Cell-laden hydrogels for osteochondral and cartilage tissue engineering.

PubMed

Yang, Jingzhou; Zhang, Yu Shrike; Yue, Kan; Khademhosseini, Ali

2017-07-15

Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue-engineered artificial matrices that can replace the damaged regions and promote tissue regeneration. Hydrogels are emerging as a promising class of biomaterials for both soft and hard tissue regeneration. Many critical properties of hydrogels, such as mechanical stiffness, elasticity, water content, bioactivity, and degradation, can be rationally designed and conveniently tuned by proper selection of the material and chemistry. Particularly, advances in the development of cell-laden hydrogels have opened up new possibilities for cell therapy. In this article, we describe the problems encountered in this field and review recent progress in designing cell-hydrogel hybrid constructs for promoting the reestablishment of osteochondral/cartilage tissues. Our focus centers on the effects of hydrogel type, cell type, and growth factor delivery on achieving efficient chondrogenesis and osteogenesis. We give our perspective on developing next-generation matrices with improved physical and biological properties for osteochondral/cartilage tissue engineering. We also highlight recent advances in biomanufacturing technologies (e.g. molding, bioprinting, and assembly) for fabrication of hydrogel-based osteochondral and cartilage constructs with complex compositions and microarchitectures to mimic their native counterparts. Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue-engineered biomaterials that replace the damaged regions and promote tissue regeneration. Cell-laden hydrogel systems have emerged as a promising tissue

Impact insertion of osteochondral grafts: Interference fit and central graft reduction affect biomechanics and cartilage damage.

PubMed

Su, Alvin W; Chen, Yunchan; Wailes, Dustin H; Wong, Van W; Cai, Shengqiang; Chen, Albert C; Bugbee, William D; Sah, Robert L

2018-01-01

An osteochondral graft (OCG) is an effective treatment for articular cartilage and osteochondral defects. Impact of an OCG during insertion into the osteochondral recipient site (OCR) can cause chondrocyte death and matrix damage. The aim of the present study was to analyze the effects of graft-host interference fit and a modified OCG geometry on OCG insertion biomechanics and cartilage damage. The effects of interference fit (radius of OCG - radius of OCR), loose (0.00 mm), moderate (0.05 mm), tight (0.10 mm), and of a tight fit with OCG geometry modification (central region of decreased radius), were analyzed for OCG cylinders and OCR blocks from adult bovine knee joints with an instrumented drop tower apparatus. An increasingly tight (OCG - OCR) interference fit led to increased taps for insertion, peak axial force, graft cartilage axial compression, cumulative and total energy delivery to cartilage, lower time of peak axial force, lesser graft advancement during each tap, higher total crack length in the cartilage surface, and lower chondrocyte viability. The modified OCG, with reduction of diameter in the central area, altered the biomechanical insertion variables and biological consequences to be similar to those of the moderate interference fit scenario. Micro-computed tomography confirmed structural interference between the OCR bone and both the proximal and distal bone segments of the OCGs, with the central regions being slightly separated for the modified OCGs. These results clarify OCG insertion biomechanics and mechanobiology, and introduce a simple modification of OCGs that facilitates insertion with reduced energy while maintaining a structural interference fit. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:377-386, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Costo-osteochondral graft for post-traumatic osteonecrosis of the radial head in an adolescent boy.

PubMed

Iwai, S; Sato, K; Nakamura, T; Okazaki, M; Itoh, Y; Toyama, Y; Ikegami, H

2011-01-01

We present a case of post-traumatic osteonecrosis of the radial head in a 13-year-old boy which was treated with costo-osteochondral grafts. A satisfactory outcome was seen at a follow-up of two years and ten months. Although costo-osteochondral grafting has been used in the treatment of defects in articular cartilage, especially in the hand and the elbow, the extension of the technique to manage post-traumatic osteonecrosis of the radial head in a child has not previously been reported in the English language literature. Complete relief of pain was obtained and an improvement in the range of movement was observed. The long-term results remain uncertain.

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.

Autologous Dual-Tissue Transplantation for Osteochondral Repair

PubMed Central

Foldager, Casper Bindzus; Jensen, Jonas; Lind, Martin

2015-01-01

Background Numerous treatment methods for osteochondral repair have been implemented, including auto- and allogeneic osteochondral transplantations, combined bone and chondrocyte transplantations, and synthetic implants, but no gold standard treatment has been established. We present preliminary data on a combined autologous bone and cartilage chips: autologous dual-tissue transplantation (ADTT); an easily applicable, low-cost treatment option for osteochondral repair. The aim of this study was to investigate the early biological and clinical outcome of ADTT. Materials Eight patients (age 32 ± 7.5 years) suffering from osteochondritis dissecans (OCD) in the knee were enrolled. The OCD lesion was debrided and the osteochondral defect was filled with autologous bone, to a level at the base of the adjacent cartilage. Cartilage biopsies from the intercondylar notch were chipped and embedded within fibrin glue in the defect. Evaluation was performed using magnetic resonance imaging, computed tomography, and clinical scores, preoperative and 1 year postoperative. Results Cartilage tissue repair evaluated using MOCART score improved from 22.5 to 52.5 (P < 0.01). Computed tomography imaging demonstrated very good subchondral bone healing with all 8 patients having a bone filling of >80%. We found improvements 1 year postoperative in the International Knee Documentation Committee score (from 35.9 to 68.1, P < 0.01), Tegner score (from 2.6 to 4.7, P < 0.05), and Knee injury and Osteoarthritis Outcome Score pain, symptoms, sport/recreation and quality of life (P < 0.05). Conclusion Treatment of OCD with ADTT resulted in very good subchondral bone restoration and good cartilage repair. Significant improvements in patient reported outcome was found at 1 year postoperative. This study suggests ADTT as a promising, low-cost, treatment option for osteochondral injuries. PMID:26175862

Recent progress in interfacial tissue engineering approaches for osteochondral defects.

PubMed

Castro, Nathan J; Hacking, S Adam; Zhang, Lijie Grace

2012-08-01

This review provides a brief synopsis of the anatomy and physiology of the osteochondral interface, scaffold-based and non-scaffold based approaches for engineering both tissues independently as well as recent developments in the manufacture of gradient constructs. Novel manufacturing techniques and nanotechnology will be discussed with potential application in osteochondral interfacial tissue engineering.

[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.

Treatment of Osteochondral Defects in the Rabbit's Knee Joint by Implantation of Allogeneic Mesenchymal Stem Cells in Fibrin Clots

PubMed Central

Berninger, Markus T.; Wexel, Gabriele; Rummeny, Ernst J.; Imhoff, Andreas B.; Anton, Martina

2013-01-01

The treatment of osteochondral articular defects has been challenging physicians for many years. The better understanding of interactions of articular cartilage and subchondral bone in recent years led to increased attention to restoration of the entire osteochondral unit. In comparison to chondral lesions the regeneration of osteochondral defects is much more complex and a far greater surgical and therapeutic challenge. The damaged tissue does not only include the superficial cartilage layer but also the subchondral bone. For deep, osteochondral damage, as it occurs for example with osteochondrosis dissecans, the full thickness of the defect needs to be replaced to restore the joint surface 1. Eligible therapeutic procedures have to consider these two different tissues with their different intrinsic healing potential 2. In the last decades, several surgical treatment options have emerged and have already been clinically established 3-6. Autologous or allogeneic osteochondral transplants consist of articular cartilage and subchondral bone and allow the replacement of the entire osteochondral unit. The defects are filled with cylindrical osteochondral grafts that aim to provide a congruent hyaline cartilage covered surface 3,7,8. Disadvantages are the limited amount of available grafts, donor site morbidity (for autologous transplants) and the incongruence of the surface; thereby the application of this method is especially limited for large defects. New approaches in the field of tissue engineering opened up promising possibilities for regenerative osteochondral therapy. The implantation of autologous chondrocytes marked the first cell based biological approach for the treatment of full-thickness cartilage lesions and is now worldwide established with good clinical results even 10 to 20 years after implantation 9,10. However, to date, this technique is not suitable for the treatment of all types of lesions such as deep defects involving the subchondral bone 11. The

Axial load-bearing capacity of an osteochondral autograft stabilized with a resorbable osteoconductive bone cement compared with a press-fit graft in a bovine model.

PubMed

Kiss, Marc-Olivier; Levasseur, Annie; Petit, Yvan; Lavigne, Patrick

2012-05-01

Osteochondral autografts in mosaicplasty are inserted in a press-fit fashion, and hence, patients are kept nonweightbearing for up to 2 months after surgery to allow bone healing and prevent complications. Very little has been published regarding alternative fixation techniques of those grafts. Osteochondral autografts stabilized with a resorbable osteoconductive bone cement would have a greater load-bearing capacity than standard press-fit grafts. Controlled laboratory study. Biomechanical testing was conducted on 8 pairs of cadaveric bovine distal femurs. For the first 4 pairs, 6 single osteochondral autografts were inserted in a press-fit fashion on one femur. On the contralateral femur, 6 grafts were stabilized with a calcium triglyceride osteoconductive bone cement. For the 4 remaining pairs of femurs, 4 groups of 3 adjacent press-fit grafts were inserted on one femur, whereas on the contralateral femur, grafts were cemented. After a maturation period of 48 hours, axial loading was applied on all single grafts and on the middle graft of each 3-in-a-row series. For the single-graft configuration, median loads required to sink the press-fit and cemented grafts by 2 and 3 mm were 281.87 N versus 345.56 N (P = .015) and 336.29 N versus 454.08 N (P = .018), respectively. For the 3-in-a-row configuration, median loads required to sink the press-fit and cemented grafts by 2 and 3 mm were 260.31 N versus 353.47 N (P = .035) and 384.83 N versus 455.68 N (P = .029), respectively. Fixation of osteochondral grafts using bone cement appears to improve immediate stability over the original mosaicplasty technique for both single- and multiple-graft configurations. Achieving greater primary stability of osteochondral grafts could potentially accelerate postoperative recovery, allowing early weightbearing and physical therapy.

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

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

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.

Osteochondral Interface Tissue Engineering Using Macroscopic Gradients of Bioactive Signals

PubMed Central

Dormer, Nathan H.; Singh, Milind; Wang, Limin; Berkland, Cory J.; Detamore, Michael S.

