fraction Local Therapy on Peripheral Nerve Regeneration Using Allografts.

    PubMed

    Mohammadi, Rahim; Mehrtash, Moein; Mehrtash, Moeid; Sajjadi, Seyedeh-Sepideh

    2016-06-01

    Adipose tissue possesses a population of multi-potent stem cells which can be differentiated to a Schwann cell phenotype and may be of benefit for treatment of peripheral nerve injuries. Effects of local therapy of nonexpanded adipose stromal vascular fraction (SVF) on peripheral nerve regeneration was studied using allografts in a rat sciatic nerve model. Thirty male white Wistar rats were divided into three experimental groups (n = 10), randomly: Sham-operated group (SHAM), allograft group (ALLO), SVF-treated group (ALLO/SVF). In SHAM group left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the ALLO group the left sciatic nerve was exposed through a gluteal muscle incision and transected proximal to the tibio-peroneal bifurcation where a 10 mm segment was excised. The same procedure was performed in the ALLO/SVF group. The harvested nerves of the rats of ALLO group were served as allograft for ALLO/SVF group and vice versa. The SHAM and ALLO groups received 100 μL phosphate buffered saline and the ALLO/SVF group received 100 μL SVF (2.25 ± 0.45 × 10(7) cells) locally where the grafting was performed. Behavioral, functional, biomechanical, and gastrocnemius muscle mass showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). Histomorphometic and immunohistochemical studies also showed earlier regeneration of axons in ALLO/SVF than in ALLO group (p < .05). Administration of nonexpanded SVF could accelerate functional recovery after nerve allografting in sciatic nerve. It may have clinical implications for the surgical management of patients after nerve transection.

  19. 21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiac allograft gene expression profiling test... Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a) Identification. A cardiac allograft gene expression profiling test system is a device that measures the...

  20. Musculoskeletal Tuberculosis.

    PubMed

    Leonard, Michael K; Blumberg, Henry M

    2017-04-01

    Musculoskeletal tuberculosis (TB) accounts for approximately 10% of all extrapulmonary TB cases in the United States and is the third most common site of extrapulmonary TB after pleural and lymphatic disease. Vertebral involvement (tuberculous spondylitis, or Pott's disease) is the most common type of skeletal TB, accounting for about half of all cases of musculoskeletal TB. The presentation of musculoskeletal TB may be insidious over a long period and the diagnosis may be elusive and delayed, as TB may not be the initial consideration in the differential diagnosis. Concomitant pulmonary involvement may not be present, thus confusing the diagnosis even further. Early diagnosis of bone and joint disease is important to minimize the risk of deformity and enhance outcome. The introduction of newer imaging modalities, including MRI (imaging procedure of choice) and CT, has enhanced the diagnostic evaluation of patients with musculoskeletal TB and for directed biopsies of affected areas of the musculoskeletal system. Obtaining appropriate specimens for culture and other diagnostic tests is essential to establish a definitive diagnosis and recover M. tuberculosis for susceptibility testing. A total of 6 to 9 months of a rifampin-based regimen, like treatment of pulmonary TB, is recommended for the treatment of drug susceptible musculoskeletal disease. Randomized trials of tuberculous spondylitis have demonstrated that such regimens are efficacious. These data and those from the treatment of pulmonary TB have been extrapolated to form the basis of treatment regimen recommendations for other forms of musculoskeletal TB.

  1. Amnion and Chorion Allografts in Combination with Coronally Advanced Flap in the Treatment of Gingival Recession: A Clinical Study

    PubMed Central

    Chakraborthy, Sonali; Sambashivaiah, Savita; Bilchodmath, Shivaprasad

    2015-01-01

    Background Guided tissue regeneration (GTR) based root coverage using different allograft membranes has been utilized to correct gingival recession defects with promising results. Amnion and chorion allograft membranes of alternative origin derived from human placental tissue has been advocated in the treatment of gingival recession. However, chorion membrane has been used in combination with amnion membrane no study has compared these allograft membranes in the treatment of gingival recession. Therefore, the purpose of this study was to clinically evaluate and compare the efficacy of amnion membrane and chorion membrane in combination with coronally advanced flap in the treatment of gingival recessions. Materials and Methods Twelve systemically healthy patients having at least 2 bilateral Miller’s Class I or Class II gingival recession were recruited and coronally advanced flap was performed with amnion membrane or chorion membrane. Clinical parameters such as gingival Index, plaque index, length of the recession, width of the recession, width of keratinized gingiva, relative attachment level were evaluated at baseline, 3 and 6 months post-surgery. Results The mean decrease in length of recession (LR) for Chorion site was 2.00±1.54mm and amnion site was 1.58±1.14mm. The gain in attachment level for amnion site was 2.17±1.53mm and for chorion site was 1.58±1.22mm. The total mean percentage of root coverage was 34% for chorion site and 22% for amnion site. Conclusion Both amnion membrane and chorion membrane has shown to be versatile allograft material to be used in the treatment of root coverage. PMID:26501023

  2. Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal tuberculosis: High sensitivity in tissue samples of HIV-infected and HIV-uninfected patients.

    PubMed

    Held, M; Laubscher, M; Workman, L; Zar, H J; Dunn, R

    2017-09-22

    GeneXpert MTB/RIF is useful for the diagnosis of pulmonary TB in adults, but there is limited evidence on its usefulness in extrapulmonary TB. To investigate the diagnostic accuracy of GeneXpert MTB/RIF in HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A prospective study of patients with suspected musculoskeletal (bone and joint) TB was undertaken. The diagnostic accuracy of GeneXpert MTB/RIF was compared with the reference standards of culture and histopathology. A total of 206 biopsies from 201 patients (23% HIV-infected) were evaluated. The sensitivity and specificity of GeneXpert MTB/RIF was 92.3% (84/91) and 99.1% (114/115), respectively. GeneXpert MTB/RIF detected 8.8% more cases than culture (84/91 (92.3%) v. 76/91 (83.5%), respectively; p=0.069). GeneXpert MTB/RIF also detected all 4 multidrug-resistant TB cases and an additional 2 rifampicin-resistant cases in culture-negative samples. The sensitivity of GeneXpert MTB/RIF in HIV-infected patients was 96.9% (31/32) v. 89.6% (43/48) in HIV-uninfected patients (p=0.225). GeneXpert MTB/RIF is an accurate test for the detection of TB in tissue samples of HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A positive GeneXpert MTB/RIF result should be regarded as microbiological confirmation of TB.

  3. Role of airway epithelial injury in murine orthotopic tracheal allograft rejection.

    PubMed

    Kuo, Elbert; Bharat, Ankit; Shih, Jennifer; Street, Tyler; Norris, Jenyi; Liu, Wei; Parks, William; Walter, Michael; Patterson, G Alexander; Mohanakumar, T

    2006-10-01

    Murine tracheal transplantation is a model used to study bronchiolitis obliterans syndrome, a major cause of morbidity and mortality after lung transplantation. Unlike murine heterotopic tracheal transplants, orthotopic transplantation does not cause luminal obliteration despite major histocompatibility antigen mismatch. Repopulation of the tracheal allografts with recipient-derived epithelium confers protection against luminal obliteration. The purpose of this study was to determine whether (1) orthotopic tracheal transplantation showed signs of allograft rejection, and (2) airway epithelial cell injury promoted orthotopic tracheal allograft rejection. Forty isogeneic (C57BL/6 to C57BL/6) and 40 allogeneic (BALB/c to C57BL/6) orthotopic tracheal transplants were performed. Damage to airway epithelial cells was induced by Sendai viral (SdV) infection and tracheal transplantation into non-reepithelializing matrix metalloproteinase-7 knockout (MMP7-KO) recipient mice. Percent fibrosis and lamina propria to cartilage ratio were calculated with computer assistance on harvested allografts. Allografts showed significantly more intramural fibrosis compared with isografts at 30, 60, and 180 days after transplant without luminal occlusion. Tracheal allografts infected with SdV showed an increase in fibrosis and lamina propria to cartilage ratio compared with noninfected controls. Allografts retrieved from MMP7-KO recipients also showed a significant increase in fibrosis and lamina propria to cartilage ratio. Although orthotopic tracheal transplantation does not cause luminal obliteration, it results in increased fibrosis in allografts. Damage to the respiratory epithelium by viral infection or defective reepithelialization after transplant as seen in MMP7-KO recipient mice leads to changes consistent with chronic allograft rejection, suggesting a role for epithelial injury in bronchiolitis obliterans syndrome development.

  4. Clinical Outcomes in Musculoskeletal Involvement of Burkholderia Pseudomallei Infection.

    PubMed

    Gouse, Mohamad; Jayasankar, Viswanath; Patole, Shalom; Veeraraghavan, Balaji; Nithyananth, Manasseh

    2017-09-01

    Musculoskeletal involvement in melioidosis is often seen in conjunction with a disseminated illness. Recent reports suggest that operative management of musculoskeletal melioidosis has favourable results. The purpose of this study was to review the patient profile and clinical outcomes of Burkholderia pseudomallei infection in the musculoskeletal system. Hospital records of 163 patients who were diagnosed to have B. pseudomallei infection between January 2009 and December 2014 were reviewed. Patients underwent surgical and nonsurgical management depending upon the tissue of involvement. Epidata software was used to record the data. The SPSS ver. 17.0 was used for analysis. Eighteen out of 24 patients who had musculoskeletal melioidosis were available for follow-up. Septic arthritis, osteomyelitis, and intramuscular abscess were the common diagnosis, with 6 patients in each group. Twelve patients required surgical intervention. All patients received a full course of parenteral ceftazidime followed by oral doxycycline and co-trimoxazole. Two out of 6 patients (33.3%) died among those who had nonsurgical management as compared to none in the group who had surgical management. This was significant at 10% level of significance (p = 0.098). The rest were followed up for a minimum of 1 year with no evidence of disease recurrence. This series describing musculoskeletal involvement in melioidosis is the largest such study from a recently recognized 'endemic' region. Of importance are the patterns of musculoskeletal involvement, pitfalls in diagnosis and adequate clinical response with timely diagnosis and appropriate surgical management.

  5. Is Dual Semitendinosus Allograft Stronger Than Turndown for Achilles Tendon Reconstruction? An In Vitro Analysis.

    PubMed

    Aynardi, Michael C; Atwater, Lara C; Melvani, Roshan; Parks, Brent G; Paez, Adrian G; Miller, Stuart D

    2017-10-01

    clinical failure (1.6 ± 1.0 mm versus 4.7 ± 0.7 mm medially and 2.2 ± 1.0 mm versus 4.8 ± 1.1 mm laterally; p < 0.001). Semitendinosus allograft failure occurred via calcaneal bone bridge fracture in eight of nine specimens. All myofascial turndowns failed via suture pullout through the fascial tissue at its insertion. In this comparative biomechanical study, dual semitendinosus allograft reconstruction showed greater tensile strength and construct deformation compared with myofascial turndown in a cadaveric model of large Achilles tendon defects. Further study of dual semitendinosus allograft for treatment of severe Achilles tendon defects with cyclic loading and investigation of clinical results will better elucidate the clinical utility and indications for this technique.

  6. Human mesenchymal stem cells: a bank perspective on the isolation, characterization and potential of alternative sources for the regeneration of musculoskeletal tissues.

    PubMed

    Moroni, Lorenzo; Fornasari, Pier Maria

    2013-04-01

    The continuous discovery of human mesenchymal stem cells (hMSCs) in different tissues is stirring up a tremendous interest as a cell source for regenerative medicine therapies. Historically, hMSCs have been always considered a sub-population of mononuclear cells present in the bone marrow (BM). Although BM-hMSCs are still nowadays considered as the most promising mesenchymal stem cell population to reach the clinics due to their capacity to differentiate into multiple tissues, hMSCs derived from other adult and fetal tissues have also demonstrated to possess similar differentiation capacities. Furthermore, different reports have highlighted a higher recurrence of hMSCs in some of these tissues as compared to BM. This offer a fascinating panorama for cell banking, since the creation of a stem cell factory could be envisioned where hMSCs are stocked and used for ad hoc clinical applications. In this review, we summarize the main findings and state of the art in hMSCs isolation, characterization, and differentiation from alternative tissue sources and we attempt to compare their potency for musculoskeletal regeneration. Copyright © 2012 Wiley Periodicals, Inc.

  7. Autograft versus Allograft for Cervical Spinal Fusion: A Systematic Review.

    PubMed

    Tuchman, Alexander; Brodke, Darrel S; Youssef, Jim A; Meisel, Hans-Jörg; Dettori, Joseph R; Park, Jong-Beom; Yoon, S Tim; Wang, Jeffrey C

    2017-02-01

    Systematic review. To compare the effectiveness and safety between iliac crest bone graft (ICBG), non-ICBG autologous bone, and allograft in cervical spine fusion. To avoid problems at the donor site, various allograft materials have been used as a substitute for autograft. However, there are still questions as to the comparative effectiveness and safety of cadaver allograft compared with autologous ICBG. A systematic search of multiple major medical reference databases was conducted to identify studies evaluating spinal fusion in patients with cervical degenerative disk disease using ICBG compared with non-ICBG autograft or allograft or non-ICBG autograft compared with allograft in the cervical spine. Radiographic fusion, patient-reported outcomes, and functional outcomes were the primary outcomes of interest. Adverse events were evaluated for safety. The search identified 13 comparative studies that met our inclusion criteria: 2 prospective cohort studies and 11 retrospective cohort studies. Twelve cohort studies compared allograft with ICBG autograft during anterior cervical fusion and demonstrated with a low evidence level of support that there are no differences in fusion percentages, pain scores, or functional results. There was insufficient evidence comparing patients receiving allograft with non-ICBG autograft for fusion, pain, revision, and functional and safety outcomes. No publications directly comparing non-ICBG autograft with ICBG were found. Although the available literature suggests ICBG and allograft may have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes following anterior cervical fusion, there are too many limitations in the available literature to draw any significant conclusions. No individual study provided greater than class III evidence, and when evaluating the overall body of literature, no conclusion had better than low evidence support. A prospective randomized trial with adequate sample size to

  8. Diagnosis of BK viral nephropathy in the renal allograft biopsy: role of fluorescence in situ hybridization.

    PubMed

    Wang, Zhen; Portier, Bryce P; Hu, Bo; Chiesa-Vottero, Andres; Myles, Jonathan; Procop, Gary W; Tubbs, Raymond R

    2012-09-01

    Early recognition of BK viral nephropathy is essential for successful management. Our aim in this study was to evaluate a novel fluorescence in situ hybridization (FISH) assay for detection of BK virus in renal transplant biopsies in the context of standard detection methods. Renal allograft biopsies (n = 108) were analyzed via H&E, immunohistochemistry (IHC) for simian virus 40, and FISH for BK virus. BK virus was detected in 16 (14.8%) cases by H&E, 13 (12%) cases by IHC, 18 (16.6%) cases by FISH, and 19 (17.6%) cases by real-time PCR; 24 of 108 showed a discrepancy in ≥1 testing modalities. Comparison of H&E, IHC, and FISH showed no statistical difference in detection of BK virus. However, performing comparisons between the different tissue-based assays in the context of plasma or urine real-time PCR results showed significant improvement in detection of BK by FISH over H&E (P = 0.02) but not IHC (P = 0.07). This novel FISH-based approach for BK virus identification in renal allograft biopsy tissue mirrored real-time PCR results and showed superior performance to detection of inclusions by H&E. Therefore, use of FISH for BK virus detection in the setting of renal allograft biopsy is a useful and sensitive detection method and could be adopted in any laboratory that currently performs FISH analysis. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  9. Decellularized Tissue and Cell-Derived Extracellular Matrices as Scaffolds for Orthopaedic Tissue Engineering

    PubMed Central

    Cheng, Christina W.; Solorio, Loran D.; Alsberg, Eben

    2014-01-01

    The reconstruction of musculoskeletal defects is a constant challenge for orthopaedic surgeons. Musculoskeletal injuries such as fractures, chondral lesions, infections and tumor debulking can often lead to large tissue voids requiring reconstruction with tissue grafts. Autografts are currently the gold standard in orthopaedic tissue reconstruction; however, there is a limit to the amount of tissue that can be harvested before compromising the donor site. Tissue engineering strategies using allogeneic or xenogeneic decellularized bone, cartilage, skeletal muscle, tendon and ligament have emerged as promising potential alternative treatment. The extracellular matrix provides a natural scaffold for cell attachment, proliferation and differentiation. Decellularization of in vitro cell-derived matrices can also enable the generation of autologous constructs from tissue specific cells or progenitor cells. Although decellularized bone tissue is widely used clinically in orthopaedic applications, the exciting potential of decellularized cartilage, skeletal muscle, tendon and ligament cell-derived matrices has only recently begun to be explored for ultimate translation to the orthopaedic clinic. PMID:24417915

  10. Stem cells, blood vessels, and angiogenesis as major determinants for musculoskeletal tissue repair.

    PubMed

    Huard, Johnny

    2018-05-22

    This manuscript summarizes 20 years of research from my laboratories at the University of Pittsburgh and more recently, at the University of Texas Health Science Center at Houston and the Steadman Philippon Research Institute in Vail, Colorado. The discovery of muscle-derived stem cells (MDSCs) did not arise from a deliberate search to find a novel population of muscle cells with high regenerative potential, but instead was conceived in response to setbacks encountered while working in muscle cell transplantation for Duchenne muscular dystrophy (DMD). DMD is a devastating inherited X-linked muscle disease characterized by progressive muscle weakness due to lack of dystrophin expression in muscle fiber sarcolemma. Although the transplantation of normal myoblasts into dystrophin-deficient muscle can restore dystrophin, this approach has been hindered by limited survival (less than 1%) of the injected cells. The fact that 99% of the cells were not surviving implantation was seen as a major weakness with this technology by most. My research team decided to investigate which cells represent the 1% of the cells surviving post-implantation. We have subsequently confirmed that the few cells which exhibit high survival post-implantation also display stem cell characteristics, and were termed "muscle-derived stem cells" or MDSCs. Herein, I will describe the origin of these MDSCs, the mechanisms of MDSC action during tissue repair, and finally the development of therapeutic strategies to improve regeneration and repair of musculoskeletal tissues. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-9, 2018. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Assessment of organ culture for the conservation of human skin allografts.

    PubMed

    Hautier, A; Sabatier, F; Stellmann, P; Andrac, L; Nouaille De Gorce, Y; Dignat-George, F; Magalon, G

    2008-03-01

    Human skin allografts are used in the treatment of severe burns and their preservation is therefore critical for optimal clinical benefit. Current preservation methods, such as 4 degrees C storage or cryopreservation, cannot prevent the decrease of tissue viability. The aim of this study was to assess viability and function of skin allografts in a new skin organ culture model, allowing conservation parameters as close as possible to physiological conditions: 32 degrees C, air-liquid interface and physiological skin tension. Twelve skin samples, harvested from 6 living surgical donors, were conserved 35 days in two conditions: conservation at 4 degrees C and organ culture. Viability and function of skin samples were investigated at Day 0, 7, 14, 21, 28 and 35 using cell culture methods (trypan blue exclusion, Colony Forming Efficiency and Growth Rate), histopathological and histoenzymological studies (Ki67 immunostaining). In the two conditions, fibroblast and keratinocyte viability was progressively affected by storage, with a significant decrease observed after 35 days. No statistical difference could be observed between the two conditions. The two methods were also comparable regarding alterations of fibroblast and keratinocyte culture parameters, which were respectively significantly reduced at Day 7 and 21, compared to fresh skin. By contrast, histopathological and histoenzymological studies revealed a better preservation of skin architecture and proliferative potential at 4 degrees C, as compared to organ culture. These results indicate that skin organ culture does not provide significant advantages for skin allograft preservation. However, its potential use as an experimental model to study skin physiology and wound healing should be further evaluated.

  12. Current status of musculoskeletal application of shear wave elastography.

    PubMed

    Ryu, JeongAh; Jeong, Woo Kyoung

    2017-07-01

    Ultrasonography (US) is a very powerful diagnostic modality for the musculoskeletal system due to the ability to perform real-time dynamic high-resolution examinations with the Doppler technique. In addition to acquiring morphologic data, we can now obtain biomechanical information by quantifying the elasticity of the musculoskeletal structures with US elastography. The earlier diagnosis of degeneration and the ability to perform follow-up evaluations of healing and the effects of treatment are possible. US elastography enables a transition from US-based inspection to US-based palpation in order to diagnose the characteristics of tissue. Shear wave elastography is considered the most suitable type of US elastography for the musculoskeletal system. It is widely used for tendons, ligaments, and muscles. It is important to understand practice guidelines in order to enhance reproducibility. Incorporating viscoelasticity and overcoming inconsistencies among manufacturers are future tasks for improving the capabilities of US elastography.

  13. Current status of musculoskeletal application of shear wave elastography

    PubMed Central

    2017-01-01

    Ultrasonography (US) is a very powerful diagnostic modality for the musculoskeletal system due to the ability to perform real-time dynamic high-resolution examinations with the Doppler technique. In addition to acquiring morphologic data, we can now obtain biomechanical information by quantifying the elasticity of the musculoskeletal structures with US elastography. The earlier diagnosis of degeneration and the ability to perform follow-up evaluations of healing and the effects of treatment are possible. US elastography enables a transition from US-based inspection to US-based palpation in order to diagnose the characteristics of tissue. Shear wave elastography is considered the most suitable type of US elastography for the musculoskeletal system. It is widely used for tendons, ligaments, and muscles. It is important to understand practice guidelines in order to enhance reproducibility. Incorporating viscoelasticity and overcoming inconsistencies among manufacturers are future tasks for improving the capabilities of US elastography. PMID:28292005

  14. Mycobacteria and allograft heart valve banking: an international survey.

    PubMed

    Warwick, R M; Magee, J G; Leeming, J P; Graham, J C; Hannan, M M; Chadwick, M; Crook, D W; Yearsley, C P; Rayner, A; Parker, R

    2008-03-01

    Since the 1970s many tissue banks have been testing allograft heart valves (HVs) for Mycobacterium tuberculosis (MTB). Donor selection for low risk of tuberculosis (TB) was introduced in the 1980s and appears to have reduced the risk of TB transmission. Regulatory guidance does not specify testing for TB, but does exclude donors with a recent history of TB. This survey of HV international bank practices revealed variations in donor selection, testing and processing of valves. Participant banks (from Europe and the USA) reported that over a period of 15 years, HV tissues from 38,413 donors were banked and 32,289 donors were tested for TB, none being positive. HV-associated tissue from 27,840 donors was stained and underwent microscopy; none of these were positive for acid-fast bacilli (AFB). Non-tuberculosis mycobacteria (NTBM) were detected by culture on 24 HVs. It is recommended that HV banks employ donor selection to exclude donors at risk of TB, to culture material for mycobacteria, and to investigate potential sources when clusters of NTBM are found to facilitate corrective and preventative actions.

  15. Tissue recovery practices and bioburden: a systematic review.

    PubMed

    Brubaker, S; Lotherington, K; Zhao, Jie; Hamilton, B; Rockl, G; Duong, A; Garibaldi, A; Simunovic, N; Alsop, D; Dao, D; Bessemer, R; Ayeni, O R

    2016-12-01

    For successful transplantation, allografts should be free of microorganisms that may cause harm to the allograft recipient. Before or during recovery and subsequent processing, tissues can become contaminated. Effective tissue recovery methods, such as minimizing recovery times (<24 h after death) and the number of experienced personnel performing recovery, are examples of factors that can affect the rate of tissue contamination at recovery. Additional factors, such as minimizing the time after asystole to recovery and the total time it takes to perform recovery, the type of recovery site, the efficacy of the skin prep performed immediately prior to recovery of tissue, and certain technical recovery procedures may also result in control of the rate of contamination. Due to the heterogeneity of reported recovery practices and experiences, it cannot be concluded if the use of other barriers and/or hygienic precautions to avoid contamination have had an effect on bioburden detected after tissue recovery. Qualified studies are lacking which indicates a need exists for evidence-based data to support methods that reduce or control bioburden.

  16. Effects of a peracetic acid disinfection protocol on the biocompatibility and biomechanical properties of human patellar tendon allografts.

    PubMed

    Lomas, R J; Jennings, L M; Fisher, J; Kearney, J N

    2004-01-01

    Patellar tendon allografts, retrieved from cadaveric human donors, are widely used for replacement of damaged cruciate ligaments. In common with other tissue allografts originating from cadaveric donors, there are concerns regarding the potential for disease transmission from the donor to the recipient. Additionally, retrieval and subsequent processing protocols expose the graft to the risk of environmental contamination. For these reasons, disinfection or sterilisation protocols are necessary for these grafts before they are used clinically. A high-level disinfection protocol, utilising peracetic acid (PAA), has been developed and investigated for its effects on the biocompatibility and biomechanics of the patellar tendon allografts. PAA disinfection did not render the grafts either cytotoxic or liable to provoke an inflammatory response as assessed in vitro . However, the protocol was shown to increase the size of gaps between the tendon fibres in the matrix and render the grafts more susceptible to digestion with collagenase. Biomechanical studies of the tendons showed that PAA treatment had no effect on the ultimate tensile stress or Young's modulus of the tendons, and that ultimate strain was significantly higher in PAA treated tendons.

  17. Autograft Versus Allograft Anterior Cruciate Ligament Reconstruction: A Prospective, Randomized Clinical Study With a Minimum 10-Year Follow-up.

    PubMed

    Bottoni, Craig R; Smith, Eric L; Shaha, James; Shaha, Steven S; Raybin, Sarah G; Tokish, John M; Rowles, Douglas J

    2015-10-01

    The use of allografts for anterior cruciate ligament (ACL) reconstruction in young athletes is controversial. No long-term results have been published comparing tibialis posterior allografts to hamstring autografts. To evaluate the long-term results of primary ACL reconstruction using either an allograft or autograft. Randomized controlled trial; Level of evidence, 1. From June 2002 to August 2003, patients with a symptomatic ACL-deficient knee were randomized to receive either a hamstring autograft or tibialis posterior allograft. All allografts were from a single tissue bank, aseptically processed, and fresh-frozen without terminal irradiation. Graft fixation was identical in all knees. All patients followed the same postoperative rehabilitation protocol, which was blinded to the therapists. Preoperative and postoperative assessments were performed via examination and/or telephone and Internet-based questionnaire to ascertain the functional and subjective status using established knee metrics. The primary outcome measures were graft integrity, subjective knee stability, and functional status. There were 99 patients (100 knees); 86 were men, and 95% were active-duty military. Both groups were similar in demographics and preoperative activity level. The mean and median ages of both groups were identical at 29 and 26 years, respectively. Concomitant meniscal and chondral pathologic abnormalities, microfracture, and meniscal repair performed at the time of reconstruction were similar in both groups. At a minimum of 10 years (range, 120-132 months) from surgery, 96 patients (97 knees) were contacted (2 patients were deceased, and 1 was unable to be located). There were 4 (8.3%) autograft and 13 (26.5%) allograft failures that required revision reconstruction. In the remaining patients whose graft was intact, there was no difference in the mean Single Assessment Numeric Evaluation, Tegner, or International Knee Documentation Committee scores. At a minimum of 10 years

  18. Harvesting keratolimbal allografts from corneoscleral buttons: a novel application of cyanoacrylate adhesive.

    PubMed

    Lim, L T; Bhatt, P R; Ramaesh, K

    2008-11-01

    To describe an alternative and novel technique using cyanoacrylate glue to achieve successful limbal tissue dissection, from an organ culture media stored corneoscleral button, without an artificial anterior chamber. A donor corneoscleral button (leftover from penetrating keratoplasty) was divided into two equal semicircular halves. A thick layer of tissue adhesive (N-butyl-2-cyanoacrylate) was spread on a sterile rubber block (the under surface of the donor punch). One half of the donor corneoscleral rim was placed epithelial side up on the adhesive and allowed to attach firmly to the block. This composite provided stability to the donor rim allowing lamellar dissection of the limbal tissue to be performed without damaging the limbal epithelium. Regular, partial-thickness limbal tissue was obtained. There was no histological evidence of glue or cellular toxicity of the harvested limbal stem cells. This harvested tissue had been grafted successfully in patients with limbal stem cell deficiency also undergoing keratoplasty. Tissue adhesive can be a simple, effective and useful tool in the dissection and harvesting of corneal limbal stem cell allografts from corneoscleral buttons stored in organ culture media.

  19. Relationship between Comorbid Health Problems and Musculoskeletal Disorders Resulting in Musculoskeletal Complaints and Musculoskeletal Sickness Absence among Employees in Korea.

    PubMed

    Baek, Ji Hye; Kim, Young Sun; Yi, Kwan Hyung

    2015-06-01

    To investigate the relationship between musculoskeletal disorders and comorbid health problems, including depression/anxiety disorder, insomnia/sleep disorder, fatigue, and injury by accident, and to determine whether certain physical and psychological factors reduce comorbid health problems. In total, 29,711 employees were selected from respondents of the Third Korean Working Conditions Survey and categorized into two groups: Musculoskeletal Complaints or Musculoskeletal Sickness Absence. Four self-reported health indicators (overall fatigue, depression/anxiety, insomnia/sleep disorder, and injury by accident) were selected as outcomes, based on their high prevalence in Korea. We used multiple logistic regression analysis to determine the relationship between comorbid health problems, musculoskeletal complaints, and sickness absence. The prevalence of musculoskeletal complaints and musculoskeletal sickness absence due to muscular pain was 32.26% and 0.59%, respectively. Compared to the reference group, depression/anxiety disorder and overall fatigue were 5.2-6.1 times more prevalent in the Musculoskeletal Complaints Group and insomnia/sleep disorder and injury by accident were 7.6-11.0 times more prevalent in the Sickness Absence Group. When adjusted for individual and work-related physical factors, prevalence of all four comorbid health problems were slightly decreased in both groups. Increases in overall fatigue and depression/anxiety disorder were observed in the Musculoskeletal Complaints Group, while increases in insomnia/sleep disorder and injury by accident were observed in the Sickness Absence Group. For management of musculoskeletal complaints and sickness absence in the workplace, differences in health problems between employees with musculoskeletal complaints and those with sickness absence as well as the physical and psychological risk factors should be considered.

  20. Osteochondral Allograft Transplantation in Cartilage Repair: Graft Storage Paradigm, Translational Models, and Clinical Applications

    PubMed Central

    Bugbee, William D.; Pallante-Kichura, Andrea L.; Görtz, Simon; Amiel, David; Sah, Robert

    2016-01-01

    The treatment of articular cartilage injury and disease has become an increasingly relevant part of orthopaedic care. Articular cartilage transplantation, in the form of osteochondral allografting, is one of the most established techniques for restoration of articular cartilage. Our research efforts over the last two decades have supported the transformation of this procedure from experimental “niche” status to a cornerstone of orthopaedic practice. In this Kappa Delta paper, we describe our translational and clinical science contributions to this transformation: (1) to enhance the ability of tissue banks to process and deliver viable tissue to surgeons and patients, (2) to improve the biological understanding of in vivo cartilage and bone remodeling following osteochondral allograft (OCA) transplantation in an animal model system, (3) to define effective surgical techniques and pitfalls, and (4) to identify and clarify clinical indications and outcomes. The combination of coordinated basic and clinical studies is part of our continuing comprehensive academic OCA transplant program. Taken together, the results have led to the current standards for OCA processing and storage prior to implantation and also novel observations and mechanisms of the biological and clinical behavior of OCA transplants in vivo. Thus, OCA transplantation is now a successful and increasingly available treatment for patients with disabling osteoarticular cartilage pathology. PMID:26234194

  1. History of osteochondral allograft transplantation.

    PubMed

    Nikolaou, V S; Giannoudis, P V

    2017-07-01

    Osteochondral defects or injuries represent the most challenging entities to treat, especially when occur to young and active patients. For centuries, it has been recognized that such defects are almost impossible to treat. However, surgeons have never stopped the effort to develop reliable methods to restore articular cartilage and salvage the endangered joint function. Osteochondral allograft transplantation in human was first introduced by Eric Lexer in 1908. Since that era, several pioneers have been worked in the field of osteochondral allotransplantation, presenting and developing the basic research, the methodology and the surgical techniques. Herein we present in brief, the history and the early clinical results of osteochondral allograft transplantation in human. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Antibody-Mediated Rejection of Single Class I MHC-Disparate Cardiac Allografts

    PubMed Central

    Hattori, Yusuke; Bucy, R. Pat; Kubota, Yoshinobu; Baldwin, William M.; Fairchild, Robert L.

    2012-01-01

    Murine CCR5−/− recipients produce high titers of antibody to complete MHC-mismatched heart and renal allografts. To study mechanisms of class I MHC antibody-mediated allograft injury, we tested the rejection of heart allografts transgenically expressing a single class I MHC disparity in wild-type C57BL/6 (H-2b) and B6.CCR5−/− recipients. Donor-specific antibody titers in CCR5−/− recipients were 30-fold higher than in wild-type recipients. B6.Kd allografts survived longer than 60 days in wild-type recipients whereas CCR5−/− recipients rejected all allografts within 14 days. Rejection was accompanied by infiltration of CD8 T cells, neutrophils, and macrophages and C4d deposition in the graft capillaries. B6.Kd allografts were rejected by CD8−/−/CCR5−/−, but not μMT−/−/CCR5−/−, recipients indicating the need for antibody but not CD8 T cells. Grafts retrieved at day 10 from CCR5−/− and CD8−/−/CCR5−/− recipients and from RAG-1−/− allograft recipients injected with anti-Kd antibodies expressed high levels of perforin, myeloperoxidase and CCL5 mRNA. These studies indicate that the continual production of anti-donor class I MHC antibody can mediate allograft rejection, that donor-reactive CD8 T cells synergize with the antibody to contribute to rejection, and that expression of three biomarkers during rejection can occur in the absence of this CD8 T cell activity. PMID:22578247

  3. Sickness absence due to musculoskeletal diagnoses and risk of diagnosis-specific disability pension: a nationwide Swedish prospective cohort study.

    PubMed

    Jansson, Catarina; Alexanderson, Kristina

    2013-06-01

    Musculoskeletal disorders constitute major public health problems. Few studies have, however, examined risk of disability pension among persons sickness absent due to musculoskeletal diagnoses. Thus, we constructed a prospective nationwide population-based cohort study based on Swedish registers, consisting of all 4,687,756 individuals living in Sweden December 31, 2004/2005, aged 20-64 years, who were not on disability or old-age pension. Those individuals who were sickness absent in 2005 due to musculoskeletal diagnoses were compared to those sickness absent due to non-musculoskeletal diagnoses and those with no sickness absence. Musculoskeletal diagnoses were categorized as follows: 1) artropathies/systemic connective tissue disorders, 2) dorsopathies, and 3) soft tissue disorders/osteopathies/chondropathies/other musculoskeletal disorders. All-cause and diagnosis-specific incident disability pension were followed from 2006 to 2009. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression. In models adjusted for socio-demographic factors and morbidity, sickness absence due to all categories of musculoskeletal diagnoses was associated with 12- to 18-fold increased risks of all-cause disability pension (adjusted model, category 2 diagnoses, IRR = 18.57, 95% CI = 18.18-18.97). Similar associations were observed among both women and men sickness absent due to all 3 musculoskeletal diagnostic categories. Moreover, increased risks of disability pension because of cancer, mental, circulatory and musculoskeletal diagnoses were observed among individuals sickness absent because of any musculoskeletal diagnostic category (disability pension due to musculoskeletal diagnoses, adjusted model, category 2 diagnoses, IRR = 50.66, 95% CI = 49.06-52.32). In conclusion, this nationwide cohort study reveals strongly increased risks of all-cause and diagnosis-specific disability pension among those sickness absent due to

  4. Risk Factors for Musculoskeletal Symptoms Among Korean Broadcast Actors.

    PubMed

    Park, Moon-Hee; Kim, Ham-Gyum; Cho, Jae-Hwan

    2015-01-01

    Musculoskeletal diseases (MSDs) are functional disabilities in the musculoskeletal area that occur when continuous damage to the muscles or tissues is caused by performing a repetitive task. These diseases are usually found in the waist, shoulder, neck, arm, and wrist. MSD is also referred to as cumulative trauma disorder, repetitive strain injury, occupational overuse syndrome, and visual display terminal, depending on the country. The condition is now commonly referred to as work-related musculoskeletal disorder. The aim of this study was to develop a prevention plan against musculoskeletal disease and to provide better health care to broadcast actors by understanding the association between musculoskeletal symptoms and working conditions. The results of the study can be utilized to maintain effective systematic resources to treat such diseases. A survey was conducted in Seoul between January 1 and May 10, 2014 with broadcast actors working in the South Korean entertainment industry. Tests with respect to musculoskeletal symptoms indicated that the study participants were likely to experience having musculoskeletal symptoms in the shoulders, waist, neck, leg/foot, hand/wrist/finger, and arm/elbow. Most of the participants reported pain on both sides of their shoulders and in their legs/feet or on the right side of the arm/elbow and in hand/wrist/finger. Pain lasted between 1 and 7 days, with an incidence of 33.8% in the neck, 36% in the shoulders, 33.3% in the arm/elbow, 47.4% in the hand/wrist/finger, 34.7% in the waist, and 39.3% in the leg/foot. This study should prove useful in determining systematic and effective resources to prevent broadcast actors from developing MSD in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Musculoskeletal adaptations to weightlessness and development of effective countermeasures

    NASA Technical Reports Server (NTRS)

    Baldwin, K. M.; White, T. P.; Arnaud, S. B.; Edgerton, V. R.; Kraemer, W. J.; Kram, R.; Raab-Cullen, D.; Snow, C. M.

    1996-01-01

    A Research Roundtable, organized by the American College of Sports Medicine with sponsorship from the National Aeronautics and Space Administration, met in November 1995 to define research strategies for effective exercise countermeasures to weightlessness. Exercise was considered both independently of, and in conjunction with, other therapeutic modalities (e.g., pharmacological nutritional, hormonal, and growth-related factors) that could prevent or minimize the structural and functional deficits involving skeletal muscle and bone in response to chronic exposure to weightlessness, as well as return to Earth baseline function if a degree of loss is inevitable. Musculoskeletal deficits and countermeasures are described with respect to: 1) muscle and connective tissue atrophy and localized bone loss, 2) reductions in motor performance, 3) potential proneness to injury of hard and soft tissues, and 4) probable interaction between muscle atrophy and cardiovascular alterations that contribute to the postural hypotension observed immediately upon return from space flight. In spite of a variety of countermeasure protocols utilized previously involving largely endurance types of exercise, there is presently no activity-specific countermeasure(s) that adequately prevent or reduce musculoskeletal deficiencies. It seems apparent that countermeasure exercises that have a greater resistance element, as compared to endurance activities, may prove beneficial to the musculoskeletal system. Many questions remain for scientific investigation to identify efficacious countermeasure protocols, which will be imperative with the emerging era of long-term space flight.