2013-01-01

Continuous gradients exist at osteochondral interfaces, which may be engineered by applying spatially patterned gradients of biological cues. In the present study, a protein-loaded microsphere-based scaffold fabrication strategy was applied to achieve spatially and temporally controlled delivery of bioactive signals in three-dimensional (3D) tissue engineering scaffolds. Bone morphogenetic protein-2 and transforming growth factor-β1-loaded poly(d,llactic- co-glycolic acid) microspheres were utilized with a gradient scaffold fabrication technology to produce microsphere-based scaffolds containing opposing gradients of these signals. Constructs were then seeded with human bone marrow stromal cells (hBMSCs) or human umbilical cord mesenchymal stromal cells (hUCMSCs), and osteochondral tissue regeneration was assessed in gradient scaffolds and compared to multiple control groups. Following a 6-week cell culture, the gradient scaffolds produced regionalized extracellular matrix, and outperformed the blank control scaffolds in cell number, glycosaminoglycan production, collagen content, alkaline phosphatase activity, and in some instances, gene expression of major osteogenic and chondrogenic markers. These results suggest that engineered signal gradients may be beneficial for osteochondral tissue engineering. PMID:20379780

Osteochondral tissue engineering: scaffolds, stem cells and applications

PubMed Central

Nooeaid, Patcharakamon; Salih, Vehid; Beier, Justus P; Boccaccini, Aldo R

2012-01-01

Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self-repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral tissue engineering, which are focused on the application of various materials forming bilayered composite scaffolds, including polymers and ceramics, discussing the variety of scaffold designs and fabrication methods being developed. Additionally, cell sources and biological protein incorporation methods are discussed, addressing their interaction with scaffolds and highlighting the potential for creating a new generation of bilayered composite scaffolds that can mimic the native interfacial tissue properties, and are able to adapt to the biological environment. PMID:22452848

Advancements in Orthopedic Intervention: Retrograde Drilling and Bone Grafting of Osteochondral Lesions of the Knee Using Magnetic Resonance Imaging Guidance

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

Seebauer, Christian J., E-mail: christian.seebauer@charite.d; Bail, Hermann J., E-mail: hermann-josef.bail@klinikum-nuernberg.d; Rump, Jens C., E-mail: jens.rump@charite.de

Computer-assisted surgery is currently a novel challenge for surgeons and interventional radiologists. Magnetic resonance imaging (MRI)-guided procedures are still evolving. In this experimental study, we describe and assess an innovative passive-navigation method for MRI-guided treatment of osteochondritis dissecans of the knee. A navigation principle using a passive-navigation device was evaluated in six cadaveric knee joint specimens for potential applicability in retrograde drilling and bone grafting of osteochondral lesions using MRI guidance. Feasibility and accuracy were evaluated in an open MRI scanner (1.0 T Philips Panorama HFO MRI System). Interactive MRI navigation allowed precise drilling and bone grafting of osteochondral lesionsmore » of the knee. All lesions were hit with an accuracy of 1.86 mm in the coronal plane and 1.4 mm the sagittal plane. Targeting of all lesions was possible with a single drilling. MRI allowed excellent assessment of correct positioning of the cancellous bone cylinder during bone grafting. The navigation device and anatomic structures could be clearly identified and distinguished throughout the entire drilling procedure. MRI-assisted navigation method using a passive navigation device is feasible for the treatment of osteochondral lesions of the knee under MRI guidance and allows precise and safe drilling without exposure to ionizing radiation. This method may be a viable alternative to other navigation principles, especially for pediatric and adolescent patients. This MRI-navigated method is also potentially applicable in many other MRI-guided interventions.« less

Natural Origin Materials for Osteochondral Tissue Engineering.

PubMed

Bonani, Walter; Singhatanadgige, Weerasak; Pornanong, Aramwit; Motta, Antonella

2018-01-01

Materials selection is a critical aspect for the production of scaffolds for osteochondral tissue engineering. Synthetic materials are the result of man-made operations and have been investigated for a variety of tissue engineering applications. Instead, the products of physiological processes and the metabolic activity of living organisms are identified as natural materials. Over the recent decades, a number of natural materials, namely, biopolymers and bioceramics, have been proposed as the main constituent of osteochondral scaffolds, but also as cell carriers and signaling molecules. Overall, natural materials have been investigated both in the bone and in the cartilage compartment, sometimes alone, but often in combination with other biopolymers or synthetic materials. Biopolymers and bioceramics possess unique advantages over their synthetic counterparts due similarity with natural extracellular matrix, the presence of cell recognition sites and tunable chemistry. However, the characteristics of natural origin materials can vary considerably depending on the specific source and extraction process. A deeper understanding of the relationship between material variability and biological activity and the definition of standardized manufacturing procedures will be crucial for the future of natural materials in tissue engineering.

Histological evaluation of calcaneal tuberosity cartilage--A proposed donor site for osteochondral autologous transplant for talar dome osteochondral lesions.

PubMed

Calder, James D F; Ballal, Moez S; Deol, Rupinderbir S; Pearce, Christopher J; Hamilton, Paul; Lutz, Michael

2015-09-01

Osteochondral Autologous Transplant (OATs) as a treatment option for Osteochondral lesions (OCLs) of the talar dome frequently uses the distal femur as the donor site which is associated with donor site morbidity in up to 50%. Some studies have described the presence of hyaline cartilage in the posterior superior calcaneal tuberosity. The aim of this study was to evaluate the posterior superior calcaneal tuberosity to determine if it can be a suitable donor site for OATs of the talus In this cadaveric study, we histologically evaluated 12 osteochondral plugs taken from the posterior superior calcaneal tuberosity and compared them to 12 osteochondral plugs taken from the talar dome. In the talar dome group, all samples had evidence of hyaline cartilage with varying degrees of GAG staining. The average hyaline cartilage thickness in the samples was 1.33 mm. There was no evidence of fibrocartilage, fibrous tissue or fatty tissue in this group. In contrast, the Calcaneal tuberosity samples had no evidence of hyaline cartilage. Fibrocartilage was noted in 3 samples only. We believe that the structural differences between the talus and calcanium grafts render the posterior superior clancaneal tuberosity an unsuitable donor site for OATs in the treatment of OCL of the talus. Copyright © 2014 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Current strategies in multiphasic scaffold design for osteochondral tissue engineering: A review.

PubMed

Yousefi, Azizeh-Mitra; Hoque, Md Enamul; Prasad, Rangabhatala G S V; Uth, Nicholas

2015-07-01

The repair of osteochondral defects requires a tissue engineering approach that aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using specifically designed scaffold-cell constructs. Biphasic and triphasic approaches utilize two or three different architectures, materials, or composites to produce a multilayered construct. This article gives an overview of some of the current strategies in multiphasic/gradient-based scaffold architectures and compositions for tissue engineering of osteochondral defects. In addition, the application of finite element analysis (FEA) in scaffold design and simulation of in vitro and in vivo cell growth outcomes has been briefly covered. FEA-based approaches can potentially be coupled with computer-assisted fabrication systems for controlled deposition and additive manufacturing of the simulated patterns. Finally, a summary of the existing challenges associated with the repair of osteochondral defects as well as some recommendations for future directions have been brought up in the concluding section of this article. © 2014 Wiley Periodicals, Inc.

High-throughput bone and cartilage micropellet manufacture, followed by assembly of micropellets into biphasic osteochondral tissue.

PubMed

Babur, Betul Kul; Futrega, Kathryn; Lott, William B; Klein, Travis Jacob; Cooper-White, Justin; Doran, Michael Robert

2015-09-01

Engineered biphasic osteochondral tissues may have utility in cartilage defect repair. As bone-marrow-derived mesenchymal stem/stromal cells (MSC) have the capacity to make both bone-like and cartilage-like tissues, they are an ideal cell population for use in the manufacture of osteochondral tissues. Effective differentiation of MSC to bone-like and cartilage-like tissues requires two unique medium formulations and this presents a challenge both in achieving initial MSC differentiation and in maintaining tissue stability when the unified osteochondral tissue is subsequently cultured in a single medium formulation. In this proof-of-principle study, we used an in-house fabricated microwell platform to manufacture thousands of micropellets formed from 166 MSC each. We then characterized the development of bone-like and cartilage-like tissue formation in the micropellets maintained for 8-14 days in sequential combinations of osteogenic or chondrogenic induction medium. When bone-like or cartilage-like micropellets were induced for only 8 days, they displayed significant phenotypic changes when the osteogenic or chondrogenic induction medium, respectively, was swapped. Based on these data, we developed an extended 14-day protocol for the pre-culture of bone-like and cartilage-like micropellets in their respective induction medium. Unified osteochondral tissues were formed by layering 12,000 osteogenic micropellets and 12,000 chondrogenic micropellets into a biphasic structure and then further culture in chondrogenic induction medium. The assembled tissue was cultured for a further 8 days and characterized via histology. The micropellets had amalgamated into a continuous structure with distinctive bone-like and cartilage-like regions. This proof-of-concept study demonstrates the feasibility of micropellet assembly for the formation of osteochondral-like tissues for possible use in osteochondral defect repair.

Use of Synthetic Osteochondral Implants to Treat Bilateral Shoulder Osteochondritis Dissecans in a Dog.

PubMed

Danielski, Alan; Farrell, Michael

2018-06-20

 An 8-month-old American Bulldog was presented for assessment of bilateral thoracic limb lameness. Computed tomographic imaging revealed large, deep osteochondritis dissecans lesions in both humeral heads.  The osteochondritis dissecans lesions were debrided and the exposed subchondral defects were prepared to receive synthetic grafts. Circular implants consisting of a surface layer of polycarbonate urethane and a deep layer of lattice-type titanium were implanted into the osteochondral defects to reconstruct the articular surface topography. Follow-up clinical examination 1.5, 3 and 9months postoperatively revealed a lack of signs of shoulder pain and resolution of thoracic limb lameness. Nine-month follow-up radiographs showed radiographic evidence of osteointegration of both implants.  Synthetic osteochondral implantation in the caudocentral aspect of the humeral head appeared technically feasible and effective in resolving lameness caused by humeral head osteochondritis dissecans. Schattauer GmbH Stuttgart.

[Treatment of Osteochondral Lesions in the Ankle: A Guideline from the Group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU)].

PubMed

Aurich, M; Albrecht, D; Angele, P; Becher, C; Fickert, S; Fritz, J; Müller, P E; Niemeyer, P; Pietschmann, M; Spahn, G; Walther, M

2017-02-01

Background: Osteochondral lesions (OCL) of the ankle are a common cause of ankle pain. Although the precise pathophysiology has not been fully elucidated, it can be assumed that a variety of factors are responsible, mainly including traumatic events such as ankle sprains. Advances in arthroscopy and imaging techniques, in particular magnetic resonance imaging (MRI), have improved the possibilities for the diagnosis of OCLs of the ankle. Moreover, these technologies aim at developing new classification systems and modern treatment strategies. Material and Methods: This article is a review of the literature. Recommendations of the group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) for the treatment of OCLs of the ankle are presented. The review gives a concise overview on the results of clinical studies and discusses advantages and disadvantages of different treatment strategies. Results: Non-operative treatment shows good results for selected indications in children and adolescents, especially in early stages of osteochondritis dissecans (OCD). However, surgical treatment is usually indicated in OCLs in adolescents and adults, depending on the size and location of the lesion. Various arthroscopic and open procedures are frequently employed, including reattachment of the fragment, local debridement of the lesion with fragment removal and curettage of the lesion, bone marrow-stimulation by microfracture or microdrilling (antegrade or retrograde), and autologous matrix-induced chondrogenesis (AMIC®) - with or without reconstruction of a subchondral bone defect or cyst by autologous cancellous bone grafting. Isolated subchondral cysts with an intact cartilage surface can be treated by retrograde drilling and possibly additional retrograde bone grafting. For larger defects or as salvage procedure, osteochondral cylinder transplantation (OATS® or Mosaicplasty®) or matrix-induced autologous chondrocyte transplantation

Implantation of Autologous Cartilage Chips Improves Cartilage Repair Tissue Quality in Osteochondral Defects: A Study in Göttingen Minipigs.

PubMed

Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Olesen, Morten Lykke; Hede, Kris Chadwick; Lind, Martin

2016-06-01

Osteochondral injuries have poor endogenous healing potential, and no standard treatment has been established. The use of combined layered autologous bone and cartilage chips for treatment of osteochondral defects has shown promising short-term clinical results. This study aimed to investigate the role of cartilage chips by comparing combined layered autologous bone and cartilage chips with autologous bone implantation alone in a Göttingen minipig model. The hypothesis was that the presence of cartilage chips would improve the quality of the repair tissue. Controlled laboratory study. Twelve Göttingen minipigs received 2 osteochondral defects in each knee. The defects were randomized to autologous bone graft (ABG) combined with autologous cartilage chips (autologous dual-tissue transplantation [ADTT]) or ABG alone. Six animals were euthanized at 6 months and 6 animals were euthanized at 12 months. Follow-up evaluation consisted of histomorphometry, immunohistochemistry, semiquantitative scoring (International Cartilage Repair Society II), and computed tomography. There was significantly more hyaline cartilage in the ADTT group (25.8%) compared with the ABG group (12.8%) at 6 months after treatment. At 12 months, the fraction of hyaline cartilage in the ABG group had significantly decreased to 4.8%, whereas the fraction of hyaline cartilage in the ADTT group was unchanged (20.1%). At 6 and 12 months, there was significantly more fibrocartilage in the ADTT group (44% and 60.8%) compared with the ABG group (24.5% and 41%). The fraction of fibrous tissue was significantly lower in the ADTT group compared with the ABG group at both 6 and 12 months. The implanted cartilage chips stained >75% positive for collagen type 4 and laminin at both 6 and 12 months. Significant differences were found in a number of International Cartilage Repair Society II subcategories. The volume of the remaining bone defect significantly decreased from 6 to 12 months in both treatment groups

A comparative study on collagen type I and hyaluronic acid dependent cell behavior for osteochondral tissue bioprinting.

PubMed

Park, Ju Young; Choi, Jong-Cheol; Shim, Jin-Hyung; Lee, Jung-Seob; Park, Hyoungjun; Kim, Sung Won; Doh, Junsang; Cho, Dong-Woo

2014-09-01

Bioprinting is a promising technique for engineering composite tissues, such as osteochondral tissues. In this study, as a first step toward bioprinting-based osteochondral tissue regeneration, we systematically examined the behavior of chondrocytes and osteoblasts to hyaluronic acid (HA) and type I collagen (Col-1) hydrogels. First, we demonstrated that cells on hydrogels that were comprised of major native tissue extracellular matrix (ECM) components (i.e. chondrocytes on HA hydrogels and osteoblasts on Col-1 hydrogels) exhibited better proliferation and cell function than cells on non-native ECM hydrogels (i.e., chondrocytes on Col-1 hydrogels and osteoblasts on HA hydrogels). In addition, cells located near their native ECM hydrogels migrated towards them. Finally, we bioprinted three-dimensional (3D) osteochondral tissue-mimetic structures composed of two compartments, osteoblast-encapsulated Col-1 hydrogels and chondrocyte-encapsulated HA hydrogels, and found viability and functions of each cell type were well maintained within the 3D structures up to 14 days in vitro. These results suggest that with proper choice of hydrogel materials, bioprinting-based approaches can be successfully applied for osteochondral tissue regeneration.

Human umbilical cord mesenchymal stromal cells in a sandwich approach for osteochondral tissue engineering

PubMed Central

Wang, Limin; Zhao, Liang; Detamore, Michael S.

2013-01-01

Cell sources and tissue integration between cartilage and bone regions are critical to successful osteochondral regeneration. In this study, human umbilical cord mesenchymal stromal cells (hUCMSCs), derived from Wharton’s jelly, were introduced to the field of osteochondral tissue engineering and a new strategy for osteochondral integration was developed by sandwiching a layer of cells between chondrogenic and osteogenic constructs before suturing them together. Specifically, hUCMSCs were cultured in biodegradable poly-l-lactic acid scaffolds for 3 weeks in either chondrogenic or osteogenic medium to differentiate cells toward cartilage or bone lineages, respectively. A highly concentrated cell solution containing undifferentiated hUCMSCs was pasted onto the surface of the bone layer at week 3 and the two layers were then sutured together to form an osteochondral composite for another 3 week culture period. Chondrogenic and osteogenic differentiation was initiated during the first 3 weeks, as evidenced by the expression of type II collagen and runt-related transcription factor 2 genes, respectively, and continued with the increase of extracellular matrix during the last 3 weeks. Histological and immunohistochemical staining, such as for glycosaminoglycans, type I collagen and calcium, revealed better integration and transition of these matrices between two layers in the composite group containing sandwiched cells compared to other control composites. These results suggest that hUCMSCs may be a suitable cell source for osteochondral regeneration, and the strategy of sandwiching cells between two layers may facilitate scaffold and tissue integration. PMID:21953869

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

Customized Fabrication of Osteochondral Tissue for Articular Joint Surface Repair

DTIC Science & Technology

2016-09-01

differentiation cues for chondrogenesis and osteogenesis, by the 3D printing method of projection stereolithography (PSL). We further test the...military medical care costs. Post Traumatic Osteoarthritis, Injury, Articular Cartilage, tissue-engineered, 3D printing , Osteochondral constructs. Major...tissue with the stem cells used. He will also be assisting with the 3D printing of the material. Funding Support: Supported by internal University

Synthetic Materials for Osteochondral Tissue Engineering.

PubMed

Iulian, Antoniac; Dan, Laptoiu; Camelia, Tecu; Claudia, Milea; Sebastian, Gradinaru

2018-01-01

The objective of an articular cartilage repair treatment is to repair the affected surface of an articular joint's hyaline cartilage. Currently, both biological and tissue engineering research is concerned with discovering the clues needed to stimulate cells to regenerate tissues and organs totally or partially. The latest findings on nanotechnology advances along with the processability of synthetic biomaterials have succeeded in creating a new range of materials to develop into the desired biological responses to the cellular level. 3D printing has a great ability to establish functional tissues or organs to cure or replace abnormal and necrotic tissue, providing a promising solution for serious tissue/organ failure. The 4D print process has the potential to continually revolutionize the current tissue and organ manufacturing platforms. A new active research area is the development of intelligent materials with high biocompatibility to suit 4D printing technology. As various researchers and tissue engineers have demonstrated, the role of growth factors in tissue engineering for repairing osteochondral and cartilage defects is a very important one. Following animal testing, cell-assisted and growth-factor scaffolds produced much better results, while growth-free scaffolds showed a much lower rate of healing.

Mechanical evaluation of a tissue-engineered zone of calcification in a bone–hydrogel osteochondral construct

PubMed Central

Hollenstein, Jérôme; Terrier, Alexandre; Cory, Esther; Chen, Albert C.; Sah, Robert L.; Pioletti, Dominique P.

2016-01-01

The objective of this study was to test the hypothesis that mechanical properties of artificial osteochondral constructs can be improved by a tissue-engineered zone of calcification (teZCC) at the bone–hydrogel interface. Experimental push-off tests were performed on osteochondral constructs with or without a teZCC. In parallel, a numerical model of the osteochondral defect treatment was developed and validated against experimental results. Experimental results showed that the shear strength at the bone–hydrogel interface increased by 100% with the teZCC. Numerical predictions of the osteochondral defect treatment showed that the shear stress at the bone–hydrogel interface was reduced with the teZCC. We conclude that a teZCC in osteochondral constructs can provide two improvements. First, it increases the strength of the bone–hydrogel interface and second, it reduces the stress at this interface. PMID:23706035

Humeral Head Reconstruction With Osteochondral Allograft Transplantation.