  6. Long-term acceptance of major histocompatibility complex mismatched cardiac allografts induced by CTLA4Ig plus donor-specific transfusion

    PubMed Central

    1993-01-01

    Allograft rejection is a T cell-dependent process. Productive T cell activation by antigen requires antigen engagement of the T cell receptor as well as costimulatory signals delivered through other T cell surface molecules such as CD28. Engagement of CD28 by its natural ligand B7 can be blocked using a soluble recombinant fusion protein, CTLA4Ig. Administration of CTLA4Ig blocks antigen-specific immune responses in vitro and in vivo, and we have shown that treatment of rats with a 7-d course of CTLA4Ig at the time of transplantation leads to prolonged survival of cardiac allografts (median 30 d), although most grafts are eventually rejected. Here, we have explored additional strategies employing CTLA4Ig in order to achieve long-term allograft survival. Our data indicate that donor-specific transfusion (DST) plus CTLA4Ig can provide effective antigen-specific immunosuppression. When DST is administered at the time of transplantation followed by a single dose of CTLA4Ig 2 d later, all animals had long-term graft survival (> 60 d). These animals had delayed responses to donor-type skin transplants, compared with normal rejection responses to third-party skin transplants. Furthermore, donor-matched second cardiac allografts were well tolerated with minimal histologic evidence of rejection. These data indicate that peritransplant use of DST followed by subsequent treatment with CTLA4Ig can induce prolonged, often indefinite, cardiac allograft acceptance. These results may be clinically applicable for cadaveric organ and tissue transplantation in humans. PMID:8228826

  7. Spleen tyrosine kinase contributes to acute renal allograft rejection in the rat

    PubMed Central

    Ramessur Chandran, Sharmila; Tesch, Greg H; Han, Yingjie; Woodman, Naomi; Mulley, William R; Kanellis, John; Blease, Kate; Ma, Frank Y; Nikolic-Paterson, David J

    2015-01-01

    Kidney allografts induce strong T-cell and antibody responses which mediate acute rejection. Spleen tyrosine kinase (Syk) is expressed by most leucocytes, except mature T cells, and is involved in intracellular signalling following activation of the Fcγ-receptor, B-cell receptor and some integrins. A role for Syk signalling has been established in antibody-dependent native kidney disease, but little is known of Syk in acute renal allograft rejection. Sprague–Dawley rats underwent bilateral nephrectomy and received an orthotopic Wistar renal allograft. Recipient rats were treated with a Syk inhibitor (CC0482417, 30 mg/kg/bid), or vehicle, from 1 h before surgery until being killed 5 days later. Vehicle-treated recipients developed severe allograft failure with marked histologic damage in association with dense leucocyte infiltration (T cells, macrophages, neutrophils and NK cells) and deposition of IgM, IgG and C3. Immunostaining identified Syk expression by many infiltrating leucocytes. CC0482417 treatment significantly improved allograft function and reduced histologic damage, although allograft injury was still clearly evident. CC0482417 failed to prevent T-cell infiltration and activation within the allograft. However, CC0482417 significantly attenuated acute tubular necrosis, infiltration of macrophages and neutrophils and thrombosis of peritubular capillaries. In conclusion, this study identifies a role for Syk in acute renal allograft rejection. Syk inhibition may be a useful addition to T-cell-based immunotherapy in renal transplantation. PMID:25529862

  8. Allelic and Epitopic Characterization of Intra-Kidney Allograft Anti-HLA Antibodies at Allograft Nephrectomy.

    PubMed

    Milongo, D; Kamar, N; Del Bello, A; Guilbeau-Frugier, C; Sallusto, F; Esposito, L; Dörr, G; Blancher, A; Congy-Jolivet, N

    2017-02-01

    The reasons for the increased incidence of de novo anti-human leukocyte antibody (HLA) donor-specific antibodies (DSAs) observed after kidney allograft nephrectomy are not fully understood. One advocated mechanism suggests that at graft loss, DSAs are not detected in the serum because they are fixed on the nonfunctional transplant; removal of the kidney allows DSAs to then appear in the blood circulation. The aim of our study was to compare anti-HLA antibodies present in the serum and in the graft at the time of an allograft nephrectomy. Using solid-phase assays, anti-HLA antibodies were searched for in the sera of 17 kidney transplant patients undergoing allograft nephrectomy. No anti-HLA antibodies were detected in the graft if they were not also detected in the serum. Eleven of the 12 patients who had DSAs detected in their sera also had DSAs detected in the grafts. Epitopic analysis revealed that most anti-HLA antibodies detected in removed grafts were directed against the donor. In summary, our data show that all anti-HLA antibodies that were detected in grafts were also detected in the sera. These intragraft anti-HLA antibodies are mostly directed against the donor at an epitopic level but not always at an antigenic level. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  9. Sterilization with electron beam irradiation influences the biomechanical properties and the early remodeling of tendon allografts for reconstruction of the anterior cruciate ligament (ACL).

    PubMed

    Schmidt, Tanja; Hoburg, Arnd; Broziat, Christine; Smith, Mark D; Gohs, Uwe; Pruss, Axel; Scheffler, Sven

    2012-08-01

    Although allografts for anterior cruciate ligament (ACL) replacement have shown advantages compared to autografts, their use is limited due to the risk of disease transmission and the limitations of available sterilization methods. Gamma sterilization has shown detrimental effects on graft properties at the high doses required for sufficient pathogen inactivation. In our previous in vitro study on human patellar tendon allografts, Electron beam (Ebeam) irradiation showed less detrimental effects compared to gamma sterilization (Hoburg et al. in Am J Sports Med 38(6):1134-1140, 2010). To investigate the biological healing and restoration of the mechanical properties of a 34 kGy Ebeam treated tendon allograft twenty-four sheep underwent ACL replacement with either a 34 kGy Ebeam treated allograft or a non-sterilized fresh frozen allograft. Biomechanical testing of stiffness, ultimate failure load and AP-laxity as well as histological analysis to investigate cell, vessel and myofibroblast-density were performed after 6 and 12 weeks. Native sheep ACL and hamstring tendons (HAT, each n = 9) served as controls. The results of a previous study analyzing the remodeling of fresh frozen allografts (n = 12) and autografts (Auto, n = 18) with the same study design were also included in the analysis. Statistics were performed using Mann-Whitney U test followed by Bonferroni-Holm correction. Results showed significantly decreased biomechanical properties during the early remodeling period in Ebeam treated grafts and this was accompanied with an increased remodeling activity. There was no recovery of biomechanical function from 6 to 12 weeks in this group in contrast to the results observed in fresh frozen allografts and autografts. Therefore, high dose Ebeam irradiation investigated in this paper cannot be recommended for soft tissue allograft sterilization.

  10. Estimating the usage of allograft in the treatment of major burns.

    PubMed

    Horner, C W M; Atkins, J; Simpson, L; Philp, B; Shelley, O; Dziewulski, P

    2011-06-01

    To assess the amount of allograft used in the past treatment of major burns and calculate a figure to guide estimation of the quantity of allograft required to treat future patients and aid resource planning. A retrospective observational study. Records of 143 patients treated with major burns at a regional centre, from January 2004 to November 2008 were accessed with biometric data and quantity of allograft used being recorded. This data was used to calculate an allograft index (cm² allograft used/burn surface area (cm²)) (AI) for each patient. 112 of the 143 patients had complete sets of data, of the 112, 89 patients survived the initial stay in hospital. For all data average AI=1.077 ± 0.090. AI varied according to burn % area with burns < 40% requiring 0.490 cm² allo/cm²burn, increasing in a logarithmic fashion (R²=0.995) for burn areas > 40%. The ability to estimate deceased donor skin requirements based on % body surface area affected is important in the care planning for patients with major burns. Our findings of 0.5 cm² allograft/cm² burn for injuries less than 40% TBSA, increasing to 1.82 cm² allograft/cm² burn for injuries up to 80% TBSA can be used for planning purposes for individual services and for burn disaster planning. Copyright © 2010 Elsevier Ltd and ISBI. All rights reserved.

  11. Automatic allograft bone selection through band registration and its application to distal femur.

    PubMed

    Zhang, Yu; Qiu, Lei; Li, Fengzan; Zhang, Qing; Zhang, Li; Niu, Xiaohui

    2017-09-01

    Clinical reports suggest that large bone defects could be effectively restored by allograft bone transplantation, where allograft bone selection acts an important role. Besides, there is a huge demand for developing the automatic allograft bone selection methods, as the automatic methods could greatly improve the management efficiency of the large bone banks. Although several automatic methods have been presented to select the most suitable allograft bone from the massive allograft bone bank, these methods still suffer from inaccuracy. In this paper, we propose an effective allograft bone selection method without using the contralateral bones. Firstly, the allograft bone is globally aligned to the recipient bone by surface registration. Then, the global alignment is further refined through band registration. The band, defined as the recipient points within the lifted and lowered cutting planes, could involve more local structure of the defected segment. Therefore, our method could achieve robust alignment and high registration accuracy of the allograft and recipient. Moreover, the existing contour method and surface method could be unified into one framework under our method by adjusting the lift and lower distances of the cutting planes. Finally, our method has been validated on the database of distal femurs. The experimental results indicate that our method outperforms the surface method and contour method.

  12. Assessment of bioburden on human and animal tissues: part 2--results of testing of human tissue and qualification of a composite sample for routine bioburden determination.

    PubMed

    Kowalski, John B; Merritt, Karen; Gocke, David; Osborne, Joel

    2012-08-01

    A quantitative method was developed and validated to assess bioburden on tissue from human donors and to compare bioburden determination results to swab culture results from the same donor. An initial study with allograft tissue from 101 donors showed a wide range of bioburden levels; values from no colony-forming units (CFU) detected to >28,000 CFU were observed. Tissues from donors that had swab cultures negative for objectionable microorganisms generally had lower bioburden than tissues from donors where objectionable microorganisms were recovered by swab culturing. In a follow-up study with 1,445 donors, a wide range of bioburden levels was again observed on tissues from donors that were swab culture negative for objectionable microorganisms. Tissues from 885 (61%) of these donors had no recoverable bioburden (<2 CFU). Importantly, tissues from 560 (39%) of the donors had recoverable bioburden which ranged from 1 to >24,000 CFU. Identification of bioburden isolates showed a diversity of genera and species. In compliance with the recent revision of the American Association of Tissue Banks K2.210 Standard, the quantitative bioburden determination method was validated with a composite tissue sample that contains bone and soft tissue sections tested together in one extraction vessel. A recovery efficiency of 68% was validated and the composite sample was shown to be representative of all of the tissues recovered from a donor. The use of the composite sample in conjunction with the quantitative bioburden determination method will facilitate an accurate assessment of the numbers and types of contaminating microorganisms on allografts prior to disinfection/sterilization. This information will ensure that disinfection/sterilization processes are properly validated and the capability of the overall allograft process is understood on a donor by donor basis.

  13. Immunomodulatory Strategies Directed Towards Tolerance of Vascularized Composite Allografts

    PubMed Central

    Michel, Sebastian G.; Villani, Vincenzo; Muraglia, Glenn M. La; Torabi, Radbeh; Leonard, David A.; Randolph, Mark A.; Colvin, Robert B.; Yamada, Kazuhiko; Madsen, Joren C.; Cetrulo, Curtis L.; Sachs, David H.

    2015-01-01

    Background Achieving tolerance of vascularized composite allografts (VCAs) would improve the risk-to-benefit ratio in patients who undergo this life-enhancing, though not life-saving, transplant. Kidney co-transplantation along with a short course of high-dose immunosuppression enables tolerance of heart allografts across a full MHC mismatch. In this study, we investigated whether tolerance of VCA across full MHC disparities could be achieved in animals already tolerant of heart and kidney allografts. Methods Miniature swine that were tolerant of heart and/or kidney allografts long-term underwent transplantation of myocutaneous VCA across the same MHC barrier. Prior to VCA transplant, Group 1 (n=3) underwent Class I-mismatched kidney transplantation; Group 2 (n=3) underwent two sequential Class I-mismatched kidney transplantations; Group 3 (n=2) underwent haploidentical MHC-mismatched heart/kidney transplantation; and Group 4 (n=2) underwent full MHC-mismatched heart/kidney transplantation. Results All three animals in Group 1 and two of three animals in Group 2 showed skin rejection ≤85 days; one animal in Group 2 showed prolonged skin survival >200 days. Animals in Groups 3 and 4 showed skin rejection ≤30 days and regained in vitro evidence of donor responsiveness. Conclusion This is the first pre-clinical study in which hearts, kidneys, and VCAs have been transplanted into the same recipient. Despite VCA rejection, tolerance of heart and kidney allografts was maintained. These results suggest that regulatory tolerance of skin is possible but not generally achieved by the same level of immunomodulation that is capable of inducing tolerance of heart and kidney allografts. Achieving tolerance of skin may require additional immunomodulatory therapies. PMID:25757218

  14. Arthroscopic single-bundle anterior cruciate ligament reconstruction with six-strand hamstring tendon allograft versus bone-patellar tendon-bone allograft.

    PubMed

    Dai, Chengliang; Wang, Fei; Wang, Xiaomeng; Wang, Ruipeng; Wang, Shengjie; Tang, Shiyu

    2016-09-01

    The aim of this study was to compare the clinical outcomes of arthroscopic single-bundle anterior cruciate ligament (ACL) reconstruction with six-strand hamstring tendon (HT) allograft versus bone-patellar tendon-bone (BPTB) allograft. The prospective randomized controlled trial was included 129 patients. Sixty-nine patients received reconstruction with six-strand HT allografts (HT group), whereas 60 patients with BPTB allografts (BPTB group). Outcome assessment included re-rupture findings, International Knee Documentation Committee (IKDC) scores, Lysholm scores, KT-1000 arthrometer, Lachman test, pivot-shift test, range of motion (ROM) and single-leg hop test. At a mean follow-up of 52 months, 113 patients (HT group, 61 patients; BPTB group, 52 patients) completed a minimum 4-year follow-up. Four patients in HT group and six in BPTB group experienced ACL re-rupture (6.2 vs. 10.3 %) and received revision surgery. Significant between-group differences were observed in KT-1000 outcomes and pivot-shift test 1 (1.2 ± 1.5 vs. 1.8 ± 1.3, p = 0.025; positive rate 6.5 vs. 18.9 %, p = 0.036), 2 (1.1 ± 1.4 vs. 1.6 ± 1.2, p = 0.044; 8.1 vs. 20.7 %, p = 0.039), 4 (1.1 ± 1.5 vs. 1.7 ± 1.4, p = 0.031; 9.7 vs. 25 %, p = 0.012) years postoperatively. The outcomes between the two groups were comparable in terms of IKDC scores, Lysholm scores, Lachman test, ROM and single-leg hop test. Six-strand HT allograft achieved superior anteroposterior and rotational stability after single-bundle ACL reconstruction. It is a reasonable graft substitute for ACL reconstruction. II.

  15. Blood Glucose Levels After Local Musculoskeletal Steroid Injections in Patients With Diabetes Mellitus: A Clinical Review.

    PubMed

    Waterbrook, Anna L; Balcik, Brenden J; Goshinska, Aaron John

    Diabetes mellitus (DM) has become an epidemic in the United States and is associated with increased risk of multiple comorbidities, including painful musculoskeletal conditions. A common treatment for many of these painful musculoskeletal conditions is local soft tissue and intra-articular corticosteroid injection (CSI). These local injections have the potential to cause elevated blood glucose levels (BGLs) and cause complications in patients with DM. Therefore, it was the objective of this investigation to review the currently available evidence that directly addresses the effects of local CSIs used for painful musculoskeletal conditions on BGL in patients with DM. PubMed, Google Scholar, EMBASE, CINAHL, and Cochrane Review databases were searched with a combination of the terms corticosteroid, glucocorticoid, steroid, injection, musculoskeletal, and diabetes. Search limits included the English language. Bibliographic references from these articles were also examined to identify pertinent literature. Clinical review. Level 3. Ten studies that met the inclusion criteria were reviewed. All these studies showed significant but transient increases in postinjection BGL after a single local CSI in patients with DM. There were no adverse reactions or complications reported. Single, local soft tissue and intra-articular musculoskeletal CSIs are most likely safe in patients with well-controlled DM.

  16. Musculoskeletal overuse injuries and heart rate variability: Is there a link?

    PubMed

    Gisselman, Angela Spontelli; Baxter, G David; Wright, Alexis; Hegedus, Eric; Tumilty, Steve

    2016-02-01

    Accurate detection and prevention of overuse musculoskeletal injuries is limited by the nature of somatic tissue injury. In the pathogenesis of overuse injuries, it is well recognized that an abnormal inflammatory response occurs within somatic tissue before pain is perceived which can disrupt the normal remodeling process and lead to subsequent degeneration. Current overuse injury prevention methods focused on biomechanical faults or performance standards lack the sensitivity needed to identify the status of tissue injury or repair. Recent evidence has revealed an apparent increase in the prevalence and impact of overuse musculoskeletal injuries in athletics. When compared to acute injuries, overuse injuries have a potentially greater negative impact on athletes' overall health burden. Further, return to sport rehabilitation following overuse injury is complicated by the fact that the absence of pain does not equate to complete physiological healing of the injured tissue. Together, this highlights the need for exercise monitoring and injury prevention methods which incorporate assessment of somatic tissue response to loading. One system primarily involved in the activation of pathways and neuromediators responsible for somatic tissue repair is the autonomic nervous system (ANS). Although not completely understood, emerging research supports the critical importance of peripheral ANS activity in the health and repair of somatic tissue injury. Due to its significant contributions to cardiac function, ANS activity can be measured indirectly with heart rate monitoring. Heart rate variability (HRV) is one index of ANS activity that has been used to investigate the relationship between athletes' physiological response to accumulating training load. Research findings indicated that HRV may provide a reflection of ANS homeostasis, or the body's stress-recovery status. This noninvasive marker of the body's primary driver of recovery has the potential to incorporate

  17. Assessment of nerve regeneration across nerve allografts treated with tacrolimus.

    PubMed

    Haisheng, Han; Songjie, Zuo; Xin, Li

    2008-01-01

    Although regeneration of nerve allotransplant is a major concern in the clinic, there have been few papers quantitatively assessing functional recovery of animals' nerve allografts in the long term. In this study, functional recovery, histopathological study, and immunohistochemistry changes of rat nerve allograft with FK506 were investigated up to 12 weeks without slaughtering. C57 and SD rats were used for transplantation. The donor's nerve was sliced and transplanted into the recipient. The sciatic nerve was epineurally sutured with 10-0 nylon. In total, 30 models of transplantation were performed and divided into 3 groups that were either treated with FK506 or not. Functional recovery of the grafted nerve was serially assessed by the pin click test, walking track analysis and electrophysiological evaluations. A histopathological study and immunohistochemistry study were done in the all of the models. Nerve allografts treated with FK506 have no immune rejection through 12 weeks. Sensibility had similarly improved in both isografts and allografts. There has been no difference in each graft. Walk track analysis demonstrates significant recovery of motor function of the nerve graft. No histological results of difference were found up to 12 weeks in each graft. In the rodent nerve graft model, FK506 prevented nerve allograft rejection across a major histocompatibility barrier. Sensory recovery seems to be superior to motor function. Nerve isograft and allograft treated with FK506 have no significant difference in function recovery, histopathological result, and immunohistochemistry changes.

  18. Central memory CD8+ T lymphocytes mediate lung allograft acceptance

    PubMed Central

    Krupnick, Alexander Sasha; Lin, Xue; Li, Wenjun; Higashikubo, Ryuiji; Zinselmeyer, Bernd H.; Hartzler, Hollyce; Toth, Kelsey; Ritter, Jon H.; Berezin, Mikhail Y.; Wang, Steven T.; Miller, Mark J.; Gelman, Andrew E.; Kreisel, Daniel

    2014-01-01

    Memory T lymphocytes are commonly viewed as a major barrier for long-term survival of organ allografts and are thought to accelerate rejection responses due to their rapid infiltration into allografts, low threshold for activation, and ability to produce inflammatory mediators. Because memory T cells are usually associated with rejection, preclinical protocols have been developed to target this population in transplant recipients. Here, using a murine model, we found that costimulatory blockade–mediated lung allograft acceptance depended on the rapid infiltration of the graft by central memory CD8+ T cells (CD44hiCD62LhiCCR7+). Chemokine receptor signaling and alloantigen recognition were required for trafficking of these memory T cells to lung allografts. Intravital 2-photon imaging revealed that CCR7 expression on CD8+ T cells was critical for formation of stable synapses with antigen-presenting cells, resulting in IFN-γ production, which induced NO and downregulated alloimmune responses. Thus, we describe a critical role for CD8+ central memory T cells in lung allograft acceptance and highlight the need for tailored approaches for tolerance induction in the lung. PMID:24569377

  19. Endogenous Memory CD8 T Cells Directly Mediate Cardiac Allograft Rejection

    PubMed Central

    Su, C. A.; Iida, S.; Abe, T.; Fairchild, R. L.

    2014-01-01

    Differences in levels of environmentally induced memory T cells that cross-react with donor MHC molecules are postulated to account for the efficacy of allograft tolerance inducing strategies in rodents versus their failure in nonhuman primates and human transplant patients. Strategies to study the impact of donor-reactive memory T cells on allografts in rodents have relied on the pre-transplant induction of memory T cells cross-reactive with donor allogeneic MHC molecules through recipient viral infection, priming directly with donor antigen, or adoptive transfer of donor-antigen primed memory T cells. Each approach accelerates allograft rejection and confers resistance to tolerance induction, but also biases the T cell repertoire to strong donor-reactivity. The ability of endogenous memory T cells within unprimed mice to directly reject an allograft is unknown. Here we show a direct association between increased duration of cold ischemic allograft storage and numbers and enhanced functions of early graft infiltrating endogenous CD8 memory T cells. These T cells directly mediate rejection of allografts subjected to prolonged ischemia and this rejection is resistant to costimulatory blockade. These findings recapitulate the clinically significant impact of endogenous memory T cells with donor reactivity in a mouse transplant model in the absence of prior recipient priming. PMID:24502272

  20. Imaging mouse lung allograft rejection with 1H MRI

    PubMed Central

    Guo, Jinbang; Huang, Howard J.; Wang, Xingan; Wang, Wei; Ellison, Henry; Thomen, Robert P.; Gelman, Andrew E.; Woods, Jason C.

    2014-01-01

    Purpose To demonstrate that longitudinal, non-invasive monitoring via MRI can characterize acute cellular rejection (ACR) in mouse orthotopic lung allografts. Methods Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig vs anti-CD4/anti-CD8 treated groups. A two-dimensional multi-slice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung at post-operative days 3, 7 and 14, just before sacrifice. Lung volume and parenchymal signal were measured, and lung compliance was calculated as volume change per pressure difference between high and low pressures. Results Normalized parenchymal signal in the control-Ig allograft increased over time, with statistical significance between day 14 and day 3 post transplantation (0.046→0.789, P < 0.05), despite large inter-mouse variations; this was consistent with histopathologic evidence of rejection. Compliance of the control-Ig allograft decreased significantly over time (0.013→0.003, P < 0.05), but remained constant in mice treated with anti-CD4/anti-CD8 antibodies. Conclusion Lung allograft rejection in individual mice can be monitored by lung parenchymal signal changes and by lung compliance through MRI. Longitudinal imaging can help us better understand the time course of individual lung allograft rejection and response to treatment. PMID:24954886

  1. Imaging mouse lung allograft rejection with (1)H MRI.

    PubMed

    Guo, Jinbang; Huang, Howard J; Wang, Xingan; Wang, Wei; Ellison, Henry; Thomen, Robert P; Gelman, Andrew E; Woods, Jason C

    2015-05-01

    To demonstrate that longitudinal, noninvasive monitoring via MRI can characterize acute cellular rejection in mouse orthotopic lung allografts. Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig versus anti-CD4/anti-CD8 treated groups. A two-dimensional multislice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung at postoperative days 3, 7, and 14, just before sacrifice. Lung volume and parenchymal signal were measured, and lung compliance was calculated as volume change per pressure difference between high and low pressures. Normalized parenchymal signal in the control-Ig allograft increased over time, with statistical significance between day 14 and day 3 posttransplantation (0.046→0.789; P < 0.05), despite large intermouse variations; this was consistent with histopathologic evidence of rejection. Compliance of the control-Ig allograft decreased significantly over time (0.013→0.003; P < 0.05), but remained constant in mice treated with anti-CD4/anti-CD8 antibodies. Lung allograft rejection in individual mice can be monitored by lung parenchymal signal changes and by lung compliance through MRI. Longitudinal imaging can help us better understand the time course of individual lung allograft rejection and response to treatment. © 2014 Wiley Periodicals, Inc.

  2. Novel bio-synthetic hybrid materials and coculture systems for musculoskeletal tissue engineering

    NASA Astrophysics Data System (ADS)

    Lee, Hyeseung Janice

    Tissue Engineering is a truly exciting field of this age, trying to regenerate and repair impaired tissues. Unlike the old artificial implants, tissue engineering aims at making a long-term functional biological replacement. One strategy for such tissue engineering requires the following three components: cells, scaffolds, and soluble factors. Cells are cultured in a three-dimensional (3D) scaffold with medium containing various soluble factors. Once a tissue is developed in vitro, then it is implanted in vivo. The overall goal of this thesis was to develop novel bio-synthetic hybrid scaffolds and coculture system for musculoskeletal tissue engineering. The most abundant cartilage extracellular matrix (ECM) components are collagen and glycosaminoglycan (GAG), which are the natural scaffold for chondrocytes. As two different peptides, collagen mimetic peptide (CMP) and hyaluronic acid binding peptide (HABPep) were previously shown to bind to collagen and hyaluronic acid (HA) of GAG, respectively, it was hypothesized that immobilizing CMP and HABP on 3D scaffold would results in an interaction between ECM components and synthetic scaffolds via peptide-ECM bindings. CMP or HABPep-conjugated photopolymerizable poly(ethylene oxide) diacrylate (PEODA) hydrogels were synthesized and shown to retain encapsulated collagen or HA, respectively. This result supported that conjugated CMP and HABPep can interact with collagen and HA, respectively, and can serve as biological linkers in 3D synthetic hydrogels. When chondrocytes or mesenchymal stem cells (MSCs) were seeded, cells in CMP-conjugated scaffolds produced significantly more amount of type II collagen and GAG, compared to those in control scaffolds. Moreover, MSCs cultured in CMP-conjugated scaffolds exhibited lower level of hypertrophic markers, cbfa-1 and type X collagen. These results demonstrated that enhanced interaction between collagen and scaffold via CMP improves chondrogenesis of chondrocytes and MSCs and

  3. Acute allograft failure in thoracic organ transplantation.

    PubMed

    Jahania, M S; Mullett, T W; Sanchez, J A; Narayan, P; Lasley, R D; Mentzer, R M

    2000-01-01

    Thoracic organ transplantation is an effective form of treatment for end-stage heart and lung disease. Despite major advances in the field, transplant patients remain at risk for acute allograft dysfunction, a major cause of early and late mortality. The most common causes of allograft failure include primary graft failure secondary to inadequate heart and lung preservation during cold storage, cellular rejection, and various donor-recipient-related factors. During cold storage and early reperfusion, heart and lung allografts are vulnerable to intracellular calcium overload, acidosis, cell swelling, injury mediated by reactive oxygen species, and the inflammatory response. Brain death itself is associated with a reduction in myocardial contractility, and recipient-related factors such as preexisting pulmonary hypertension can lead to acute right heart failure and the pulmonary reimplantation response. The development of new methods to prevent or treat these various causes of acute graft failure could lead to a marked improvement in short- and long-term survival of patients undergoing thoracic organ transplantation.

  4. Cost effectiveness of meniscal allograft for torn discoid lateral meniscus in young women.

    PubMed

    Ramme, Austin J; Strauss, Eric J; Jazrawi, Laith; Gold, Heather T

    2016-09-01

    A discoid meniscus is more prone to tears than a normal meniscus. Patients with a torn discoid lateral meniscus are at increased risk for early onset osteoarthritis requiring total knee arthroplasty (TKA). Optimal management for this condition is controversial given the up-front cost difference between the two treatment options: the more expensive meniscal allograft transplantation compared with standard partial meniscectomy. We hypothesize that meniscal allograft transplantation following excision of a torn discoid lateral meniscus is more cost-effective compared with partial meniscectomy alone because allografts will extend the time to TKA. A decision analytic Markov model was created to compare the cost effectiveness of two treatments for symptomatic, torn discoid lateral meniscus: meniscal allograft and partial meniscectomy. Probability estimates and event rates were derived from the scientific literature, and costs and benefits were discounted by 3%. One-way sensitivity analyses were performed to test model robustness. Over 25 years, the partial meniscectomy strategy cost $10,430, whereas meniscal allograft cost on average $4040 more, at $14,470. Partial meniscectomy postponed TKA an average of 12.5 years, compared with 17.30 years for meniscal allograft, an increase of 4.8 years. Allograft cost $842 per-year-gained in time to TKA. Meniscal allografts have been shown to reduce pain and improve function in patients with discoid lateral meniscus tears. Though more costly, meniscal allografts may be more effective than partial meniscectomy in delaying TKA in this model. Additional future long term clinical studies will provide more insight into optimal surgical options.

  5. Analysis of human acellular nerve allograft reconstruction of 64 injured nerves in the hand and upper extremity: a 3 year follow-up study.

    PubMed

    Zhu, Shuang; Liu, Jianghui; Zheng, Canbin; Gu, Liqiang; Zhu, Qingtang; Xiang, Jianping; He, Bo; Zhou, Xiang; Liu, Xiaolin

    2017-08-01

    Human acellular nerve allografts have been increasingly applied in clinical practice. This study was undertaken to investigate the functional outcomes of nerve allograft reconstruction for nerve defects in the upper extremity. A total of 64 patients from 13 hospitals were available for this follow-up study after nerve repair using human acellular nerve allografts. Sensory and motor recovery was examined according to the international standards for motor and sensory nerve recovery. Subgroup analysis and logistic regression analysis were conducted to identify the relationship between the known factors and the outcomes of nerve repair. Mean follow-up time was 355 ± 158 (35-819) days; mean age was 35 ± 11 (14-68) years; average nerve gap length was 27 ± 13 (10-60) mm; no signs of infection, tissue rejection or extrusion were observed among the patients; 48/64 (75%) repaired nerves experienced meaningful recovery. Univariate analysis showed that site and gap length significantly influenced prognosis after nerve repair using nerve grafts. Delay had a marginally significant relationship with the outcome. A multivariate logistic regression model revealed that gap length was an independent predictor of nerve repair using human acellular nerve allografts. The results indicated that the human acellular nerve allograft facilitated safe and effective nerve reconstruction for nerve gaps 10-60 mm in length in the hand and upper extremity. Factors such as site and gap length had a statistically significant influence on the outcomes of nerve allograft reconstruction. Gap length was an independent predictor of nerve repair using human acellular nerve allografts. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Osteoinductive effect of bone bank allografts on human osteoblasts in culture.

    PubMed

    de la Piedra, Concepción; Vicario, Carlos; de Acuña, Lucrecia Rodríguez; García-Moreno, Carmen; Traba, Maria Luisa; Arlandis, Santiago; Marco, Fernando; López-Durán, Luis

    2008-02-01

    Incorporation of a human bone allograft requires osteoclast activity and growth of recipient osteoblasts. The aim of this work was to study the effects produced by autoclavated and -80 degrees C frozen bone allografts on osteoblast proliferation and synthesis of interleukin 6 (IL6), activator of bone resorption, aminoterminal propeptide of procollagen I (PINP), marker of bone matrix formation, and osteoprotegerin (OPG), inhibitor of osteoclast activity and differentiation. Allografts were obtained from human femoral heads. Human osteoblasts were cultured in the presence (problem group) or in the absence (control group) of allografts during 15 days. Allografts produced a decrease in osteoblast proliferation in the first week of the experiment, and an increase in IL6 mRNA, both at 3 h and 2 days, and an increase in the IL6 released to the culture medium the second day of the experiment. We found a decrease in OPG released to the culture on the 2nd and fourth days. These results suggest an increase in bone resorption and a decrease in bone formation in the first week of the experiment. In the second week, allografts produced an increase in osteoblast proliferation and PINP release to the culture medium, indicating an increase in bone formation; an increase in OPG released to the culture medium, which would indicate a decrease in bone resorption; and a decrease in IL6, indicating a decrease in bone resorption stimulation. These results demonstrate that autoclavated and -80 degrees C frozen bone allografts produce in bone environment changes that regulate their own incorporation to the recipient bone.

  7. Donor and procurement related issues in vascularized composite allograft transplantation.

    PubMed

    McDiarmid, Sue V

    2013-12-01

    To understand the unique requirements of vascularized composite allograft (VCA) donation and procurement practices and the integral role of the established nationwide organ procurement organizations in organ procurement. The recent issuance of a Final Rule (July 2013) by the United States Secretary of Health that redefines VCAs as organs rather than tissues, opens up the potential to formalize policies and procedures, under the auspices of the Organ Procurement and Transplantation Network, that can improve VCA donation, procurement practices, develop allocation algorithms and provide transparent oversight. Improved VCA donation rates, procurement procedures and broader sharing nationwide of VCA donors will have important implications in advancing the emerging field of VCA transplantation.

  8. Sporicidal efficacy of genipin: a potential theoretical alternative for biomaterial and tissue graft sterilization.

    PubMed

    Reich, Michael S; Akkus, Ozan

    2013-09-01

    Terminal sterilization of musculoskeletal allografts by gamma radiation minimizes the risk of disease transmission but impairs allograft mechanical properties. Commonly employed crosslinking agents can sterilize tissues without affecting mechanical properties adversely; however, these agents are toxic. Genipin is reported to be a benign crosslinking agent that strengthens mechanical properties of tissues; however, the antimicrobial capacity of genipin is largely unknown. The present study's aims were: (1) to assess the sporicidal potential of genipin, (2) to improve antimicrobial capacity by changing chemical and physical treatment conditions. To establish genipin's sterilization potential Bacillus subtilis var. niger spore strips were treated with 0-10% genipin in PBS or in 1:1 DMSO:PBS up to 72 h at room temperature (RT). Sterilizing doses and concentrations of genipin were used to treat B. pumilus and Geobacillus stearothermophilus spores to assess broader spectrum sporicidal activity of genipin. Scanning electron microscopy (SEM) was performed to evaluate gross morphological changes after genipin treatment. Optimal sterilization conditions were determined by evaluating the effects of temperature (RT-50 °C), DMSO:PBS ratio (0:100-100:0), and treatment duration (24-72 h) on B. subtilis. Genipin penetration of full thickness bovine patellar tendon and cortical bone specimens was observed to assess the feasibility of the agent for treating grafts. Initial studies showed that after 72 h of treatment at RT with 0.63-10% genipin/DMSO:PBS B. subtilis spore strips were sterilized; 0.63% genipin/PBS did not sterilize spore strips at 72 h at RT. Genipin doses and concentrations that sterilized B. subtilis spore strips sterilized B. pumilus and G. stearothermophilus spore strips. SEM revealed no gross morphological differences between untreated and treated spores. Treatment optimization resulted in sterilization within 24 h with 100% PBS, and DMSO facilitated sporicidal

  9. Is It Worthwhile Treating Occluded Cold Stored Venous Allografts by Thrombolysis?

    PubMed

    Balaz, P; Wohlfahrt, P; Rokosny, S; Maly, S; Bjorck, M

    2016-09-01

    Thrombolysis has been reported to be suboptimal in occluded vein grafts and cryopreserved allografts, and there are no data on the efficacy of thrombolysis in occluded cold stored venous allografts. The aim was to evaluate early outcomes, secondary patency and limb salvage rates of thrombolysed cold stored venous allograft bypasses and to compare the outcomes with thrombolysis of autologous bypasses. This was a single center study of consecutive patients with acute and non-acute limb ischemia between September 1, 2000, and January 1, 2014, with occlusion of cold stored venous allografts, and between January 1, 2012, and January 1, 2014, with occlusion of autologous bypass who received intra-arterial thrombolytic therapy. Sixty-one patients with occlusion of an infrainguinal bypass using a cold stored venous allograft (n = 35) or an autologous bypass (n = 26) underwent percutaneous intra-arterial thrombolytic therapy. The median duration of thrombolysis was 20 h (IQR 18-24) with no difference between the groups (p = .14). The median follow up was 18.5 months (IQR 11.0-52.0). Secondary patency rates of thrombolysed bypass at 6 and 12 months were 44 ± 9% and 32 ± 9% in patients with a venous allograft bypass and 46 ± 10% and 22 ± 8% with an autologous bypass, with no difference between groups (p = .40). Limb salvage rates at 1, 6, and 12 months after thrombolysis in the venous allograft group were 83 ± 7%, 72 ± 8% and 63 ± 9%, and in the autologous group 91 ± 6%, 76 ± 9%, and 65 ± 13%, with no difference between groups (p = .69). Long-term results of thrombolysis of venous allograft bypasses are similar to those of autologous bypasses. Occluded cold stored venous allograft can be successfully re-opened in most cases with a favorable effect on limb salvage. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  10. Adhesion monitoring of skin grafts by photoacoustic measurement: experiment using rat allograft models

    NASA Astrophysics Data System (ADS)

    Yamazaki, Mutsuo; Sato, Shunichi; Saito, Daizo; Okada, Yoshiaki; Ashida, Hiroshi; Obara, Minoru

    2004-07-01

    Adhesion monitoring of grafted skins is very important in successful treatment of severe burns and traumas. However, current diagnosis of skin grafting is usually done by visual observation, which is not reliable and gives no quantitative information on the skin graft adhesion. When the grafted skin adheres well, neovascularities will be generated in the grafted skin tissue, and therefore adhesion may be monitored by detecting the neovascularities. In this study, we attempted to measure photoacoustic signals originate from the neovascularities by irradiating the grafted skins with 532-nm nanosecond light pulses in rat autograft and allograft models. The measurement showed that immediately after skin grafting, photoacoustic signal originate from the blood in the dermis was negligibly small, while 6 - 24 hours after skin grafting, signal was observed from the dermis in the graft. We did not observe a significant difference between the signals from the autograft and the allograft models. These results indicate that neovascularization would take place within 6 hours after skin grafting, and the rejection reaction would make little effect on adhesion within early hours after grafting.