PubMed

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

2015-09-01

To synthesize, in a systematic review, the available clinical evidence of osteochondral allograft transplants for large osteochondral defects of the humeral head. The Medline, Embase, and Cochrane databases were searched for studies reporting clinical or radiographic outcomes of osteochondral allograft transplantation for humeral head defects. Descriptive statistics were provided for all outcomes. After checking for data normality, we compared postoperative and preoperative values using the Student t test. We included 12 studies (8 case reports and 4 case series) in this review. The study group consisted of 35 patients. The mean age was 35.4 ± 18.1 years; 77% of patients were male patients. Thirty-three patients had large Hill-Sachs lesions due to instability, 1 had an osteochondritis dissecans lesion, and 1 had an iatrogenic lesion after resection of synovial chondromatosis. The mean lesion size was 3 ± 1.4 cm (anteroposterior) by 2.25 ± 0.3 cm (medial-lateral), representing on average 40.5% ± 4.73% of the native articular surface. Of the 35 patients, 3 received a fresh graft, with all others receiving frozen grafts. Twenty-three femoral heads, 10 humeral heads, and 2 sets of osteochondral plugs were used. The mean length of follow-up was 57 months. Significant improvements were seen in forward flexion at 6 months (68° ± 18.1°, P < .001), forward flexion at 12 months (83.42° ± 18.3°, P < .001), and external rotation at 12 months (38.72° ± 18.8°, P < .001). American Shoulder and Elbow Surgeons scores improved by 14 points (P = .02). Radiographic studies at final follow-up showed allograft necrosis in 8.7% of cases, resorption in 36.2%, and glenohumeral arthritic changes in 35.7%. Complication rates were between 20% and 30%, and the reoperation rate was 26.67%. Although only 3 patients received fresh allografts, there were no reports of graft resorption, necrosis, or arthritic changes in these patients. Humeral head allograft-most commonly used in the

Osteochondral integration of multiply incised pure cartilage allograft: repair method of focal chondral defects in a porcine model.

PubMed

Bardos, Tamas; Farkas, Boglarka; Mezes, Beata; Vancsodi, Jozsef; Kvell, Krisztian; Czompoly, Tamas; Nemeth, Peter; Bellyei, Arpad; Illes, Tamas

2009-11-01

A focal cartilage lesion has limited capacity to heal, and the repair modalities used at present are still unable to provide a universal solution. Pure cartilage graft implantation appears to be a simple option, but it has not been applied widely as cartilage will not reattach easily to the subchondral bone. We used a multiple-incision technique (processed chondrograft) to increase cartilage graft surface. We hypothesized that pure cartilage graft with augmented osteochondral fusion capacity may be used for cartilage repair and we compared this method with other repair techniques. Controlled laboratory study. Full-thickness focal cartilage defects were created on the medial femoral condyle of 9-month-old pigs; defects were repaired using various methods including bone marrow stimulation, autologous chondrocyte implantation, and processed chondrograft. After the repair, at weeks 6 and 24, macroscopic and histologic evaluation was carried out. Compared with other methods, processed chondrograft was found to be similarly effective in cartilage repair. Defects without repair and defects treated with bone marrow stimulation appeared slightly irregular with fibrocartilage filling. Autologous chondrocyte implantation produced hyalinelike cartilage, although its cellular organization was distinguishable from the surrounding articular cartilage. Processed chondrograft demonstrated good osteochondral integration, and the resulting tissue appeared to be hyaline cartilage. The applied cartilage surface processing method allows acceptable osteochondral integration, and the repair tissue appears to have good macroscopic and histologic characteristics. If further studies confirm its efficacy, this technique could be considered for human application in the future.

Potential role of pre-existing blood vessels for vascularization and mineralization of osteochondral grafts: an intravital microscopic study in mice.

PubMed

Rothenfluh, Dominique A; Demhartner, Thomas J; Fraitzl, Christian R; Cecchini, Marco G; Ganz, Reinhold; Leunig, Michael

2004-06-01

The aim of this study was to develop an experimental model that allows to elude the potential role of the preexisting graft microvasculature for vascularization and mineralization of osteochondral grafts. For that purpose, the II-IV metatarsals of fetal DDY-mice known to be nonvascularized at day 16 of gestation (M16) but vascularized at day 18 (M18) were freshly transplanted into dorsal skin fold chambers of adult DDY mice. Using intravital microscopy angiogenesis, leukocyte-endothelium interaction and mineralization were assessed for 12 days. Angiogenesis occurred at 32 hours in M18, but not before 57 hours in M16 (p = 0.002), with perfusion of these vessels at 42 hours (p = 0.005) and 65 hours (p = 0.1), respectively. Vessels reached a density three times as high as that of the recipient site at day 6, remaining constant until day 12 in M18, whereas in M16 vascular density increased from day 6 and reached that of M18 at day 12 (p = 0.04). Leukocyte-endothelium interaction showed sticker counts elevated by a factor of 4-5 in M18 as compared to M16. Mineralization of osteochondral grafts did not differ between M16 and M18, which significantly increased in both groups throughout the observation period. We propose the faster kinetics in the angiogenic response to M18 and the elevated counts of sticking leukocytes to rest on the potential of establishing end-to-end anastomoses (inosculation) of the vascularized graft with recipient vessels.

Magnetic resonance imaging of hyaline cartilage regeneration in neocartilage graft implantation.

PubMed

Tan, C F; Ng, K K; Ng, S H; Cheung, Y C

2003-12-01

The purpose of this study was to investigate the regenerative potential of hyaline cartilage in a neocartilage graft implant with the aid of MR cartilage imaging using a rabbit model. Surgical osteochondral defects were created in the femoral condyles of 30 mature New Zealand rabbits. The findings of neocartilage in autologous cartilage grafts packed into osteochondral defects were compared with control group of no implant to the osteochondral defect. The outcome of the implantations was correlated with histologic and MR cartilage imaging findings over a 3-month interval. Neocartilage grafts packed into osteochondral defects showed regeneration of hyaline cartilage at the outer layer of the implant using MR cartilage imaging. Fibrosis of fibrocartilage developed at the outer layer of the autologous cartilage graft together with an inflammatory reaction within the osteochondral defect. This animal study provides evidence of the regenerative ability of hyaline cartilage in neocartilage transplants to repair articular cartilage.

A human osteoarthritis osteochondral organ culture model for cartilage tissue engineering.

PubMed

Yeung, P; Zhang, W; Wang, X N; Yan, C H; Chan, B P

2018-04-01

In vitro human osteoarthritis (OA)-mimicking models enabling pathophysiological studies and evaluation of emerging therapies such as cartilage tissue engineering are of great importance. We describe the development and characterization of a human OA osteochondral organ culture. We also apply this model for evaluation of the phenotype maintenance of a human MSC derived engineered cartilage, as an example of emerging therapeutics, under long term exposure to the OA-mimicking environment. We also test the sensitivity of the model to a series of external factors and a potential disease-modifying agent, in terms of chondrogenic phenotype maintenance of the engineered cartilage, under OA-mimicking environment. Excised joint tissues from total knee replacement surgeries were carved into numerous miniaturized and standardized osteochondral plugs for subsequent OA organ culture. The organ cultures were characterized in detail before being co-cultured with a tissue engineered cartilage. The chondrogenic phenotype of the tissue engineered cartilage co-cultured in long term up to 8 weeks under this OA-mimicking microenvironment was evaluated. Using the same co-culture model, we also screened for a number of biomimetic environmental factors, including oxygen tension, the presence of serum and the application of compression loading. Finally, we studied the effect of a matrix metalloprotease inhibitor, as an example of potential disease-modifying agents, on the co-cultured engineered cartilage. We demonstrate that cells in the OA organ culture were viable while both the typical chondrogenic phenotype and the characteristic OA phenotype were maintained for long period of time. We then demonstrate that upon co-culture with the OA-mimicking organ culture, the engineered cartilage initially exhibited a more fibrocartilage phenotype but progressively reverted back to the chondrogenic phenotype upon long term co-culture up to 8 weeks. The engineered cartilage was also found to be

Stem cell- and scaffold-based tissue engineering approaches to osteochondral regenerative medicine

PubMed Central

Sundelacruz, Sarah; Kaplan, David L.

2009-01-01

In osteochondral tissue engineering, cell recruitment, proliferation, differentiation, and patterning are critical for forming biologically and structurally viable constructs for repair of damaged or diseased tissue. However, since constructs prepared ex vivo lack the multitude of cues present in the in vivo microenvironment, cells often need to be supplied with external biological and physical stimuli to coax them towards targeted tissue functions. To determine which stimuli to present to cells, bioengineering strategies can benefit significantly from endogenous examples of skeletogenesis. As an example of developmental skeletogenesis, the developing limb bud serves as an excellent model system in which to study how an osteochondral structures form from undifferentiated precursor cells. Alongside skeletal formation during embryogenesis, bone also possesses innate regenerative capacity, displaying remarkable ability to heal after damage. Bone fracture healing shares many features with bone development, driving the hypothesis that the regenerative process generally recapitulates development. Similarities and differences between the two modes of bone formation may offer insight into the special requirements for healing damaged or diseased bone. Thus, endogenous fracture healing, as an example of regenerative skeletogenesis, may also inform bioengineering strategies. In this review, we summarize the key cellular events involving stem and progenitor cells in developmental and regenerative skeletogenesis, and discuss in parallel the corresponding cell- and scaffold-based strategies that tissue engineers employ to recapitulate these events in vitro. PMID:19508851

Fluoroscopy-guided retrograde core drilling and cancellous bone grafting in osteochondral defects of the talus.

PubMed

Anders, Sven; Lechler, Philipp; Rackl, Walter; Grifka, Joachim; Schaumburger, Jens

2012-08-01

In undetached osteochondral lesions (OCL) of the talus both revitalisation of the subchondral necrosis and cartilage preservation are essential. For these cases, we assess the results of minimally invasive retrograde core drilling and cancellous bone grafting. Forty-one osteochondral lesions of the talus (12x grade I, 22x grade II and 7x grade III according to the Pritsch classification, defect sizes 7-14 mm) in 38 patients (mean age 33.2 years) treated by fluoroscopy-guided retrograde core drilling and autologous cancellous bone grafting were evaluated by clinical scores and MRI. The mean follow-up was 29.0 (±13) months. The AOFAS score increased significantly from 47.3 (±15.3) to 80.8 (±18.6) points. Lesions with intact cartilage (grades I and II) had a tendency to superior results than grade III lesions (83.1 ± 17.3 vs. 69.4 ± 22.2 points, p = 0.07). First-line treatments and open distal tibial growth plates led to significantly better outcomes (each p < 0.05). Age, gender, BMI, time to follow-up, defect localisation or a traumatic origin did not influence the score results. On a visual analogue scale pain intensity reduced from 7.5 (±1.5) to 3.7 (±2.6) while subjective function increased from 4.6 (±2.0) to 8.2 (±2.3) (each p < 0.001). In MRI follow-ups, five of the 41 patients showed a complete bone remodelling. In two cases demarcation was detectable. The technique reported is a highly effective therapeutic option in OCL of the talus with intact cartilage grades I and II. However, second-line treatments and grade III lesions with cracked cartilage surface can not be generally recommended for this procedure.

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

The Stromal Vascular Fraction From Fat Tissue in the Treatment of Osteochondral Knee Defect: Case Report

PubMed Central

Salikhov, Ramil Z.; Masgutov, Ruslan F.; Chekunov, Mikhail A.; Tazetdinova, Leysan G.; Masgutova, Galina; Teplov, Oleg V.; Galimov, Damir; Plakseichuk, Yuri; Yagudin, Ramil; Pankov, Igor O.; Rizvanov, Albert

2018-01-01

In this study we applied autologous fat tissue stromal vascular fraction (SVF) cells in combination with microfracturing technique in a 36-year-old man with an osteochondral lesion of the medial femoral condyle 8 months after the injury. Cell material was generated by fat tissue liposuction from the anterior abdominal wall with subsequent extraction of the SVF and injected through a mini-arthrotomy portal with subsequent fibrin sealant fixation. The follow-up period was 2 years. Clinical score improved from 23 to 96 according to IKDC and from 10 to 90 according to EQ-VAS at 24 months follow-up. Magnetic resonance imaging (MRI) before the surgery revealed an osteochondral lesion with development of significant trabecular edema that remained unchanged for 6 months despite conservative treatment. MRI 1 and 2 years after the surgery showed the recovery of the damaged cartilage thickness with somewhat uneven structure and a decrease in the trabecular edema of the femoral condyle. The use of SVF cells with fibrin sealant fixation might be a promising approach in the treatment of osteochondral joint lesions. Further studies are required. PMID:29900170

Clinical and Radiological Regeneration of Large and Deep Osteochondral Defects of the Knee by Bone Augmentation Combined With Matrix-Guided Autologous Chondrocyte Transplantation.

PubMed

Zellner, Johannes; Grechenig, Stephan; Pfeifer, Christian G; Krutsch, Werner; Koch, Matthias; Welsch, Goetz; Scherl, Madeleine; Seitz, Johannes; Zeman, Florian; Nerlich, Michael; Angele, Peter

2017-11-01

Large osteochondral defects of the knee are a challenge for regenerative treatment. While matrix-guided autologous chondrocyte transplantation (MACT) represents a successful treatment for chondral defects, the treatment potential in combination with bone grafting by cancellous bone or bone block augmentation for large and deep osteochondral defects has not been evaluated. To evaluate 1- to 3-year clinical outcomes and radiological results on magnetic resonance imaging (MRI) after the treatment of large osteochondral defects of the knee with bone augmentation and MACT. Special emphasis is placed on different methods of bone grafting (cancellous bone grafting or bone block augmentation). Case series; Level of evidence, 4. Fifty-one patients were included. Five patients were lost to follow-up. This left 46 patients (mean age, 28.2 years) with a median follow-up time of 2 years. The 46 patients had 47 deep, large osteochondral defects of the knee joint (1 patient with bilateral defects; mean defect size, 6.7 cm 2 ). The origin of the osteochondral defects was osteochondritis dissecans (n = 34), osteonecrosis (n = 8), or subchondral cysts (n = 5). Depending on the depth, all defects were treated by cancellous bone grafting (defect depth ≤10 mm; n = 16) or bone block augmentation (defect depth >10 mm; n = 31) combined with MACT. Clinical outcomes were followed at 3 months, 6 months, 1 year, 2 years, and 3 years and evaluated using the International Knee Documentation Committee (IKDC) score and Cincinnati score. A magnetic resonance imaging (MRI) evaluation was performed at 1 and 2 years, and the magnetic resonance observation of cartilage repair tissue (MOCART) score with additional specific subchondral bone parameters (bone regeneration, bone signal quality, osteophytes, sclerotic areas, and edema) was analyzed. The clinical outcome scores revealed a significant increase at follow-up (6 months to 3 years) compared with the preclinical results. The median IKDC score

A novel, visible light-induced, rapidly cross-linkable gelatin scaffold for osteochondral tissue engineering

PubMed Central

Mazaki, Tetsuro; Shiozaki, Yasuyuki; Yamane, Kentaro; Yoshida, Aki; Nakamura, Mariko; Yoshida, Yasuhiro; Zhou, Di; Kitajima, Takashi; Tanaka, Masato; Ito, Yoshihiro; Ozaki, Toshifumi; Matsukawa, Akihiro

2014-01-01

Osteochondral injuries remain difficult to repair. We developed a novel photo-cross-linkable furfurylamine-conjugated gelatin (gelatin-FA). Gelatin-FA was rapidly cross-linked by visible light with Rose Bengal, a light sensitizer, and was kept gelled for 3 weeks submerged in saline at 37°C. When bone marrow-derived stromal cells (BMSCs) were suspended in gelatin-FA with 0.05% Rose Bengal, approximately 87% of the cells were viable in the hydrogel at 24 h after photo-cross-linking, and the chondrogenic differentiation of BMSCs was maintained for up to 3 weeks. BMP4 fusion protein with a collagen binding domain (CBD) was retained in the hydrogels at higher levels than unmodified BMP4. Gelatin-FA was subsequently employed as a scaffold for BMSCs and CBD-BMP4 in a rabbit osteochondral defect model. In both cases, the defect was repaired with articular cartilage-like tissue and regenerated subchondral bone. This novel, photo-cross-linkable gelatin appears to be a promising scaffold for the treatment of osteochondral injury. PMID:24662725

Results of Bone Peg Grafting for Capitellar Osteochondritis Dissecans in Adolescent Baseball Players.

PubMed

Oshiba, Hiroyuki; Itsubo, Toshiro; Ikegami, Shota; Nakamura, Koichi; Uchiyama, Shigeharu; Kato, Hiroyuki

2016-12-01

Bone peg grafting (BPG) has been advocated for early-stage humeral capitellar osteochondritis dissecans (COCD). However, the clinical and radiological results of BPG, along with its indications, have not been described in detail. COCD classified as International Cartilage Repair Society (ICRS) osteochondritis dissecans (OCD) I or II in adolescent baseball players can be treated successfully by BPG. Case series; Level of evidence, 4 METHODS: Eleven male baseball players (age range at surgery, 13-16 years) who underwent BPG for COCD were enrolled in this study. No improvement had been seen in any patient after 6 months of preoperative nonthrowing observation. During surgery, 2 to 5 bone pegs were inserted into the COCD lesion after confirmation of lesion stability to the bony floor. All patients were directly evaluated at 12 and 24 months after surgery by physical findings, radiological prognosis, and magnetic resonance imaging (MRI). Of the 11 patients, 10 could return to comparable baseball ability levels within 12 months. The Timmerman-Andrews score improved significantly from a mean ± SD of 171.8 ± 12.1 preoperatively to 192.3 ± 6.5 at the final observation. Radiological healing of the lesions was determined as complete in 8 patients and partial in 3. Patients possessing a centrally positioned lesion or a lesion <75% of the size of the capitellum tended most strongly to achieve complete radiological healing, while growth plate status appeared unrelated to outcome. The mean Henderson MRI score improved from 6.3 ± 1.5 to 4.8 ± 1.6 at 12 and 24 months after BPG, respectively. MRI findings also suggested that remodeling of COCD lesions had continued to up to 24 months postoperatively. BPG enabled 91% of COCD patients with ICRS OCD I or II to return to preoperative baseball abilities within 12 months. Integration of the grafted site may continue until at least 24 months postoperatively. An ICRS OCD I or II lesion with central positioning and/or occupying <75% of

Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

NASA Astrophysics Data System (ADS)

Shim, Jin-Hyung; Lee, Jung-Seob; Kim, Jong Young; Cho, Dong-Woo

2012-08-01

The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed.

Autologous Bone Plug Supplemented With Autologous Chondrocyte Implantation in Osteochondral Defects of the Knee.

PubMed

Bhattacharjee, Atanu; McCarthy, Helen S; Tins, Bernhard; Roberts, Sally; Kuiper, J H; Harrison, Paul E; Richardson, James B

2016-05-01

Structural and functional outcome of bone graft with first- or second-generation autologous chondrocyte implantation (ACI) in treating cartilage and subchondral bone defect has not been reported previously. To evaluate the outcome of simultaneous transplantation of an autologous bone plug with first- or second-generation ACI for restoration of concomitant subchondral bone and full-thickness cartilage defect in the femoral condyle of the knee. Case series; Level of evidence, 4. Seventeen patients (mean ± SD age, 27 ± 7 years; range, 17-40 years)-12 with osteochondritis dissecans (International Cartilage Repair Society [ICRS] grades 3 and 4) and 5 with an isolated osteochondral defect (ICRS grade 4)-had the defect reconstructed with implantation of a unicortical autologous bone graft combined with ACI (the OsPlug technique). Functional outcome was assessed with Lysholm scores obtained preoperatively and at 1 and 5 years postoperatively. The repair site was evaluated with the Oswestry Arthroscopy Score (OAS), MOCART score (magnetic resonance observation of cartilage repair tissue), and ICRS II histology score. Formation of a subchondral lamina and lateral integration of the bone grafts were evaluated from magnetic resonance imaging scans. The mean defect size was 4.5 ± 2.6 cm(2) (range, 1-9 cm(2)), and the mean depth was 11.3 ± 5 mm (range, 5-18 mm). The preoperative Lysholm score improved from 45 (interquartile range [IQR], 24; range, 16-79) to 77 (IQR, 28; range, 41-100) at 1 year (P = .001) and 70 (IQR, 35; range, 33-91) at 5 years (P = .009). The mean OAS of the repair site was 6.2 (range, 0-9) at a mean of 1.3 years. The mean MOCART score was 61 ± 22 (range, 20-85) at 2.6 ± 1.8 years. Histology demonstrated generally good integration of the repair cartilage with the underlying bone. Poor lateral integration of the bone graft, as assessed on magnetic resonance imaging scan, and a low OAS were significantly associated with a poor Lysholm score and failure. A

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

Gellan Gum-Based Hydrogels for Osteochondral Repair.