  11. Human osteoblast cells: isolation, characterization, and growth on polymers for musculoskeletal tissue engineering.

    PubMed

    El-Amin, Saadiq F; Botchwey, Edward; Tuli, Richard; Kofron, Michelle D; Mesfin, Addisu; Sethuraman, Swaminathan; Tuan, Rocky S; Laurencin, Cato T

    2006-03-01

    We performed a detailed examination of the isolation, characterization, and growth of human osteoblast cells derived from trabecular bone. We further examined the morphology, phenotypic gene expression, mineralization,and growth of these human osteoblasts on polyester polymers used for musculoskeletal tissue engineering. Polylactic-co-glycolic acid [PLAGA (85:15, 50:50, 75:25)], and poly-lactic acid (L-PLA, D,L-PLA) were examined. The osteoblastic expression of key phenotypic markers osteocalcin, alkaline phosphatase, collagen, and bone sialoprotein at 4 and 8 weeks was examined. Reverse transcription-polymerase chain reaction studies revealed that trabecular-derived osteoblasts were positive for all markers evaluated with higher levels expressed over long-term culture. These cells also revealed mineralization and maturation as evidenced by energy dispersive X-ray analysis and scanning electron microscopy. Growth studies on PLAGA at 50:50,75:25, and 85:15 ratios and PLA in the L and DL isoforms revealed that human osteoblasts actively grew, with significantly higher cell numbers attached to scaffolds composed of PLAGA 50:50 in the short term and PLAGA 85:15 in the long term compared with PLA (p < 0.05). We believe human cell adhesion among these polymeric materials may be dependent on differences in cellular integrin expression and extracellular matrix protein elaboration. (c) 2005 Wiley Periodicals, Inc.

  12. Biological variation in musculoskeletal injuries: current knowledge, future research and practical implications.

    PubMed

    Collins, Malcolm; September, Alison V; Posthumus, Michael

    2015-12-01

    Evidence from familial and genetic association studies have reported that DNA sequence variants play an important role, together with non-genetic factors, in the aetiology of both exercise-associated and occupational-associated acute and chronic musculoskeletal soft tissue injuries. The associated variants, which have been identified to date, may contribute to the interindividual variation in the structure and, by implication, mechanical properties of the collagen fibril and surrounding matrix within musculoskeletal soft tissues, as well as their response to mechanical loading and other stimuli. Future work should focus on the establishment of multidisciplinary international consortia for the identification of biologically relevant variants involved in modulating injury risk. These consortia will improve the limitations of the published hypothesis-driven genetic association studies, since they will allow resources to be pooled in recruiting large well-characterised cohorts required for whole-genome screening. Finally, clinicians and coaches need to be aware that many direct-to-consumer companies are currently marketing genetic tests directly to athletes without it being requested by an appropriately qualified healthcare professional, and without interpretation alongside other clinical indicators or lifestyle factors. These specific genetic tests are premature and are not necessarily required to evaluate susceptibility to musculoskeletal soft tissue injury. Current practice should rather consider susceptibility through known risk factors such as a positive family history of a specific injury, a history of other tendon and/or ligament injuries and participation in activities associated with the specific musculoskeletal injuries. Potential susceptible athletes may then be individually managed to reduce their risk profile. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Scapular allograft reconstruction after total scapulectomy: surgical technique and functional results.

    PubMed

    Capanna, Rodolfo; Totti, Francesca; Van der Geest, Ingrid C M; Müller, Daniel A

    2015-08-01

    Scapular allograft reconstruction after total scapulectomy preserving the rotator cuff muscles is an oncologically safe procedure and results in good functional outcome with a low complication rate. The data of 6 patients who underwent scapular allograft reconstruction after a total scapulectomy for tumor resection were retrospectively reviewed. At least 1 of the rotator cuff muscles was preserved and the size-matched scapular allograft fixed to the residual host acromion with a plate and screws. The periscapular muscles and the residual joint capsule were sutured to the corresponding insertions of the allograft. The mean follow-up was 5.5 years (range, 24-175 months). In all patients, a wide surgical margin was achieved. The average functional scores were 20 points for the International Society of Limb Salvage score and 60 points for the American Shoulder and Elbow Surgeons score. Mean active shoulder flexion of 60° (range, 30°-90°) and mean active abduction of 62° (range, 30°-90°) were achieved. During the follow-up, 1 patient (16.6%) had a local recurrence and lung metastasis, whereas the remaining 5 patients (83.3%) were disease free. Two breakages of the osteosynthesis and 2 allograft fractures were observed, necessitating a revision surgery in 2 cases (33.3%). In this series, no infection, allograft resorption, or shoulder instability occurred. Allograft substitution of a completely removed scapula is an oncologically safe procedure, with good functional results, avoiding common complications in prosthetic replacements such as infection and dislocation of the shoulder joint. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  14. A Preliminary Clinical Comparison of the Use of Fascia Lata Allograft and Autogenous Connective Tissue Graft in Multiple Gingival Recession Coverage Based on the Tunnel Technique.

    PubMed

    Bednarz, Wojciech; Żurek, Jacek; Gedrange, Thomas; Dominiak, Marzena

    2016-01-01

    The most effective method for treating gingival recessions (GR) is with an autogenous connective tissue graft (CTG) via flap surgery. Often, however, the amount of CTG that can be grafted is insufficient to cover all of a patient's gingival recessions at one time. The objective of this study was to provide a 6-month comparative assessment of the results of covering multiple Miller Class I and II gingival recessions with a Fascia Lata Allograft (FL) and a CTG harvested from palatal mucosa. The study comprised a total of 30 people who underwent multiple gingival recession (GR) procedures using a modified, coronally advanced tunnel technique (MCAT). The patients were divided into two groups of 15 according to the type of materials used for gingival augmentation purposes: FL for the test group and CTG for the control group. A clinical assessment was made at baseline, as well as 3 and 6 months following surgery. The following factors were assessed: recession depth, recession width, probing depth, clinical attachment level, height of keratinized tissue (HKT), distance between the cemento-enamel junction and the muco-gingival junction (CEJ-MGJ), API, SBI. The following values were calculated: average root coverage (ARC), complete root coverage (CRC). No statistically significant differences were observed between the groups in terms of clinical parameters assessed after 6 months, apart from CRC, which was 94.87 ± 0.14 mm in the control group and 94.24 ± 0.20 mm in the study group (p = 0.034). The average HKT in the control group after 6 months amounted to 2.86 ± 1.60 mm, and in the test group to 3.09 ± 0.95 mm, which translates into an increase in comparison to the baseline values of 0.73 mm (p < 0.001) and 0.48 mm (p = 0.017), respectively. FL Allografts may serve as an alternative to autogenous CTG in multiple gingival recession coverage procedures based on the tunnel technique.

  15. Myocardial Tissue Engineering for Regenerative Applications.

    PubMed

    Fujita, Buntaro; Zimmermann, Wolfram-Hubertus

    2017-09-01

    This review provides an overview of the current state of tissue-engineered heart repair with a special focus on the anticipated modes of action of tissue-engineered therapy candidates and particular implications as to transplant immunology. Myocardial tissue engineering technologies have made tremendous advances in recent years. Numerous different strategies are under investigation and have reached different stages on their way to clinical translation. Studies in animal models demonstrated that heart repair requires either remuscularization by delivery of bona fide cardiomyocytes or paracrine support for the activation of endogenous repair mechanisms. Tissue engineering approaches result in enhanced cardiomyocyte retention and sustained remuscularization, but may also be explored for targeted paracrine or mechanical support. Some of the more advanced tissue engineering approaches are already tested clinically; others are at late stages of pre-clinical development. Process optimization towards cGMP compatibility and clinical scalability of contractile engineered human myocardium is an essential step towards clinical translation. Long-term allograft retention can be achieved under immune suppression. HLA matching may be an option to enhance graft retention and reduce the need for comprehensive immune suppression. Tissue-engineered heart repair is entering the clinical stage of the translational pipeline. Like in any effective therapy, side effects must be anticipated and carefully controlled. Allograft implantation under immune suppression is the most likely clinical scenario. Strategies to overcome transplant rejection are evolving and may further boost the clinical acceptance of tissue-engineered heart repair.

  16. Playing-related musculoskeletal disorders in music students-associated musculoskeletal signs.

    PubMed

    Steinmetz, A; Möller, H; Seidel, W; Rigotti, T

    2012-12-01

    Pain and overuse are common problems for musicians. Up to 80% of professional musicians suffer from playing-related musculoskeletal disorders (PRMD). The prevalence rate in music students is very high as well. Sufficient data on the underlying musculoskeletal dysfunctions however is scarce. Additionally, the self-assessment of health in musicians seems to differ compared to non-musicians, which might influence their attitudes concerning preventive strategies. Evaluation of frequency of PRMD in music students, investigation of signs and symptoms in music students compared to non-music controls, comparison of self-reported health and well-being between the two groups. Prospective, cross-sectional, case control, non-randomized. Other (University volunteers). Music students in comparison to a non-music control group. Musculoskeletal examination and questionnaire of 36 volunteers of a music university and 19 volunteer students of an university of education were analyzed. The total number of musculoskeletal dysfunctions and differences between the student groups were examined. The personal pain and health self-rating were compared between music and non-music students. Eighty one percent of musicians experienced PRMD. Musicians experienced 6.19 pain regions on average compared to 4.31 of non-musicians. Musicians experiencing PRMD reported significantly (P<0.05) more pain locations than musicians without. Music students presented with nearly the double amount (8.39 versus 4.37) of musculoskeletal dysfunctions per person compared to the non-music control group. Nevertheless, musicians significantly (P<0.05) rated their health more positively than the controls. Musicians presented with more pain regions and a higher amount of musculoskeletal dysfunctions. Further studies evaluating the clinical relevance and their role in the development of PRMD are warranted. Screening of musicians for musculoskeletal dysfunction may identify those musicians at increased risk. Early

  17. Sonography of the musculoskeletal system in dogs and cats.

    PubMed

    Kramer, M; Gerwing, M; Hach, V; Schimke, E

    1997-01-01

    Sonography of the musculoskeletal system in dogs and cats was undertaken to evaluate the application of this imaging procedure in orthopedics. In most of the patients a 7.5 MHz linear transducer was used because of its flat application surface and its resolving power. The evaluation of bone by sonography is limited, but sonography can provide addition information regarding the bone surface and surrounding soft tissue. Ultrasound is valuable for assessing joint disease. Joint effusion, thickening of the joint capsule and cartilage defects can be identified sonographically. It is also possible to detect bone destruction. Instabilities are often identified with the help of a dynamic examination. Soft tissue abnormalities of the musculoskeletal system lend themselves to sonographic evaluation. Partial or complete muscles or tendon tears are able to be differentiated and the healing process can be monitored. Most of the diseases that are in the area of the biceps or the achilles tendon, such as dislocation of the tendon, old injuries with scarification, free dissecates in the tendonsheath, tendinitis and/or tendosynovitis can be differentiated by sonography. In addition, with clinical and laboratory findings, it is often possible to make a correct diagnosis with ultrasound in patients with abscesses, foreign bodies, hematomas, soft tissue tumors and lipomas.

  18. Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity.

    PubMed

    Collins, Kelsey H; Herzog, Walter; MacDonald, Graham Z; Reimer, Raylene A; Rios, Jaqueline L; Smith, Ian C; Zernicke, Ronald F; Hart, David A

    2018-01-01

    Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i.e., muscle, bone, tendon, and joints) that result from obesity-associated metabolic disturbances are less frequently interrogated. As musculoskeletal diseases can lead to the worsening of MetS, this underscores the imminent need to understand the cause and effect relations between the two, and the convergence between inflammatory pathways that contribute to MSK damage. Muscle mass is a key predictor of longevity in older adults, and obesity-induced sarcopenia is a significant risk factor for adverse health outcomes. Muscle is highly plastic, undergoes regular remodeling, and is responsible for the majority of total body glucose utilization, which when impaired leads to insulin resistance. Furthermore, impaired muscle integrity, defined as persistent muscle loss, intramuscular lipid accumulation, or connective tissue deposition, is a hallmark of metabolic dysfunction. In fact, many common inflammatory pathways have been implicated in the pathogenesis of the interrelated tissues of the musculoskeletal system (e.g., tendinopathy, osteoporosis, and osteoarthritis). Despite these similarities, these diseases are rarely evaluated in a comprehensive manner. The aim of this review is to summarize the common pathways that lead to musculoskeletal damage and disease that result from and contribute to MetS. We propose the overarching hypothesis that there

  19. Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity

    PubMed Central

    Collins, Kelsey H.; Herzog, Walter; MacDonald, Graham Z.; Reimer, Raylene A.; Rios, Jaqueline L.; Smith, Ian C.; Zernicke, Ronald F.; Hart, David A.

    2018-01-01

    Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i.e., muscle, bone, tendon, and joints) that result from obesity-associated metabolic disturbances are less frequently interrogated. As musculoskeletal diseases can lead to the worsening of MetS, this underscores the imminent need to understand the cause and effect relations between the two, and the convergence between inflammatory pathways that contribute to MSK damage. Muscle mass is a key predictor of longevity in older adults, and obesity-induced sarcopenia is a significant risk factor for adverse health outcomes. Muscle is highly plastic, undergoes regular remodeling, and is responsible for the majority of total body glucose utilization, which when impaired leads to insulin resistance. Furthermore, impaired muscle integrity, defined as persistent muscle loss, intramuscular lipid accumulation, or connective tissue deposition, is a hallmark of metabolic dysfunction. In fact, many common inflammatory pathways have been implicated in the pathogenesis of the interrelated tissues of the musculoskeletal system (e.g., tendinopathy, osteoporosis, and osteoarthritis). Despite these similarities, these diseases are rarely evaluated in a comprehensive manner. The aim of this review is to summarize the common pathways that lead to musculoskeletal damage and disease that result from and contribute to MetS. We propose the overarching hypothesis that there

  20. Coordinated development of the limb musculoskeletal system: Tendon and muscle patterning and integration with the skeleton.

    PubMed

    Huang, Alice H

    2017-09-15

    Functional movement and stability of the limb depends on an organized and fully integrated musculoskeletal system composed of skeleton, muscle, and tendon. Much of our current understanding of musculoskeletal development is based on studies that focused on the development and differentiation of individual tissues. Likewise, research on patterning events have been largely limited to the primary skeletal elements and the mechanisms that regulate soft tissue patterning, the development of the connections between tissues, and their interdependent development are only beginning to be elucidated. This review will therefore highlight recent exciting discoveries in this field, with an emphasis on tendon and muscle patterning and their integrated development with the skeleton and skeletal attachments. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Electrocardiographic Characteristics of Potential Organ Donors and Associations with Cardiac Allograft Utilization

    PubMed Central

    Khush, Kiran K.; Menza, Rebecca; Nguyen, John; Goldstein, Benjamin A.; Zaroff, Jonathan G.; Drew, Barbara J.

    2012-01-01

    Background Current regulations require that all cardiac allograft offers for transplantation must include an interpreted 12-lead electrocardiogram (ECG). However, little is known about the expected ECG findings in potential organ donors, or the clinical significance of any identified abnormalities in terms of cardiac allograft function and suitability for transplantation. Methods and Results A single experienced reviewer interpreted the first ECG obtained after brainstem herniation in 980 potential organ donors managed by the California Transplant Donor Network from 2002-2007. ECG abnormalities were summarized, and associations between specific ECG findings and cardiac allograft utilization for transplantation were studied. ECG abnormalities were present in 51% of all cases reviewed. The most common abnormalities included voltage criteria for left ventricular hypertrophy (LVH), prolongation of the corrected QT interval (QTc), and repolarization changes (ST/T wave abnormalities). Fifty seven percent of potential cardiac allografts in this cohort were accepted for transplantation. LVH on ECG was a strong predictor of allograft non-utilization. No significant associations were seen between QTc prolongation, repolarization changes and allograft utilization for transplantation, after adjusting for donor clinical variables and echocardiographic findings. Conclusions We have performed the first comprehensive study of ECG findings in potential donors for cardiac transplantation. Many of the common ECG abnormalities seen in organ donors may result from the heightened state of sympathetic activation that occurs after brainstem herniation, and are not associated with allograft utilization for transplantation. PMID:22615333

  2. Estimated Nephron Number of the Donor Kidney: Impact on Allograft Kidney Outcomes.

    PubMed

    Schachtner, T; Reinke, P

    Low birth weights have been associated with a reduction in nephron number with compensatory hypertrophy of existing glomeruli. The impact of donor birth weight as an estimate of nephron number on allograft function, however, has not been examined. We collected donor birth weight, kidney weight, and volume from 91 living kidney donor-recipient pairs before nephrectomy and after 12, 36, and 60 months. Nephron number was calculated from donor birth weight and age. Donor birth weight, kidney weight/body surface area (BSA), and kidney volume showed a moderate positive correlation with allograft estimated glomerular filtration rate (eGFR) at 12 months (P < .05). Donor age showed a negative moderate correlation with allograft eGFR at 12 months (P = .015). The strongest correlation with allograft eGFR was observed for calculated donor kidney nephron number at 12, 36, and 60 months (R, 0.340, 0.305, and 0.476, respectively; P < .05). No impact was observed on allograft daily proteinuria of any investigated marker (P > .05). Recipients of donors with birth weight <2.5 kg had need of a significantly greater number of antihypertensive drugs (P < .05). Calculated nephron number from donor birth weight and age is suggested to be superior to donor kidney weight/BSA and volume regarding allograft function. Calculated nephron number could estimate expected eGFR and guide decision making in cases of impaired allograft function. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Reported infections after human tissue transplantation before and after new Food and Drug Administration (FDA) regulations, United States, 2001 through June, 2010.

    PubMed

    Mallick, Tarun K; Mosquera, Alexis; Zinderman, Craig E; St Martin, Laura; Wise, Robert P

    2012-06-01

    Processors distributed about 1.5 million human tissue allografts in the U.S. in 2007. The potential for transmitting infections through allografts concerns clinicians and patients. In 2005, FDA implemented Current Good Tissue Practice (CGTP) rules requiring tissue establishments to report to FDA certain serious infections after allograft transplantations. We describe infection reports following tissue transplants received by FDA from 2005 through June, 2010, and compare reporting before and after implementation of CGTP rules. We identified reports received by FDA from January 2001 through June, 2010, for infections in human tissue recipients, examining the reports by tissue type, organism, time to onset, severity, and reporter characteristics. Among 562 reports, 83 (20.8/year) were received from 2001-2004, before the CGTP rules, 43 in the 2005 transition year, and 436 (96.9/year) from 2006 through June, 2010, after the rules. Tissue processors accounted for 84.2% of reports submitted after the rules, compared to 26.5% previously. Bacterial infections were the most commonly reported organisms before (64.6%) and after (62.2%) the new rules. Afterward, 2.5% (11) of reports described deaths, and 33.7% (147) involved hospitalizations. Before the rules, 13% (11) described deaths, and another 72% involved hospitalizations. Reports received by the FDA quadrupled since 2005, suggesting that CGTP regulations have contributed to increased reporting and improved tissue safety surveillance. However, these data do not confirm that the reported infections were caused by suspect tissues; most reports may represent routine post-surgical infections not actually due to allografts.

  4. [Musculoskeletal pain].

    PubMed

    Casser, H-R; Schaible, H-G

    2015-10-01

    Among the clinically relevant pain conditions, pain in the musculoskeletal system is most frequent. This article reports extensive epidemiological data on musculoskeletal system pain in Germany and worldwide. Since back pain is most frequent, the diagnostics and therapeutic algorithms of acute, recurring, and chronic lower back pain in Germany will be particularly addressed. The importance of the physiologic-organic, the cognitive-emotional, the behavioral, and the social level to diagnostics and treatment will be discussed. We will also focus on osteoarthritic pain and address its epidemiology, clinical importance, and significance for the health care system. This article will list some reasons why the musculoskeletal system in particular is frequently the site of chronic pain. The authors believe that these reasons are to be sought in the complex structures of the musculoskeletal system; in the particular sensitivity of the deep somatic nociceptive system for long-term sensitization processes, as well as the ensuing nervous system reactions; and in the interactions between the nervous and immune systems. The article will give some insights into the research carried out on this topic in Germany.

  5. Diagnostic value of plasma and bronchoalveolar lavage samples in acute lung allograft rejection: differential cytology.

    PubMed

    Speck, Nicole E; Schuurmans, Macé M; Murer, Christian; Benden, Christian; Huber, Lars C

    2016-06-21

    Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

  6. Comparative evaluation of guided tissue regeneration with use of collagen-based barrier freeze-dried dura mater allograft for mandibular class 2 furcation defects (a comparative controlled clinical study).

    PubMed

    Patel, Sandeep; Kubavat, Ajay; Ruparelia, Brijesh; Agarwal, Arvind; Panda, Anup

    2012-01-01

    The aim of periodontal surgery is complete regeneration. The present study was designed to evaluate and compare clinically soft tissue changes in form of probing pocket depth, gingival shrinkage, attachment level and hard tissue changes in form of horizontal and vertical bone level using resorbable membranes. Twelve subjects with bilateral class 2 furcation defects were selected. After initial phase one treatment, open debridement was performed in control site while freezedried dura mater allograft was used in experimental site. Soft and hard tissue parameters were registered intrasurgically. Nine months reentry ensured better understanding and evaluation of the final outcome of the study. Guided tissue regeneration is a predictable treatment modality for class 2 furcation defect. There was statistically significant reduction in pocket depth as compared to control (p < 0.01). There is statistically significant increase in periodontal attachment level within control and experimental sites showed better results (p < 0.01). For hard tissue parameter, significant defect fill resulted in experimental group, while in control group, less significant defect fill was found in horizontal direction and nonsignificant defect fill was found in vertical direction. The results showed statistically significant improvement in soft and hard tissue parameters and less gingival shrinkage in experimental sites compared to control site. The use of FDDMA in furcation defects helps us to achieve predictable results. This cross-linked collagen membrane has better handling properties and ease of procurement as well as economic viability making it a logical material to be used in regenerative surgeries.

  7. Outcomes After Dermal Allograft Reconstruction of Chronic or Subacute Pectoralis Major Tendon Ruptures.

    PubMed

    Neumann, Julie A; Klein, Christopher M; van Eck, Carola F; Rahmi, Hithem; Itamura, John M

    2018-01-01

    Avoiding delay in the surgical management of pectoralis major (PM) ruptures optimizes outcomes. However, this is not always possible, and when a tear becomes chronic or when a subacute tear has poor tissue quality, a graft can facilitate reconstruction. The primary aim was to evaluate the clinical outcomes of PM reconstruction with dermal allograft augmentation for chronic tears or for subacute tears with poor tissue quality. A second aim was to determine patient and surgical factors affecting outcome. Case series; Level of evidence, 4. Nineteen consecutive patients (19 PM ruptures) with a mean ± SD age of 39.1 ± 8.4 years were retrospectively reviewed at 26.4 ± 16.0 months following PM tendon reconstruction with dermal allograft. Surgery was performed at 19.2 ± 41.2 months after injury (median, 7.6 months; range, 1.1-185.4 months). Several outcome scores were recorded pre- and postoperatively, including Disabilities of the Arm, Shoulder, and Hand (DASH), as well as visual analog scale (VAS) (range, 0-10; 0 = no pain) and Single Assessment Numeric Evaluation (SANE). Range of motion, Constant score, American Shoulder and Elbow Surgeons (ASES) score, Simple Shoulder Test score, and complications/reoperations were recorded postoperatively. Scores improved significantly for the DASH (preoperative, 34.9; postoperative, 8.0; P < .001) and VAS (preoperative, 5.0; postoperative, 1.5; P = .011). There was a trend toward improved SANE scores (preoperative, 15.0; postoperative, 80.0; P = .097), but the difference was not statistically significant, likely because of the small number of patients having preoperative SANE scores for review. Increased age was associated with higher VAS scores ( r = 0.628, P = .016) and less forward flexion ( r = -0.502, P = .048) and external rotation ( r = -0.654, P = .006). Patients with workers' compensation had lower scores for 3 measures: SANE (75.8 vs 88.4, P = .040), Constant (86.7 vs 93.4, P = .019), and ASES (81.9 vs 97.4, P = .016

  8. Soft tissue grafting to improve implant esthetics

    PubMed Central

    Kassab, Moawia M

    2010-01-01

    Dental implants are becoming the treatment of choice to replace missing teeth, especially if the adjacent teeth are free of restorations. When minimal bone width is present, implant placement becomes a challenge and often resulting in recession and dehiscence around the implant that leads to subsequent gingival recession. To correct such defect, the author turned to soft tissue autografting and allografting to correct a buccal dehiscence around tooth #24 after a malpositioned implant placed by a different surgeon. A 25-year-old woman presented with the chief complaint of gingival recession and exposure of implant threads around tooth #24. The patient received three soft tissue grafting procedures to augment the gingival tissue. The first surgery included a connective tissue graft to increase the width of the keratinized gingival tissue. The second surgery included the use of autografting (connective tissue graft) to coronally position the soft tissue and achieve implant coverage. The third and final surgery included the use of allografting material Alloderm to increase and mask the implant from showing through the gingiva. Healing period was uneventful for the patient. After three surgical procedures, it appears that soft tissue grafting has increased the width and height of the gingiva surrounding the implant. The accomplished thickness of gingival tissue appeared to mask the showing of implant threads through the gingival tissue and allowed for achieving the desired esthetic that the patient desired. The aim of the study is to present a clinical case with soft tissue grafting procedures. PMID:23662087

  9. Inhibition of the purinergic pathway prolongs mouse lung allograft survival.

    PubMed

    Liu, Kaifeng; Vergani, Andrea; Zhao, Picheng; Ben Nasr, Moufida; Wu, Xiao; Iken, Khadija; Jiang, Dawei; Su, Xiaofeng; Fotino, Carmen; Fiorina, Paolo; Visner, Gary A

    2014-08-01

    Lung transplantation has limited survival with current immunosuppression. ATP is released from activated T cells, which act as costimulatory molecules through binding to the purinergic receptor P2XR7. We investigated the role of blocking the ATP/purinergic pathway, primarily P2XR7, using its inhibitor oxidized ATP (oATP) in modulating rejection of mouse lung allografts. Mouse lung transplants were performed using mice with major histocompatibility complex mismatch, BALB/c to C57BL6. Recipients received suramin or oATP, and lung allografts were evaluated 15 to ≥ 60 days after transplantation. Recipients were also treated with oATP after the onset of moderate to severe rejection to determine its ability to rescue lung allografts. Outcomes measures included lung function, histology, thoracic imaging, and allo-immune responses. Blocking purinergic receptors with the nonselective inhibitor suramin or with the P2XR7-selective inhibitor oATP reduced acute rejection and prolonged lung allograft survival for ≥ 60 days with no progression in severity. There were fewer inflammatory cells within lung allografts, less rejection, and improved lung function, which was maintained over time. CD4 and CD8 T cells were reduced within lung allografts with impaired activation with prolonged impairment of CD8 responses. In vitro, oATP reduced CD8 activation of Th1 inflammatory cytokines IFN-γ and TNF-α and cytolytic machinery, granzyme B. Cotreatment with immunosuppressive agents, cyclosporine, rapamycin, or CTLA-4Ig resulted in no additive benefits, and oATP alone resulted in better outcomes than cyclosporine alone. This study illustrates a potential new pathway to target in hopes of prolonging survival of lung transplant recipients.

  10. The composition of human cortical allograft bone derived from FDA/AATB-screened donors.

    PubMed

    Pietrzak, William S; Woodell-May, Jennifer

    2005-07-01

    Allograft human bone is an integral part of the surgeons' armamentarium and will continue to be for the near future. The intraoperative handling and/or mechanical properties are critical to its function. These properties are significantly influenced by the composition and the structure of the bone, which varies from donor to donor. Published studies of human bone composition use bone derived from a population that may differ from the population of qualified donors from which allograft bone is derived and may not well represent the pool of clinical allograft bone. This study investigated the cortical bone composition from 20 donors (males and females, 17 to 65 years of age) that had passed the US Food and Drug Administration and American Association of Tissue Banks screening procedures for donor qualification. As such, this represents a subset of the general population. The analysis yielded the following composition: mineral (ash) = 67.0% +/- 1.3% (w/w); matrix (predominantly type I collagen and other proteins) = 31.9% +/- 1.1% (w/w); and lipid (hexane extractables) = 1.1% +/- 1.5% (w/w). In general, these results were well within the ranges specified in the literature, with the significance being the demonstration of low variability within the study population. No age or gender compositional dependency was evident in this series, possibly as a result of the relatively homogenous population, which may have limited the ability to observe trends. Visually, the bone powders ranged from nearly white to red-brown. The more intense colors appeared to be associated with greater lipid content, perhaps indicating the presence of residual oxidized lipids.

  11. The development of biomarkers for degenerative musculoskeletal conditions.

    PubMed

    Jayabalan, Prakash; Sowa, Gwendolyn A

    2014-02-01

    With an aging population, degenerative musculoskeletal conditions will become more prevalent with significantly increasing costs to society over the next several decades. The majority of these conditions are diagnosed radiographically, at which point the disease process is often more advanced and challenging to treat. The commonly available radiographic studies also do not adequately provide information as to the exact pain generator and findings often do not correlate either to patient symptoms or function. Personalized medicine involves formulating treatments based on a patient's own biology. The development of biological markers (biomarkers) pertaining to disease is a rapidly growing area within this field of medicine. For degenerative musculoskeletal conditions, biomarkers have the potential to provide an early non-invasive method of assessing the location and severity of tissue damage and presence of inflammation. By outlining mechanisms of disease they could allow the formulation of further treatment targets and through sub-categorizing patients into different groups based on their biomarker profile, one could provide more efficacious treatments for patients. The present article is a review of the development of biomarkers for these purposes specifically as they pertain to degenerative musculoskeletal conditions.

  12. The biomechanical behavior on the interface of tumor arthrosis/allograft prosthetic composite by finite element analysis

    NASA Astrophysics Data System (ADS)

    Chen, H. Z.; Jiang, W.; Zou, W.; Luo, J. M.; Chen, J. Y.; Tu, C. Q.; Xing, B. B.; Gu, Z. W.; Zhang, X. D.

    2008-11-01

    The biomechanical behavior of the uniting interface between the allograft bone and the autogenetic bone plays an important role in the treatment of the proximal femur massive defects with artificial tumor arthrosis/allograft prosthetic composite (TAAPC). According to the CT data of a patient, a 3D medical treatment model of TAAPC was established. Under the loads of 1.5 and 2.5 times standard body weight (70 kg), the mechanical behavior of the treatment model was analyzed by finite element analysis (FEA) for three typical healing periods. The results show that there are significant differences in the stress values and distribution in different healing periods. With healing of osteotomy, the hardness of the tissue of the uniting interface increases, the stress in uniting area was increased greatly and the stress concentration decreased. After cured the stress almost reached the level of normal bone. In the initial stage of healing, the healing training is not encouraged because there is an obvious risk of fracture of prosthesis and bone cement. In addition, porous hydroxyapatite (HA) ceramic used as bone tissue scaffold for this case, not only facilitates the generation of new bone, but also can avoid this risk caused by the non-uniting interface.

  13. Mucormycosis (zygomycosis) of renal allograft

    PubMed Central

    Gupta, Krishan L.; Joshi, Kusum; Kohli, Harbir S.; Jha, Vivekanand; Sakhuja, Vinay

    2012-01-01

    Fungal infection is relatively common among renal transplant recipients from developing countries. Mucormycosis, also known as zygomycosis, is one of the most serious fungal infections in these patients. The most common of presentation is rhino-cerebral. Isolated involvement of a renal allograft is very rare. A thorough search of literature and our medical records yielded a total of 24 cases with mucormycosis of the transplanted kidney. There was an association with cytomegalovirus (CMV) infection and anti-rejection treatment in these patients and most of these transplants were performed in the developing countries from unrelated donors. The outcome was very poor with an early mortality in 13 (54.5%) patients. Renal allograft mucormycosis is a relatively rare and potentially fatal complication following renal transplantation. Early diagnosis, graft nephrectomy and appropriate antifungal therapy may result in an improved prognosis for these patients. PMID:26069793

  14. Donor Predictors of Allograft Utilization and Recipient Outcomes after Heart Transplantation

    PubMed Central

    Khush, Kiran K.; Menza, Rebecca; Nguyen, John; Zaroff, Jonathan G.; Goldstein, Benjamin A.

    2013-01-01

    Background Despite a national organ donor shortage and a growing population of patients with end-stage heart disease, the acceptance rate of donor hearts for transplantation is low. We sought to identify donor predictors of allograft non-utilization, and to determine whether these predictors are in fact associated with adverse recipient post-transplant outcomes. Methods and Results We studied a cohort of 1,872 potential organ donors managed by the California Transplant Donor Network from 2001–2008. Forty five percent of available allografts were accepted for heart transplantation. Donor predictors of allograft non-utilization included age>50 years, female sex, death due to cerebrovascular accident, hypertension, diabetes, a positive troponin assay, left ventricular dysfunction and regional wall motion abnormalities, and left ventricular hypertrophy. For hearts that were transplanted, only donor cause of death was associated with prolonged recipient hospitalization post-transplant, and only donor diabetes was predictive of increased recipient mortality. Conclusions While there are many donor predictors of allograft discard in the current era, these characteristics appear to have little effect on recipient outcomes when the hearts are transplanted. Our results suggest that more liberal use of cardiac allografts with relative contraindications may be warranted. PMID:23392789

  15. Histopathology of spleen allograft rejection in miniature swine

    PubMed Central

    Dor, Frank J M F; Gollackner, Bernd; Kuwaki, Kenji; Ko, Dicken S C; Cooper, David K C; Houser, Stuart L

    2005-01-01

    Spleen transplantation (SpTx) has established donor-specific tolerance in rodents, but not in large animals or humans. We report the histopathology of rejection in an established model of SpTx in major histocompatibility complex (MHC)-defined miniature swine. Of the 17 SpTx, rejection was observed in two grafts transplanted into untreated, MHC-matched, minor antigen-disparate recipients (group 1, n = 4), but not in the two that received a 12-day course of cyclosporin A (CyA). Rejection also occurred in five grafts transplanted into fully MHC-disparate recipients (group 2, n = 12), one of which was untreated and four of which received some form of immunosuppressive therapy. One recipient of an MHC class-I-mismatched spleen treated with 12 days of CyA did not show rejection. Following biopsy and/or necropsy, fixed allograft tissue sections were treated with multiple stains, immunohistochemical markers and TUNEL assay. Common features of rejection occurred in grafts from both groups, but with varying time courses. Necrosis developed as early as day 8 in group 2 and day 27 in group 1, ranging from focal fibrinoid necrosis of arteriolar walls and sinusoids to diffuse liquefactive necrosis, usually associated with haemorrhage. Other features of rejection included white pulp expansion by atypical cells and decreased staining of basement membranes and reticular fibres. A doubling of the baseline TUNEL index preceded histologically identifiable rejection. This study establishes histologic guidelines for diagnosing and, perhaps, in future studies, predicting acute rejection of splenic allografts transplanted across known histocompatibility barriers in a large-animal model. PMID:15676033

  16. Metabolomic Profiling in Individuals with a Failing Kidney Allograft

    PubMed Central

    Biancone, Luigi; Bussolino, Stefania; Merugumala, Sai; Tezza, Sara; D’Addio, Francesca; Ben Nasr, Moufida; Valderrama-Vasquez, Alessandro; Usuelli, Vera; De Zan, Valentina; El Essawy, Basset; Venturini, Massimo; Secchi, Antonio; De Cobelli, Francesco; Lin, Alexander; Chandraker, Anil; Fiorina, Paolo

    2017-01-01

    Background Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. Methods To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls. Results LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels. Conclusions We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function. PMID:28052095

  17. Metabolomic Profiling in Individuals with a Failing Kidney Allograft.

    PubMed

    Bassi, Roberto; Niewczas, Monika A; Biancone, Luigi; Bussolino, Stefania; Merugumala, Sai; Tezza, Sara; D'Addio, Francesca; Ben Nasr, Moufida; Valderrama-Vasquez, Alessandro; Usuelli, Vera; De Zan, Valentina; El Essawy, Basset; Venturini, Massimo; Secchi, Antonio; De Cobelli, Francesco; Lin, Alexander; Chandraker, Anil; Fiorina, Paolo

    2017-01-01

    Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls. LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels. We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function.

  18. Early application of Met-RANTES ameliorates chronic allograft nephropathy.

    PubMed

    Song, Erwei; Zou, Hequn; Yao, Yousheng; Proudfoot, Amanda; Antus, Balazs; Liu, Shanying; Jens, Lutz; Heemann, Uwe

    2002-02-01

    Initial insults to kidney allografts, characterized by infiltration of mononuclear inflammatory cells, contribute to chronic allograft nephropathy. Chemokines such as RANTES (regulated upon activation, normal T cell expressed) are thought to be responsible for the recruitment and activation of infiltrating cells. The present study investigated whether early application of Met-RANTES, a chemokine receptor antagonist that blocks the effects of RANTES, can protect renal allografts from long-term deterioration. Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients and treated with cyclosporine A (1.5 mg/kg/day) for the first 10 days following transplantation, together with either Met-RANTES at 40 microg/day, 200 microg/day or vehicle for the first 7 days. Animals were harvested at 2 and 28 weeks after transplantation for histologic, immunohistologic and molecular analysis. Met-RANTES treatment reduced the infiltration of lymphocytes and macrophages in allografts at 2 weeks after transplantation, accompanied by decreased mRNA expression of interleukin (IL)-2, IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and RANTES. At post-transplantation week 28, Met-RANTES treatment at high and low doses reduced urinary protein excretion and significantly ameliorated glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal proliferation of graft arteries and mononuclear cell infiltration. However, creatinine clearance was not influenced by Met-RANTES. Furthermore, Met-RANTES suppressed the mRNA expression of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-B (PDGF-B). Blockade of chemokine receptors by Met-RANTES diminishes early infiltration and activation of mononuclear cells in the grafts, and thus reduces the pace of chronic allograft nephropathy.

  19. Mast cell phenotypes in the allograft after lung transplantation.

    PubMed

    Banga, Amit; Han, Yingchun; Wang, Xiaofeng; Hsieh, Fred H

    2016-07-01

    The burden of mast cell (MC) infiltration and their phenotypes, MC-tryptase (MCT ) and MC-tryptase/chymase (MCTC ), after lung transplantation (LT) has not been evaluated in human studies. We reviewed 20 transbronchial lung biopsy (TBLB) specimen from patients with early normal allograft (<6 months post-LT, n=5), late normal allograft (>6 months, n=5), A2 or worse acute cellular rejection (ACR, n=5), and chronic lung allograft dysfunction (CLAD, n=5). Slides were immunostained for tryptase and chymase. Total MC, MCT , MCTC and MCTC to-MCT ratio were compared between the four groups using a generalized linear mixed model. Irrespective of clinicopathologic diagnosis, MC burden tends to increase with time (r(2) =.56, P=.009). MCTC phenotype was significantly increased in the CLAD group (8.2±4.9 cells per HPF) in comparison with the other three groups (early normal: 1.6±1.7, P=.0026; late normal: 2.5±2.3, P=.048; ACR: 2.7±3.5, P=.021). Further, the ratio of MCTC to MCT was significantly increased in CLAD group as compared to the other three groups (P<.001 for all comparisons). The burden of MC may increase in the allograft as function of time. Patients with CLAD have an increased relative and absolute burden of MCTC phenotype MC. Future studies are needed to confirm these findings and evaluate the potential pathologic role of MCTC in allograft dysfunction. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Nanostructured Biomaterials for Tissue Engineered Bone Tissue Reconstruction

    PubMed Central

    Chiara, Gardin; Letizia, Ferroni; Lorenzo, Favero; Edoardo, Stellini; Diego, Stomaci; Stefano, Sivolella; Eriberto, Bressan; Barbara, Zavan

    2012-01-01

    Bone tissue engineering strategies are emerging as attractive alternatives to autografts and allografts in bone tissue reconstruction, in particular thanks to their association with nanotechnologies. Nanostructured biomaterials, indeed, mimic the extracellular matrix (ECM) of the natural bone, creating an artificial microenvironment that promotes cell adhesion, proliferation and differentiation. At the same time, the possibility to easily isolate mesenchymal stem cells (MSCs) from different adult tissues together with their multi-lineage differentiation potential makes them an interesting tool in the field of bone tissue engineering. This review gives an overview of the most promising nanostructured biomaterials, used alone or in combination with MSCs, which could in future be employed as bone substitutes. Recent works indicate that composite scaffolds made of ceramics/metals or ceramics/polymers are undoubtedly more effective than the single counterparts in terms of osteoconductivity, osteogenicity and osteoinductivity. A better understanding of the interactions between MSCs and nanostructured biomaterials will surely contribute to the progress of bone tissue engineering. PMID:22312283

  1. Massive bone allograft: a salvage procedure for complex bone loss due to high-velocity missiles--a long-term follow-up.

    PubMed

    Salai, M; Volks, S; Blankstein, A; Chechik, A; Amit, Y; Horosowski, H

    1990-07-01

    The treatment of high-velocity missile injury to the limbs is often associated with segmental bone loss, as well as damage to neurovascular and soft tissue. In such "limb threatening" cases, massive bone allograft can fill the bone defect and offer stability to the soft tissue reconstruction. The return of function in the affected limb is relatively rapid when using this method as a primary procedure. The indications for use of this technique and illustrative case reports are presented and discussed.

  2. Lateral Meniscal Allograft Transplant via a Medial Approach Leads to Less Extrusion.

    PubMed

    Choi, Nam-Hong; Choi, Jeong-Ki; Yang, Bong-Seok; Lee, Doe-Hyun; Victoroff, Brian N

    2017-10-01

    Accurate positioning of the bony bridge is crucial to prevent extrusion of meniscal allografts after transplant. However, oblique or lateralized placement of the bony bridge of the lateral meniscal allograft may occur due to technical error or a limited visual field. The patellar tendon may be an obstacle to approaching the anterior horn of the lateral meniscus, resulting in a laterally placed allograft. Therefore, lateral meniscal transplant through a medial arthrotomy would be an alternative approach. However, no report exists regarding allograft extrusion when comparing medial and lateral arthrotomy techniques in lateral meniscal transplants. Extrusion of the midbody of the allograft is less severe and the rotation of the bony bridge is less oblique in lateral meniscal allograft transplants through the medial parapatellar approach than those through the lateral approach. Cohort study; Level of evidence, 3. A bony bridge was used to perform 55 lateral meniscal transplants through either a medial or a lateral arthrotomy. Thirty-two allografts were transplanted through a medial arthrotomy and 23 were transplanted through a lateral arthrotomy, not randomly. Because correct positioning of the bony trough through the medial arthrotomy was easier than that through the lateral arthrotomy, the method of the arthrotomy was changed for the latter. The procedure for both groups was identical except for the arthrotomy technique, and rehabilitation was identical for both groups. Follow-up magnetic resonance imaging was conducted for all patients to measure the postoperative extrusion and obliquity of the bony bridge of the allograft. On the coronal view, extrusion was measured as the distance between the outer edge of the articular cartilage of the lateral tibial plateau and the outer edge of the meniscal allograft. On the axial view, a line (line B) was drawn along the longitudinal axis of the bony bridge. The posterior tibial condylar tangential line was drawn between the

  3. Adipose Gene Expression Profile Changes With Lung Allograft Reperfusion.

    PubMed

    Diamond, Joshua M; Arcasoy, Selim; McDonnough, Jamiela A; Sonett, Joshua R; Bacchetta, Matthew; D'Ovidio, Frank; Cantu, Edward; Bermudez, Christian A; McBurnie, Amika; Rushefski, Melanie; Kalman, Laurel H; Oyster, Michelle; D'Errico, Carly; Suzuki, Yoshikazu; Giles, Jon T; Ferrante, Anthony; Lippel, Matthew; Singh, Gopal; Lederer, David J; Christie, Jason D

    2017-01-01

    Obesity is a risk factor for primary graft dysfunction (PGD), a form of lung injury resulting from ischemia-reperfusion after lung transplantation, but the impact of ischemia-reperfusion on adipose tissue is unknown. We evaluated differential gene expression in thoracic visceral adipose tissue (VAT) before and after lung reperfusion. Total RNA was isolated from thoracic VAT sampled from six subjects enrolled in the Lung Transplant Body Composition study before and after allograft reperfusion and quantified using the Human Gene 2.0 ST array. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed enrichment for genes involved in complement and coagulation cascades and Jak-STAT signaling pathways. Overall, 72 genes were upregulated and 56 genes were downregulated in the postreperfusion time compared with baseline. Long pentraxin-3, a gene and plasma protein previously associated with PGD, was the most upregulated gene (19.5-fold increase, p = 0.04). Fibronectin leucine-rich transmembrane protein-3, a gene associated with cell adhesion and receptor signaling, was the most downregulated gene (4.3-fold decrease, p = 0.04). Ischemia-reperfusion has a demonstrable impact on gene expression in visceral adipose tissue in our pilot study of nonobese, non-PGD lung transplant recipients. Future evaluation will focus on differential adipose tissue gene expression and the development of PGD after transplant. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Allied health management of technology-related musculoskeletal complaints among children and adolescents.

    PubMed

    Ciccarelli, Marina; Fraser, Kerri; Vaz, Sharmila

    2016-12-01

    Children and adolescents are prolific users of information and communication technologies (ICT) in learning, leisure, and social communication activities. High exposure to ICT is associated with musculoskeletal injuries in adults; however, the management of ICT physical complaints in children is not well-understood. An online survey of allied health professionals (occupational therapists, physiotherapists, and chiropractors) was undertaken to determine (i) the number of children and adolescents in Perth, Western Australia who accessed treatment for musculoskeletal complaints related to use of technology; (ii) the typical frequency and duration of service provision; and (iii) the nature of treatment provided. Costs associated with service provision were estimated. Data from 101 identified the most commonly treated musculoskeletal complaints among children and adolescents included: non-specific neck pain; thoracic postural pain disorder; non-specific low back pain; and lumbar postural pain disorder. Approximately 1445 children were treated in the previous 12 months; with one-third of chiropractors each reported treating 31+ children. Most common treatments were soft tissue release, mobilisation, flexibility and conditioning exercises, soft tissue massage and kinesio-taping. Verbal education about healthy use of technology was provided by most clinicians (88%), with some inconsistent recommendations. The estimated cost of treatment was AUD$1,057,715; of which AUD$544,886 was health system funded. Children and adolescents received allied health treatment for a range of musculoskeletal complaints associated with ICT use. The potential long-term impacts on their health and wellbeing, and the economic burden associated with this health issue warrant the development of systematic risk reduction strategies. © 2016 Occupational Therapy Australia.

  5. Understanding Mechanobiology: Physical Therapists as a Force in Mechanotherapy and Musculoskeletal Regenerative Rehabilitation

    PubMed Central

    Thompson, William R.; Scott, Alexander; Loghmani, M. Terry; Ward, Samuel R.

    2016-01-01

    Achieving functional restoration of diseased or injured tissues is the ultimate goal of both regenerative medicine approaches and physical therapy interventions. Proper integration and healing of the surrogate cells, tissues, or organs introduced using regenerative medicine techniques are often dependent on the co-introduction of therapeutic physical stimuli. Thus, regenerative rehabilitation represents a collaborative approach whereby rehabilitation specialists, basic scientists, physicians, and surgeons work closely to enhance tissue restoration by creating tailored rehabilitation treatments. One of the primary treatment regimens that physical therapists use to promote tissue healing is the introduction of mechanical forces, or mechanotherapies. These mechanotherapies in regenerative rehabilitation activate specific biological responses in musculoskeletal tissues to enhance the integration, healing, and restorative capacity of implanted cells, tissues, or synthetic scaffolds. To become future leaders in the field of regenerative rehabilitation, physical therapists must understand the principles of mechanobiology and how mechanotherapies augment tissue responses. This perspective article provides an overview of mechanotherapy and discusses how mechanical signals are transmitted at the tissue, cellular, and molecular levels. The synergistic effects of physical interventions and pharmacological agents also are discussed. The goals are to highlight the critical importance of mechanical signals on biological tissue healing and to emphasize the need for collaboration within the field of regenerative rehabilitation. As this field continues to emerge, physical therapists are poised to provide a critical contribution by integrating mechanotherapies with regenerative medicine to restore musculoskeletal function. PMID:26637643

  6. Graphic-based musculoskeletal model for biomechanical analyses and animation.

    PubMed

    Chao, Edmund Y S

    2003-04-01

    The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the 'Virtual Human' reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. This paper details the design, capabilities, and features of the VIMS development at Johns Hopkins University, an effort possible only through academic and commercial collaborations. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of this unique database and simulation technology. This integrated system will impact on medical education, basic research, device development and application, and clinical patient care related to musculoskeletal diseases, trauma, and rehabilitation.

  7. Lineage mapping and characterization of the native progenitor population in cellular allograft.

    PubMed

    Neman, Josh; Duenas, Vincent; Kowolik, Claudia; Hambrecht, Amanda; Chen, Mike; Jandial, Rahul

    2013-02-01

    The gold standard for bone grafting remains the autograft. However, the attractiveness of autograft is counterbalanced by donor site morbidity. To mimic autograft-and its fundamental properties of osteoconductivity, osteoinductivity, and osteogenicity-novel bone grafting materials such as cellular allograft (Osteocel Plus) are composed of allograft in which the progenitor cells are preserved. However, the true identity of these cells remains obscure largely due to the lack of specific bona fide antigenic markers for stem versus progenitor cells. To characterize the stem and progenitor population in cellular allograft, Osteocel Plus. To determine whether cells endogenous to a cellular allograft undergo extensive self-renewal (a functional hallmark of stem cells), we employed a novel use of lineage mapping using a modern and refined replication incompetent lentiviral library with high complexity to uniquely label single cells with indelible genetic tags faithfully passed on to all progeny, allowing identification of highly proliferative clones. We used genetic and proteomic profiling as well as functional assays to show that these cells are capable of multipotential differentiation (the second functional hallmark of stem cells). Use of these two functional hallmarks enabled us to establish the existence of a stem and progenitor cell population in cellular allografts. Specifically, we employed (1) cellular dissociation and (2) in vitro expansion and differentiation capacity of cells released from cellular allograft. We determined differential gene expression profiling of a bona fide human mesenchymal stem cell line and cells from cellular allograft using focused PCR arrays mesenchymal stem cell (MSC) and osteogenesis associated. Proteomic profiling of cells from cellular allograft was performed using (1) immunofluorescence for BMP-2, Runx2 SMADs, CD44, Stro-1, Collagen, RANKL, Osterix Osteocalcin, and Ki67; (2) flow cytometry for Ki67, CD44, Stro-1, Thy1, CD146, and

  8. Characterization of Skin Allograft Use in Thermal Injury

    DTIC Science & Technology

    2013-01-01

    of burn surgery. New York: Marcel Dekker; 2004. 6. Burd A, Lam PK, Lau H. Allogenic skin: transplant or dressing? Burns 2002;28:358–66. 7...with CPA, and the feet (1.4%) and groin (0.5%) together have CPA placed at ɚ% of all engraftments (Figure 5). When propensity matched for TBSA ( N = 72...nonallografted and allografted patients propensity matched on TBSA Variable No. Nonallograft N Allograft P TBSA 36 34.83 ± 18.74 (0.5–90) 36 35.14

  9. Kidney allograft survival of African American and Caucasian American recipients with lupus.

    PubMed

    Contreras, G; Li, H; Gonzalez-Suarez, M; Isakova, T; Scialla, J J; Pedraza, F; Mattiazzi, A; Diaz-Wong, R; Sageshima, J; Brito, Y; Guerra, G; Acevedo, B; Sajid Ali, A; Kershaw, T J; Chen, L; Burke, G W; Kupin, W; Ciancio, G; Roth, D

    2014-02-01

    African Americans with lupus who receive kidney transplants have high prevalence of predictors of allograft failure, which can explain their poor outcomes. Of 1223 African Americans and 1029 Caucasian Americans with lupus who received kidney transplants from deceased donors between 1987 and 2006 with complete records in the UNOS program, 741 pairs were matched in 16 predictors employing a predicted probability of group membership. The primary outcome was allograft failure. Main secondary outcomes were rejection, allograft failure due to rejection, and mortality. Matched pairs were predominantly women (82%) with a mean age of 39 years. Twenty-four percent of recipients received kidneys from expanded criteria donors. African Americans and Caucasian Americans matched well (p ≥ 0.05): donor age, gender and race; recipient age, gender, education and insurance; dialysis prior to transplant, kidneys from expanded criteria donors, cold ischemia time, history of prior kidney transplant, panel reactive antibodies, human leukocyte antigens mismatch, blood type compatibility, transplant Era, and follow-up time. Contrary to the unmatched cohort with significantly higher allograft failure rate (events per 100 patient-years) in African Americans compared to Caucasian Americans (10.49 vs 6.18, p<0.001), matched pairs had similar allograft failure rates (8.41 vs 7.81, p=0.418). Matched pairs also had similar rates of rejections (9.82 vs 9.39, p=0.602), allograft failure due to rejection (6.19 vs 5.71, p=0.453), and mortality (2.79 vs 3.52, p=0.097). In lupus recipients of kidney transplants from deceased donors, African American and Caucasian Americans have similar allograft failure rates when predictors are matched between groups.

  10. Augmenting kidney mass at transplantation abrogates chronic renal allograft injury in rats.

    PubMed

    Mackenzie, H S; Azuma, H; Troy, J L; Rennke, H G; Tilney, N L; Brenner, B M

    1996-03-01

    Conventional renal transplantation, which substitutes a single allograft for two native kidneys, imposes an imbalance between nephron supply and the metabolic and excretory demands of the recipient. This discrepancy, which stimulates hyperfunction and hypertrophy of viable allograft nephrons, may be intensified by nephron loss through ischemia-reperfusion injury or acute rejection episodes occurring soon after transplantation. In other settings where less than 50% of the total renal mass remains, progressive glomerular injury develops through mechanisms associated with compensatory nephron hyperfiltration and hypertrophy. To determine whether responses to nephron loss contribute to chronic injury in renal allografts, nephron supply was restored to near-normal levels by transplanting Lewis recipients with two Fisher 344 kidneys (group 2A) compared with the standard single allograft F344 --> LEW rat model of late renal allograft failure (group 1A). At 20 weeks, indices of injury were observed in 1A but not 2A rats. These indices included proteinuria (1A: 45 +/- 13; 2A: 4.0 +/- 0.29 mg/day) and glomerulosclerosis (1A: 23 +/- 4.9%, 2A: 0.7 +/- 0.3%) (p < .05). Double-allograft recipients maintained near normal renal structure and function, whereas 1A rats showed evidence of compensatory hyperfiltration (single-nephron glomerular filtration rate of 63 +/- 10 versus 44 +/- 2.0 nl/min in 2A rats) and hypertrophy (mean glomerular volume of 2.64 +/- 0.15 versus 1.52 +/- 0.05 microns3 x 10(6) in 2A rats) (p < .05). Thus, we conclude that a major component of late allograft injury is attributable to processes associated with inadequate transplanted renal mass, a finding that has major implications for kidney transplantation biology and policy.

  11. Effect of a stable prostacyclin analogue on canine renal allograft rejection.

    PubMed Central

    Tobimatsu, M; Ueda, Y; Toyoda, K; Saito, S; Konomi, K

    1987-01-01

    The effect of OP-41483 (Ono Pharmaceutical Co., Osaka, Japan), a stable prostacyclin analogue, on canine renal allograft rejection was investigated. Administration for 4 days after transplantation significantly increased renal cortical blood flow and urine output when compared with untreated dogs with renal allografts. Serum creatinine levels remained relatively low during postoperative days 1-4. Mean animal survival time was prolonged. Vascular lesions and mononuclear cell infiltration were greatly diminished in biopsy specimens removed on day 4. This stable prostacyclin analogue provided a degree of protection against canine renal allograft rejection. Images Figs. 1A and B. PMID:3545109

  12. Utility of an allograft tendon for scoliosis correction via the costo-transverse foreman.

    PubMed

    Sun, Dong; McCarthy, Michael; Dooley, Adam C; Ramakrishnaiah, Raghu H; Shelton, R Shane; McLaren, Sandra G; Skinner, Robert A; Suva, Larry J; McCarthy, Richard E

    2017-01-01

    Current convex tethering techniques for treatment of scoliosis have centered on anterior convex staples or polypropylene tethers. We hypothesized that an allograft tendon tether inserted via the costo-transverse foramen would correct an established spinal deformity. In the pilot study, six 8-week-old pigs underwent allograft tendon tethering via the costo-transverse foreman or sham to test the strength of the transplanted tendon to retard spine growth. After 4 months, spinal deformity in three planes was induced in all animals with allograft tendons. In the treatment study, the allograft tendon tether was used to treat established scoliosis in 11 8-week-old pigs (spinal deformity > 50°). Once the deformity was observed (4 months) animals were assigned to either no treatment group or allograft tendon tether group and progression assessed by monthly radiographs. At final follow-up, coronal Cobb angle and maximum vertebral axial rotation of the treatment group was significantly smaller than the non-treatment group, whereas sagittal kyphosis of the treatment group was significantly larger than the non-treatment group. In sum, a significant correction was achieved using a unilateral allograft tendon spinal tether, suggesting that an allograft tendon tethering approach may represent a novel fusion-less procedure to correct idiopathic scoliosis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:183-192, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  13. Primary vascularization of allografts governs their immunogenicity and susceptibility to tolerogenesis

    PubMed Central

    Kant, Cavit D.; Akiyama, Yoshinobu; Tanaka, Katsunori; Shea, Susan; Connolly, Sarah E; Germana, Sharon; Winn, Henry J.; LeGuern, Christian; Tocco, Georges; Benichou, Gilles

    2013-01-01

    We investigated the influence of allograft primary vascularization on alloimmunity, rejection and tolerance in mice. First, we showed that fully allogeneic primarily vascularized and conventional skin transplants were rejected at the same pace. Remarkably, however, short-term treatment of mice with anti-CD40L antibodies achieved long-term survival of vascularized skin and cardiac transplants but not conventional skin grafts. Non-vascularized skin transplants triggered vigorous direct and indirect pro-inflammatory type 1 T cell responses (IL-2 and γIFN) while primarily-vascularized skin allografts failed to trigger a significant indirect alloresponse. Similar lack of indirect alloreactivity was also observed after placement of different vascularized organ transplants including hearts and kidneys while hearts placed under the skin (non-vascularized) triggers potent indirect alloresponses. Altogether, these results suggest that primary vascularization of allografts is associated with lack of indirect T cell alloreactivity. Finally, we show that long-term survival of vascularized skin allografts induced by anti-CD40L antibodies was associated with a combined lack of indirect alloresponse and a shift of the direct alloresponse towards a type 2 cytokine (IL-4, IL-10) secretion pattern but no activation/expansion of regulatory T cells. Therefore, primary vascularization of allografts governs their immunogenicity and tolerogenicity. PMID:23833234

  14. Clinical utility of histological features of polyomavirus allograft nephropathy.

    PubMed

    Gaber, Lillian W; Egidi, M Francesca; Stratta, Robert J; Lo, Agnes; Moore, Linda W; Gaber, A Osama

    2006-07-27

    The purpose of this study was to determine if histological features of polyomavirus allograft nephropathy (PVAN) are associated with the clinical presentation and outcomes of PVAN. We examined the histological features of initial and follow-up biopsies of 20 kidney and kidney-pancreas transplant recipients with PVAN during a time prior to routine surveillance. The subjects' demographics, clinical characteristics, and outcomes were compared based upon classification of histological features of PVAN on initial biopsy. Diabetes mellitus (45%) and a history of tacrolimus-induced nephrotoxicity (35%) appeared to be prevalent in subjects with PVAN. Although histological severity of PVAN did not predict or correlate with the clinical course of PVAN, subjects with pattern C on initial PVAN biopsy presented later posttransplant, had higher serum creatinine level at presentation, and had significant allograft deterioration at follow-up than subjects with either pattern A or B on initial biopsy. Resolution of PVAN was noted in 60% of follow-up biopsies and occurred more frequently in subjects with pattern B on initial biopsy. Most subjects developed chronic allograft nephropathy after PVAN and viral clearance did not abrogate the progression to chronic allograft nephropathy. These data indicate that histologic patterns of PVAN may have clinical correlation to disease presentation and prognosis.

  15. Utility of T2 mapping and dGEMRIC for evaluation of cartilage repair after allograft chondrocyte implantation in a rabbit model.

    PubMed

    Endo, J; Watanabe, A; Sasho, T; Yamaguchi, S; Saito, M; Akagi, R; Muramatsu, Y; Mukoyama, S; Katsuragi, J; Akatsu, Y; Fukawa, T; Okubo, T; Osone, F; Takahashi, K

    2015-02-01

    To investigate the effectiveness of quantitative Magnetic resonance imaging (MRI) for evaluating the quality of cartilage repair over time following allograft chondrocyte implantation using a three-dimensional scaffold for osteochondral lesions. Thirty knees from 15 rabbits were analyzed. An osteochondral defect (diameter, 4 mm; depth, 1 mm) was created on the patellar groove of the femur in both legs. The defects were filled with a chondrocyte-seeded scaffold in the right knee and an empty scaffold in the left knee. Five rabbits each were euthanized at 4, 8, and 12 weeks and their knees were examined via macroscopic inspection, histological and biochemical analysis, and quantitative MRI (T2 mapping and dGEMRIC) to assess the state of tissue repair following allograft chondrocyte implantation with a three-dimensional scaffold for osteochondral lesions. Comparatively good regenerative cartilage was observed both macroscopically and histologically. In both chondrocyte-seeded and control knees, the T2 values of repair tissues were highest at 4 weeks and showed a tendency to decrease with time. ΔR1 values of dGEMRIC also tended to decrease with time in both groups, and the mean ΔR1 was significantly lower in the CS-scaffold group than in the control group at all time points. ΔR1 = 1/r (R1post - R1pre), where r is the relaxivity of Gd-DTPA(2-), R1 = 1/T1 (longitudinal relaxation time). T2 mapping and dGEMRIC were both effective for evaluating tissue repair after allograft chondrocyte implantation. ΔR1 values of dGEMRIC represented good correlation with histologically and biochemically even at early stages after the implantation. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  16. Does Donor Age of Nonirradiated Achilles Tendon Allograft Influence Mid-Term Results of Revision ACL Reconstruction?

    PubMed Central

    Zaffagnini, Stefano; Roberti di Sarsina, Tommaso; Bonanzinga, Tommaso; Nitri, Marco; Macchiarola, Luca; Stefanelli, Federico; Lucidi, Gianandrea; Grassi, Alberto

    2018-01-01

    Purpose  The purpose of the present study was to investigate if the donor age of nonirradiated Achilles tendon allograft could influence the clinical results of revision anterior cruciate ligament (ACL) reconstruction. Methods  All patients that underwent ACL revision between 2004 and 2008 with at least 4 years of follow-up were included. For all the patients that met the inclusion criteria, the age of the graft donor was obtained from the tissue bank. Lysholm score was administered to patients that met inclusion criteria. In addition, patients were divided in two groups based on the donor age (<45 years vs. ≥45 years), and the baseline characteristics and outcomes were compared. Results  Fifty-two patients were evaluated at a mean 4.8 ± 0.8 years follow-up with Lysholm score. The Lysholm significantly improved from 62.3 ± 6.6 at preoperative status to 84.4 ± 12.3 at final follow-up. The mean donor age was 48.7 ± 8.4 years; a significant difference in Lysholm score was noted between patients that received an allograft with a donor age <45 years (14 patients; 27%) and those receiving an allograft with a donor age ≥45 years (38; 73%) (89.5 ± 3.2 vs. 80.1 ± 11.1, respectively; p  = 0.0469). The multiple regression model showed the donor age, the final follow-up, and the preoperative Lysholm score as significant predictors of postoperative Lysholm score ( p  < 0.0002). Conclusion  Donor age of nonirradiated Achilles tendon allograft influenced the mid-term results of revision ACL reconstruction, thus advising the use of grafts from young donors. Level of Evidence  Level III, retrospective comparative study. PMID:29675501

  17. Comparative clinical evaluation of acellular dermal matrix allograft and connective tissue graft for the treatment of gingival recession.

    PubMed

    Rahmani, M E; Lades, Mohammad A Rigi

    2006-05-01

    "Gingival recession is a condition reported to occur due to abnormal periodontal anatomy, poor hygiene, excessive occlusal forces, toothbrush abrasion, and even iatrogenic or factitious causes. Though various surgical techniques are available to treat this problem, the most common is the palatal soft tissue autograft. Recently, an acellular dermal matrix allograft (ADMA) has been available as a substitute for the palatal tissue harvest. The aim of this study is to compare the ADMA with the conventional subepithelial connective tissue graft (SCTG) in the treatment of gingival recession." Fourteen patients with 20 gingival recessions of Miller's grade I and II were selected and randomized in two groups of control (SCTG ) and test (ADMA). In each group ten recession defects were treated. The following parameters were measured at baseline and then at six months post surgery: recession height (RH), recession width (RW), probing depth (PD), attached gingiva (AG), keratinized gingiva (KG), and clinical attachment level (CAL). All parameters were analyzed using the two-sample t-test. Data analysis was performed using SPSS (version 11) software. The following mean changes (mm) occurred in SCTG and ADMA, respectively: 2.60+/-0.97 and 2.90+/-0.81 decrease in RH; 1.70+/-1.01 and 1.65+/-0.67 decrease in RW; 2.50+/-0.97 and 2.95+/-0.69 increase in KG; 2.25+/-0.92 and 2.65+/-0.85 increase in AG; 2.60+/-1.08 and 2.75+/-0.92 decrease in CAL; and finally 0.05+/-0.50 and 0.10+/-0.46 decrease in PD for the SCTG and ADMA groups, respectively. The percentage of root coverage for the two groups was 70.12%+/-22.81% and 72.08%+/-14.12%, respectively. The changes from baseline to the six-month visit were significant for both groups in terms of all parameters but PD. However, the differences in mean changes were not significant between the two groups in any of the parameters. These findings imply the ADMA and SCTG techniques could produce the same results when used for the successful

  18. Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ouzounian, T.J.; Thompson, L.; Grogan, T.J.

    The detection of musculoskeletal sepsis, especially following joint replacement, continues to be a challenging problem. Often, even with invasive diagnostic evaluation, the diagnosis of infection remains uncertain. This is a report on the first 55 Indium-111 white blood cell (WBC) images performed in 39 patients for the evaluation of musculoskeletal sepsis. There were 40 negative and 15 positive Indium-111 WBC images. These were correlated with operative culture and tissue pathology, aspiration culture, and clinical findings. Thirty-eight images were performed for the evaluation of possible total joint sepsis (8 positive and 30 negative images); 17 for the evaluation of nonarthroplasty-related musculoskeletalmore » sepsis (7 positive and 10 negative images). Overall, there were 13 true-positive, 39 true-negative, two false-positive, and one false-negative images. Indium-111 WBC imaging is a sensitive and specific means of evaluating musculoskeletal sepsis, especially following total joint replacement.« less

  19. Kidney-induced cardiac allograft tolerance in miniature swine is dependent on MHC-matching of donor cardiac and renal parenchyma.

    PubMed

    Madariaga, M L; Michel, S G; La Muraglia, G M; Sekijima, M; Villani, V; Leonard, D A; Powell, H J; Kurtz, J M; Farkash, E A; Colvin, R B; Allan, J S; Cetrulo, C L; Huang, C A; Sachs, D H; Yamada, K; Madsen, J C

    2015-06-01

    Kidney allografts possess the ability to enable a short course of immunosuppression to induce tolerance of themselves and of cardiac allografts across a full-MHC barrier in miniature swine. However, the renal element(s) responsible for kidney-induced cardiac allograft tolerance (KICAT) are unknown. Here we investigated whether MHC disparities between parenchyma versus hematopoietic-derived "passenger" cells of the heart and kidney allografts affected KICAT. Heart and kidney allografts were co-transplanted into MHC-mismatched recipients treated with high-dose tacrolimus for 12 days. Group 1 animals (n = 3) received kidney and heart allografts fully MHC-mismatched to each other and to the recipient. Group 2 animals (n = 3) received kidney and heart allografts MHC-matched to each other but MHC-mismatched to the recipient. Group 3 animals (n = 3) received chimeric kidney allografts whose parenchyma was MHC-mismatched to the donor heart. Group 4 animals (n = 3) received chimeric kidney allografts whose passenger leukocytes were MHC-mismatched to the donor heart. Five of six heart allografts in Groups 1 and 3 rejected <40 days. In contrast, heart allografts in Groups 2 and 4 survived >150 days without rejection (p < 0.05). These data demonstrate that KICAT requires MHC-matching between kidney allograft parenchyma and heart allografts, suggesting that cells intrinsic to the kidney enable cardiac allograft tolerance. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. Examining the interaction of force and repetition on musculoskeletal disorder risk: a systematic literature review.

    PubMed

    Gallagher, Sean; Heberger, John R

    2013-02-01

    Our aims were (a) to perform a systematic literature review of epidemiological studies that examined the interaction of force and repetition with respect to musculoskeletal disorder (MSD) risk, (b) to assess the relationship of force and repetition in fatigue failure studies of musculoskeletal tissues, and (c) to synthesize these findings. Many epidemiological studies have examined the effects of force and repetition on MSD risk; however, relatively few have examined the interaction between these risk factors. In a literature search, we identified 12 studies that allowed evaluation of a force-repetition interaction with respect to MSD risk. Identified studies were subjected to a methodological quality assessment and critical review. We evaluated laboratory studies of fatigue failure to examine tissue failure responses to force and repetition. Of the 12 epidemiological studies that tested a Force x Repetition interaction, 10 reported evidence of interaction. Based on these results, the suggestion is made that force and repetition may be interdependent in terms of their influence on MSD risk. Fatigue failure studies of musculoskeletal tissues show a pattern of failure that mirrors the MSD risk observed in epidemiological studies. Evidence suggests that there may be interdependence between force and repetition with respect to MSD risk. Repetition seems to result in modest increases in risk for low-force tasks but rapid increases in risk for high-force tasks. This interaction may be representative of a fatigue failure process in affected tissues.

  1. Role of T-cell-specific nuclear factor κB in islet allograft rejection.

    PubMed

    Porras, Delia Lozano; Wang, Ying; Zhou, Ping; Molinero, Luciana L; Alegre, Maria-Luisa

    2012-05-27

    Pancreatic islet transplantation has the potential to cure type 1 diabetes, a chronic lifelong disease, but its clinical applicability is limited by allograft rejection. Nuclear factor κB (NF-κB) is a transcription factor important for survival and differentiation of T cells. In this study, we tested whether NF-κB in T cells is required for the rejection of islet allografts. Mice expressing a superrepressor form of NF-κB selectively in T cells (IκBαΔN-Tg mice) with or without the antiapoptotic factor Bcl-xL, or mice with impaired T-cell receptor (TCR)- and B cell receptor-driven NF-κB activity (CARMA1-KO mice) were rendered diabetic and transplanted with islet allografts. Secondary skin transplantation in long-term acceptors of islet allografts was used to test for the development of donor-specific tolerance. Immune infiltration of the transplanted islets was examined by immunofluorescence. TCR-transgenic CD4 T cells were used to follow T-cell priming and differentiation. Islet allograft survival was prolonged in IκBαΔN-Tg mice, although the animals did not develop donor-specific tolerance. Reduced NF-κB activity did not prevent T-cell priming or differentiation but reduced survival of activated T cells, as transgenic expression of Bcl-xL restored islet allograft rejection in IκBαΔN-Tg mice. Abolishing TCR- and B cell receptor-driven activation of NF-κB selectively by CARMA1 deficiency prevented T-cell priming and islet allograft rejection. Our data suggest that T cell-NF-κB plays an important role in the rejection of islet allografts. Targeting NF-κB selectively in lymphocytes seems a promising approach to facilitate acceptance of transplanted islets.

  2. Stem cell derived endochondral cartilage stimulates bone healing by tissue transformation

    PubMed Central

    Bahney, Chelsea S; Hu, Diane P; Taylor, Aaron J; Ferro, Federico; Britz, Hayley M; Hallgrimsson, Benedikt; Johnstone, Brian; Miclau, Theodore; Marcucio, Ralph S

    2016-01-01

    Although bone has great capacity for repair, there are a number of clinical situations (fracture non-unions, spinal fusions, revision arthroplasty, segmental defects) in which auto- or allografts augment bone regeneration. Critical failures associated with current grafting treatments include osteonecrosis and limited integration between graft and host tissue. We speculated that the underlying problem with current bone grafting techniques is that they promote bone regeneration through direct osteogenesis. We hypothesized that using cartilage to promote endochondral bone regeneration would leverage normal developmental and repair sequences to produce a well-vascularized regenerate that integrates with the host tissue. In this study we use a translational murine model of a segmental tibia defect to test the clinical utility of bone regeneration from a cartilage graft. We further test the mechanism by which cartilage promotes bone regeneration using in vivo lineage tracing and in vitro culture experiments. Our data show that cartilage grafts support regeneration of a vascularized and integrated bone tissue in vivo, and subsequently propose a translational tissue engineering platform using chondrogenesis of MSCs. Interestingly, lineage tracing experiments show the regenerate was graft derived, suggesting transformation of the chondrocytes into bone. In vitro culture data shows that cartilage explants mineralize with the addition of BMP or by exposure to HUVEC conditioned medium, indicating that endothelial cells directly promote ossification. This study provides pre-clinical data for endochondral bone repair that has potential to significantly improve patient outcomes in a variety of musculoskeletal diseases and injuries. Further, in contrast to the dogmatic view that hypertrophic chondrocytes undergo apoptosis prior to bone formation, our data suggest cartilage can transform into bone by activating the pluripotent transcription factor Oct4A. Together these data

  3. Exercise and Regulation of Bone and Collagen Tissue Biology.

    PubMed

    Kjaer, Michael; Jørgensen, Niklas Rye; Heinemeier, Katja; Magnusson, S Peter

    2015-01-01

    The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle, ensuring force transmission, storing energy, protecting joint surface and stability, and ensuring the transfer of muscular forces into resulting limb movement. The musculoskeletal connective tissue structure is relatively stable, but mechanical loading and subsequent mechanotransduction and molecular anabolic signaling can result in some adaptation of the connective tissue, its size, its strength, and its mechanical properties, whereby it can improve its capacity by 5-20% with regular physical activity. For several of the mechanically loaded connective tissues, only limited information regarding molecular and cellular signaling pathways and their adaptation to exercise is available. In contrast to tissue responses with exercise, lack of mechanical tissue loading through inactivity or immobilization of the human body will result in a dramatic loss of connective tissue content, structure, and tolerable load within weeks, to a degree (30-40%) that mimics that of contractile skeletal musculature. This illustrates the importance of regular mechanical load in order to preserve the stabilizing role of the connective tissue for the overall function of the musculoskeletal system in both daily activity and exercise. © 2015 Elsevier Inc. All rights reserved.

  4. Use of polyvinylpyrrolidone-iodine solution for sterilisation and preservation improves mechanical properties and osteogenesis of allografts

    NASA Astrophysics Data System (ADS)

    Zhao, Yantao; Hu, Xiantong; Li, Zhonghai; Wang, Fuli; Xia, Yang; Hou, Shuxun; Zhong, Hongbin; Zhang, Feimin; Gu, Ning

    2016-12-01

    Allografts eliminate the disadvantages associated with autografts and synthetic scaffolds but are associated with a disease-transmission risk. Therefore, allograft sterilisation is crucial. We aimed to determine whether polyvinylpyrrolidone-iodine (PVP-I) can be used for sterilisation and as a new wet-preservation method. PVP-I-sterilised and preserved allografts demonstrated improved mechanical property, osteogenesis, and excellent microbial inhibition. A thigh muscle pouch model of nude mice showed that PVP-I-preserved allografts demonstrated better ectopic formation than Co60-sterilised allografts (control) in vivo (P < 0.05). Furthermore, the PVP-I-preserved group showed no difference between 24 h and 12 weeks of allograft preservation (P > 0.05). PVP-I-preserved allografts showed more hydrophilic surfaces and PVP-I-sterilised tendons showed higher mechanical strength than Co60-sterilised tendons (P < 0.05). The level of residual PVP-I was higher without washing and with prolonged preservation (P < 0.05). In vitro cellular tests showed that appropriate PVP-I concentration was nontoxic to preosteoblast cells, and cellular differentiation measured by alkaline phosphatase activity and osteogenic gene markers was enhanced (P < 0.05). Therefore, the improved biological performance of implanted allografts may be attributable to better surface properties and residual PVP-I, and PVP-I immersion can be a simple, easy method for allograft sterilisation and preservation.