PubMed

Costa, Lígia; Silva-Correia, Joana; Oliveira, J Miguel; Reis, Rui L

2018-01-01

Gellan gum (GG) is a widely explored natural polysaccharide that has been gaining attention in tissue engineering (TE) and regenerative medicine field, and more recently in osteochondral TE approaches. Taking advantage of its inherent features such as biocompatibility, biodegradability, similarity with the extracellular matrix and easy functionalization, GG-based hydrogels have been studied for their potential for cartilage and bone tissue regeneration. Several preclinical studies describe the successful outcome of GG in cartilage tissue engineering. By its turn, GG composites have also been proposed in several strategies to guide bone formation. The big challenge in osteochondral TE approaches is still to achieve cartilage and bone regeneration simultaneously through a unique integrated bifunctional construct. The potential of GG to be used as polymeric support to reach both bone and cartilage regeneration has been demonstrated. This chapter provides an overview of GG properties and the functionalization strategies employed to tailor its behaviour to a particular application. The use of GG in soft and hard tissues regeneration approaches, as well in osteochondral integrated TE strategies is also revised.

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.

Osteochondral Autograft from the Ipsilateral Femoral Head by Surgical Dislocation for Treatment of Femoral Head Fracture Dislocation: A Case Report.

PubMed

Won, Yougun; Lee, Gi Soo; Kim, Sang Bum; Kim, Sun Joong; Yang, Kyu Hyun

2016-11-01

As anatomical reduction of the articular surface of femoral head fractures and restoration of damaged cartilage are essential for good long-term results, many treatment options have been suggested, including fixation of the fracture using various surgical exposures and implants, as well as arthroscopic irrigation and debridement, bone marrow stimulating techniques, osteochondral allograft, autograft, and autogenous chondrocyte implantation. We report a case of osteochondral autograft harvested from its own femoral articular surface through surgical hip dislocation. The osteochondral graft was harvested from the inferior non-weight-bearing articular surface and grafted to the osteochondral defect. One year later, the clinical and radiological results were good, without the collapse of the femoral head or arthritic change. This procedure introduced in our case is considered convenient and able to lessen surgical time without morbidity of the donor site associated with the harvest.

Osteochondral autograft transplantation for juvenile osteochondritis dissecans of the knee: a series of twelve cases.

PubMed

Sasaki, Ken; Matsumoto, Tomoyuki; Matsushita, Takehiko; Kubo, Seiji; Ishida, Kazunari; Tei, Katsumasa; Akisue, Toshihiro; Kurosaka, Masahiro; Kuroda, Ryosuke

2012-11-01

The purpose of this study was to evaluate the clinical outcomes of osteochondral autograft transplantation (OAT) for juvenile osteochondritis dissecans (JOCD) lesions of the knee, especially time to return to sports. Twelve knee JOCD lesions with OCD grade 3 and 4 categorised by magnetic resonance imaging (MRI) were treated with OAT. Nine male and two female skeletally immature patients averaging 13.7 years old were included. The OCD lesions were assessed arthroscopically and then fixed in situ using multiple osteochondral plugs harvested under fluoroscopy from the distal femoral condyle without damaging the physis. International Cartilage Repair Society (ICRS) score and Lysholm score were assessed pre- and postoperatively. After a mean follow-up of 26.2 ± 15.1 months, the International Knee Documentation Committee (IKDC) subjective score significantly improved (p < 0.01). According to the IKDC score, objective assessment showed that ten of 12 (83 %) had excellent results (score: A) after OAT and significantly improved (p < 0.01). Based on ICRS criteria, results were satisfactory in all patients. No patients experienced complications at the graft harvest site. All patients returned to their previous level of athletic activity at an average of 5.7 months after the surgery. OAT for JOCD of the knee provided satisfactory results in all patients at a mean follow-up of 26.2 months.

Non-destructive monitoring of viability in an ex vivo organ culture model of osteochondral tissue.

PubMed

Elson, K M; Fox, N; Tipper, J L; Kirkham, J; Hall, R M; Fisher, J; Ingham, E

2015-06-30

Organ culture is an increasingly important tool in research, with advantages over monolayer cell culture due to the inherent natural environment of tissues. Successful organ cultures must retain cell viability. The aim of this study was to produce viable and non-viable osteochondral organ cultures, to assess the accumulation of soluble markers in the conditioned medium for predicting tissue viability. Porcine femoral osteochondral plugs were cultured for 20 days, with the addition of Triton X-100 on day 6 (to induce necrosis), camptothecin (to induce apoptosis) or no toxic additives. Tissue viability was assessed by the tissue destructive XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide tetrazolium salt) assay method and LIVE/DEAD® staining of the cartilage at days 0, 6 and 20. Tissue structure was assessed by histological evaluation using haematoxylin & eosin and safranin O. Conditioned medium was assessed every 3-4 days for glucose depletion, and levels of lactate dehydrogenase (LDH), alkaline phosphatase (AP), glycosaminoglycans (GAGs), and matrix metalloproteinase (MMP)-2 and MMP-9. Necrotic cultures immediately showed a reduction in glucose consumption, and an immediate increase in LDH, GAG, MMP-2 and MMP-9 levels. Apoptotic cultures showed a delayed reduction in glucose consumption and delayed increase in LDH, a small rise in MMP-2 and MMP-9, but no significant effect on GAGs released into the conditioned medium. The data showed that tissue viability could be monitored by assessing the conditioned medium for the aforementioned markers, negating the need for tissue destructive assays. Physiologically relevant whole- or part-joint organ culture models, necessary for research and pre-clinical assessment of therapies, could be monitored this way, reducing the need to sacrifice tissues to determine viability, and hence reducing the sample numbers necessary.

Hydrogen Supplementation of Preservation Solution Improves Viability of Osteochondral Grafts

PubMed Central

Yamada, Takuya; Onuma, Kenji; Kuzuno, Jun; Ujihira, Masanobu; Kurokawa, Ryosuke; Sakai, Rina; Takaso, Masashi

2014-01-01

Allogenic osteochondral tissue (OCT) is used for the treatment of large cartilage defects. Typically, OCTs collected during the disease-screening period are preserved at 4°C; however, the gradual reduction in cell viability during cold preservation adversely affects transplantation outcomes. Therefore, improved storage methods that maintain the cell viability of OCTs are needed to increase the availability of high-quality OCTs and improve treatment outcomes. Here, we evaluated whether long-term hydrogen delivery to preservation solution improved the viability of rat OCTs during cold preservation. Hydrogen-supplemented Dulbecco's Modified Eagles Medium (DMEM) and University of Wisconsin (UW) solution both significantly improved the cell viability of OCTs during preservation at 4°C for 21 days compared to nonsupplemented media. However, the long-term cold preservation of OCTs in DMEM containing hydrogen was associated with the most optimal maintenance of chondrocytes with respect to viability and morphology. Our findings demonstrate that OCTs preserved in DMEM supplemented with hydrogen are a promising material for the repair of large cartilage defects in the clinical setting. PMID:25506061

Integrating biologically inspired nanomaterials and table-top stereolithography for 3D printed biomimetic osteochondral scaffolds

NASA Astrophysics Data System (ADS)

Castro, Nathan J.; O'Brien, Joseph; Zhang, Lijie Grace

2015-08-01

The osteochondral interface of an arthritic joint is notoriously difficult to regenerate due to its extremely poor regenerative capacity and complex stratified architecture. Native osteochondral tissue extracellular matrix is composed of numerous nanoscale organic and inorganic constituents. Although various tissue engineering strategies exist in addressing osteochondral defects, limitations persist with regards to tissue scaffolding which exhibit biomimetic cues at the nano to micro scale. In an effort to address this, the current work focused on 3D printing biomimetic nanocomposite scaffolds for improved osteochondral tissue regeneration. For this purpose, two biologically-inspired nanomaterials have been synthesized consisting of (1) osteoconductive nanocrystalline hydroxyapatite (nHA) (primary inorganic component of bone) and (2) core-shell poly(lactic-co-glycolic) acid (PLGA) nanospheres encapsulated with chondrogenic transforming growth-factor β1 (TGF-β1) for sustained delivery. Then, a novel table-top stereolithography 3D printer and the nano-ink (i.e., nHA + nanosphere + hydrogel) were employed to fabricate a porous and highly interconnected osteochondral scaffold with hierarchical nano-to-micro structure and spatiotemporal bioactive factor gradients. Our results showed that human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation were greatly improved in the biomimetic graded 3D printed osteochondral construct in vitro. The current work served to illustrate the efficacy of the nano-ink and current 3D printing technology for efficient fabrication of a novel nanocomposite hydrogel scaffold. In addition, tissue-specific growth factors illustrated a synergistic effect leading to increased cell adhesion and directed stem cell differentiation.

Sol gel-derived hydroxyapatite films over porous calcium polyphosphate substrates for improved tissue engineering of osteochondral-like constructs.

PubMed

Lee, Whitaik David; Gawri, Rahul; Pilliar, Robert M; Stanford, William L; Kandel, Rita A

2017-10-15

Integration of in vitro-formed cartilage on a suitable substrate to form tissue-engineered implants for osteochondral defect repair is a considerable challenge. In healthy cartilage, a zone of calcified cartilage (ZCC) acts as an intermediary for mechanical force transfer from soft to hard tissue, as well as an effective interlocking structure to better resist interfacial shear forces. We have developed biphasic constructs that consist of scaffold-free cartilage tissue grown in vitro on, and interdigitated with, porous calcium polyphosphate (CPP) substrates. However, as CPP degrades, it releases inorganic polyphosphates (polyP) that can inhibit local mineralization, thereby preventing the formation of a ZCC at the interface. Thus, we hypothesize that coating CPP substrate with a layer of hydroxyapatite (HA) might prevent or limit this polyP release. To investigate this we tested both inorganic or organic sol-gel processing methods, asa barrier coating on CPP substrate to inhibit polyP release. Both types of coating supported the formation of ZCC in direct contact with the substrate, however the ZCC appeared more continuous in the tissue formed on the organic HA sol gel coated CPP. Tissues formed on coated substrates accumulated comparable quantities of extracellular matrix and mineral, but tissues formed on organic sol-gel (OSG)-coated substrates accumulated less polyP than tissues formed on inorganic sol-gel (ISG)-coated substrates. Constructs formed with OSG-coated CPP substrates had greater interfacial shear strength than those formed with ISG-coated and non-coated substrates. These results suggest that the OSG coating method can modify the location and distribution of ZCC and can be used to improve the mechanical integrity of tissue-engineered constructs formed on porous CPP substrates. Articular cartilage interfaces with bone through a zone of calcified cartilage. This study describes a method to generate an "osteochondral-like" implant that mimics this

Plant grafting: insights into tissue regeneration.