  5. The Influence of Liquids on the Mechanical Properties of Allografts in Bone Impaction Grafting.

    PubMed

    Putzer, David; Ammann, Christoph Gert; Coraça-Huber, Débora; Lechner, Ricarda; Schmölz, Werner; Nogler, Michael

    2017-10-01

    Allografts are used to compensate for bone defects resulting from revision surgery, tumor surgery, and reconstructive bone surgery. Although it is well known that the reduction of fat content of allografts increases mechanical properties, the content of liquids with a known grain size distribution has not been assessed so far. The aim of the study was to compare the mechanical properties of dried allografts (DA) with allografts mixed with a saline solution (ASS) and with allografts mixed with blood (AB) having a similar grain size distribution. Fresh-frozen morselized bone chips were cleaned chemically, sieved, and reassembled in specific portions with a known grain size distribution. A uniaxial compression was used to assess the yield limit, initial density, density at yield limit, and flowability of the three groups before and after compaction with a fall hammer apparatus. No statistically significant difference could be found for the yield limit between DA and ASS (p = 0.339) and between ASS and AB (p = 0.554). DA showed a statistically significant higher yield limit than AB (p = 0.022). Excluding the effect of the grain size distribution on the mechanical properties, it was shown that allografts have a lower yield limit when lipids are present. The liquid content of allografts seems to play an inferior role as no statistically significant difference could be found between DA and ASS. It is suggested, in accordance with other studies, to chemically clean allografts before implantation to reduce the contamination risk and the fat content.

  6. Tobacco smoke exposure in either the donor or recipient before transplantation accelerates cardiac allograft rejection, vascular inflammation, and graft loss.

    PubMed

    Khanna, Ashwani K; Xu, Jianping; Uber, Patricia A; Burke, Allen P; Baquet, Claudia; Mehra, Mandeep R

    2009-11-03

    Tobacco exposure in cardiac transplant recipients, before and after transplantation, may increase the risk of cardiac allograft vasculopathy and allograft loss, but no direct evidence for this phenomenon is forthcoming. In this experimental study, we investigated early consequences of tobacco smoke exposure in cardiac transplant donors and recipients with an emphasis on alloinflammatory mediators of graft outcome. Using heterotopic rat cardiac transplantation, we tested the effects of donor or recipient tobacco smoke exposure in 6 groups of animals (rat heterotopic cardiac transplantation) as follows: tobacco-naïve allogeneic rejecting controls (n=6), tobacco-naïve nonrejecting controls (n=3; killed on day 5 to simulate survival times of tobacco-treated animals), isografts (n=3), both donor and recipient rats exposed to tobacco smoke (n=4), only donor rats exposed to tobacco smoke (n=7), and only recipient rats exposed to tobacco smoke (n=6). Polymerase chain reaction studies of tissue and peripheral (systemic) protein expression were performed to evaluate inflammatory (tumor necrosis factor-alpha, interferon-gamma, interleukin-6) and alloimmune (interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) pathways, as was histological analysis of the cardiac allografts. Our experiments reveal that pretransplantation tobacco exposure in donors and/or recipients results in heightened systemic inflammation and increased oxidative stress, reduces posttransplantation cardiac allograft survival by 33% to 57%, and increases intragraft inflammation (tumor necrosis factor-alpha, interferon-gamma, interleukin-6) and alloimmune activation (CD3, interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) with consequent myocardial and vascular destruction. These sentinel findings confirm that tobacco smoke exposure in either donors or recipients leads to accelerated allograft rejection, vascular inflammation, and graft loss

  7. The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

    PubMed

    Tsuchimoto, Akihiro; Nakano, Toshiaki; Hasegawa, Shoko; Masutani, Kosuke; Matsukuma, Yuta; Eriguchi, Masahiro; Nagata, Masaharu; Nishiki, Takehiro; Kitada, Hidehisa; Tanaka, Masao; Kitazono, Takanari; Tsuruya, Kazuhiko

    2017-08-01

    Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = -0.30, P = 0.019). High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

  8. ARFI-based tissue elasticity quantification and kidney graft dysfunction: first clinical experiences.

    PubMed

    Stock, K F; Klein, B S; Cong, M T Vo; Regenbogen, C; Kemmner, S; Büttner, M; Wagenpfeil, S; Matevossian, E; Renders, L; Heemann, U; Küchle, C

    2011-01-01

    Beyond the medical history, the clinical exam and lab findings, non-invasive ultrasound parameters such as kidney size and Doppler values (e.g. the resistive index) are important tools assisting clinical decision making in the monitoring of renal allografts. The gold standard for the diagnosis of renal allograft dysfunction remains the renal biopsy; while an invasive procedure, the justifiable necessity for this derives from its definitive nature a requirement beyond the synopses of all non-invasive tools. "Acoustic Radiation Force Impulse Imaging"(ARFI)-quantification is a novel ultrasound-based technology measuring tissue elasticity properties. So far experience related to this new method has not been reported in renal transplant follow-up. The purpose of this study was to evaluate changes in ARFI-measurements between clinically stable renal allografts and biopsy-proven transplant dysfunction. We employed "Virtual Touch™ tissue quantification" (Siemens Acuson, S2000) for the quantitative measurement of tissue stiffness in the cortex of transplant kidneys. We performed initial baseline and later disease-evaluative ultrasound examinations in 8 renal transplant patients in a prospective study design. Patients were first examined during stable allograft function with a routine post-transplant renal ultrasound protocol. A second follow-up examination was carried out on subsequent presentation with transplant dysfunction prior to allograft biopsy and histological evaluation. All patiens were examined using ARFI-quantification (15 measurements/kidney). Resistive indices (RI) were calculated using pulsed-wave Doppler ultrasound, and transplant kidney size was measured on B-mode ultrasound images. All biopsies were evaluated histologically by a reference nephropathologist unaware of the results of the ultrasound studies. Histopathological diagnoses were based on biopsy results, taking clinical and laboratory findings into account. Finally we calculated the relative

  9. Legal changes necessitate proactive management of Musculoskeletal Disorders: the role of electrodiagnostic functional assessment Soft Tissue Management program.

    PubMed

    Cusimano-Reaston, MaryRose; Carney, Brendan

    2011-01-01

    Musculoskeletal Disorders (MSD) often classified as sprains and strains to the low back, neck, shoulder or knee are the leading cost drivers in the workers compensation system. In 2009, soft tissue muscle injuries accounted for 40% of total injury cases requiring days away from work. The demand on U.S. employers to comply with all applicable mandates has exponentially increased as the regulatory landscape grows more complex evidenced by recent legislation from Equal Employment Opportunity Commission (EEOC), American With Disability Act 2.0 and Center for Medicare and Medicaid Services (CMS) Mandatory Reporting Act. Employers should revisit their return to work policies and engage in the interactive process to stay in compliance and avoid legal quagmire. EFA Soft Tissue Management (STM) is a comprehensive and compliant risk management program for objective diagnosis of work-related injuries that directs timely and proper allocation of resources to optimize injured worker (IW) outcomes. This bookend solution comparing pre- and post-loss data is a best practice to accurately determine between compensable acute workplace injury and exacerbation of a preexisting injury from chronic unrelated conditions. The EFA is an evidenced-based objective tool to assist in measuring functional status of the IW and make return to work determinations.

  10. [Identifying the specific causes of kidney allograft loss: A population-based study].

    PubMed

    Lohéac, Charlotte; Aubert, Olivier; Loupy, Alexandre; Legendre, Christophe

    2018-04-01

    Results of kidney transplantation have been improving but long-term allograft survival remains disappointing. The objective of the present study was to identify the specific causes of renal allograft loss, to assess their incidence and long-term outcomes. A total of 4783 patients from four French centres, transplanted between January 2004 and January 2014 were prospectively included. A total of 9959 kidney biopsies (protocol and for cause) performed between January 2004 and March 2015 were included. Donor and recipient clinical and biological parameters as well as anti-HLA antibody directed against the donor were included. The main outcome was the long-term kidney allograft survival, including the study of the associated causes of graft loss, the delay of graft loss according to their causes and the determinants of graft loss. There were 732 graft losses during the follow-up period (median time: 4.51 years) with an identified cause in 95.08 %. Kidney allograft survival at 9 years post-transplant was 78 %. The causes of allograft loss were: antibody-mediated rejection (31.69 %), thrombosis (25.55 %), medical intercurrent disease (14.62 %), recurrence of primary renal disease (7.1 %), BK- or CMV-associated nephropathy (n=35, 4.78 %), T cell-mediated rejection (4.78 %), urological disease (2.46 %) and calcineurin inhibitor nephrotoxicity (1.09 %). The main causes of allograft loss were antibody-mediated rejection and thrombosis. These results encourage efforts to prevent and detect these complications earlier in order to improve allograft survival. Copyright © 2018 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

  11. Soluble CD30 correlates with clinical but not subclinical renal allograft rejection.

    PubMed

    Hirt-Minkowski, Patricia; Roth, Michèle; Hönger, Gideon; Amico, Patrizia; Hopfer, Helmut; Schaub, Stefan

    2013-01-01

    Soluble CD30 (sCD30) has been proposed as a promising noninvasive biomarker for clinical renal allograft rejection, but its diagnostic characteristics regarding detection of subclinical rejection have not been assessed. We investigated sCD30 in 146 consecutive kidney allograft recipients under tacrolimus-mycophenolate-based immunosuppression having 250 surveillance biopsies at 3 and 6 months as well as 52 indication biopsies within the first year post-transplant. Allograft histology results were classified as (i) acute Banff score zero or interstitial infiltrates only, (ii) tubulitis t1, (iii) tubulitis t2-3 and (iv) isolated vascular compartment inflammation. sCD30 correlated well with the extent of clinical (P < 0.0001), but not subclinical tubulointerstitial rejection (P = 0.06). To determine diagnostic characteristics of sCD30, histological groups were assigned to two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (tubulitis t1-3 and isolated vascular compartment inflammation). For clinical allograft inflammation, AUC was 0.87 (sensitivity 89%, specificity 79%; P = 0.0006); however, for subclinical inflammation, AUC was only 0.59 (sensitivity 50%, specificity 69%; P = 0.47). In conclusion, sCD30 correlated with clinical, but not subclinical renal allograft rejection limiting its clinical utility as a noninvasive rejection screening biomarker in patients with stable allograft function receiving tacrolimus-mycophenolate-based immunosuppression. © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation.

  12. Defining kidney allograft benefit from successful pancreas transplant: separating fact from fiction.

    PubMed

    Wiseman, Alexander C; Stites, Erik; Kennealey, Peter

    2018-06-06

    To define the natural history of kidney allograft loss related to recurrent diabetes following transplant, and to understand the potential benefit of pancreas transplantation upon kidney allograft survival. A postulated benefit of simultaneous pancreas kidney transplant is that, unlike kidney transplant alone, euglycemia from the added pancreas allograft may confer a nephroprotective benefit and prevent recurrent diabetic nephropathy in the renal allograft. Recent large database analyses and long-term histological assessments have been published that assist in quantifying the problem of recurrent diabetic nephropathy and answering the question of the potential benefits of euglycemia. Further data may be extrapolated from larger single-center series that follow the prognosis of early posttransplant diabetes mellitus as another barometer of risk from diabetic nephropathy and graft loss. Recurrent diabetic nephropathy following kidney transplant is a relatively rare, late occurrence and its clinical significance is significantly diminished by the competing risks of death and chronic alloimmune injury. Although there are hints of a protective effect upon kidney graft survival with pancreas transplant, these improvements are small and may take decades to appreciate. Clinical decision-making regarding pancreas transplant solely based upon nephroprotective effects of the kidney allograft should be avoided.

  13. Effects of Trypsinization and Mineralization on Intrasynovial Tendon Allograft Healing to Bone

    PubMed Central

    Qu, Jin; van Alphen, Nick A.; Thoreson, Andrew R.; Chen, Qingshan; An, Kai-Nan; Amadio, Peter C.; Schmid, Thomas M.; Zhao, Chunfeng

    2014-01-01

    The purpose of the current study was to develop a novel technology to enhance tendon-to-bone interface healing by trypsinizing and mineralizing (TM) an intrasynovial tendon allograft in a rabbit bone tunnel model. Eight rabbit flexor digitorum profundus (FDP) tendons were used to optimize the trypsinization process. An additional 24 FDP tendons were stratified into control and TM groups; in each group, 4 tendons were used for in vitro evaluation of TM and 8 were transplanted into proximal tibial bone tunnels in rabbits. The samples were evaluated histologically and with mechanical testing at postoperative week 8. Maximum failure strength and linear stiffness were not significantly different between the control and TM tendons. A thin fibrous band of scar tissue formed at the graft-to-bone interface in the control group. However, only the TM group showed obvious new bone formation inside the tendon graft and a visible fibrocartilage layer at the bone tunnel entrance. This study is the first to explore effects of TM on the intrasynovial allograft healing to a bone tunnel. TM showed beneficial effects on chondrogenesis, osteogenesis, and integration of the intrasynovial tendon graft, but mechanical strength was the same as the control tendons in this short-term in vivo study. PMID:25611186

  14. Connective Tissue Disorders

    MedlinePlus

    ... syndrome, and osteogenesis imperfecta Autoimmune disorders, such as lupus and scleroderma Cancers, like some types of soft tissue sarcoma Each disorder has its own symptoms and needs different treatment. NIH: National Institute of Arthritis and Musculoskeletal and Skin Diseases

  15. Bioactive scaffold for bone tissue engineering: An in vivo study

    NASA Astrophysics Data System (ADS)

    Livingston, Treena Lynne

    Massive bone loss of the proximal femur is a common problem in revision cases of total hip implants. Allograft is typically used to reconstruct the site for insertion of the new prosthesis. However, for long term fixation and function, it is desirable that the allograft becomes fully replaced by bone tissue and aids in the regeneration of bone to that site. However, allograft use is typically associated with delayed incorporation and poor remodeling. Due to these profound limitations, alternative approaches are needed. Tissue engineering is an attractive approach to designing improved graft materials. By combining osteogenic activity with a resorbable scaffold, bone formation can be stimulated while providing structure and stability to the limb during incorporation and remodeling of the scaffold. Porous, surface modified bioactive ceramic scaffolds (pSMC) have been developed which stimulate the expression of the osteoblastic phenotype and production of bone-like tissue in vitro. The scaffold and two tissue-engineered constructs, osteoprogenitor cells seeded onto scaffolds or cells expanded in culture to form bone tissue on the scaffolds prior to implantation, were investigated in a long bone defect model. The rate of incorporation was assessed. Both tissue-engineered constructs stimulated bone formation and comparable repair at 2 weeks. In a rat femoral window defect model, bone formation increased over time for all groups in concert with scaffold resorption, leading to a 40% increase in bone and 40% reduction of the scaffold in the defect by 12 weeks. Both tissue-engineered constructs enhanced the rate of mechanical repair of long bones due to better bony union with the host cortex. Long bones treated with tissue engineered constructs demonstrated a return in normal torsional properties by 4 weeks as compared to 12 weeks for long bones treated with pSMC. Culture expansion of cells to produce bone tissue in vitro did not accelerate incorporation over the treatment

  16. Decellularized Allografts for Right Ventricular Outflow Tract Reconstruction in Children.

    PubMed

    da Costa, Francisco Diniz Affonso; Etnel, Jonathan R G; Torres, Renato; Balbi Filho, Eduardo M; Torres, Rafael; Calixto, Allyson; Mulinari, Leonardo A

    2017-09-01

    Determine the midterm outcomes of decellularized allografts for right ventricular outflow tract (RVOT) reconstruction in children less than 12 years of age. The study included all consecutive patients submitted to RVOT reconstruction with decellularized allografts between June 2006 and June 2016. Besides clinical and echocardiographic control, 20 patients with more than five years of follow-up were evaluated with computed tomography (CT) scans to determine allograft diameters and calcium scores. Structural valve deterioration was defined as any peak gradient above 40 mm Hg and/or insufficiency of moderate or severe degree. Conduit failure was defined as the need for allograft reintervention. There were 59 patients with a median age of six years (range = 0.01-12 years). The most common operation was the Ross procedure (34%). Mean clinical follow-up was 5.4 (2.8) years and was 94% complete. At eight years, only two patients needed a reintervention, with a 90.9% freedom from this event. Structural valve deterioration occurred in 13 patients, 5 due to stenosis and 8 due to insufficiency, with a freedom from structural valve deterioration due to any cause of 64.9% at eight years. Late CT scans demonstrated the absence or minimal calcification of the conduits. Decellularized allografts for RVOT reconstruction in children were associated with a low incidence of structural valve deterioration and conduit failure. Although these results still need to be confirmed in larger series and with longer follow-up, our data suggest favorable outcomes, at least in the first decade after the operation.

  17. Treatment options for renal cell carcinoma in renal allografts: a case series from a single institution.

    PubMed

    Swords, Darden C; Al-Geizawi, Samer M; Farney, Alan C; Rogers, Jeffrey; Burkart, John M; Assimos, Dean G; Stratta, Robert J

    2013-01-01

    Renal cell carcinoma (RCC) is more common in renal transplant and dialysis patients than the general population. However, RCC in transplanted kidneys is rare, and treatment has previously consisted of nephrectomy with a return to dialysis. There has been recent interest in nephron-sparing procedures as a treatment option for RCC in allograft kidneys in an effort to retain allograft function. Four patients with RCC in allograft kidneys were treated with nephrectomy, partial nephrectomy, or radiofrequency ablation. All of the patients are without evidence of recurrence of RCC after treatment. We found nephron-sparing procedures to be reasonable initial options in managing incidental RCCs diagnosed in functioning allografts to maintain an improved quality of life and avoid immediate dialysis compared with radical nephrectomy of a functioning allograft. However, in non-functioning renal allografts, radical nephrectomy may allow for a higher chance of cure without the loss of transplant function. Consequently, radical nephrectomy should be utilized whenever the allograft is non-functioning and the patient's surgical risk is not prohibitive. © 2013 John Wiley & Sons A/S.

  18. Assessment of the relationship between ACE I/D gene polymorphism and renal allograft survival.

    PubMed

    Yang, Chun-Hua; Lu, Yi; Chen, Xue-Xia; Xian, Wen-Feng; Tu, Wei-Feng; Li, Hong-Yan

    2015-12-01

    The relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and renal allograft survival after renal transplantation from the published reports are still debatable. This study was performed to evaluate the relationship between the ACE I/D gene polymorphism and renal allograft survival after renal transplantation using meta-analysis. Eligible studies were identified from PubMed and Cochrane Library on 1 November 2014, and eligible studies were recruited and synthesized using a meta-analysis methodology. Twelve investigations were included in this meta-analysis for the assessment of the relationship between the ACE I/D gene polymorphism and renal allograft survival. In this meta-analysis, the ACE I/D gene polymorphism was not associated with renal allograft survival after renal transplantation for overall populations, Caucasians, Brazilians and Africans. Interestingly, the ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. However, more studies should be performed to confirm this association. © The Author(s) 2015.

  19. [Ursolic acid inhibits corneal graft rejection following orthotopic allograft transplantation in rats].

    PubMed

    Wang, Bo; Wu, Jing; Ma, Ming; Li, Ping-Ping; Yu, Jian

    2015-04-01

    To investigate the effects of ursolic acid on corneal graft rejection in a rat model of othotopic corneal allograft transplantation. Forty-eight recipient Wistar rats were divided into normal control group with saline treatment (group A), autograft group with saline treatment (group B), SD rat allograft group with saline treatment (group C), and SD rat allograft group with intraperitoneal ursolic acid (UA) treatment group (group D). The rats received saline or UC (20 mg·kg(-1)·d(-1)) treatment for 12 days following othotopic graft transplantation. The grafts were evaluated using the Larkin corneal rejection rating system, and the graft survival was assessed with Kaplan-Meier analysis. On day 14, the grafts were harvested for histological examination, Western blotting, and assessment of expressions of interlukin-2 (IL-2), interferon-γ (IFN-γ), nuclear transcription factor-κB (NF-κB) p65, vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1). The allograft survival was significantly longer in group D than in group C (29.12±9.58 vs 9.67±2.16 days, P<0.05). UC treatment obviously reduced the expression levels of IL-2, IFN-γ, NF-κBp65, ICAM-1 and VEGF and increased inhibitory kappa B alpha (IκB-α) expression in the grafts, where no obvious inflammatory cell infiltration or corneal neovascularization was found. As a NF-κB inhibitor, ursolic acid can prevent corneal neovascularization and corneal allograft rejection to promote graft survival in rats following orthotopic corneal allograft transplantation.

  20. Stress Altered Stem Cells with Decellularized Allograft to Improve Rate of Nerve Regeneration

    DTIC Science & Technology

    2015-12-01

    AWARD  NUMBER:      W81XWH-­13-­1-­0298   TITLE:    “Stress Altered Stem Cells with Decellularized Allograft to Improve Rate of Nerve Regeneration...Cells with Decellularized Allograft to Improve Rate of Nerve Regeneration 5b. GRANT NUMBER W81XWH-13-1-0298 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S... allograft , neural regeneration, stem cells, stress altered cells, peripheral nerve injury model, nerve graft 3 This comprehensive final report summarizes

  1. Personal experience with the procurement of 132 liver allografts

    PubMed Central

    Yanaga, K.; Tzakis, A.G.; Starzl, T.E.

    2010-01-01

    A single donor surgeon's experience procuring the livers from 132 donors is described. Thirty-seven grafts (28.9%) had hepatic arterial anomalies, 19 (14.4%) of which required arterial reconstruction prior to transplantation. Of the 121 grafts evaluated for early function, 103 grafts (85.2%) functioned well, whereas 14 grafts (11.6%) functioned poorly and 4 grafts (3.3%) failed to function at all. The variables associated with less than optimal function of the graft consisted of donor age (P < 0.05), duration of donor's stay in the intensive care unit (P < 0.005), abnormal graft appearance (P < 0.05), and such recipient problems as vascular thromboses during or immediately following transplantation (P < 0.005). A new preservation fluid, University of Wisconsin solution, allowed safe and longer cold storage of the liver allograft than did Euro-Collins' solution (P < 0.0001). A parameter of liver allograft viability, which is simple and predictive of allograft function prior to the actual transplant procedure, is urgently needed. PMID:2803485

  2. Engineering complex orthopaedic tissues via strategic biomimicry.

    PubMed

    Qu, Dovina; Mosher, Christopher Z; Boushell, Margaret K; Lu, Helen H

    2015-03-01

    The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, wherein overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g., bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g., bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g., bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

  3. Engineering Complex Orthopaedic Tissues via Strategic Biomimicry

    PubMed Central

    Qu, Dovina; Mosher, Christopher Z.; Boushell, Margaret K.; Lu, Helen H.

    2014-01-01

    The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, whereby overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g. bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g. bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g. bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

  4. Therapies for Musculoskeletal Disease: Can we Treat Two Birds with One Stone?

    PubMed Central

    Girgis, Christian M.; Mokbel, Nancy; DiGirolamo, Douglas J.

    2014-01-01

    Musculoskeletal diseases are highly prevalent with staggering annual health care costs across the globe. The combined wasting of muscle (sarcopenia) and bone (osteoporosis)— both in normal aging and pathologic states—can lead to vastly compounded risk for fracture in patients. Until now, our therapeutic approach to the prevention of such fractures has focused solely on bone, but our increasing understanding of the interconnected biology of muscle and bone has begun to shift our treatment paradigm for musculoskeletal disease. Targeting pathways that centrally regulate both bone and muscle (eg, GH/IGF-1, sex steroids, etc.) and newly emerging pathways that might facilitate communication between these 2 tissues (eg, activin/myostatin) might allow a greater therapeutic benefit and/or previously unanticipated means by which to treat these frail patients and prevent fracture. In this review, we will discuss a number of therapies currently under development that aim to treat musculoskeletal disease in precisely such a holistic fashion. PMID:24633910

  5. Importance of Donor Chondrocyte Viability for Osteochondral Allografts.

    PubMed

    Cook, James L; Stannard, James P; Stoker, Aaron M; Bozynski, Chantelle C; Kuroki, Keiichi; Cook, Cristi R; Pfeiffer, Ferris M

    2016-05-01

    Osteochondral allograft (OCA) transplantation provides a biological treatment option for functional restoration of large articular cartilage defects in multiple joints. While successful outcomes after OCA transplantation have been linked to viable donor chondrocytes, the importance of donor cell viability has not been comprehensively validated. To use a canine model to determine the importance of donor chondrocyte viability at the time of implantation with respect to functional success of femoral condylar OCAs based on radiographic, gross, cell viability, histologic, biochemical, and biomechanical outcome measures. Controlled laboratory study. After approval was obtained from the institutional animal care and use committee, adult female dogs (N = 16) were implanted with 8-mm cylindrical OCAs from male dogs in the lateral and medial femoral condyles of 1 knee. OCAs were preserved for 28 or 60 days after procurement, and chondrocyte viability was quantified before implantation. Two different storage media, temperatures, and time points were used to obtain a spectrum of percentage chondrocyte viability at the time of implantation. A successful outcome was defined as an OCA that was associated with graft integration, maintenance of hyaline cartilage, lack of associated cartilage disorder, and lack of fibrillation, fissuring, or fibrous tissue infiltration of the allograft based on subjective radiographic, gross, and histologic assessments at 6 months after implantation. Chondrocyte viability ranged from 23% to 99% at the time of implantation. All successful grafts had >70% chondrocyte viability at the time of implantation, and no graft with chondrocyte viability <70% was associated with a successful outcome. Live-dead stained sections and histologic findings with respect to cell morphological features suggested that successful grafts were consistently composed of viable chondrocytes in lacunae, while grafts that were not successful were composed of nonviable

  6. Musculoskeletal ultrasound for interventional physiatry.

    PubMed

    De Muynck, M; Parlevliet, T; De Cock, K; Vanden Bossche, L; Vanderstraeten, G; Özçakar, L

    2012-12-01

    More and more physiatrists are interested in learning how to use musculoskeletal ultrasonography in their clinical practice. The possibility of high resolution, dynamic, comparative and repeatable imaging makes it an important diagnostic tool for soft tissue pathology. There is also growing interest to use sonography for guiding interventions such as aspirations and infiltrations. In daily practice these are often done blindly or palpation-guided. To improve the accuracy of interventions, fluoroscopy or computed tomography were traditionally used for guidance. Since sonography is non-ionizing, readily available and relatively low cost, it has become the first choice to guide many musculoskeletal interventions. Ultrasound allows real-time imaging of target and needle as well as surrounding vulnerable structures such as vessels and nerves. Many different techniques are proposed in the literature. Interventions under ultrasound guidance have been proven to be more accurate than unguided ones. Further studies are required to prove better clinical results and fewer complications. Infection is the most dreaded complication. This review wants to highlight technical aspects of ultrasound guidance of interventions and give a survey of different interventions that have been introduced, with emphasis on applications in Physical Medicine and Rehabilitation. Results and complications are discussed. Finally training requirements and modalities are presented.

  7. Cost analysis of fresh-frozen femoral head allografts: is it worthwhile to run a bone bank?

    PubMed

    Benninger, E; Zingg, P O; Kamath, A F; Dora, C

    2014-10-01

    To assess the sustainability of our institutional bone bank, we calculated the final product cost of fresh-frozen femoral head allografts and compared these costs with the use of commercial alternatives. Between 2007 and 2010 all quantifiable costs associated with allograft donor screening, harvesting, storage, and administration of femoral head allografts retrieved from patients undergoing elective hip replacement were analysed. From 290 femoral head allografts harvested and stored as full (complete) head specimens or as two halves, 101 had to be withdrawn. In total, 104 full and 75 half heads were implanted in 152 recipients. The calculated final product costs were €1367 per full head. Compared with the use of commercially available processed allografts, a saving of at least €43 119 was realised over four-years (€10 780 per year) resulting in a cost-effective intervention at our institution. Assuming a price of between €1672 and €2149 per commercially purchased allograft, breakeven analysis revealed that implanting between 34 and 63 allografts per year equated to the total cost of bone banking. ©2014 The British Editorial Society of Bone & Joint Surgery.

  8. Combat musculoskeletal wounds in a US Army Brigade Combat Team during operation Iraqi Freedom.

    PubMed

    Belmont, Philip J; Thomas, Dimitri; Goodman, Gens P; Schoenfeld, Andrew J; Zacchilli, Michael; Burks, Rob; Owens, Brett D

    2011-07-01

    A prospective, longitudinal analysis of musculoskeletal combat injuries sustained by a large combat-deployed maneuver unit has not previously been performed. A detailed description of the musculoskeletal combat casualty care statistics, distribution of wounds, and mechanisms of injury incurred by a US Army Brigade Combat Team during "The Surge" phase of Operation Iraqi Freedom was performed using a centralized casualty database and an electronic medical record system. Among the 4,122 soldiers deployed, there were 242 musculoskeletal combat wounds in 176 combat casualties. The musculoskeletal combat casualty rate for the Brigade Combat Team was 34.2 per 1,000 soldier combat-years. Spine, pelvis, and long bone fractures comprised 55.9% (33 of 59) of the total fractures sustained in combat. Explosions accounted for 80.7% (142 of 176) of all musculoskeletal combat casualties. Musculoskeletal combat casualty wound incidence rates per 1,000 combat-years were as follows: major amputation, 2.1; minor amputation, 0.6; open fracture, 5.0; closed fracture, 6.4; and soft-tissue/neurovascular injury, 32.8. Among musculoskeletal combat casualties, the likelihood of a gunshot wound causing an open fracture was significantly greater (45.8% [11 of 24]) when compared with explosions (10.6% [15 of 142]) (p = 0.0006). Long bone amputations were more often caused by explosive mechanisms than gunshot wounds. A large burden of complex orthopedic injuries has resulted from the combat experience in Operation Iraqi Freedom. This is because of increased enemy reliance on explosive devices, the use of individual and vehicular body armor, and improved survivability of combat-injured soldiers.

  9. One load to rule them all: mechanical control of the musculoskeletal system in development and aging.

    PubMed

    Shwartz, Yulia; Blitz, Einat; Zelzer, Elazar

    2013-10-01

    The musculoskeletal system functions because of the precise and coordinated assembly of its components, namely bones and joints, muscles, tendons and ligaments. This coordination requires cross-talk between the tissues, which is mediated by various molecular and mechanical cues. In this review, we summarize the progress that has been made in understanding the involvement of mechanical loads exerted by the musculature in the development of skeletal and tendinous tissues, in their integration into one functional unit and in the maintenance of this system. In addition, we discuss the possible role of muscle load in aging and propose new directions for future studies of the musculoskeletal system. © 2013 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  10. The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Indonesia.

    PubMed

    Hilmy, Nazly; Manjas, Menkher; Ferdiansyah; Abbas, Basril; Morales Pedraza, Jorge

    2009-05-01

    In 1986, the National Nuclear Energy Agency (Batan) in Jakarta started the research and development for the setting up of a tissue bank (Batan Research Tissue Bank/BRTB) by preserving fresh amnion or fetal membranes by lyophilisation and then sterilising by gamma irradiation. During the period of 1990 and 2000, three more tissue banks were set up, i.e., Biomaterial Centre in Surabaya, Jamil Tissue Bank in Padang, and Sitanala Tissue Bank in Tangerang. In 1994, BRTB produced bone allografts. The banks established under the IAEA program concentrated its work on the production of amnion, bone and soft tissues allografts, as well as bone xenografts. These tissues (allografts and xenografts) were sterilised using gamma irradiation (about 90%) and the rest were sterilized by ETO and those products have been used in the treatment of patients at more than 50 hospitals in Indonesia. In 2004, those tissue banks produced 8,500 grafts and 5,000 of them were amnion grafts for eye treatment and wound dressing. All of those grafts were used for patients as well as for research. In 2006, the production increased to 9,000 grafts. Although the capacity of those banks can produce more grafts, we are facing problems on getting raw materials from suitable donors. To fulfill the demand of bone grafts we also produced bone xenografts. The impact of the IAEA program in tissue banking activities in Indonesia can be summarised as follows: to support the national program on importing substitutes for medical devices. The price of imported tissues are between US$ 50 and US$ 6,000 per graft. Local tissue bank can produce tissues with the same quality with the price for about 10-30% of the imported tissues.

  11. Robotic trans-abdominal transplant nephrectomy for a failed renal allograft.

    PubMed

    Mulloy, M R; Tan, M; Wolf, J H; D'Annunzio, S H; Pollinger, H S

    2014-12-01

    Minimally invasive surgery for removal of a failed renal allograft has not previously been reported. Herein, we report the first robotic trans-abdominal transplant nephrectomy (TN). A 34-year-old male with Alport's syndrome lost function of his deceased donor allograft after 12 years and presented with fever, pain over his allograft and hematuria. The operation was performed intra-abdominally using the Da Vinci Robotic Surgical System with four trocars. The total operative time was 235 min and the estimated blood loss was less than 25 cm(3). There were no peri-operative complications observed and the patient was discharged to home less than 24 h postoperatively. The utilization of robotic technology facilitated the successful performance of a minimally invasive, trans-abdominal TN. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  12. Experience with a bone bank operation and allograft bone infection in recipients at a medical centre in southern Taiwan.

    PubMed

    Liu, J W; Chao, L H; Su, L H; Wang, J W; Wang, C J

    2002-04-01

    To assess the contamination rate of allograft bones at retrieval and the infection rate of the implanted allograft bone, we audited a bone bank retrospectively and reviewed the medical charts of allograft bone recipients between June 1999 and June 2000 at a medical centre in southern Taiwan. The bone bank did its utmost to minimize allograft contamination with hospital-acquired pathogens by adopting purposefully designed criteria for selection of donors. This protocol included sterilization with soaking of the retrieved allograft in a solution of a first-generation cephalosporin before storage and prophylaxis in recipients with first-generation cephalosporin. The contamination rates at allograft retrieval from living and cadaveric donors were 2.7% and 12.4%, respectively (P<0.001). Culture of 262 specimens taken at allograft implant revealed 12 (4.6%) positive for culture. Of the 12 patients implanted with allograft bones positive for culture, nine (75.0%) had allograft bone infection, while three (25.0%) did not. Among the 250 recipients with sterile allograft bones, four (1.6%) were found to have allograft infection. None of the cases of infection required removal of the allograft bones, and all cases were successfully treated with tailored antimicrobial therapy based on susceptibility tests on isolated bacteria. The overall infection rate was 5.0%, which compared favourably with those in other series. A prospective cohort study is needed to determine which of the varied sterilization methodologies gives the best and/or most cost-effective outcome. Copyright 2002 The Hospital Infection Society.

  13. Assessment of cryopreserved donor skin viability: the experience of the regional tissue bank of Siena.

    PubMed

    Pianigiani, E; Tognetti, L; Ierardi, F; Mariotti, G; Rubegni, P; Cevenini, G; Perotti, R; Fimiani, M

    2016-06-01

    Skin allografts from cadaver donors are an important resource for treating extensive burns, slow-healing wounds and chronic ulcers. A high level of cell viability of cryopreserved allografts is often required, especially in burn surgery, in Italy. Thus, we aimed to determine which conditions enable procurement of highly viable skin in our Regional Skin Bank of Siena. For this purpose, we assessed cell viability of cryopreserved skin allografts procured between 2011 and 2013 from 127 consecutive skin donors, before and after freezing (at day 15, 180, and 365). For each skin donor, we collected data concerning clinical history (age, sex, smoking, phototype, dyslipidemia, diabetes, cause of death), donation process (multi-tissue or multi-organ) and timing of skin procurement (assessment of intervals such as death-harvesting, harvesting-banking, death-banking). All these variables were analysed in the whole case study (127 donors) and in different groups (e.g. multi-organ donors, non refrigerated multi-tissue donors, refrigerated multi-tissue donors) for correlations with cell viability. Our results indicated that cryopreserved skin allografts with higher cell viability were obtained from female, non smoker, heartbeating donors died of cerebral haemorrhage, and were harvested within 2 h of aortic clamping and banked within 12 h of harvesting (13-14 h from clamping). Age, cause of death and dyslipidaemia or diabetes did not appear to influence cell viability. To maintain acceptable cell viability, our skin bank needs to reduce the time interval between harvesting and banking, especially for refrigerated donors.

  14. Two-Stage, In Silico Deconvolution of the Lymphocyte Compartment of the Peripheral Whole Blood Transcriptome in the Context of Acute Kidney Allograft Rejection

    PubMed Central

    Shannon, Casey P.; Balshaw, Robert; Ng, Raymond T.; Wilson-McManus, Janet E.; Keown, Paul; McMaster, Robert; McManus, Bruce M.; Landsberg, David; Isbel, Nicole M.; Knoll, Greg; Tebbutt, Scott J.

    2014-01-01

    Acute rejection is a major complication of solid organ transplantation that prevents the long-term assimilation of the allograft. Various populations of lymphocytes are principal mediators of this process, infiltrating graft tissues and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific biology associated with rejection is therefore critical. Measuring genome-wide changes in transcript abundance in peripheral whole blood cells can deliver a comprehensive view of the status of the immune system. The heterogeneous nature of the tissue significantly affects the sensitivity and interpretability of traditional analyses, however. Experimental separation of cell types is an obvious solution, but is often impractical and, more worrying, may affect expression, leading to spurious results. Statistical deconvolution of the cell type-specific signal is an attractive alternative, but existing approaches still present some challenges, particularly in a clinical research setting. Obtaining time-matched sample composition to biologically interesting, phenotypically homogeneous cell sub-populations is costly and adds significant complexity to study design. We used a two-stage, in silico deconvolution approach that first predicts sample composition to biologically meaningful and homogeneous leukocyte sub-populations, and then performs cell type-specific differential expression analysis in these same sub-populations, from peripheral whole blood expression data. We applied this approach to a peripheral whole blood expression study of kidney allograft rejection. The patterns of differential composition uncovered are consistent with previous studies carried out using flow cytometry and provide a relevant biological context when interpreting cell type-specific differential expression results. We identified cell type-specific differential expression in a variety of leukocyte sub-populations at the time of rejection. The tissue-specificity of these differentially

  15. Transplantation of Tissue-Engineered Cartilage in an Animal Model (Xenograft and Autograft): Construct Validation.

    PubMed

    Nemoto, Hitoshi; Watson, Deborah; Masuda, Koichi

    2015-01-01

    Tissue engineering holds great promise for cartilage repair with minimal donor-site morbidity. The in vivo maturation of a tissue-engineered construct can be tested in the subcutaneous tissues of the same species for autografts or of immunocompromised animals for allografts or xenografts. This section describes detailed protocols for the surgical transplantation of a tissue-engineered construct into an animal model to assess construct validity.

  16. Clinical and Histomorphometric Assessment of Lateral Alveolar Ridge Augmentation Using a Corticocancellous Freeze-Dried Allograft Bone Block.