PubMed

Melnyk, Charles W

2017-02-01

For millennia, people have cut and joined different plants together through a process known as grafting. The severed tissues adhere, the cells divide and the vasculature differentiates through a remarkable process of regeneration between two genetically distinct organisms as they become one. Grafting is becoming increasingly important in horticulture where it provides an efficient means for asexual propagation. Grafting also combines desirable roots and shoots to generate chimeras that are more vigorous, more pathogen resistant and more abiotic stress resistant. Thus, it presents an elegant and efficient way to improve plant productivity in vegetables and trees using traditional techniques. Despite this horticultural importance, we are only beginning to understand how plants regenerate tissues at the graft junction. By understanding grafting better, we can shed light on fundamental regeneration pathways and the basis for self/non-self recognition. We can also better understand why many plants efficiently graft whereas others cannot, with the goal of improving grafting so as to broaden the range of grafted plants to create even more desirable chimeras. Here, I review the latest findings describing how plants graft and provide insight into future directions in this emerging field.

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

Toward a patient-specific tissue engineered vascular graft

PubMed Central

Best, Cameron; Strouse, Robert; Hor, Kan; Pepper, Victoria; Tipton, Amy; Kelly, John; Shinoka, Toshiharu; Breuer, Christopher

2018-01-01

Integrating three-dimensional printing with the creation of tissue-engineered vascular grafts could provide a readily available, patient-specific, autologous tissue source that could significantly improve outcomes in newborns with congenital heart disease. Here, we present the recent case of a candidate for our tissue-engineered vascular graft clinical trial deemed ineligible due to complex anatomical requirements and consider the application of three-dimensional printing technologies for a patient-specific graft. We 3D-printed a closed-disposable seeding device and validated that it performed equivalently to the traditional open seeding technique using ovine bone marrow–derived mononuclear cells. Next, our candidate’s preoperative imaging was reviewed to propose a patient-specific graft. A seeding apparatus was then designed to accommodate the custom graft and 3D-printed on a commodity fused deposition modeler. This exploratory feasibility study represents an important proof of concept advancing progress toward a rationally designed patient-specific tissue-engineered vascular graft for clinical application. PMID:29568478

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

Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering.

PubMed

Steinmetz, Neven J; Aisenbrey, Elizabeth A; Westbrook, Kristofer K; Qi, H Jerry; Bryant, Stephanie J

2015-07-01

A bioinspired multi-layer hydrogel was developed for the encapsulation of human mesenchymal stem cells (hMSCs) as a platform for osteochondral tissue engineering. The spatial presentation of biochemical cues, via incorporation of extracellular matrix analogs, and mechanical cues, via both hydrogel crosslink density and externally applied mechanical loads, were characterized in each layer. A simple sequential photopolymerization method was employed to form stable poly(ethylene glycol)-based hydrogels with a soft cartilage-like layer of chondroitin sulfate and low RGD concentrations, a stiff bone-like layer with high RGD concentrations, and an intermediate interfacial layer. Under a compressive load, the variation in hydrogel stiffness within each layer produced high strains in the soft cartilage-like layer, low strains in the stiff bone-like layer, and moderate strains in the interfacial layer. When hMSC-laden hydrogels were cultured statically in osteochondral differentiation media, the local biochemical and matrix stiffness cues were not sufficient to spatially guide hMSC differentiation after 21 days. However dynamic mechanical stimulation led to differentially high expression of collagens with collagen II in the cartilage-like layer, collagen X in the interfacial layer and collagen I in the bone-like layer and mineral deposits localized to the bone layer. Overall, these findings point to external mechanical stimulation as a potent regulator of hMSC differentiation toward osteochondral cellular phenotypes. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Development of tissue-engineered self-expandable aortic stent grafts (Bio stent grafts) using in-body tissue architecture technology in beagles.

PubMed

Kawajiri, Hidetake; Mizuno, Takeshi; Moriwaki, Takeshi; Ishibashi-Ueda, Hatsue; Yamanami, Masashi; Kanda, Keiichi; Yaku, Hitoshi; Nakayama, Yasuhide

2015-02-01

In this study, we aimed to describe the development of tissue-engineered self-expandable aortic stent grafts (Bio stent graft) using in-body tissue architecture technology in beagles and to determine its mechanical and histological properties. The preparation mold was assembled by insertion of an acryl rod (outer diameter, 8.6 mm; length, 40 mm) into a self-expanding nitinol stent (internal diameter, 9.0 mm; length, 35 mm). The molds (n = 6) were embedded into the subcutaneous pouches of three beagles for 4 weeks. After harvesting and removing each rod, the excessive fragile tissue connected around the molds was trimmed, and thus tubular autologous connective tissues with the stent were obtained for use as Bio stent grafts (outer diameter, approximately 9.3 mm in all molds). The stent strut was completely surrounded by the dense collagenous membrane (thickness, ∼150 µm). The Bio stent graft luminal surface was extremely flat and smooth. The graft wall of the Bio stent graft possessed an elastic modulus that was almost two times higher than that of the native beagle abdominal aorta. This Bio stent graft is expected to exhibit excellent biocompatibility after being implanted in the aorta, which may reduce the risk of type 1 endoleaks or migration. © 2014 Wiley Periodicals, Inc.

Hard tissue remodeling using biofabricated coralline biomaterials.

PubMed

Vago, Razi; Plotquin, Daniel; Bunin, Alex; Sinelnikov, Igor; Atar, Dan; Itzhak, David

2002-01-04

Biotechnical and biomedical approaches were combined in an attempt to identify potential uses of biofabricated marine carbonate materials in biomedical applications, particularly as biomatrices for remodeling bone and cartilage tissue. After grafting, it is desirable for bone ingrowth to proceed as quickly as possible because the strength of the implanted region depends on a good mechanical bond forming between the implant and surrounding regions in the body. Ingrowth can take place as a result of growth of tissue and cells into the implanted porous material, or it may be promoted by transplanting cells seeded onto such a material. The rate at which ingrowth occurs is dependent on many factors, including pore size and the interconnectivity of the implanted structure. In vivo graftings into osteochondral defects demonstrated that our biofabricated porous material is highly biocompatible with cartilage and bone tissue. The biofabricated matrix was well incorporated into the biphasic osteochondral area. Resorption was followed by bone and cartilage formation, and after 4 months, the biomaterial had been replaced by new tissue. Ossification was induced and enhanced without introduction of additional factors. We believe that this is the first time that such biofabricated materials have been used for biomedical purposes. In face of the obvious environmental disadvantages of harvesting from limited natural resources, we propose the use of bioengineered coralline and other materials such as those cultured by our group under field and laboratory conditions as a possible biomatrix for hard tissue remodeling.

Osteochondral graft from the pre-achilles area for replacement of articular surface defects

NASA Astrophysics Data System (ADS)

Kuznetsov, V. V.; Pahomov, I. A.; Prohorenko, V. M.; Sadovoy, M. A.; Korel, A. V.; Zaydman, A. M.; Repin, A. V.; Gudi, S. M.; Korochkin, S. B.

2017-09-01

We substantiate a new technique for obtaining osteochondral autograft to replace osteochondral defects resulting from various lesions of the talar trochlea by means of morphological examination of the following microslides: talar cartilage (cadaver material), cartilage portion of the pre-achilles zone of the calcaneum, lateral femoral condyle, and necrotic area of the talus. Examination of the specimens of the pre-achilles cartilage of the calcaneus revealed a large number of poorly differentiated chondroblasts in the homogeneously stained extracellular matrix; the presence of all zones (superficial zone, zone of columnar structures, and "tidemark"). This is indicative of structural and functional preservation of this cartilage, which therefore can be considered as an autograft material.

Tissue-engineered lymphatic graft for the treatment of lymphedema

PubMed Central

Kanapathy, Muholan; Patel, Nikhil M.; Kalaskar, Deepak M.; Mosahebi, Afshin; Mehrara, Babak J.; Seifalian, Alexander M.

2015-01-01

Background Lymphedema is a chronic debilitating condition and curative treatment is yet to be found. Tissue engineering approach, which combines cellular components, scaffold, and molecular signals hold great potential in the treatment of secondary lymphedema with the advent of lymphatic graft to reconstruct damaged collecting lymphatic vessel. This review highlights the ideal characteristics of lymphatic graft, the limitation and challenges faced, and the approaches in developing tissue-engineered lymphatic graft. Methods Literature on tissue engineering of lymphatic system and lymphatic tissue biology was reviewed. Results The prime challenge in the design and manufacturing of this graft is producing endothelialized conduit with intraluminal valves. Suitable scaffold material is needed to ensure stability and functionality of the construct. Endothelialization of the construct can be enhanced via biofunctionalization and nanotopography, which mimics extracellular matrix. Nanocomposite polymers with improved performance over existing biomaterials are likely to benefit the development of lymphatic graft. Conclusions With the in-depth understanding of tissue engineering, nanotechnology, and improved knowledge on the biology of lymphatic regeneration, the aspiration to develop successful lymphatic graft is well achievable. PMID:25248852

Regulation of decellularized tissue remodeling via scaffold-mediated lentiviral delivery in anatomically-shaped osteochondral constructs.