    PubMed

    Ahmadi, Roya Shariatmadar; Sayar, Ferena; Rakhshan, Vahid; Iranpour, Babak; Jahanbani, Jahanfar; Toumaj, Ahmad; Akhoondi, Nasrin

    2017-06-01

    Horizontal ridge augmentation with allografts has attracted notable attention because of its proper success rate and the lack of disadvantages of autografts. Corticocancellous block allografts have not been adequately studied in humans. Therefore, this study clinically and histomorphometrically evaluated the increase in ridge width after horizontal ridge augmentation using corticocancellous block allografts as well as implant success after 12 to 18 months after implantation. In 10 patients receiving implants (3 women, 7 men; mean age = 45 years), defective maxillary alveolar ridges were horizontally augmented using freeze-dried bone allograft blocks. Ridge widths were measured before augmentation, immediately after augmentation, and ∼6 months later in the reentry surgery for implantation. This was done at points 2 mm (A) and 5 mm (B) apically to the crest. Biopsy cores were acquired from the implantation site. Implant success was assessed 15.1 ± 2.7 months after implantation (range = 12-18 months). Data were analyzed using Friedman and Dunn tests (α = 0.05). At point A, ridge widths were 2.77 ± 0.37, 8.02 ± 0.87, and 6.40 ± 0.66 mm, respectively, before surgery, immediately after surgery, and before implantation. At point B, ridge widths were 3.40 ± 0.39, 9.35 ± 1.16, and 7.40 ± 1.10 mm, respectively, before surgery, immediately after surgery, and before implantation. The Friedman test showed significant increases in ridge widths, both at point A and point B (both P = .0000). Postaugmentation resorption was about 1.5-2 mm and was statistically significant at points A and B (P < .05, Dunn). The percentage of newly formed bone, residual graft material, and soft tissue were 33.0% ± 11.35% (95% confidence interval [CI] = 24.88%-41.12%), 37.50% ± 19.04% (95% CI = 23.88%-51.12%), and 29.5%, respectively. The inflammation was limited to grades 1 or zero. Twelve to 18 months after implantation, no implants caused pain or showed exudates or pockets. Radiographic

  17. Loss of Myeloid Related Protein-8/14 Exacerbates Cardiac Allograft Rejection

    PubMed Central

    Shimizu, Koichi; Libby, Peter; Rocha, Viviane Z.; Folco, Eduardo J.; Shubiki, Rica; Grabie, Nir; Jang, Sunyoung; Lichtman, Andrew H.; Shimizu, Ayako; Hogg, Nancy; Simon, Daniel I.; Mitchell, Richard N.; Croce, Kevin

    2011-01-01

    Background The calcium-binding proteins myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) form MRP-8/14 heterodimers (S100A8/A9, calprotectin) that regulate myeloid cell function and inflammatory responses, and serve as early serum markers for monitoring acute allograft rejection. Despite functioning as a pro-inflammatory mediator, the pathophysiological role of MRP-8/14 complexes in cardiovascular disease is incompletely defined. This study investigated the role of MRP-8/14 in cardiac allograft rejection using MRP-14-deficient mice (MRP14-/-) that lack MRP-8/14 complexes. Methods and Results We examined parenchymal rejection (PR) after major histocompatibility complex (MHC) class II allomismatched cardiac transplantation (bm12 donor heart and B6 recipients) in wild-type (WT) and MRP14-/- recipients. Allograft survival averaged 5.9 ± 2.9 weeks (n=10) in MRP14-/- recipients, compared to > 12 weeks (n = 15, p < 0.0001) in WT recipients. Two weeks after transplantation, allografts in MRP14-/- recipients had significantly higher PR scores (2.8 ± 0.8, n=8) than did WT recipients (0.8 ± 0.8, n=12, p<0.0001). Compared to WT recipients, allografts in MRP14-/- recipients had significantly increased T-cell and macrophage infiltration, as well as increased mRNA levels of IFN-γ and IFN-γ–associated chemokines (CXCL9, CXCL10, and CXCL11), IL-6, and IL-17, with significantly higher levels of Th17 cells. MRP14-/- recipients also had significantly more lymphocytes in the adjacent paraaortic lymph nodes than did WT recipients (cell number per lymph node: 23.7 ± 0.7 × 105 for MRP14-/- vs. 6.0 ± 0.2 × 105 for WT, p < 0.0001). The dendritic cells (DCs) of the MRP14-/- recipients of bm12 hearts expressed significantly higher levels of the co-stimulatory molecules CD80 and CD86 than did those of WT recipients 2 weeks after transplantation. Mixed leukocyte reactions using allo-EC-primed MRP14-/- DCs resulted in significantly higher antigen-presenting function than

  18. Imaging review of lipomatous musculoskeletal lesions

    PubMed Central

    Burt, Ashley M.; Huang, Brady K.

    2017-01-01

    Lipomatous lesions are common musculoskeletal lesions that can arise within the soft tissues, bone, neurovascular structures, and synovium. The majority of these lesions are benign, and many of the benign lesions can be diagnosed by radiologic evaluation. However, radiologic differences between benign and malignant lipomatous lesions may be subtle and pathologic correlation is often needed. The use of sonography, computed tomography (CT), and magnetic resonance imaging (MRI) is useful not only in portraying fat within the lesion, but also for evaluating the presence and extent of soft tissue components. Lipomas make up most soft tissue lipomatous lesions, but careful evaluation must be performed to distinguish these lesions from a low-grade liposarcoma. In addition to the imaging appearance, the location of the lesion and the patient demographics can be utilized to help diagnose other soft tissue lipomatous lesions, such as elastofibroma dorsi, angiolipoma, lipoblastoma, and hibernoma. Osseous lipomatous lesions such as a parosteal lipoma and intraosseous lipoma occur less commonly as their soft tissue counterpart, but are also benign. Neurovascular and synovial lipomatous lesions are much rarer lesions but demonstrate more classic radiologic findings, particularly on MRI. A review of the clinical, radiologic, and pathologic characteristics of these lesions is presented. PMID:28474576

  19. The emergence and pitfalls of international tissue banking.

    PubMed

    Phillips, Glyn O

    2018-05-23

    The rapid growth of tissue banking and associated international organisations following the fall of the Berlin wall in 1991 is described. This surge in collaboration led to a world-wide constructive movement to use and to produce human tissues. As the years progressed industrialisation, led by the USA, improved the quality of tissue allografts but led higher costs and consolidation within the developing industry. The growth of litigation more than kept pace with the industrial progress. One landmark case is described, the outcome of which could revolutionise the current practices now applied to eliminate possible viral contamination of implanted tissue grafts.

  20. Jugular venous valved conduit (Contegra) matches allograft performance in infant truncus arteriosus repair.

    PubMed

    Hickey, Edward J; McCrindle, Brian W; Blackstone, Eugene H; Yeh, Thomas; Pigula, Frank; Clarke, David; Tchervenkov, Christo I; Hawkins, John

    2008-05-01

    Limited availability and durability of allograft conduits require that alternatives be considered. We compared bovine jugular venous valved (JVV) and allograft conduit performance in 107 infants who survived truncus arteriosus repair. Children were prospectively recruited between 2003 and 2007 from 17 institutions. The median z-score for JVV (n=27, all 12 mm) was +2.1 (range +1.2 to +3.2) and allograft (n=80, 9-15mm) was +1.7 (range -0.4 to +3.6). Propensity-adjusted comparison of conduit survival was undertaken using parametric risk-hazard analysis and competing risks techniques. All available echocardiograms (n=745) were used to model deterioration of conduit function in regression equations adjusted for repeated measures. Overall conduit survival was 64+/-9% at 3 years. Conduit replacement was for conduit stenosis (n=16) and/or pulmonary artery stenosis (n=18) or regurgitation (n=1). The propensity-adjusted 3-year freedom from replacement for in-conduit stenosis was 96+/-4% for JVV and 69+/-8% for allograft (p=0.05). The risk of intervention or replacement for branch pulmonary artery stenosis was similar for JVV and allograft. Smaller conduit z-score predicted poor conduit performance (p<0.01) with best outcome between +1 and +3. Although JVV conduits were a uniform diameter, their z-score more consistently matched this ideal. JVV exhibited a non-significant trend towards slower progression of conduit regurgitation and peak right ventricular outflow tract (RVOT) gradient. In addition, catheter intervention was more successful at slowing subsequent gradient progression in children with JVV versus those with allograft (p<0.01). JVV does match allograft performance and may be advantageous. It is an appropriate first choice for repair of truncus arteriosus, and perhaps other small infants requiring RVOT reconstruction.

  1. Fox smell abrogates the effect of herbal odor to prolong mouse cardiac allograft survival.

    PubMed

    Jin, Xiangyuan; Uchiyama, Masateru; Zhang, Qi; Niimi, Masanori

    2014-05-09

    Herbal medicines have unique odors, and the act of smelling may have modulatory effects on the immune system. We investigated the effect of olfactory exposure to Tokishakuyaku-san (TJ-23), a Japanese herbal medicine, on alloimmune responses in a murine model of cardiac allograft transplantation. Naïve or olfactory-dysfunctional CBA mice underwent transplantation of a C57BL/6 heart and were exposed to the odor of TJ-23 until rejection. Some naïve CBA recipients of an allograft were given olfactory exposure to Sairei-to (TJ-114), trimethylthiazoline (TMT), individual components of TJ-23, or a TJ-23 preparation lacking one component. Adoptive transfer studies were performed to determine whether regulatory cells were generated. Untreated CBA mice rejected their C57BL/6 allografts acutely, as did olfactory-dysfunctional CBA mice exposed to the odor of TJ-23. CBA recipients of a C57BL/6 heart given olfactory exposure to TJ-23 had significantly prolonged allograft survival, whereas those exposed to the odor of TJ-114, TMT, one component of TJ-23, or TJ-23 lacking a component did not. Secondary allograft recipients that were given, at 30 days after transplantation, either whole splenocytes, CD4+ cells, or CD4+CD25+ cells from primary recipients exposed to the odor of TJ-23 had indefinitely prolonged allograft survival. Prolonged survival of cardiac allografts and generation of regulatory cells was associated with exposure to the odor of TJ-23 in our model. The olfactory area of the brain may have a role in the modulation of immune responses.

  2. Long-term tolerance to kidney allografts in a preclinical canine model.

    PubMed

    Kuhr, Christian S; Yunusov, Murad; Sale, George; Loretz, Carol; Storb, Rainer

    2007-08-27

    Durable immune tolerance supporting vascularized allotransplantation offers the possibility of extending graft survival and avoiding harmful complications of chronic immunosuppression. Immune tolerance to renal allografts was induced in a preclinical canine model through engraftment of donor hematopoietic cells using a combination of low-dose total body irradiation and a short course of immunosuppression. Subsequently, donor renal allografts were transplanted accompanied by bilateral native nephrectomies. With 5-year follow up, we found normal renal function in all recipients and no histological evidence of acute or chronic rejection. This tolerance does not extend universally to donor skin grafts, however, with two of four animals rejecting delayed donor skin grafts. Hematopoietic chimerism produces durable and robust immune tolerance to kidney allografts, although incomplete tolerance to donor skin grafting.

  3. MRI of the Musculoskeletal System: Advanced Applications using High and Ultrahigh Field MRI.

    PubMed

    Alizai, Hamza; Chang, Gregory; Regatte, Ravinder R

    2015-09-01

    In vivo MRI has revolutionized the diagnosis and treatment of musculoskeletal disorders over the past 3 decades. Traditionally performed at 1.5 T, MRI at higher field strengths offers several advantages over lower field strengths including increased signal-to-noise ratio, higher spatial resolution, improved spectral resolution for spectroscopy, improved sensitivity for X-nucleus imaging, and decreased image acquisition times. However, the physics of imaging at higher field strengths also presents technical challenges. These include B0 and B1+ field inhomogeneity, design and construction of dedicated radiofrequency (RF) coils for use at high field, increased chemical shift and susceptibility artifacts, increased RF energy deposition (specific absorption rate), increased metal artifacts, and changes in relaxation times compared with the lower field scanners. These challenges were overcome in optimizing high-field (HF) (3 T) MRI over a decade ago. HF MRI systems have since gained universal acceptance for clinical musculoskeletal imaging and have also been widely utilized for the study of musculoskeletal anatomy and physiology. Recently there has been an increasing interest in exploring musculoskeletal applications of ultrahigh field (UHF) (7 T) systems. However, technical challenges similar to those encountered when moving from 1.5 T to 3 T have to be overcome to optimize 7 T musculoskeletal imaging. In this narrative review, we discuss the many potential opportunities and technical challenges presented by the HF and UHF MRI systems. We highlight recent developments in in vivo imaging of musculoskeletal tissues that benefit most from HF imaging including cartilage, skeletal muscle, and bone. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. A Novel Therapy to Attenuate Acute Kidney Injury and Ischemic Allograft Damage after Allogenic Kidney Transplantation in Mice

    PubMed Central

    Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann

    2015-01-01

    Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20–50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells. PMID:25617900

  5. A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice.

    PubMed

    Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann; Wensvoort, Gert; Rong, Song

    2015-01-01

    Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20-50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.

  6. Early Focal Segmental Glomerulosclerosis as a Cause of Renal Allograft Primary Nonfunction

    PubMed Central

    Griffin, Emma J.; Thomson, Peter C.; Kipgen, David; Clancy, Marc; Daly, Conal

    2013-01-01

    Background. Primary focal segmental glomerulosclerosis (FSGS) is one of the commonest causes of glomerular disease and if left untreated will often progress to established renal failure. In many cases the best treatment option is renal transplantation; however primary FSGS may rapidly recur in renal allografts and may contribute to delayed graft function. We present a case of primary nonfunction in a renal allograft due to biopsy-proven FSGS. Case Report. A 32-year-old man presented with serum albumin of 22 g/L, proteinuria quantified at 12 g/L, and marked peripheral oedema. Renal biopsy demonstrated tip-variant FSGS. Despite treatment, the patient developed progressive renal dysfunction and was commenced on haemodialysis. Cadaveric renal transplantation was undertaken; however this was complicated by primary nonfunction. Renal biopsies failed to demonstrate evidence of acute rejection but did demonstrate clear evidence of FSGS. The patient was treated to no avail. Discussion. Primary renal allograft nonfunction following transplantation is often due to acute kidney injury or acute rejection. Recurrent FSGS is recognised as a phenomenon that drives allograft dysfunction but is not traditionally associated with primary nonfunction. This case highlights FSGS as a potentially aggressive process that, once active in the allograft, may prove refractory to targeted treatment. Preemptive therapies in patients deemed to be at high risk of recurrent disease may be appropriate and should be considered. PMID:23781382

  7. Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection

    PubMed Central

    Lerret, Nadine M.; Li, Ting; Wang, Jiao-Jing; Kang, Hee-Kap; Wang, Sheng; Wang, Xueqiong; Jie, Chunfa; Kanwar, Yashpal S.; Abecassis, Michael M.

    2015-01-01

    The myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remains unclear. Using a stringent mouse model of allogeneic kidney transplantation, we demonstrated that acute allograft rejection occurred equally in MyD88-sufficient (wild-type [WT]) and MyD88−/− recipients. However, MyD88 deficiency resulted in spontaneous diminution of graft infiltrating effector cells, including CD11b−Gr-1+ cells and activated CD8 T cells, as well as subsequent restoration of near-normal renal graft function, leading to long-term kidney allograft acceptance. Compared with T cells from WT recipients, T cells from MyD88−/− recipients failed to mount a robust recall response upon donor antigen restimulation in mixed lymphocyte cultures ex vivo. Notably, exogenous IL-6 restored the proliferation rate of T cells, particularly CD8 T cells, from MyD88−/− recipients to the proliferation rate of cells from WT recipients. Furthermore, MyD88−/− T cells exhibited diminished expression of chemokine receptors, specifically CCR4 and CXCR3, and the impaired ability to accumulate in the kidney allografts despite an otherwise MyD88-sufficient environment. These results provide a mechanism linking the lack of intrinsic MyD88 signaling in T cells to the effective control of the rejection response that results in spontaneous resolution of acute rejection and long-term graft protection. PMID:25788530

  8. Virtual Interactive Musculoskeletal System (VIMS) in orthopaedic research, education and clinical patient care.

    PubMed

    Chao, Edmund Y S; Armiger, Robert S; Yoshida, Hiroaki; Lim, Jonathan; Haraguchi, Naoki

    2007-03-08

    The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the "Virtual Human" reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of these unique database and simulation technology. This integrated system, model library and database will impact on orthopaedic education, basic research, device development and application, and clinical patient care related to musculoskeletal joint system reconstruction, trauma management, and rehabilitation.

  9. Endogenous Memory CD8 T Cells Are Activated Within Cardiac Allografts Without Mediating Rejection

    PubMed Central

    Setoguchi, Kiyoshi; Hattori, Yusuke; Iida, Shoichi; Baldwin, William M.; Fairchild, Robert L.

    2013-01-01

    Endogenous memory CD8 T cells infiltrate MHC-mismatched cardiac allografts within 12–24 hours post-transplant in mice and are activated to proliferate and produce IFN-γ. To more accurately assess the graft injury directly imposed by these endogenous memory CD8 T cells, we took advantage of the ability of anti-LFA-1 mAb given to allograft recipients on days 3 and 4 post-transplant to inhibit the generation of primary effector T cells. When compared to grafts from IgG treated recipients on day 7 post-transplant, allografts from anti-LFA-1 mAb treated recipients had increased numbers of CD8 T cells but these grafts had marked decreases in expression levels of mRNA encoding effector mediators associated with graft injury and decreases in donor-reactive CD8 T cells producing IFN-γ. Despite this decreased activity within the allograft, CD8 T cells in allografts from recipients treated with anti-LFA-1 mAb continued to proliferate up to day 7 post-transplant and did not upregulate expression of the exhaustion marker LAG-3 but did have decreased expression of ICOS. These results indicate that endogenous memory CD8 T cells infiltrate and proliferate in cardiac allografts in mice but do not express sufficient levels of functions to mediate overt graft injury and acute rejection. PMID:23914930

  10. Musculoskeletal Fitness and Risk of Mortality.

    ERIC Educational Resources Information Center

    Katzmarzyk, Peter T.; Craig, Cora L.

    2002-01-01

    Quantified the relationship between musculoskeletal fitness and all-cause mortality in Canada, using measures of musculoskeletal fitness (situps, pushups, grip strength, and sit- and-reach trunk flexibility) from adult male and female participants in the Canadian Fitness Survey. Results indicated that some components of musculoskeletal fitness,…

  11. Iliac Crest Bone Graft versus Local Autograft or Allograft for Lumbar Spinal Fusion: A Systematic Review.

    PubMed

    Tuchman, Alexander; Brodke, Darrel S; Youssef, Jim A; Meisel, Hans-Jörg; Dettori, Joseph R; Park, Jong-Beom; Yoon, S Tim; Wang, Jeffrey C

    2016-09-01

    Systematic review. To compare the effectiveness and safety between iliac crest bone graft (ICBG) and local autologous bone and allograft in the lumbar spine. A systematic search of multiple major medical reference databases identified studies evaluating spinal fusion in patients with degenerative joint disease using ICBG, local autograft, or allograft in the thoracolumbar spine. Six comparative studies met our inclusion criteria. A "low" strength of the overall body of evidence suggested no difference in fusion percentages in the lumbar spine between local autograft and ICBG. We found no difference in fusion percentages based on low evidence comparing allograft with ICBG autograft. There were no differences in pain or functional results comparing local autograft or allograft with ICBG autograft. Donor site pain and hematoma/seroma occurred more frequently in ICBG autograft group for lumbar fusion procedures. There was low evidence around the estimate of patients with donor site pain following ICBG harvesting, ranging from 16.7 to 20%. With respect to revision, low evidence demonstrated no difference between allograft and ICBG autograft. There was no evidence comparing patients receiving allograft with local autograft for fusion, pain, functional, and safety outcomes. In the lumbar spine, ICBG, local autograft, and allograft have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes. However, ICBG is associated with an increased risk for donor site-related complications. Significant limitations exist in the available literature when comparing ICBG, local autograft, and allograft for lumbar fusion, and thus ICBG versus other fusion methods necessitates further investigation.

  12. [Musculoskeletal-related chest pain].

    PubMed

    Sturm, C; Witte, T

    2017-01-01

    Approximately 10-50% of chest pains are caused by musculoskeletal disorders. The association is twice as frequent in primary care as in emergency admissions. This article provides an overview of the most important musculoskeletal causes of chest pain and on the diagnostics and therapy. A selective search and analysis of the literature related to the topic of musculoskeletal causes of chest pain were carried out. Non-inflammatory diseases, such as costochondritis and fibromyalgia are frequent causes of chest pain. Inflammatory diseases, such as rheumatoid arthritis, spondyloarthritis and systemic lupus erythematosus are much less common but are more severe conditions and therefore have to be diagnosed and treated. The diagnostics and treatment often necessitate interdisciplinary approaches. Chest pain caused by musculoskeletal diseases always represents a diagnosis by exclusion of other severe diseases of the heart, lungs and stomach. Physiotherapeutic and physical treatment measures are particularly important, including manual therapy, transcutaneous electrical stimulation and stabilization exercises, especially for functional myofascial disorders.

  13. Reverse engineering development: Crosstalk opportunities between developmental biology and tissue engineering.

    PubMed

    Marcucio, Ralph S; Qin, Ling; Alsberg, Eben; Boerckel, Joel D

    2017-11-01

    The fields of developmental biology and tissue engineering have been revolutionized in recent years by technological advancements, expanded understanding, and biomaterials design, leading to the emerging paradigm of "developmental" or "biomimetic" tissue engineering. While developmental biology and tissue engineering have long overlapping histories, the fields have largely diverged in recent years at the same time that crosstalk opportunities for mutual benefit are more salient than ever. In this perspective article, we will use musculoskeletal development and tissue engineering as a platform on which to discuss these emerging crosstalk opportunities and will present our opinions on the bright future of these overlapping spheres of influence. The multicellular programs that control musculoskeletal development are rapidly becoming clarified, represented by shifting paradigms in our understanding of cellular function, identity, and lineage specification during development. Simultaneously, advancements in bioartificial matrices that replicate the biochemical, microstructural, and mechanical properties of developing tissues present new tools and approaches for recapitulating development in tissue engineering. Here, we introduce concepts and experimental approaches in musculoskeletal developmental biology and biomaterials design and discuss applications in tissue engineering as well as opportunities for tissue engineering approaches to inform our understanding of fundamental biology. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2356-2368, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  14. INDUCTION OF DONOR-SPECIFIC TRANSPLANTATION TOLERANCE TO SKIN AND CARDIAC ALLOGRAFTS USING MIXED CHIMERISM IN (A + B → A) IN RATS

    PubMed Central

    Markus, Peter M.; Selvaggi, Gennaro; Cai, Xin; Fung, John J.; Starzl, Thomas E.

    2010-01-01

    Mixed allogeneic chimerism (A + B → A) was induced in rats by reconstitution of lethally irradiated LEW recipients with a mixture of T-cell depleted (TCD) syngeneic and TCD allogeneic ACI bone marrow. Thirty-seven percent of animals repopulated as stable mixed lymphopoietic chimeras, while the remainder had no detectable allogeneic chimerism. When evaluated for evidence of donor-specific transplantation tolerance, only those recipients with detectable allogeneic lymphoid chimerism exhibited acceptance of donor-specific skin and cardiac allografts. Despite transplantation over a major histocompatibility complex (MHO)- and minor-disparate barrier, animals accepted donor-specific ACI skin and primarily vascularized cardiac allografts permanently, while rejecting third party Brown Norway (BN) grafts. The tolerance induced was also donor-specific in vitro as evidenced by specific hyporeactivity to the allogeneic donor lymphoid elements, yet normal reactivity to MHC-disparate third party rat lymphoid cells. This model for mixed chimerism in the rat will be advantageous to investigate specific transplantation tolerance to primarily vascularized solid organ grafts that can be performed with relative ease in the rat, but not in the mouse, and may provide a method to study the potential existence of organ- or tissue-specific alloantigens in primarily vascularized solid organ allografts. PMID:8162277

  15. Post-traumatic implant-supported restoration of the anterior maxillary teeth using cancellous bone block allografts.

    PubMed

    Nissan, Joseph; Gross, Ora; Mardinger, Ofer; Ghelfan, Oded; Sacco, Roberto; Chaushu, Gavriel

    2011-12-01

    To prospectively evaluate the outcome of dental implants placed in the post-traumatic anterior maxilla after ridge augmentation with cancellous freeze-dried block bone allografts. Patients presenting with a history of anterior dentoalveolar trauma with bony deficiencies in the sagittal (≥3 mm) and vertical (<3 mm) planes according to computed tomography were included. The recipient sites were reconstructed with cancellous bone block allografts. After 6 months of healing, implants were placed. The primary outcomes of interest were 1) bone measurements taken before grafting, at the time of implant placement, and at stage 2 operations; 2) implant survival; and 3) complications. The sample was composed of 20 consecutive patients with a mean age of 25 ± 7 years. We used 28 cancellous allogeneic bone blocks, and 31 implants were inserted. Of the 31 implants, 12 were immediately restored. The mean follow-up was 42 ± 15 months. Graft and implant survival rates were 92.8% and 96.8%, respectively. Mean bone gain in the sagittal and vertical planes was 5 ± 0.5 mm horizontally and 2 ± 0.5 mm (P < .001). Successful restoration was achieved in all patients with fixed implant-supported prostheses. Soft tissue complications occurred in 7 patients (35%). Complications after cementation of the crowns were seen in 3 implants (9.6%). All implants remained clinically osseointegrated at the end of the follow-up examination. There was no crestal bone loss around the implants beyond the first implant thread. Cancellous block allograft can be used successfully for post-traumatic implant-supported restoration in the anterior maxilla. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Tendon tissue engineering: Adipose 1 derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems

    PubMed Central

    James, R; Kumbar, S G; Laurencin, C T; Balian, G; Chhabra, A B

    2011-01-01

    Tendon tissue engineering with a biomaterial scaffold that mimics the tendon extracellular matrix (ECM) and is biomechanically suitable when combined with readily available autologous cells may provide successful regeneration of defects in tendon. Current repair strategies using suitable autografts and freeze-dried allografts lead to a slow repair process that is sub-optimal and fails to restore function, particularly in difficult clinical situations such as zone II flexor tendon injuries of the hand. We have investigated the effect of GDF-5 on cell proliferation and gene expression by primary rat adipose-derived stromal cells (ADSCs) that were cultured on poly(DL-lactide-co-glycolide) PLAGA fiber scaffold and compared to PLAGA 2D film scaffold. The electrospun scaffold mimics the collagen fiber bundles present in native tendon tissue, and supports the adhesion and proliferation of multipotent ADSCs. Gene expression of scleraxis, the neotendon marker was upregulated 7 – 8 fold at 1 week with GDF-5 treatment when cultured on 3D electrospun scaffold, and was significantly higher at 2 weeks compared to 2D films with or without GDF-5 treatment. Expression of the genes that encode the major tendon ECM protein, collagen type I, was increased by 4 fold starting at 1 week on treatment with 100ng/mL GDF-5, and at all time points the expression was significantly higher compared to 2D films irrespective of GDF-5 treatment. Thus stimulation with GDF-5 can modulate primary ADSCs on PLAGA fiber scaffold to produce a soft, collagenous musculoskeletal tissue that fulfills the need for tendon regeneration. PMID:21436509

  17. Functional MRI detects perfusion impairment in renal allografts with delayed graft function.

    PubMed

    Hueper, Katja; Gueler, Faikah; Bräsen, Jan Hinrich; Gutberlet, Marcel; Jang, Mi-Sun; Lehner, Frank; Richter, Nicolas; Hanke, Nils; Peperhove, Matti; Martirosian, Petros; Tewes, Susanne; Vo Chieu, Van Dai; Großhennig, Anika; Haller, Hermann; Wacker, Frank; Gwinner, Wilfried; Hartung, Dagmar

    2015-06-15

    Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF. Copyright © 2015 the American Physiological Society.

  18. Multilayer scaffolds in orthopaedic tissue engineering.

    PubMed

    Atesok, Kivanc; Doral, M Nedim; Karlsson, Jon; Egol, Kenneth A; Jazrawi, Laith M; Coelho, Paulo G; Martinez, Amaury; Matsumoto, Tomoyuki; Owens, Brett D; Ochi, Mitsuo; Hurwitz, Shepard R; Atala, Anthony; Fu, Freddie H; Lu, Helen H; Rodeo, Scott A

    2016-07-01

    The purpose of this study was to summarize the recent developments in the field of tissue engineering as they relate to multilayer scaffold designs in musculoskeletal regeneration. Clinical and basic research studies that highlight the current knowledge and potential future applications of the multilayer scaffolds in orthopaedic tissue engineering were evaluated and the best evidence collected. Studies were divided into three main categories based on tissue types and interfaces for which multilayer scaffolds were used to regenerate: bone, osteochondral junction and tendon-to-bone interfaces. In vitro and in vivo studies indicate that the use of stratified scaffolds composed of multiple layers with distinct compositions for regeneration of distinct tissue types within the same scaffold and anatomic location is feasible. This emerging tissue engineering approach has potential applications in regeneration of bone defects, osteochondral lesions and tendon-to-bone interfaces with successful basic research findings that encourage clinical applications. Present data supporting the advantages of the use of multilayer scaffolds as an emerging strategy in musculoskeletal tissue engineering are promising, however, still limited. Positive impacts of the use of next generation scaffolds in orthopaedic tissue engineering can be expected in terms of decreasing the invasiveness of current grafting techniques used for reconstruction of bone and osteochondral defects, and tendon-to-bone interfaces in near future.

  19. A20 Haploinsufficiency Aggravates Transplant Arteriosclerosis in Mouse Vascular Allografts: Implications for Clinical Transplantation

    PubMed Central

    Cervantes, Jesus Revuelta; Wojcik, Brandon M.; Parulkhar, Anshul; Mele, Alessandra; LoGerfo, Philip J.; Siracuse, Jeffrey J.; Csizmadia, Eva; da Silva, Cleide G.; Ferran, Christiane

    2016-01-01

    Background Inflammation is central to the pathogenesis of transplant arteriosclerosis (TA). We questioned whether physiologic levels of anti-inflammatory A20 influence TA severity. Methods We performed major histocompatibility complex (MHC) mismatched aorta to carotid artery interposition grafts, using wild type (WT) or A20 heterozygote (HET) C57BL/6 (H-2b) donors and BALB/c (H-2d) recipients, and conversely BALB/c donors and WT/HET recipients. We analyzed aortic allografts by histology, immunohistochemistry, immunofluorescence, and gene profiling (qPCR). We validated select in vivo A20 targets in human and mouse smooth muscle cell (SMC) cultures. Results We noted significantly greater intimal hyperplasia in HET vs. WT allografts, indicating aggravated TA. Inadequate upregulation of A20 in HET allografts after transplantation was associated with excessive NF-κB activation, gauged by higher levels of IκBα, p65, VCAM-1, ICAM-1, CXCL10, CCL2, TNF, and IL-6 (mostly localized to SMC). Correspondingly, cytokine-induced upregulation of TNF and IL-6 in human and mouse SMC cultures inversely correlated with A20 expression. Aggravated TA in HET vs. WT allografts correlated with increased intimal SMC proliferation, and a higher number of infiltrating IFNγ+ and Granzyme B+ CD4+ T cells and natural killer cells, and lower number of FoxP3+ regulatory T cells. A20 haploinsufficiency in allograft recipients did not influence TA. Conclusions A20 haploinsufficiency in vascular allografts aggravates lesions of TA by exacerbating inflammation, SMC proliferation, and infiltration of pathogenic T cells. A20 single nucleotide polymorphisms (SNPs) associating with lower A20 expression or function in donors of vascularized allografts may inform risk and severity of TA, highlighting the clinical implications of our findings. PMID:27495763

  20. Interplay between immune responses to HLA and non-HLA self-antigens in allograft rejection.

    PubMed

    Angaswamy, Nataraju; Tiriveedhi, Venkataswarup; Sarma, Nayan J; Subramanian, Vijay; Klein, Christina; Wellen, Jason; Shenoy, Surendra; Chapman, William C; Mohanakumar, T

    2013-11-01

    Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection. Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo- and autoimmunity leading to allograft dysfunction. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  1. Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts.

    PubMed Central

    MacMillan-Crow, L A; Crow, J P; Kerby, J D; Beckman, J S; Thompson, J A

    1996-01-01

    Inflammatory processes in chronic rejection remain a serious clinical problem in organ transplantation. Activated cellular infiltrate produces high levels of both superoxide and nitric oxide. These reactive oxygen species interact to form peroxynitrite, a potent oxidant that can modify proteins to form 3-nitrotyrosine. We identified enhanced immunostaining for nitrotyrosine localized to tubular epithelium of chronically rejected human renal allografts. Western blot analysis of rejected tissue demonstrated that tyrosine nitration was restricted to a few specific polypeptides. Immunoprecipitation and amino acid sequencing techniques identified manganese superoxide dismutase, the major antioxidant enzyme in mitochondria, as one of the targets of tyrosine nitration. Total manganese superoxide dismutase protein was increased in rejected kidney, particularly in the tubular epithelium; however, enzymatic activity was significantly decreased. Exposure of recombinant human manganese superoxide dismutase to peroxynitrite resulted in a dose-dependent (IC50 = 10 microM) decrease in enzymatic activity and concomitant increase in tyrosine nitration. Collectively, these observations suggest a role for peroxynitrite during development and progression of chronic rejection in human renal allografts. In addition, inactivation of manganese superoxide dismutase by peroxynitrite may represent a general mechanism that progressively increases the production of peroxynitrite, leading to irreversible oxidative injury to mitochondria. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8876227

  2. Iliac Crest Bone Graft versus Local Autograft or Allograft for Lumbar Spinal Fusion: A Systematic Review

    PubMed Central

    Tuchman, Alexander; Brodke, Darrel S.; Youssef, Jim A.; Meisel, Hans-Jörg; Dettori, Joseph R.; Park, Jong-Beom; Yoon, S. Tim; Wang, Jeffrey C.

    2016-01-01

    Study Design  Systematic review. Objective  To compare the effectiveness and safety between iliac crest bone graft (ICBG) and local autologous bone and allograft in the lumbar spine. Methods  A systematic search of multiple major medical reference databases identified studies evaluating spinal fusion in patients with degenerative joint disease using ICBG, local autograft, or allograft in the thoracolumbar spine. Results  Six comparative studies met our inclusion criteria. A “low” strength of the overall body of evidence suggested no difference in fusion percentages in the lumbar spine between local autograft and ICBG. We found no difference in fusion percentages based on low evidence comparing allograft with ICBG autograft. There were no differences in pain or functional results comparing local autograft or allograft with ICBG autograft. Donor site pain and hematoma/seroma occurred more frequently in ICBG autograft group for lumbar fusion procedures. There was low evidence around the estimate of patients with donor site pain following ICBG harvesting, ranging from 16.7 to 20%. With respect to revision, low evidence demonstrated no difference between allograft and ICBG autograft. There was no evidence comparing patients receiving allograft with local autograft for fusion, pain, functional, and safety outcomes. Conclusion  In the lumbar spine, ICBG, local autograft, and allograft have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes. However, ICBG is associated with an increased risk for donor site-related complications. Significant limitations exist in the available literature when comparing ICBG, local autograft, and allograft for lumbar fusion, and thus ICBG versus other fusion methods necessitates further investigation. PMID:27556001

  3. CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction

    PubMed Central

    Li, Jing; Shi, Yuan; Xie, Ke-Liang; Yin, Hai-Fang; Yan, Lu-nan; Lau, Wan-yee; Wang, Guo-Lin

    2016-01-01

    Chronic liver allograft dysfunction (CLAD) remains the most common cause of patient morbidity and allograft loss in liver transplant patients. However, the pathogenesis of CLAD has not been completely elucidated. By establishing rat CLAD models, in this study, we identified the informative CLAD-associated genes using isobaric tags for relative and absolute quantification (iTRAQ) proteomics analysis and validated these results in recipient rat liver allografts. CXCL4, CXCR3, EGFR, JAK2, STAT3, and Collagen IV were associated with CLAD pathogenesis. We validated that CXCL4 is upstream of these informative genes in the isolated hepatic stellate cells (HSC). Blocking CXCL4 protects against CLAD by reducing liver fibrosis. Therefore, our results indicated that therapeutic approaches that neutralize CXCL4, a newly identified target of fibrosis, may represent a novel strategy for preventing and treating CLAD after liver transplantation. PMID:28053995

  4. CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction.

    PubMed

    Li, Jing; Liu, Bin; Shi, Yuan; Xie, Ke-Liang; Yin, Hai-Fang; Yan, Lu-Nan; Lau, Wan-Yee; Wang, Guo-Lin

    2016-01-01

    Chronic liver allograft dysfunction (CLAD) remains the most common cause of patient morbidity and allograft loss in liver transplant patients. However, the pathogenesis of CLAD has not been completely elucidated. By establishing rat CLAD models, in this study, we identified the informative CLAD-associated genes using isobaric tags for relative and absolute quantification (iTRAQ) proteomics analysis and validated these results in recipient rat liver allografts. CXCL4, CXCR3, EGFR, JAK2, STAT3, and Collagen IV were associated with CLAD pathogenesis. We validated that CXCL4 is upstream of these informative genes in the isolated hepatic stellate cells (HSC). Blocking CXCL4 protects against CLAD by reducing liver fibrosis. Therefore, our results indicated that therapeutic approaches that neutralize CXCL4, a newly identified target of fibrosis, may represent a novel strategy for preventing and treating CLAD after liver transplantation.

  5. Delaying Shoulder Motion and Strengthening and Increasing Achilles Allograft Thickness for Glenoid Resurfacing Did Not Improve the Outcome for a 30-Year-Old Patient with Postarthroscopic Glenohumeral Chondrolysis

    PubMed Central

    Skedros, John G.; Henrie, Tanner R.; Mears, Chad S.

    2014-01-01

    Although interposition soft-tissue (biologic) resurfacing of the glenoid with humeral hemiarthroplasty has been considered an option for end-stage glenohumeral arthritis, the results of this procedure are highly unsatisfactory in patients less than 40 years old. Achilles tendon allograft is popular for glenoid resurfacing because it can be made robust by folding it. But one reason that the procedure might fail in younger patients is that the graft is not initially thick enough for the young active patient. Most authors report folding the graft only once to achieve two-layer thickness. We report the case of a 30-year-old male who had postarthroscopic glenohumeral chondrolysis that was treated with Achilles tendon allograft resurfacing of the glenoid and humeral hemiarthroplasty. An important aspect of our case is that the tendon was folded so that it was 50–100% thicker than most allograft constructs reported previously. We also used additional measures to enhance allograft resiliency and bone incorporation: (1) multiple nonresorbable sutures to attach the adjacent graft layers, (2) additional resorbable suture anchors and nonresorbable sutures in order to more robustly secure the graft to the glenoid, and (3) delaying postoperative motion and strengthening. However, despite these additional measures, our patient did not have an improved outcome. PMID:25580331

  6. Reliability and validity of the Korean version of the Short Musculoskeletal Function Assessment questionnaire for patients with musculoskeletal disorder.

    PubMed

    Jung, Kyoung-Sim; Jung, Jin-Hwa; In, Tae-Sung; Cho, Hwi-Young

    2016-09-01

    [Purpose] The purpose of this study was to establish the reliability and validity of the Short Musculoskeletal Function Assessment questionnaire, which was translated into Korean, for patients with musculoskeletal disorder. [Subjects and Methods] Fifty-five subjects (26 males and 29 females) with musculoskeletal diseases participated in the study. The Short Musculoskeletal Function Assessment questionnaire focuses on a limited range of physical functions and includes a dysfunction index and a bother index. Reliability was determined using the intraclass correlation coefficient, and validity was examined by correlating short musculoskeletal function assessment scores with the 36-item Short-Form Health Survey (SF-36) score. [Results] The reliability was 0.97 for the dysfunction index and 0.94 for the bother index. Validity was established by comparison with Korean version of the SF-36. [Conclusion] This study demonstrated that the Korean version of the Short Musculoskeletal Function Assessment questionnaire is a reliable and valid instrument for the assessment of musculoskeletal disorders.

  7. In Vivo Efficacy of Fresh vs. Frozen Osteochondral Allografts in the Goat at 6 Months is Associated with PRG4 Secretion

    PubMed Central

    Pallante-Kichura, Andrea L.; Chen, Albert C.; Temple-Wong, Michele M.; Bugbee, William D.; Sah, Robert L.

    2014-01-01

    The long-term efficacy of osteochondral allografts is due to the presence of viable chondrocytes within graft cartilage. Chondrocytes in osteochondral allografts, especially those at the articular surface that normally produce the lubricant proteoglycan-4 (PRG4), are susceptible to storage-associated death. The hypothesis of this study was that the loss of chondrocytes within osteochondral grafts leads to decreased PRG4 secretion, after graft storage and subsequent implant. The objectives were to determine the effect of osteochondral allograft treatment (FROZEN vs. FRESH) on secretion of functional PRG4 after (i) storage, and (ii) 6months in vivo in adult goats. FROZEN allograft storage reduced PRG4 secretion from cartilage by ~85% compared to FRESH allograft storage. After 6months in vivo, the PRG4-secreting function of osteochondral allografts was diminished with prior FROZEN storage by ~81% versus FRESH allografts and by ~84% versus non-operated control cartilage. Concomitantly, cellularity at the articular surface in FROZEN allografts was ~96% lower than FRESH allografts and non-operated cartilage. Thus, the PRG4-secreting function of allografts appears to be maintained in vivo based on its state after storage. PRG4 secretion may be not only a useful marker of allograft performance, but also a biological process protecting the articular surface of grafts following cartilage repair. PMID:23362152

  8. Peripheral blood sampling for the detection of allograft rejection: biomarker identification and validation.

    PubMed

    Heidt, Sebastiaan; San Segundo, David; Shankar, Sushma; Mittal, Shruti; Muthusamy, Anand S R; Friend, Peter J; Fuggle, Susan V; Wood, Kathryn J

    2011-07-15

    Currently, acute allograft rejection can only be detected reliably by deterioration of graft function confirmed by allograft biopsy. A huge drawback of this method of diagnosis is that substantial organ damage has already taken place at the time that rejection is diagnosed. Discovering and validating noninvasive biomarkers that predict acute rejection, and chronic allograft dysfunction, is of great importance. Many studies have investigated changes in the peripheral blood in an attempt to find biomarkers that reflect changes in the graft directly or indirectly. Herein, we will review the promises and limitations of the peripheral blood biomarkers that have been described in the literature so far.

  9. Work activities and musculoskeletal discomforts amongst active older Albertans on alternative employment trajectories.

    PubMed

    Doan, Jon B; Copeland, Jennifer L; Brown, Lesley A; Newman, Jeff T; Hudson, D Shane

    2014-01-01

    Bridge employment (scheduled paid work after retirement age) may promote successful aging and continued health, as work can be an important component of daily physical activity. Appropriate work demands for older adults are neither well-established nor well-applied, however, and excessive loading or increased perceptions of discomfort may negate the health benefits of work activity. This study examined work status and musculoskeletal discomfort (MSD) amongst older Albertans. 1044 Albertans aged 55 years and older participating in an organized 'Games' received a research package. Enclosed in the package were an introductory letter, a return envelope, and modified versions of validated questionnaires examining leisure and work activities, activity frequency, and perceptions of musculoskeletal health. 228 respondents were classified into one of three employment trajectory groups: fully retired, fully employed, or bridge employed. Groups differed in age, and both employed groups more frequently reported MSDs in all body areas. Bridge employed reported increased 'occasional' frequency of musculoskeletal injury risk factors, while both groups reported similar overall ratings of work-related exertion. The increased MSDs reported by bridge employed adults may be the result of irregularity of work activity and soft tissue loading. Detailed examination of work demands and musculoskeletal injuries amongst bridge employed adults could help define safer levels for less regular work activity.

  10. Kidney versus Islet Allograft Survival after Induction of Mixed Chimerism with Combined Donor Bone Marrow Transplantation

    PubMed Central

    Oura, Tetsu; Ko, Dicken S.C.; Boskovic, Svjetlan; O'Neil, John J.; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R. Neal; Cosimi, A. B.; Kawai, Tatsuo

    2016-01-01

    Background We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC-mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. Methods A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that includes low dose total body and thymic irradiation, horse ATG (Atgam), six doses of anti-CD154 monoclonal antibody (mAb) and a one month course of cyclosporine (CyA) (Islet-A). In Islet-B, anti-CD8 mAb was administered in place of CyA. In Islet-C, two recipients were treated with Islet-B but without Atgam. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and bone marrow transplantation (Kidney-A) following the same conditioning regimen used in Islet-A. Results The majority of Kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned Islet/BM recipients (Islet-A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to calcineurin inhibitor (CNI) toxicity, three recipients were treated with anti-CD8 mAb in place of CNI. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet-C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Conclusion Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CNI-free regimen that includes anti-CD8 mAb. However, unlike the kidney allograft, islet allograft

  11. Kidney Versus Islet Allograft Survival After Induction of Mixed Chimerism With Combined Donor Bone Marrow Transplantation.

    PubMed

    Oura, Tetsu; Ko, Dicken S C; Boskovic, Svjetlan; O'Neil, John J; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R Neal; Cosimi, A B; Kawai, Tatsuo

    2016-01-01

    We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that included low-dose total body and thymic irradiation, horse Atgam (ATG), six doses of anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine (CyA) (Islet A). In Islet B, anti-CD8 mAb was administered in place of CyA. In Islet C, two recipients were treated with Islet B, but without ATG. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and BM transplantation (Kidney A) following the same conditioning regimen used in Islet A. The majority of kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned islet/BM recipients (Islet A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to CyA toxicity, three recipients were treated with anti-CD8 mAb in place of CyA. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CyA-free regimen that included anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more

  12. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.

    PubMed

    Mehra, Mandeep R; Crespo-Leiro, Maria G; Dipchand, Anne; Ensminger, Stephan M; Hiemann, Nicola E; Kobashigawa, Jon A; Madsen, Joren; Parameshwar, Jayan; Starling, Randall C; Uber, Patricia A

    2010-07-01

    The development of cardiac allograft vasculopathy remains the Achilles heel of cardiac transplantation. Unfortunately, the definitions of cardiac allograft vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, cardiac allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers. This document represents a working formulation for an international nomenclature of cardiac allograft vasculopathy, similar to the development of the system for adjudication of cardiac allograft rejection by histology.

  13. Fresh vein allograft survival in dogs after cyclosporine treatment.

    PubMed

    Mingoli, A; Edwards, J D; Feldhaus, R J; Hunter, W J; Naspetti, R; Cavallari, N; Sapienza, P; Kretchmar, D H; Cavallaro, A

    1996-04-01

    Synthetic grafts are widely used for peripheral arterial reconstructions when autologous veins are not available, but their results have not been satisfactory. Venous allograft may be used as an alternative to synthetic prostheses. The aim of the study was to explore the immunosuppressive efficacy of Cyclosporine A (CyA) as a means of preventing venous allograft failures and rejection. We utilized 56 mongrel dogs. Immunological incompatibility was checked with the skin graft method. Donor inferior vena cava was transplanted into the infrarenal abdominal aorta of recipient animals. One group (group 1, 10 dogs) served as a control and three groups received CyA treatment regimens. Group 2 (10 dogs) received postoperative oral CyA treatment for 30 days. Group 3 (12 dogs) received a vein graft pretreated with a CyA solution without postoperative immunosuppressive therapy. Group 4 (9 dogs) received a vein graft pretreated with a CyA solution and postoperative CyA treatment for 30 days. Allografts were examined at 30 days for patency, aneurysmal dilatation, gross structural changes, inflammatory response, and lymphocytic infiltration. Sex chromatine assessment determined the origin (donor or recipient) of the endothelial cells. The allografts from groups 1 and 3 showed significant aneurysmal dilatation and perivenous inflammation when compared to dogs treated with oral CyA therapy (P < 0.0002). Moreover allografts treated with CyA therapy had a better-developed venous neointima (P < 0.009) with less fibrin (P < 0.02) and thinner medial (P < 0.0009) with less fibrin (P < 0.02), and thinner medial (P < 0.0009) and adventitial layers (P < 0.02). No significant differences were observed in neointimal thickness among the four groups. Lymphocytic infiltration was greater in the group of animals who did not receive oral CyA therapy (P < 0.0004). Barr bodies status showed significant differences between oral CyA treated groups and nontreated groups (P < 0.0003). Oral CyA therapy

  14. Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

    PubMed Central

    Wang, Xiaojie; Hao, Jianqiang; Leung, Gigi; Breitkopf, Trisia; Wang, Eddy; Kwong, Nicole; Akhoundsadegh, Noushin; Warnock, Garth L.; Shapiro, Jerry; McElwee, Kevin J.

    2015-01-01

    Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P < 0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation. PMID:26000314

  15. Geographic inequities in liver allograft supply and demand: does it affect patient outcomes?

    PubMed

    Rana, Abbas; Kaplan, Bruce; Riaz, Irbaz B; Porubsky, Marian; Habib, Shahid; Rilo, Horacio; Gruessner, Angelika C; Gruessner, Rainer W G

    2015-03-01

    Significant geographic inequities mar the distribution of liver allografts for transplantation. We analyzed the effect of geographic inequities on patient outcomes. During our study period (January 1 through December 31, 2010), 11,244 adult candidates were listed for liver transplantation: 5,285 adult liver allografts became available, and 5,471 adult recipients underwent transplantation. We obtained population data from the 2010 United States Census. To determine the effect of regional supply and demand disparities on patient outcomes, we performed linear regression and multivariate Cox regression analyses. Our proposed disparity metric, the ratio of listed candidates to liver allografts available varied from 1.3 (region 11) to 3.4 (region 1). When that ratio was used as the explanatory variable, the R(2) values for outcome measures were as follows: 1-year waitlist mortality, 0.23 and 1-year posttransplant survival, 0.27. According to our multivariate analysis, the ratio of listed candidates to liver allografts available had a significant effect on waitlist survival (hazards ratio, 1.21; 95% confidence interval, 1.04-1.40) but was not a significant risk factor for posttransplant survival. We found significant differences in liver allograft supply and demand--but these differences had only a modest effect on patient outcomes. Redistricting and allocation-sharing schemes should seek to equalize regional supply and demand rather than attempting to equalize patient outcomes.

  16. Lipidomics comparing DCD and DBD liver allografts uncovers lysophospholipids elevated in recipients undergoing early allograft dysfunction.

    PubMed

    Xu, Jin; Casas-Ferreira, Ana M; Ma, Yun; Sen, Arundhuti; Kim, Min; Proitsi, Petroula; Shkodra, Maltina; Tena, Maria; Srinivasan, Parthi; Heaton, Nigel; Jassem, Wayel; Legido-Quigley, Cristina

    2015-12-04

    Finding specific biomarkers of liver damage in clinical evaluations could increase the pool of available organs for transplantation. Lipids are key regulators in cell necrosis and hence this study hypothesised that lipid levels could be altered in organs suffering severe ischemia. Matched pre- and post-transplant biopsies from donation after circulatory death (DCD, n = 36, mean warm ischemia time = 2 min) and donation after brain death (DBD, n = 76, warm ischemia time = none) were collected. Lipidomic discovery and multivariate analysis (MVA) were applied. Afterwards, univariate analysis and clinical associations were conducted for selected lipids differentiating between these two groups. MVA grouped DCD vs. DBD (p = 6.20 × 10(-12)) and 12 phospholipids were selected for intact lipid measurements. Two lysophosphatidylcholines, LysoPC (16:0) and LysoPC (18:0), showed higher levels in DCD at pre-transplantation (q < 0.01). Lysophosphatidylcholines were associated with aspartate aminotransferase (AST) 14-day post-transplantation (q < 0.05) and were more abundant in recipients undergoing early allograft dysfunction (EAD) (p < 0.05). A receiver-operating characteristics (ROC) curve combining both lipid levels predicted EAD with 82% accuracy. These findings suggest that LysoPC (16:0) and LysoPC (18:0) might have a role in signalling liver tissue damage due to warm ischemia before transplantation.

  17. Absence of MyD88 Signaling Induces Donor-Specific Kidney Allograft Tolerance

    PubMed Central

    Noordmans, Gerda A.; O’Brien, Maya R.; Ma, Jin; Zhao, Cathy Y.; Zhang, Geoff Y.; Kwan, Tony K.T.; Alexander, Stephen I.; Chadban, Steven J.

    2012-01-01

    Toll-like receptors (TLRs) play a fundamental role in innate immunity and provide a link between innate and adaptive responses to an allograft; however, whether the development of acute and chronic allograft rejection requires TLR signaling is unknown. Here, we studied TLR signaling in a fully MHC-mismatched, life-sustaining murine model of kidney allograft rejection. Mice deficient in the TLR adaptor protein MyD88 developed donor antigen-specific tolerance, which protected them from both acute and chronic allograft rejection and increased their survival after transplantation compared with wild-type controls. Administration of an anti-CD25 antibody to MyD88-deficient recipients depleted CD4+CD25+FoxP3+ cells and broke tolerance. In addition, defective development of Th17 immune responses to alloantigen both in vitro and in vivo occurred, resulting in an increased ratio of Tregs to Th17 effectors. Thus, MyD88 deficiency was associated with an altered balance of Tregs over Th17 cells, promoting tolerance instead of rejection. This study provides evidence that targeting innate immunity may be a clinically relevant strategy to facilitate transplantation tolerance. PMID:22878960

  18. Histomorphometric analysis of newly formed bone after maxillary sinus floor augmentation using ground cortical bone allograft and internal collagen membrane.

    PubMed

    Kolerman, Roni; Tal, Haim; Moses, Ofer

    2008-11-01

    Maxillary sinus floor augmentation is the treatment of choice when insufficient alveolar bone height prevents placement of standard dental implants in the posterior edentulous maxilla. The objective of this study was to histologically and histometrically evaluate new bone formation after maxillary sinus floor augmentation using ground cortical bone allograft. Mineralized freeze-dried bone allograft (FDBA) was used for sinus floor augmentation. After 9 months, 23 biopsies were taken from 19 patients. Routine histologic processing using hematoxylin and eosin and Mallory staining was performed. Histologic evaluation revealed a mean of 29.1% newly formed bone, 51.9% connective tissue, and 19% residual graft material. Graft particles were mainly in close contact with newly formed bone, primarily with features of mature bone with numerous osteocytes, and, to a lesser extent, with marrow spaces. There was no evidence of acute inflammatory infiltrate. FDBA is biocompatible and osteoconductive when used in maxillary sinus-augmentation procedures, and it may be used safely without interfering with the normal reparative bone process.

  19. The value of energy spectral CT in the differential diagnosis between benign and malignant soft tissue masses of the musculoskeletal system.

    PubMed

    Sun, Xin; Shao, Xiaodong; Chen, Haisong

    2015-06-01

    To explore the value of energy spectral CT in the differential diagnosis between benign and malignant tumor of the musculoskeletal system. Energy spectral CT scan was performed on 100 patients with soft tissue mass caused by musculoskeletal tumors found by MRI. Solid areas with homogenous density were chosen as region of interests (ROI), avoiding necrosis, hemorrhage and calcification region. Select the optimal keV on single energy images, and then the keV-CT curve was automatically generated. All 100 cases of tumors proved by histological examination were divided into four groups, 38 cases were in benign group, 10 cases in borderline group, 49 cases in malignant group, and 3 cases of lipoma (that were analyzed separately since its curve was arc shaped, significantly different from other curves). The formula used to calculate the slope of spectral curve was as follows: slope=(Hu40 keV-Hu80 keV)/40. As the slope was steep within the range of 40-80 keV based on preliminary observations, 40 keV and 80 keV were used as the reference points to calculate the slope value of the energy spectral curve. Kruskal-Wallis rank sum test was applied for statistical analysis, and P<0.05 was considered to indicate a statistically significant difference. The spectral curve of benign group was gradually falling type with a mean slope of 0.75 ± 0.30, that of malignant group was sharply falling type with a mean slope of 1.64 ± 1.00, and that of borderline group was a falling type between the above two groups with a mean slope of 1.34 ± 0.45. The differences of slopes between benign and malignant group, benign and borderline group were of statistical significance (P<0.05) respectively. The spectral curves of 3 cases of lipoma showed arc shaped rising type with a mean slope of -2.00. Spectral curve is useful in the differential diagnosis of benign and malignant tumor of the musculoskeletal system. Arc shaped curve is a specific sign for tumors containing abundant fat. Copyright © 2015

  20. MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Xiaoyou; Dong, Changgui; Jiang, Zhengyao

    Kidney transplantation is the major therapeutic option for end-stage kidney diseases. However, acute rejection could cause allograft loss in some of these patients. Emerging evidence supports that microRNA (miRNA) dysregulation is implicated in acute allograft rejection. In this study, we used next-generation sequencing to profile miRNA expression in normal and acutely rejected kidney allografts. Among 75 identified dysregulated miRNAs, miR-10b was the most significantly downregulated miRNAs in rejected allografts. Transfecting miR-10b inhibitor into human renal glomerular endothelial cells recapitulated key features of acute allograft rejection, including endothelial cell apoptosis, release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor α, interferon-γ, andmore » chemokine (C–C motif) ligand 2) and chemotaxis of macrophages whereas transfection of miR-10b mimics had opposite effects. Downregulation of miR-10b directly derepressed the expression of BCL2L11 (an apoptosis inducer) as revealed by luciferase reporter assay. Taken together, miR-10b downregulation mediates many aspects of disease pathogenicity of acute kidney allograft rejection. Restoring miR-10b expression in glomerular endothelial cells could be a novel therapeutic approach to reduce acute renal allograft loss. - Highlights: • miR-10b was the most downregulated microRNAs in acutely rejected renal allografts. • miR-10b downregulation triggered glomerular endothelial cell apoptosis. • miR-10b downregulation induced release of pro-inflammatory cytokines. • miR-10b downregulation derepressed its pro-apoptotic target BCL2L11.« less

  1. Effects of Particle Size and Porosity on In Vivo Remodeling of Settable Allograft Bone/Polymer Composites

    PubMed Central

    Prieto, Edna M.; Talley, Anne D.; Gould, Nicholas R.; Zienkiewicz, Katarzyna J.; Drapeau, Susan J.; Kalpakci, Kerem N.

    2014-01-01

    Established clinical approaches to treat bone voids include the implantation of autograft or allograft bone, ceramics, and other bone void fillers (BVFs). Composites prepared from lysine-derived polyurethanes and allograft bone can be injected as a reactive liquid and set to yield BVFs with mechanical strength comparable to trabecular bone. In this study, we investigated the effects of porosity, allograft particle size, and matrix mineralization on remodeling of injectable and settable allograft/polymer composites in a rabbit femoral condyle plug defect model. Both low viscosity (LV) and high viscosity (HV) grafts incorporating small (<105 μm) particles only partially healed at 12 weeks, and the addition of 10% demineralized bone matrix did not enhance healing. In contrast, composite grafts with large (105 – 500 μm) allograft particles healed at 12 weeks post-implantation, as evidenced by radial μCT and histomorphometric analysis. This study highlights particle size and surface connectivity as influential parameters regulating the remodeling of composite bone scaffolds. PMID:25581686

  2. Randomized prospective study comparing tri-cortical iliac crest autograft to allograft in the lateral column lengthening component for operative correction of adult acquired flatfoot deformity.

    PubMed

    Dolan, Christopher M; Henning, Jeffrey A; Anderson, John G; Bohay, Donald R; Kornmesser, Marc J; Endres, Terrence J

    2007-01-01

    Operative treatment of stage II posterior tibial tendon insufficiency (PTTI) is controversial. Many soft-tissue and bony procedures and various combinations of the two have been reported for treatment of stage II PTTI. Orthopaedists recognize the lateral column lengthening component of the procedure as a successful reconstructive technique. The use of cortical allograft for lateral column lengthening in the correction of pes planus in the pediatric patient population has been routine. In the adult population, however, tricortical iliac crest autograft has been the bone graft of choice. Harvest of this autograft can precipitate significant morbidity and cost. Therefore, we undertook this randomized controlled trial to compare graft incorporation and healing of allograft and autograft in the lateral column lengthening component of adult flatfoot reconstruction. Lateral column lengthening was done as a component of operative correction for stage II PTTI in adult patients (older than 18 years) by two surgeons using similar procedures. The patients were randomized to either the allograft or autograft procedures. The primary endpoint was graft incorporation and healing as assessed by radiographs. The study included 33 randomized feet in 31 patients. We followed 18 feet in the allograft group and 15 in the autograft group to the point of union. There were 21 women and 10 men. There were no delayed unions, nonunions, or hardware failures. All patients in both groups achieved bony union by the 12-week followup evaluation. Two superficial foot infections were successfully treated with oral antibiotics. Two patients in the autograft group continued to have hip donor site pain at 3 months. This study suggests that union rates of allograft and autograft (iliac crest bone graft) are equal. The use of allograft in the lateral column lengthening component of operative correction of adult stage II PTTI appears to be a viable alternative to the use of iliac crest autograft and

  3. Virtual interactive musculoskeletal system (VIMS) in orthopaedic research, education and clinical patient care

    PubMed Central

    Chao, Edmund YS; Armiger, Robert S; Yoshida, Hiroaki; Lim, Jonathan; Haraguchi, Naoki

    2007-01-01

    The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the "Virtual Human" reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of these unique database and simulation technology. This integrated system, model library and database will impact on orthopaedic education, basic research, device development and application, and clinical patient care related to musculoskeletal joint system reconstruction, trauma management, and rehabilitation. PMID:17343764

  4. Influence of socioeconomic status on allograft and patient survival following kidney transplantation.

    PubMed

    Ward, Frank L; O'Kelly, Patrick; Donohue, Fionnuala; ÓhAiseadha, Coilin; Haase, Trutz; Pratschke, Jonathan; deFreitas, Declan G; Johnson, Howard; Conlon, Peter J; O'Seaghdha, Conall M

    2015-06-01

    Whether socioeconomic status confers worse outcomes after kidney transplantation is unknown. Its influence on allograft and patient survival following kidney transplantation in Ireland was examined. A retrospective, observational cohort study of adult deceased-donor first kidney transplant recipients from 1990 to 2009 was performed. Those with a valid Irish postal address were assigned a socioeconomic status score based on the Pobal Hasse-Pratschke deprivation index and compared in quartiles. Cox proportional hazards models and Kaplan-Meier survival analysis were used to investigate any significant association of socioeconomic status with patient and allograft outcomes. A total of 1944 eligible kidney transplant recipients were identified. The median follow-up time was 8.2 years (interquartile range 4.4-13.3 years). Socioeconomic status was not associated with uncensored or death-censored allograft survival (hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.99-1.00, P = 0.33 and HR 1.0, 95% CI 0.99-1.00, P = 0.37, respectively). Patient survival was not associated with socioeconomic status quartile (HR 1.0, 95% CI 0.93-1.08, P = 0.88). There was no significant difference among quartiles for uncensored or death-censored allograft survival at 5 and 10 years. There was no socioeconomic disparity in allograft or patient outcomes following kidney transplantation, which may be partly attributable to the Irish healthcare model. This may give further impetus to calls in other jurisdictions for universal healthcare and medication coverage for kidney transplant recipients. © 2015 Asian Pacific Society of Nephrology.

  5. Effect of in vitro gingival fibroblast seeding on the in vivo incorporation of acellular dermal matrix allografts in dogs.

    PubMed

    Novaes, Arthur B; Marchesan, Julie Teresa; Macedo, Guilherme O; Palioto, Daniela B

    2007-02-01

    Acellular dermal matrix allograft (ADMA) has been used in various periodontal procedures with successful results. Because ADMA has no blood vessels or cells, slower healing and incorporation are observed compared to a subepithelial connective tissue graft. Fibroblasts accelerate the healing process by regulation of matrix deposition and synthesis of a variety of growth factors. Thus, the objective of this study was to evaluate histologically if gingival fibroblasts affect healing and incorporation of ADMA in dogs when used as a subepithelial allograft. Gingival fibroblasts were established from explant culture from the connective tissue of keratinized gingiva collected from the maxilla of seven mongrel dogs. ADMA was seeded with gingival fibroblasts and transferred to dogs. Surgery was performed bilaterally, and the regions were divided into two groups: ADMA+F (ADMA containing fibroblasts) and ADMA (ADMA only). Biopsies were performed after 2, 4, and 8 weeks of healing. The quantity of blood vessels was significantly higher in the ADMA+F group at 2 weeks of healing (Kruskal-Wallis; P <0.05). There was no statistical difference (P >0.05) in the number of cell layers, epithelial area, or inflammatory infiltrate between the two groups at any stage of healing. The enhanced vascularization in vivo in early stages supports the important role of fibroblasts in improving graft performance and wound healing of cultured graft substitutes.

  6. Low molecular weight fucan prevents transplant coronaropathy in rat cardiac allograft model.

    PubMed

    Alkhatib, Bassam; Freguin-Bouilland, Caroline; Lallemand, Françoise; Henry, Jean Paul; Litzler, Pierre-Yves; Marie, Jean Paul; Richard, Vincent; Thuillez, Christian; Plissonnier, Didier

    2006-06-01

    Transplant arteriosclerosis is the main cause of long-term failure after cardiac transplantation. Vascular rejection is thought to be due to intimal proliferation occurring in response to arterial wall immune-mediated injury. A low molecular weight fucan (LMWF) compound, a sulfated polysaccharide, has been demonstrated to increase plasma levels of stromal cell-derived factor 1 (SDF-1) and consequently to mobilize bone marrow-derived vascular progenitor cells (BMVPC). The aim of this study was to evaluate the capacity of LMWF to prevent coronary intimal proliferation in a rat cardiac allograft model. Heterotopic abdominal cardiac graftings were performed in Brown Norway (BN) and Lewis (LEW) rats. Animals were divided into 4 groups of 10 rats. Two groups were treated intramuscularly with LMWF (5 mg/kg/day) (one BN to BN isograft group, and one BN to LEW allograft group); and two control groups were LMWF-untreated (one BN to BN isograft group and one BN to LEW allograft group). All animals were treated by cyclosporin (15 mg/kg/day) sub-cutaneously and sacrificed at day 30. The cardiac grafts were assessed by morphometry of structural parameters and by histological and immunohistochemical analyses. All cardiac isografts were devoid of any coronary and parenchymal lesions. In contrast, the majority of untreated allografts developed coronary intimal proliferation in close association with intimal and adventitial inflammatory CD68(+) cell infiltration. Further, the parenchyma exhibited large areas of actin(+) cells (myofibroblasts) of recipient origin colocalized with the CD68(+) infiltrating cells. Interestingly, all LMWF-treated allografts were well protected against coronary and parenchymal lesions and the coronary arteries exhibited an intimal monolayer of flat cells, which however were CD34 negative. treatment with LMWF appeared very effective in this rat cardiac allograft model to prevent arterial and parenchymal lesions occurring in response to alloimmune injury

  7. Lower kidney allograft survival in African-Americans compared to Hispanic-Americans with lupus.

    PubMed

    Gonzalez-Suarez, M L; Contreras, G

    2017-10-01

    Background and objective African-Americans and Hispanic-Americans with lupus are the two most common minority groups who receive kidney transplants in the USA. It is unknown if African-Americans and Hispanic-Americans with lupus have similar outcomes after kidney transplantation. In this study, we assessed whether African-Americans compared to Hispanic-Americans have worse kidney allograft survival after risk factors of rejection and other prognostic factors were matched between both groups. Methods Out of 1816 African-Americans and 901 Hispanic-Americans with lupus, who received kidney transplants between 1987 and 2006 and had complete records in the UNOS program, 478 pairs were matched in 16 baseline predictors and follow-up time employing a predicted probability of group membership. The primary outcome was kidney allograft survival. Main secondary outcomes were rejection, allograft failure attributed to rejection, and mortality. Results Matched pairs were predominantly women (81%) with the mean age of 36 years. 96% were on dialysis before transplantation. 89% of recipients received kidneys from deceased donors and 15.5% from expanded criteria donors. 12% of recipients had zero HLA mismatch. African-Americans compared to Hispanic-Americans had lower cumulative allograft survival during 12-year follow-up ( p < 0.001). African-Americans compared to Hispanic-Americans had higher rates of rejection (10.4 vs 6.73 events/100 patients-years; p = 0.0002) and allograft failure attributed to rejection (6.31 vs 3.99; p = 0.0023). However, African-Americans and Hispanic-Americans had similar mortality rates (2.71 vs 2.31; p = 0.4269). Conclusions African-Americans compared to Hispanic-Americans with lupus had lower kidney allograft survival when recognized risk factors of rejection were matched between groups.

  8. Comparative clinical study of a subepithelial connective tissue graft and acellular dermal matrix graft for the treatment of gingival recessions: six- to 12-month changes.

    PubMed

    de Souza, Sérgio Luís Scombatti; Novaes, Arthur Belém; Grisi, Daniela Corrêa; Taba, Mário; Grisi, Márcio Fernando de Moraes; de Andrade, Patrícia Freitas

    2008-07-01

    Different techniques have been proposed for the treatment of gingival recession. This study compared the clinical results of gingival recession treatment using a subepithelial connective tissue graft and an acellular dermal matrix allograft. Seven patients with bilateral Miller class I or II gingival recession were selected. Twenty-six recessions were treated and randomly assigned to the test group. In each case the contralateral recession was assigned to the control group. In the control group, a connective tissue graft in combination with a coronally positioned flap was used; in the test group, an acellular dermal matrix allograft was used as a substitute for palatal donor tissue. Probing depth, clinical attachment level, gingival recession, and width of keratinized tissue were measured two weeks prior to surgery and at six and 12 months post-surgery. There were no statistically significant differences between the groups in terms of recession reduction, clinical attachment gain, probing pocket depth, and increase in the width of the keratinized tissue after six or 12 months. There was no statistically significant increase in the width of keratinized tissue between six and 12 months for either group. Within the limitations of this study, it can be suggested that the acellular dermal matrix allograft may be a substitute for palatal donor tissue in root coverage procedures and that the time required for additional gain in the amount of keratinized tissue may be greater for the acellular dermal matrix than for the connective tissue procedures.

  9. Associations between multimorbidity and additional burden for working-age adults with specific forms of musculoskeletal conditions: a cross-sectional study.

    PubMed

    Lowe, Dianne B; Taylor, Michael J; Hill, Sophie J

    2017-04-04

    Multiple health conditions are increasingly a problem for adults with musculoskeletal conditions. However, multimorbidity research has focused primarily on the elderly and those with a limited subset of musculoskeletal disorders. We sought to determine whether associations between multimorbidity and additional burden differ with specific forms of musculoskeletal conditions among working-age adults. Data were sourced from a nationally representative Australian survey. Specific musculoskeletal conditions examined were osteoarthritis; inflammatory arthritis; other forms of arthritis or arthropathies; musculoskeletal conditions not elsewhere specified; gout; back pain; soft tissue disorders; or osteoporosis. Multimorbidity was defined as the additional presence of one or more of the Australian National Health Priority Area conditions. Burden was assessed by self-reported measures of: (i) self-rated health (ii) musculoskeletal-related healthcare and medicines utilisation and, (iii) general healthcare utilisation. Associations between multimorbidity and additional health or healthcare utilisation burden among working-age adults (aged 18 - 64 years of age) with specific musculoskeletal conditions were estimated using logistic regression, adjusting for confounders. Interaction terms were fitted to identify whether there were specific musculoskeletal conditions where multimorbidity was more strongly associated with poorer health or greater healthcare utilisation than in the remaining musculoskeletal group. Among working-age adults, for each of the specified musculoskeletal conditions, multimorbidity was associated with similar, increased likelihood of additional self-rated health burden and certain types of healthcare utilisation. While there were differences in the relationships between multimorbidity and burden for each of the specific musculoskeletal conditions, no one specific musculoskeletal condition appeared to be consistently associated with greater additional

  10. Complications of immobilization and bed rest. Part 1: Musculoskeletal and cardiovascular complications.

    PubMed Central

    Dittmer, D. K.; Teasell, R.

    1993-01-01

    Prolonged bed rest and immobilization inevitably lead to complications. Such complications are much easier to prevent than to treat. Musculoskeletal complications include loss of muscle strength and endurance, contractures and soft tissue changes, disuse osteoporosis, and degenerative joint disease. Cardiovascular complications include an increased heart rate, decreased cardiac reserve, orthostatic hypotension, and venous thromboembolism. Images Figures 1-2 Figures 3-4 PMID:8324411

  11. Timing of Pregnancy After Kidney Transplantation and Risk of Allograft Failure.

    PubMed

    Rose, C; Gill, J; Zalunardo, N; Johnston, O; Mehrotra, A; Gill, J S

    2016-08-01

    The optimal timing of pregnancy after kidney transplantation remains uncertain. We determined the risk of allograft failure among women who became pregnant within the first 3 posttransplant years. Among 21 814 women aged 15-45 years who received a first kidney-only transplant between 1990 and 2010 captured in the United States Renal Data System, n = 729 pregnancies were identified using Medicare claims. The probability of allograft failure from any cause including death (ACGL) at 1, 3, and 5 years after pregnancy was 9.6%, 25.9%, and 36.6%. In multivariate analyses, pregnancy in the first posttransplant year was associated with an increased risk of ACGL (hazard ratio [HR]: 1.18; 95% confidence interval [CI] 1.00, 1.40) and death censored graft loss (DCGL) (HR:1.25; 95% CI 1.04, 1.50), while pregnancy in the second posttransplant year was associated with an increased risk of DCGL (HR: 1.26; 95% CI 1.06, 1.50). Pregnancy in the third posttransplant year was not associated with an increased risk of ACGL or DCGL. These findings demonstrate a higher incidence of allograft failure after pregnancy than previously reported and that the increased risk of allograft failure extends to pregnancies in the second posttransplant year. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  12. [Feasibility study of dynamic contrast enhanced magnetic resonance imaging qualitative diagnosis of musculoskeletal tumors].

    PubMed

    Zhang, J; Zuo, P L; Cheng, K B; Yu, A H; Cheng, X G

    2016-04-18

    To investigate the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in differentiating musculoskeletal tumors with different behaviours of pathological findings before therapy. A total of 34 subjects of musculoskeletal tumors were involved in this retrospective analysis. DCE-MRI was performed using a fat-saturated 3D VIBE (volumetric interpolated breath-hold exam) imaging sequence with following parameters: FA, 10 degree; TR/TE, 5.6/2.4 ms; slice thickness, 4.0 mm with no intersection gap; field of view, 310 mm×213 mm; matrix, 256×178; voxel size, 1.2 mm×1.2 mm×4.0 mm; parallel imaging acceleration factor. The actuation time for the DCE-MRI sequence was 255 s with a temporal resolution of 5 s and 40 image volumes. Using pathological results as a gold standard, tumors were divided into benign, borderline and malignant tumors. Toft's model was used for calculation of K(trans) (volume transfer constant), Ve (extravascular extracellular space distribute volume per unit tissue volume) and Kep (microvascular permeability reflux constant). Those parameters were compared between the lesions and the control tissues using paired t tests. The one-way analysis of variance was used to assess the difference among benign, borderline and malignant tumors. P values <0.05 difference was statistically significant. Based on the WHO Classification of Tumours of Soft Tissue and Bone(2012) criteria, 34 patients were divided into three groups: 11 for benign tumors, 12 for borderline tumors, and 11 for malignancies. Compared with control tissues, K(trans) and Kep showed no difference, but Ve was increased in benign tumors, Kep showed no difference, but K(trans) and Ve were increased in borderline tumors,K(trans), Kep and Ve were increased in malignant tumors. K(trans) (P<0.001) and Kep (P<0.01) were significantly higher in malignant tumors than in benign and borderline tumors, but did not show any difference between benign tumors and borderline

  13. Post-operative infection with fresh frozen allograft: reported outcomes of a hospital-based bone bank over 14 years.

    PubMed

    Man, Wing Yum; Monni, Toni; Jenkins, Ruth; Roberts, Paul

    2016-06-01

    Femoral head bone allografts have traditionally been used to provide mechanical stability to areas of bony deficiency, or for its osteoinductive and osteoconductive properties. Concerns have been raised over increased infection rates following the use of fresh-frozen graft tissue. This retrospective study aims to investigate the outcomes of fresh frozen femoral heads kept in a regulated, non-commercial bone bank at a university teaching hospital.The local bone bank database was used to identify released femoral heads during a 14 year study period (September 1999-December 2013) whereby a retrospective review of patient records was undertaken to determine clinical outcome. During the observed study period, 427 femoral heads were released from cold storage. Of these, 270 femoral heads had a mean follow-up of 347 days. 157 femoral heads were excluded due to insufficient follow-up data (n = 132) or discarded due to breaks in the cold chain prior to use (n = 25). Of the 270 included femoral heads, 231 (85.6 %) had no reported complications with good graft incorporation. In the remaining 39 with reported complications, only 5 (2.6 %) developed a postoperative infection. Our findings suggest that the use of fresh frozen allograft does not materially increase the risk of post-operative bacterial infection. Our reported post-operative infection rates are comparable with infection rates of other similar studies on fresh frozen allograft use.

  14. Involvement of dendritic cells in allograft rejection new implications of dendritic cell-endothelial cell interactions.

    PubMed

    Schlichting, C L; Schareck, W D; Kofler, S; Weis, M

    2007-04-01

    For almost half a century immunologists have tried to tear down the MHC barrier, which separates two unrelated individuals during transplantation. Latest experimental data suggest that a breakthrough in vitro is imminent. Dendritic cells (DCs), which activate naïve allo-reactive T-cells (TCs), play a central role in the establishment of allo-antigen-specific immunity. Allograft solid organ rejection is initiated at the foreign endothelial cell (EC) layer, which forms an immunogenic barrier for migrating DCs. Thus, DC/EC interactions might play a crucial role in antigen-specific allograft rejection. Organ rejection is mediated by host allo-reactive TCs, which are activated by donor DCs (direct activation) or host DCs (indirect activation). Direct allo-antigen presentation by regulatory dendritic cells (DCreg) can play an instructive role towards tolerance induction. Several groups established that, DCregs, if transplanted beforehand, enter host thymus, spleen, or bone marrow where they might eventually establish allo-antigen-specific tolerance. A fundamental aspect of DC function is migration throughout the entire organism. After solid organ transplantation, host DCs bind to ECs, invade allograft tissues, and finally transmigrate into lymphoid vessels and secondary lymphoid organs, where they present allo-antigens to naïve host TCs. Recent data suggest that in vitro manipulated DCregs may mediate allo-transplantation tolerance induction. However, the fundamental mechanisms on how such DCregs cause host TCs in the periphery towards tolerance remain unclear. One very promising experimental concept is the simultaneous manipulation of DC direct and indirect TC activation/suppression, towards donor antigen-specific allo-transplantation tolerance. The allo-antigen-specific long-term tolerance induction mediated by DCreg pre-transplantation (with simultaneous short-term immunosuppression) has become reproducible in the laboratory animal setting. Despite the shortcomings

  15. Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues

    PubMed Central

    Nassari, Sonya; Duprez, Delphine; Fournier-Thibault, Claire

    2017-01-01

    Skeletal muscles belong to the musculoskeletal system, which is composed of bone, tendon, ligament and irregular connective tissue, and closely associated with motor nerves and blood vessels. The intrinsic molecular signals regulating myogenesis have been extensively investigated. However, muscle development, homeostasis and regeneration require interactions with surrounding tissues and the cellular and molecular aspects of this dialogue have not been completely elucidated. During development and adult life, myogenic cells are closely associated with the different types of connective tissue. Connective tissues are defined as specialized (bone and cartilage), dense regular (tendon and ligament) and dense irregular connective tissue. The role of connective tissue in muscle morphogenesis has been investigated, thanks to the identification of transcription factors that characterize the different types of connective tissues. Here, we review the development of the various connective tissues in the context of the musculoskeletal system and highlight their important role in delivering information necessary for correct muscle morphogenesis, from the early step of myoblast differentiation to the late stage of muscle maturation. Interactions between muscle and connective tissue are also critical in the adult during muscle regeneration, as impairment of the regenerative potential after injury or in neuromuscular diseases results in the progressive replacement of the muscle mass by fibrotic tissue. We conclude that bi-directional communication between muscle and connective tissue is critical for a correct assembly of the musculoskeletal system during development as well as to maintain its homeostasis in the adult. PMID:28386539

  16. Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues.

    PubMed

    Nassari, Sonya; Duprez, Delphine; Fournier-Thibault, Claire

    2017-01-01

    Skeletal muscles belong to the musculoskeletal system, which is composed of bone, tendon, ligament and irregular connective tissue, and closely associated with motor nerves and blood vessels. The intrinsic molecular signals regulating myogenesis have been extensively investigated. However, muscle development, homeostasis and regeneration require interactions with surrounding tissues and the cellular and molecular aspects of this dialogue have not been completely elucidated. During development and adult life, myogenic cells are closely associated with the different types of connective tissue. Connective tissues are defined as specialized (bone and cartilage), dense regular (tendon and ligament) and dense irregular connective tissue. The role of connective tissue in muscle morphogenesis has been investigated, thanks to the identification of transcription factors that characterize the different types of connective tissues. Here, we review the development of the various connective tissues in the context of the musculoskeletal system and highlight their important role in delivering information necessary for correct muscle morphogenesis, from the early step of myoblast differentiation to the late stage of muscle maturation. Interactions between muscle and connective tissue are also critical in the adult during muscle regeneration, as impairment of the regenerative potential after injury or in neuromuscular diseases results in the progressive replacement of the muscle mass by fibrotic tissue. We conclude that bi-directional communication between muscle and connective tissue is critical for a correct assembly of the musculoskeletal system during development as well as to maintain its homeostasis in the adult.

  17. BK-virus nephropathy and simultaneous C4d positive staining in renal allografts.

    PubMed

    Honsová, E; Lodererová, A; Viklický, O; Boucek, P

    2005-10-01

    The role of antibodies in rejection of transplanted kidneys was the subject of debate at the last two Banff meetings and in medical journals. Diffuse C4d positive staining of peritubular capillaries (PTCs) was recognized as a marker of antibody-mediated rejection and this morphological feature was included in the updated Banff schema. At the same time polyomavirus infection of the renal allografts has been reported more frequently and is emerging as an important cause of renal allograft dysfunction and graft loss. At the present time, BK-virus nephropathy (BKN) represents the most common viral disease affecting renal allografts. BKN was identified in 6 patients in 12 biopsies and 2 graft nephrectomy specimens of 1115 biopsies between September 2000 and December 2003. Definite virus identification was done by immunohistochemistry. The reason for graft nephrectomies was graft failure due to BKN in a recipient after kidney-pancreas transplantation with good function of his pancreas graft and the necessity of continuing immunosuppression. Detection of C4d deposits was performed by immunofluorescence or by immunohistochemistry. In graftectomy samples C4d detection was performed by immunohistochemistry and retrospectively in all cases of BKN. Focal C4d positive PTCs and BKN were found simultaneously in 9 of 12 needle biopsies and in both graft nephrectomy samples. Detection of C4d by immunohistochemistry disclosed focal C4d positive staining in kidney tissue but diffuse in the sites where BK-virus inclusions in tubular epithelial cells were found. The complement system is part of the host defense response and is crucial to our natural ability to ward off infection. In cases of BKN, virus likely gains access to the bloodstream through injured tubular walls and via PTCs. Vascular endothelium in the PTCs represents a potential target antigen for alloresponse, and simultaneously possibly represents an imprint of complement activation or complement production in the places

  18. Prevalence of musculoskeletal diseases in Guatemala, Central America: the COPCORD study of 2 populations.

    PubMed

    Obregón-Ponce, Ariel; Iraheta, Isa; García-Ferrer, Helga; Mejia, Bayardo; García-Kutzbach, Abraham

    2012-06-01

    Guatemala is a multiethnic, multilingual, and multicultural country. We have evaluated 2 different ethnic groups from (1) San Juan Sacatepéquez County (SJSC), a rural population (30% illiterate), with 65% from Kaqchiquel ethnic group; and (2) Zone 5 of Guatemala City (Z5GC), an urban population (6.6% illiterate), with 95.5% mestizos. This study aimed to measure simultaneously the prevalence of rheumatic diseases in these 2 Guatemalan populations, both located in the State of Guatemala. A convenience sample of 4000 inhabitants 15 years and older was selected in each group. The Core Community Oriented Program for Control of Rheumatic Diseases Questionnaire was used in this survey. Phase 1 was for screening (identification of study subjects), phase 2 was for obtaining information from subjects with musculoskeletal complaints, and phase 3 was for rheumatologic diagnostic purposes. Phases 1 and 2 were performed by 6 interviewers. Phase 3 was completed by 4 rheumatologists. In phase I, 8000 subjects were identified in both groups. In phase II, 949 subjects reported musculoskeletal complaints: 371 (39%) in Z5GC and 578 (61%) in SJSC. In phase III, 419 patients were clinically evaluated: 141 (34%) in Z5GC and 278 (66%) in SJSC. The most prevalent musculoskeletal diseases were (1) osteoarthritis, (2) soft tissue rheumatism, (3) rheumatoid arthritis, (4) low back pain, and (5) arthralgias of unknown etiology. Osteoarthritis and soft tissue rheumatism were significantly more common in the rural population. The most prevalent musculoskeletal diseases in Guatemala seem to be similar to those in most previous Community Oriented Program for Control of Rheumatic Diseases studies. Most subjects were still working. Further studies examining medical care received and impact on function can now be of interest.

  19. Distal Tibia Allograft Glenoid Reconstruction in Recurrent Anterior Shoulder Instability: Clinical and Radiographic Outcomes.

    PubMed

    Provencher, Matthew T; Frank, Rachel M; Golijanin, Petar; Gross, Daniel; Cole, Brian J; Verma, Nikhil N; Romeo, Anthony A

    2017-05-01

    To assess the clinical and radiographic outcomes of patients with recurrent anterior shoulder instability treated with fresh distal tibia allograft (DTA) glenoid reconstruction. Consecutive patients with a minimum 15% anterior glenoid bone loss associated with recurrent anterior instability who underwent stabilization with DTA glenoid reconstruction were retrospectively reviewed. Patients were evaluated with the American Shoulder and Elbow Society score, Western Ontario shoulder instability index, and single numerical assessment evaluation score at a minimum 2 years after surgery. All patients also underwent postoperative imaging evaluation with computed tomography where graft incorporation and allograft angle were measured. Statistical analysis was performed with paired t-tests, with P < .05 considered significant. A total of 27 patients (100% male) with an average age of 31 ± 5 years and an average follow-up of 45 months (range, 30-66) were included. There were significant improvements in preoperative to postoperative American Shoulder and Elbow Society score (63-91, P < .01), Western Ontario shoulder instability index (46% to 11% of normal, P < .01), and single numerical assessment evaluation score (50-90.5, P < .01) outcomes. Analysis of computed tomography data at an average 1.4 years postoperatively (available for 25 patients) showed an allograft healing rate of 89% (range, 80% to 100%), average allograft angle of 14.9° (range, 6.6° to 29.3°), and average allograft lysis of 3% (range, 0% to 25%). Grafts with lesser allograft angles (<15°) were better opposed to the anterior glenoid, showing superior healing and graft incorporation. There were no cases of recurrent instability. At an average follow-up of 45 months, fresh DTA reconstruction for recurrent anterior shoulder instability results in a clinically stable joint with excellent clinical outcomes and minimal graft resorption. Optimal allograft placement resulted in superior bony incorporation

  20. Irradiated Hamstring Tendon Allograft Versus Autograft for Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction: Midterm Clinical Outcomes.

    PubMed

    Tian, Shaoqi; Wang, Bin; Liu, Lun; Wang, Yuanhe; Ha, Chengzhi; Li, Qicai; Yang, Xu; Sun, Kang

    2016-10-01

    Most studies on grafts for anterior cruciate ligament (ACL) reconstruction (ACLR) have been of autografts or nonirradiated allografts with a single-bundle (SB) technique. Outcome reports evaluating anatomic double-bundle (DB) ACLR with a hamstring tendon autograft versus irradiated allograft are rare. To compare the clinical outcomes of arthroscopic anatomic DB ACLR with a hamstring tendon autograft versus irradiated allograft. Randomized controlled trial; Level of evidence, 2. Between 2008 and 2009, a total of 107 patients undergoing arthroscopic DB ACLR were prospectively randomized consecutively into 1 of 2 groups (autograft [Auto] group and irradiated allograft [Ir-Allo] group). All the surgical procedures were performed by the same senior surgeon using the DB reconstruction technique. All irradiated hamstring tendon allografts were sterilized with 2.5 Mrad of irradiation before distribution and were obtained from a single certified tissue bank. Graft fixation on the femoral side was by an Endobutton, and on the tibial side by a bioabsorbable interference screw augmented with a staple. The same rehabilitation protocol was applied to all patients. Before surgery and at a mean of 6.9 years of follow-up, patients were evaluated by the same observer according to objective and subjective clinical evaluations including detailed history, physical examination, radiography, functional knee ligament testing, KT-2000 arthrometer testing, Harner vertical jump and Daniel 1-legged hop tests, Lysholm score, Tegner score, International Knee Documentation Committee (IKDC) standard evaluation form, and Cincinnati knee score. A total of 83 patients (Auto: n = 40 [mean age, 29.2 ± 6.9 years]; Ir-Allo: n = 43 [mean age, 28.6 ± 7.2 years]) fulfilled follow-up and clinical evaluations. No significant differences were found between the 2 groups according to the overall IKDC functional and subjective evaluations as well as testing of activity levels. Significant between

  1. Lateral column lengthening using allograft interposition and cervical plate fixation.

    PubMed

    Philbin, Terrence M; Pokabla, Christopher; Berlet, Gregory C

    2008-10-01

    Lateral column lengthening has been used successfully in the treatment of stage II adult-acquired pes planovalgus deformity. The purpose of this study is to review the union rate when allograft material is used and the osteotomy stabilized with a cervical plate. A retrospective review was performed on 28 feet in 26 patients who underwent correction of stage II pes planovalgus deformity using a lateral column lengthening with allograft tricortical iliac crest stabilized with a cervical plate. Patients were evaluated preoperatively and postoperatively using a modified American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale and the Short Form-12 health survey, as well as radiographically by assessing the talonavicular coverage angle. At a mean follow-up of 9 months, the mean total modified AOFAS score and pain subscore were significantly higher (45.6 and 25.0, respectively) versus preoperatively (27.3 and 11.2, respectively). Graft incorporation occurred in all but one case, and the average length of time to union was 10.06 weeks. Complications included 4 hardware removals, 1 nonunion, 1 graft penetration of the calcaneocuboid joint, and 2 cases of calcaneocuboid joint arthritis. Lateral column lengthening using allograft tricortical iliac crest bone graft with cervical plate fixation is a viable option for the correction of acquired pes planovalgus deformity. Allograft bone avoids donor site morbidity of autogenous iliac crest grafts and was not shown to increase rates of nonunion. Cervical plate fixation avoids the necessity of penetrating the graft with a screw and is associated with high patient satisfaction and radiographic union.

  2. Healing bone lesion defects using injectable CaSO4 /CaPO4 -TCP bone graft substitute compared to cancellous allograft bone chips in a canine model.

    PubMed

    Hall, Deborah J; Turner, Thomas M; Urban, Robert M

    2018-04-16

    CaSO 4 /CaPO 4 -TCP bone graft substitute has been shown to be effective for treatment of bone lesion defects, but its mechanical, histological, and radiographic characteristics have not been studied in direct comparison with a conventional treatment such as cancellous allograft bone. Thirteen canines had a critical-size axial defect created bilaterally into the proximal humerus. CaSO 4 /CaPO 4 -TCP bone graft substitute (PRO-DENSE™, Wright Medical Technology) was injected into the defect in one humerus, and an equal volume of freeze-dried cancellous allograft bone chips was placed in the contralateral defect. The area fraction of new bone, residual graft, and fibrous tissue and the compressive strength and elastic modulus of bone within the defects were determined after 6, 13, or 26 weeks and correlated with radiographic changes. The data were analyzed using Friedman and Mann-Whitney tests. There was more bone in defects treated with the CaSO 4 /CaPO 4 -TCP bone graft substitute compared to defects treated with cancellous bone allograft at all three time points, and the difference at 13 weeks was significant (p = 0.025). The new bone was significantly stronger and stiffer in defects treated with the CaSO 4 /CaPO 4 -TCP bone graft substitute compared to defects treated with cancellous bone allograft at 13 (p = 0.046) and 26 weeks (p = 0.025). At 26 weeks, all defects treated with CaSO 4 /CaPO 4 -TCP bone graft substitute demonstrated complete healing with new bone, whereas healing was incomplete in all defects treated with cancellous allograft chips. The CaSO 4 /CaPO 4 -TCP bone graft substitute could provide faster and significantly stronger healing of bone lesions compared to the conventional treatment using freeze-dried cancellous allograft bone. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

  3. Surgical treatment of infective endocarditis with aortic and tricuspid valve involvement using cryopreserved aortic and mitral valve allografts.

    PubMed

    Ostrovsky, Yury; Spirydonau, Siarhei; Shchatsinka, Mikalai; Shket, Aliaksandr

    2015-05-01

    Surgical treatment of infective and prosthetic endocarditis using allografts gives good results. Aortic allograft implantation is a common technique, while tricuspid valve replacement with a mitral allograft is very rare. Multiple valve disease in case of infective endocarditis is a surgical challenge as such patients are usually in a grave condition and results of surgical treatment are often unsatisfactory. In this article we describe a clinical case of successful surgical treatment in a patient with active infective endocarditis of aortic and tricuspid valve, complicated by an aortic-right ventricular fistula. The aortic valve and ascending aorta were replaced with a cryopreserved aortic allograft; the tricuspid valve was replaced with a cryopreserved mitral allograft. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  4. Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems.

    PubMed

    James, R; Kumbar, S G; Laurencin, C T; Balian, G; Chhabra, A B

    2011-04-01

    Tendon tissue engineering with a biomaterial scaffold that mimics the tendon extracellular matrix (ECM) and is biomechanically suitable, and when combined with readily available autologous cells, may provide successful regeneration of defects in tendon. Current repair strategies using suitable autografts and freeze-dried allografts lead to a slow repair process that is sub-optimal and fails to restore function, particularly in difficult clinical situations such as zone II flexor tendon injuries of the hand. We have investigated the effect of GDF-5 on cell proliferation and gene expression by primary rat adipose-derived stem cells (ADSCs) that were cultured on a poly(DL-lactide-co-glycolide) PLAGA fiber scaffold and compared to a PLAGA 2D film scaffold. The electrospun scaffold mimics the collagen fiber bundles present in native tendon tissue, and supports the adhesion and proliferation of multipotent ADSCs. Gene expression of scleraxis, the neotendon marker, was upregulated seven- to eightfold at 1 week with GDF-5 treatment when cultured on a 3D electrospun scaffold, and was significantly higher at 2 weeks compared to 2D films with or without GDF-5 treatment. Expression of the genes that encode the major tendon ECM protein, collagen type I, was increased by fourfold starting at 1 week on treatment with 100 ng mL(-1) GDF-5, and at all time points the expression was significantly higher compared to 2D films irrespective of GDF-5 treatment. Thus stimulation with GDF-5 can modulate primary ADSCs on a PLAGA fiber scaffold to produce a soft, collagenous musculoskeletal tissue that fulfills the need for tendon regeneration.

  5. Development of tissue bank.

    PubMed

    Narayan, R P

    2012-05-01

    The history of tissue banking is as old as the use of skin grafting for resurfacing of burn wounds. Beneficial effects of tissue grafts led to wide spread use of auto and allograft for management of varied clinical conditions like skin wounds, bone defects following trauma or tumor ablation. Availability of adequate amount of tissues at the time of requirement was the biggest challenge that forced clinicians to find out techniques to preserve the living tissue for prolonged period of time for later use and thus the foundation of tissue banking was started in early twentieth century. Harvesting, processing, storage and transportation of human tissues for clinical use is the major activity of tissue banks. Low temperature storage of processed tissue is the best preservation technique at present. Tissue banking organization is a very complex system and needs high technical expertise and skilled personnel for proper functioning in a dedicated facility. A small lapse/deviation from the established protocol leads to loss of precious tissues and or harm to recipients as well as the risk of transmission of deadly diseases and tumors. Strict tissue transplant acts and stringent regulations help to streamline the whole process of tissue banking safe for recipients and to community as whole.

  6. Both rejection and tolerance of allografts can occur in the absence of secondary lymphoid tissues

    PubMed Central

    Kant, Cavit D.; Akiyama, Yoshinobu; Tanaka, Katsunori; Shea, Susan; Yamada, Yohei; Connolly, Sarah E; Marino, Jose; Tocco, Georges; Benichou, Gilles

    2014-01-01

    In this study, we show that aly/aly mice, which are devoid of lymph nodes and Peyer’s patches, rejected acutely fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts were also rejected acutely by splenectomized aly/aly mice (aly/aly-spl−) devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8+ T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected in aly/aly-spl− mice. Actually, aly/aly-spl− mice having spontaneously accepted a heart allotransplant displayed donor-specific tolerance also accepted skin grafts from the same but not a third-party donor via a mechanism involving CD4+ regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs. PMID:25535285

  7. Musculoskeletal problems in Parkinson's disease: neglected issues.

    PubMed

    Kim, Young Eun; Lee, Woong-Woo; Yun, Ji Young; Yang, Hui June; Kim, Han-Joon; Jeon, Beom S

    2013-07-01

    To identify the prevalence and clinical features of musculoskeletal problems in patients with Parkinson disease (PD) compared to controls. 400 PD patients and 138 age- and sex-matched controls were interviewed by physicians about their musculoskeletal problems. The prevalence of musculoskeletal problems was significantly higher in the PD group than in the control group (66.3% vs. 45.7%, P < 0.001). Commonly involved body sites were the low back, knee, and shoulder in that order. The low back was more frequently involved in the PD group than in the control group (44.3% vs. 24.6%, P < 0.001), and the shoulder tended to be more involved in the PD group than in the control group (15.0% vs. 8.7%, P = 0.061). However, the knee was similarly involved in both group (12.3% vs. 18.0%, P = 0.121). Among the past diagnoses associated with musculoskeletal problems, frozen shoulder, low back pain, osteoporosis and fracture were more common in the PD group than in the control group (P < 0.05). Older age, female, and a higher score on the Unified Parkinson's Disease Rating Scale I & II were associated with musculoskeletal problems in the PD group. Only 26.8% of the PD patients and 52.5% of the controls with musculoskeletal problems answered that their musculoskeletal problems were recovering. Furthermore, musculoskeletal problems in the PD group tended to receive less treatment than that of the control group (P = 0.052). Musculoskeletal problems were more common in the PD group than in the controls. Furthermore, despite PD patients having a higher prevalence, they did not receive adequate treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Knee salvage procedures: The indications, techniques and outcomes of large osteochondral allografts

    PubMed Central

    Chui, Karen; Jeys, Lee; Snow, Martyn

    2015-01-01

    The overall incidence of osteochondral defect in the general population is estimated to be 15 to 30 per 100000 people. These lesions can become symptomatic causing pain, swelling and decreased function of the knee, and may eventually progress to osteoarthritis. In the young and active population, partial or total knee arthroplasty (TKA) is rarely the treatment of choice due to risk of early failure. Osteochondral allograft transplantation has been demonstrated to be a safe and effective treatment of large osteochondral and chondral defects of the knee in appropriately selected patients. The treatment reduces pain, improves function and is a viable limb salvage procedure for patients, especially young and active patients for whom TKA is not recommended. Either large dowels generated with commercially available equipment or free hand shell allografts can be implanted in more posterior lesions. Current recommendations for fresh allografts stored at 4C advise implantation within 21-28 d of procurement for optimum chondrocyte viability, following screening and testing protocols. Higher rates of successful allograft transplantation are observed in younger patients, unipolar lesions, normal or corrected malalignment, and defects that are treated within 12 mo of symptom onset. Patients with bipolar lesions, uncorrectable malalignment, advanced osteoarthritis, and those over 40 tend to have less favourable outcomes. PMID:25893177

  9. Effectiveness and Safety of a Thermosensitive Hydrogel Cultured Epidermal Allograft for Burns.

    PubMed

    Yoon, Jaechul; Yang, Hyeong-Tae; Yim, Haejun; Cho, Yong-Suk; Kym, Dohern; Hur, Jun; Chun, Wook; Lee, Jong-Wook; Yoon, Chunjae

    2017-12-01

    To retest the safety and effectiveness of a thermosensitive hydrogel-type cultured epithelial allograft (KeraHeal-Allo; MCTT, Seoul, South Korea) and identify the subjective experience of patients and doctors with this product. Prospective interventional phase 3 study in 3 burn centers near Seoul, South Korea. Thirty-three patients with deep second-degree burns larger than 200 cm (for intervention and control sites of 100 cm each) were enrolled. A cultured epithelial allograft containing 2 × 10/1.5 mL keratinocytes was applied to each patient's intervention site. Three principal investigators (1 in each institution) evaluated the effectiveness of the allograft at their institution and the others'. Researchers administered a subjective satisfaction survey during each patient's last visit. The primary end point of the study was the re-epithelialization period. The re-epithelialization period for the intervention was 2.8 ± 2.2 days faster than that of control sites at other institutions (P < .001) and 2.5 ± 3.4 days faster than that of control sites in the same institution (P < .001). There were no reported adverse events. Satisfaction scores provided by patients and doctors showed significantly high scores on all items. This type of cultured epithelial allograft is safe and well received by patients and providers and promotes re-epithelialization.

  10. Macrophages: Contributors to Allograft Dysfunction, Repair or Innocent Bystanders?

    PubMed Central

    Mannon, Roslyn B.

    2012-01-01

    Purpose of this review Macrophages are members of the innate immune response. However, their role in the adaptive immune response is not known. The purpose of this review is to highlight our current understanding of macrophage structure and function and how they may participate in allograft injury. Recent Findings Studies in acute kidney injury models identify macrophages as key mediators of inflammatory injury while more recent studies indicate that they may play a reparative role, depending on phenotype—M1 or M2 type macrophages. Mregs, generated in vitro, appear to have immune suppressive abilities and a unique phenotype. In solid organ transplant, the emphasis of studies has been on acute or chronic injury. These data are derived from animal models using depletion of macrophages or antagonizing their activation and inflammatory responses. The relative contribution of macrophage phenotype in transplantation has not been explored. Summary These studies suggest that macrophages play an injurious role in acute cellular allograft rejection, as well as in chronic injury. Infiltration of an allograft with macrophages is also associated with worse graft function and poor prognosis. Further studies are needed to understand the mechanisms of macrophage mediated injury, explore their potential reparative role and determine if they or their functional products are biomarkers of poor graft outcomes. PMID:22157320

  11. Macrophages: contributors to allograft dysfunction, repair, or innocent bystanders?

    PubMed

    Mannon, Roslyn B

    2012-02-01

    Macrophages are members of the innate immune response. However, their role in the adaptive immune response is not known. The purpose of this review is to highlight our current understanding of macrophage structure and function and how they may participate in allograft injury. Studies in acute kidney injury models identify macrophages as key mediators of inflammatory injury, while more recent studies indicate that they may play a reparative role, depending on phenotype - M1 or M2 type macrophages. Mregs, generated in vitro, appear to have immune suppressive abilities and a unique phenotype. In solid-organ transplant, the emphasis of studies has been on acute or chronic injury. These data are derived from animal models using depletion of macrophages or antagonizing their activation and inflammatory responses. The relative contribution of macrophage phenotype in transplantation has not been explored. These studies suggest that macrophages play an injurious role in acute cellular allograft rejection, as well as in chronic injury. Infiltration of an allograft with macrophages is also associated with worse graft function and poor prognosis. Further studies are needed to understand the mechanisms of macrophage-mediated injury, explore their potential reparative role, and determine if they or their functional products are biomarkers of poor graft outcomes.

  12. Musculoskeletal modelling in dogs: challenges and future perspectives.

    PubMed

    Dries, Billy; Jonkers, Ilse; Dingemanse, Walter; Vanwanseele, Benedicte; Vander Sloten, Jos; van Bree, Henri; Gielen, Ingrid

    2016-05-18

    Musculoskeletal models have proven to be a valuable tool in human orthopaedics research. Recently, veterinary research started taking an interest in the computer modelling approach to understand the forces acting upon the canine musculoskeletal system. While many of the methods employed in human musculoskeletal models can applied to canine musculoskeletal models, not all techniques are applicable. This review summarizes the important parameters necessary for modelling, as well as the techniques employed in human musculoskeletal models and the limitations in transferring techniques to canine modelling research. The major challenges in future canine modelling research are likely to centre around devising alternative techniques for obtaining maximal voluntary contractions, as well as finding scaling factors to adapt a generalized canine musculoskeletal model to represent specific breeds and subjects.

  13. Reversible renal allograft dysfunction and proteinuria from nutcracker-like syndrome: a case report.

    PubMed

    Krishnan, S G S; Pritsiolas, J; Susin, M; Linden, E; Beil-Levi, E; Gitman, M; Mossey, R; Bhaskaran, M

    2007-06-01

    A 27-year-old Hispanic man with hypertension and renal failure was on hemodialysis for 4 years prior to receiving a living donor renal transplant from his 19-year-old sister. His serum creatinine decreased to 1.7 mg/dL at 3 weeks posttransplant with a urine protein creatinine ratio (UP) of 0.1 (g/g). Over the next 2 months, he experienced repeated episodes of allograft dysfunction with elevation of creatinine and proteinuria levels, associated with a lymphocele. Doppler studies of the allograft revealed renal vein compression. His symptoms responded to aspiration of the fluid collection, resolving completely with surgical drainage. We believe that the episodes of allograft dysfunction and proteinuria were related to recurrent lymphocele, causing a nutcracker-like syndrome.

  14. Organogenesis of the Musculoskeletal System in Horse Embryos and Early Fetuses.

    PubMed

    Barreto, Rodrigo da Silva Nunes; Rodrigues, Márcio Nogueira; Carvalho, Rafael Cardoso; De Oliveira E Silva, Fernanda Menezes; Rigoglio, Náthia Nathaly; Jacob, Júlio César Ferraz; Gastal, Eduardo Leite; Miglino, Maria Angélica

    2016-06-01

    Musculoskeletal system development involves heterotypical inductive interactions between tendons, muscles, and cartilage and knowledge on organogenesis is required for clarification of its function. The aim of this study was to describe the organogenesis of horse musculoskeletal system between 21 and 105 days of gestation, using detailed macroscopic and histological analyses focusing on essential developmental steps. At day 21 of gestation the skin was translucid, but epithelial condensation and fibrocartilaginous tissues were observed on day 25 of pregnancy. Smooth muscle was seen in lymphatic and blood vessel walls and the beginning of cartilaginous chondrocranium was detected at day 30 of gestation. At day 45, typical chondroblasts and chondrocytes were observed and at day 55, mandibular processes expanded toward the ventral midline of the pharynx. At day 75, muscles became thicker and muscle fibers were seen developing in carpal and metacarpal joints with the beginning of the ossification process. At day 105, major muscle groups, similar to those seen in an adult equine, were observed. The caudal area of the nasal capsule and trabecular cartilages increased in size and became ossified, developing into the ethmoid bone. The presence of nasal, frontal, parietal, and occipital bones was observed. In conclusion, novel features of equine musculoskeletal system development have been described here and each process was linked with an early musculoskeletal event. Data presented herein will facilitate a better understanding of the equine muscular system organogenesis and aid in the detection of congenital deformities. Anat Rec, 299:722-729, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Hospital Resource Use with Donation after Cardiac Death Allografts in Liver Transplantation: A Matched Controlled Analysis from 2007 to 2011.

    PubMed

    Singhal, Ashish; Wima, Koffi; Hoehn, Richard S; Quillin, R Cutler; Woodle, E Steve; Paquette, Ian M; Paterno, Flavio; Abbott, Daniel E; Shah, Shimul A

    2015-05-01

    Although donation after cardiac death (DCD) liver allografts have been used to expand the donor pool, concerns exist regarding primary nonfunction and biliary complications. Our aim was to compare resource use and outcomes of DCD allografts with donation after brain death (DBD) liver allografts. Using a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified 11,856 patients who underwent deceased donor liver transplantation (LT) from 2007 to 2011. Patients were divided into 2 cohorts based on type of allograft (DCD vs DBD). Matched pair analysis (n = 613 in each group) was used to compare outcomes of the 2 donor types. Donation after cardiac death allografts comprised 5.2% (n = 613) of all LTs in the studied cohort; DCD allograft recipients were healthier and had lower median Model of End-Stage Liver Disease (MELD) score (17 vs 19; p < 0.0001). Post LT, there was no significant difference in length of stay, perioperative mortality, and discharge to home rates. However, DCD allografts were associated with higher direct cost ($110,414 vs $99,543; p < 0.0001) and 30-day readmission rates (46.4% vs 37.1%; p < 0.0001). Matched analysis revealed that DCD allografts were associated with higher direct cost, readmission rates, and inferior graft survival. While confirming the previous reports of inferior graft survival associated with DCD allografts, this is the first national report to show increased financial and resource use associated with DCD compared with DBD allografts in a matched recipient cohort. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Sporotrichal Tenosynovitis Diagnosed Helpfully by Musculoskeletal Ultrasonography

    PubMed Central

    Shimizu, Takashi; Akita, Shosuke; Harada, Yoshinori; Oguro, Eri; Okita, Yasutaka; Shigesaka, Minoru; Matsuoka, Hidetoshi; Nii, Takuro; Teshigawara, Satoru; Kudo-Tanaka, Eriko; Tsuji, Soichiro; Matsushita, Masato; Ohshima, Shiro; Hoshida, Yoshihiko; Hashimoto, Jun; Saeki, Yukihiko

    2017-01-01

    A 72-year-old man presented with persistent oligoarthritis and positive results for rheumatoid factor and was suspected of having rheumatoid arthritis (RA). However, the musculoskeletal ultrasonography (MSUS) findings were not consistent with those of typical RA. He had undergone surgery for carpal tunnel syndrome, which allowed both histopathological and microbiological examinations to be performed. A synovial tissue culture was positive for Sporothrix schenckii, and he was diagnosed with sporotrichal tenosynovitis. He received anti-fungal therapy, and the sporotrichal tenosynovitis resolved. This case suggests that MSUS is a useful modality, and sporotrichal tenosynovitis, though rare, should be considered in the differential diagnosis of RA. PMID:28502945

  17. Musculoskeletal disorders of pregnancy, delivery and postpartum.

    PubMed

    Borg-Stein, Joanne; Dugan, Sheila A

    2007-08-01

    Gender-specific care of musculoskeletal impairments is increasingly important in women's health. This is most relevant and of paramount importance as it relates to identification and management of musculoskeletal and peripheral neurologic disorders of pregnancy, delivery, and postpartum. The specific anatomic and physiologic changes of pregnancy predispose to a specific set of diagnoses. Virtually all women experience some degree of musculoskeletal discomfort during pregnancy. This article provides an overview of the more common pregnancy-related musculoskeletal conditions and includes a discussion of epidemiology, risk factors, diagnosis, prognosis, and management.

  18. Restrictive allograft syndrome and idiopathic pleuroparenchymal fibroelastosis: do they really have the same histology?

    PubMed

    Montero, Maria A; Osadolor, Tina; Khiroya, Reena; Salcedo, Maria Teresa; Robertus, Jan L; Rice, Alexandra; Nicholson, Andrew G; Roman, Antonio; Monforte, Victor

    2017-06-01

    Restrictive allograft syndrome (RAS) and idiopathic pleuroparenchymal fibroelastosis (IPPFE) are two different diseases reported to share the same histology. RAS relates to chronic allograft dysfunction in lung transplantation, with IPPFE being a rare condition in native lungs. Our aim is to compare their histologies alongside biopsies of usual interstitial pneumonia (UIP), to determine if there are differences that might help to elucidate the pathogenesis. We selected four postmortem allograft lungs from patients who developed a clear clinical RAS pattern, five biopsies diagnosed as IPPFE, five UIP biopsies and five sections of normal lung. Histopathological features were described without knowledge of clinical and radiological features. Both RAS allografts and IPPFE biopsies showed intra-alveolar fibrosis and elastosis (IAFE), but RAS allografts also showed concomitant obliterative bronchiolitis, vascular lymphoplasmacytic inflammation within fibrointimal thickening, less fibroblastic foci (FF) at the advancing edge of the fibrosis (one against 14.4 FF in 2 mm 2 ) and a slight reduction of the capillary network compared to UIP (P = 0.07) and controls (P = 0.06). The main differences seen in UIP were the lack of IAFE and the presence of honeycomb change. RAS and PPFE histopathology both show IAFE, but display various differences, particularly in their vascular morphology that may allow further understanding of pathogenesis. © 2017 John Wiley & Sons Ltd.

  19. Musculoskeletal pain among Polish music school students.

    PubMed

    Nawrocka, Agnieszka; Mynarski, Władysław; Powerska-Didkowska, Aneta; Grabara, Małgorzata; Garbaciak, Wiesław

    2014-06-01

    To assess the prevalence and intensity of musculoskeletal pain and to estimate probability of developing playing-related musculoskeletal disorders, depending on risk factors, including gender, years of playing the musical instrument, frequency of practice (number of days per week), average daily practice time, and habitual physical activity level, in young instrumentalists. A total of 225 instrumentalists aged 10-18 years, including 107 string-players, 64 keyboardists, and 54 wind-players, were investigated. The Nordic Musculoskeletal Questionnaire (NMQ) together with a numerical visual-analogue pain intensity scale (VAS) was used to assess the participants' musculoskeletal pain. The young instrumentalists most often complained of pain located in the neck (60.4%), wrists (44.4%), and upper (41.7%) and lower back (38.2%) areas. Girls complained of musculoskeletal pain significantly more often than the boys. A probability of the pain symptoms was increased with each consecutive year of practice (OR 1.135; 95%CI 1.021-1.261). Musculoskeletal pain in various body parts had already commenced at a young age in our sample of music students, and there was a gender difference (girls were more often affected). Results of our study suggest that an early prophylaxis of playing-related musculoskeletal disorders is needed among young musicians playing the various instruments.

  20. Acellular dermal matrix allografts to achieve increased attached gingiva. Part 2. A histological comparative study.

    PubMed

    Wei, Pein-Chi; Laurell, Lars; Lingen, Mark W; Geivelis, Milton

    2002-03-01

    In part 1 of this study, we compared the clinical efficacy of freeze-dried acellular dermal matrix (ADM) allograft in 6 patients with autogenous free gingival graft (FGG) in 6 patients for increasing the width of attached gingiva in the mandibular anterior area. The purpose of the present study was to histologically compare the microstructure of ADM and FGG treated sites from the same group. Biopsies were harvested from all 12 patients at 6 months postsurgery. The biopsies included the grafted sites with adjacent alveolar mucosa and gingiva propria and also donor palatal mucosa saved at the time of surgery. The 5 microm thick, neutral buffered formalin fixed, paraffin-embedded tissue sections were stained with hematoxylin and eosin (H&E), Masson's trichrome, and Verhoeff-van Gieson stains in order to investigate the density of collagen and elastic fibers. Additional sections were stained with periodic acid-Schiff (PAS) and Papanicolaou's stain to identify the presence of glycogen granules in the epithelial layer and to highlight the keratin layer respectively. The unique appearance of ADM-derived tissue did not parallel any known oral mucosa. The connective tissue portion contained dense to extremely dense collagen fibers along with scattered elastic fibers. The demarcations between the ADM graft and the coronal gingiva as well as the apical alveolar mucosa were usually not very defined. A moderate to thin epithelial layer, with heterogeneous expression of keratinization and flat epithelium-connective tissue interface, covered the lamina propria. Both the thickness of the epithelium and the degree of keratinization decreased in apical direction, being mostly para- or orthokeratinized in the area close to gingiva and non-keratinized adjacent to the alveolar mucosa. In the FGG-treated sites, the density of collagen fibers was less than in ADM-derived tissue, palatal mucosa, and gingiva. Elastic fibers were very sparse, comparable to gingiva, but much less than in ADM