PubMed

Rowland, Christopher R; Glass, Katherine A; Ettyreddy, Adarsh R; Gloss, Catherine C; Matthews, Jared R L; Huynh, Nguyen P T; Guilak, Farshid

2018-05-30

Cartilage-derived matrix (CDM) has emerged as a promising scaffold material for tissue engineering of cartilage and bone due to its native chondroinductive capacity and its ability to support endochondral ossification. Because it consists of native tissue, CDM can undergo cellular remodeling, which can promote integration with host tissue and enables it to be degraded and replaced by neotissue over time. However, enzymatic degradation of decellularized tissues can occur unpredictably and may not allow sufficient time for mechanically competent tissue to form, especially in the harsh inflammatory environment of a diseased joint. The goal of the current study was to engineer cartilage and bone constructs with the ability to inhibit aberrant inflammatory processes caused by the cytokine interleukin-1 (IL-1), through scaffold-mediated delivery of lentiviral particles containing a doxycycline-inducible IL-1 receptor antagonist (IL-1Ra) transgene on anatomically-shaped CDM constructs. Additionally, scaffold-mediated lentiviral gene delivery was used to facilitate spatial organization of simultaneous chondrogenic and osteogenic differentiation via site-specific transduction of a single mesenchymal stem cell (MSC) population to overexpress either chondrogenic, transforming growth factor-beta 3 (TGF-β3), or osteogenic, bone morphogenetic protein-2 (BMP-2), transgenes. Controlled induction of IL-1Ra expression protected CDM hemispheres from inflammation-mediated degradation, and supported robust bone and cartilage tissue formation even in the presence of IL-1. In the absence of inflammatory stimuli, controlled cellular remodeling was exploited as a mechanism for fusing concentric CDM hemispheres overexpressing BMP-2 and TGF-β3 into a single bi-layered osteochondral construct. Our findings demonstrate that site-specific delivery of inducible and tunable transgenes confers spatial and temporal control over both CDM scaffold remodeling and neotissue composition. Furthermore

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.

Lesion Size Does Not Predict Outcomes in Fresh Osteochondral Allograft Transplantation.

PubMed

Tírico, Luis E P; McCauley, Julie C; Pulido, Pamela A; Bugbee, William D

2018-03-01

Cartilage repair algorithms use lesion size to choose surgical techniques when selecting a cartilage repair procedure. The association of fresh osteochondral allograft (OCA) size with graft survivorship and subjective patient outcomes is still unknown. To determine if lesion size (absolute or relative) affects outcomes after OCA transplantation. Cohort study; Level of evidence, 3. The study included 156 knees in 143 patients who underwent OCA transplantation from 1998 to 2014 for isolated femoral condyle lesions. The mean age was 29.6 ± 11.4 years, and 62.9% were male. The majority of patients (62.2%) presented for cartilage repair because of osteochondritis dissecans. The mean graft area, used as a surrogate for absolute size of the lesion, was 6.4 cm 2 (range, 2.3-11.5 cm 2 ). The relative size of the lesion was calculated as the tibial width ratio (TWR; ratio of graft area to tibial width) and affected femoral condyle ratio (AFCR; ratio of graft area to affected femoral condyle width) using preoperative radiographs. All patients had a minimum follow-up of 2 years. Further surgical procedures were documented, and graft failure was defined as revision OCA transplantation or conversion to arthroplasty. International Knee Documentation Committee (IKDC) pain, function, and total scores were obtained. Satisfaction with OCA transplantation was assessed. The mean follow-up among patients with grafts remaining in situ was 6.0 years (range, 1.9-16.5 years). The OCA failure rate was 5.8%. Overall survivorship of the graft was 97.2% at 5 years and 93.5% at 10 years. No difference in postoperative outcomes between groups was found in absolute or relative size. Change in IKDC scores (from preoperative to latest follow-up) was greater for knees with large lesions compared to knees with small lesions, among all measurement methods. Overall satisfaction with the results of OCA transplantation was 89.8%. The size of the lesion, either absolute or relative, does not influence

Chitosan-Based Bilayer Hydroxyapatite Nanorod Composite Scaffolds for Osteochondral Regeneration

NASA Astrophysics Data System (ADS)

Swanson, Shawn

Osteochondral defects involve injury to bone and cartilage. As articular cartilage is worn down, bone in the joint begins to rub together, causing bone spurs. This is known as osteoarthritis, and is a common issue among the aging population. This problem presents an interesting opportunity for tissue engineering. Tissue engineering is an approach to treatment of tissue defects where synthetic, three dimensional (3-D) scaffolds are implanted in a defect to facilitate healing. The osteochondral scaffold consists of two regions in the form of a bilayer scaffold- one to mimic bone with osteoconductive properties, and one to mimic cartilage with biomimetic properties. One approach to improving the osteoconductivity of tissue engineering scaffolds is the addition of hydroxyapatite (HAp), the main mineral phase in bone. HAp with nanorod morphology is desirable because it is biomimetic for the calcium phosphate found in bone. Incorporating HAp nanorods in bone tissue engineering scaffolds to form a composite material may increase scaffold osteoconductivity. The cartilage scaffold is fabricated from chitosan and hyaluronic acid (HA). HA is a known component of cartilage and thus is biomimetic. The bilayer scaffolds were seeded with osteoblast-like MG-63 cells to investigate cell migration and were evaluated with Alamar Blue proliferation assay. The cells successfully migrated to the bone region of the scaffold, indicating that the bilayer scaffold provides a promising osteochondral scaffold.

[Tissue engineering applied to the trachea as a graft].

PubMed

Barrera-Ramírez, Elisa; Rico-Escobar, Edna; Garrido-Cardona, Rubén E

2016-01-01

Tissue engineering offers, through new technologies, an ex vivo generation of organs and functional tissues as grafts for transplants, for the improvement and substitution of biological functions, with an absence of immunological response. The treatment of extended tracheal lesions is a substitution of the affected segment; nevertheless, the allogeneic transplant has failed and the use of synthetic materials has not had good results. New tissue engineering technology is being developed to offer a tracheal graft for a posterior implantation. The purpose of this article is to review all the methods and components used by the engineering of tissue for tracheal grafts.

The versatile subepithelial connective tissue graft: a literature update.

PubMed

Karthikeyan, B V; Khanna, Divya; Chowdhary, Kamedh Yashawant; Prabhuji, M Lv

2016-01-01

Harmony between hard and soft tissue morphologies is essential for form, function, and a good esthetic outlook. Replacement grafts for correction of soft tissue defects around the teeth have become important to periodontal plastic and implant surgical procedures. Among a multitude of surgical techniques and graft materials reported in literature, the subepithelial connective tissue graft (SCTG) has gained wide popularity and acceptance. The purpose of this article is to acquaint clinicians with the current understanding of the versatile SCTG. Key factors associated with graft harvesting as well as applications, limitations, and complications of SCTGs are discussed. This connective tissue has shown excellent short- and long-term stability, is easily available, and is economical to use. The SCTG should be considered as an alternative in all periodontal reconstruction surgeries.

Graft survival of diabetic versus nondiabetic donor tissue after initial keratoplasty.

PubMed

Vislisel, Jesse M; Liaboe, Chase A; Wagoner, Michael D; Goins, Kenneth M; Sutphin, John E; Schmidt, Gregory A; Zimmerman, M Bridget; Greiner, Mark A

2015-04-01

To compare corneal graft survival using tissue from diabetic and nondiabetic donors in patients undergoing initial Descemet stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty (PKP). A retrospective chart review of pseudophakic eyes that underwent DSAEK or PKP was performed. The primary outcome measure was graft failure. Cox proportional hazard regression and Kaplan-Meier survival analyses were used to compare diabetic versus nondiabetic donor tissue for all keratoplasty cases. A total of 183 eyes (136 DSAEK, 47 PKP) were included in the statistical analysis. Among 24 procedures performed using diabetic donor tissue, there were 4 cases (16.7%) of graft failure (3 DSAEK, 1 PKP), and among 159 procedures performed using nondiabetic donor tissue, there were 18 cases (11.3%) of graft failure (12 DSAEK, 6 PKP). Cox proportional hazard ratio of graft failure for all cases comparing diabetic with nondiabetic donor tissue was 1.69, but this difference was not statistically significant (95% confidence interval, 0.56-5.06; P = 0.348). There were no significant differences in Kaplan-Meier curves comparing diabetic with nondiabetic donor tissue for all cases (P = 0.380). Statistical analysis of graft failure by donor diabetes status within each procedure type was not possible because of the small number of graft failure events involving diabetic tissue. We found similar rates of graft failure in all keratoplasty cases when comparing tissue from diabetic and nondiabetic donors, but further investigation is needed to determine whether diabetic donor tissue results in different graft failure rates after DSAEK compared with PKP.

The use of embryonic cells in the treatment of osteochondral defects of the knee: an ovine in vivo study.

PubMed

Manunta, Andrea Fabio; Zedde, Pietro; Pilicchi, Susanna; Rocca, Stefano; Pool, Roy R; Dattena, Maria; Masala, Gerolamo; Mara, Laura; Casu, Sara; Sanna, Daniela; Manunta, Maria Lucia; Passino, Eraldo Sanna

2016-01-01

the aim of this study was to determine whether local delivery of embryonic stem-like (ESL) cells into osteochondral defects in the femoral condyles of sheep would enhance regeneration of hyaline articular cartilage. male ESL cells embedded in fibrin glue were engrafted into osteochondral defects in the medial condyles (ESL-M) of the left femur in 22 ewes. An identical defect was created in the medial condyle of the contralateral stifle joint and left untreated as a control (empty defect, ED). The ewes were divided into 5 groups. Four sheep each were euthanized at 1, 2, 6, and 12 months from surgery, and 6 ewes were euthanized 24 months post-implantation. To study the effect of varying loads on the long-term regeneration process, an identical defect was also created and ESL cell engraftment performed in the lateral condyle (ESL-L) of the left stifle joint of the animals in the 12- and 24-month groups. The evaluation of regenerated tissue was performed by biomechanical, macroscopic, histological, immunohistochemical (collagen type II) and fluorescent in situ hybridization (FISH) assays. no significant differences were found between treated and control sites in the biomechanical assays at any time point. ESL cell grafts showed significantly greater macroscopic evidence of regeneration as compared to controls at 24 months after surgery; significantly better histological evidence of repair in ESL-M samples versus controls was found throughout the considered period. At 24 months from surgery there was significantly improved integration of graft edges with the host tissue in the ESL-M as compared to the ESL-L samples, demonstrating that load bearing positively affects the long-term regeneration process. ESL cells enhanced the regeneration of hyaline cartilage. FISH confirmed that the regenerative tissue originated from ESL cells. ESL cells are able to self-renew for prolonged periods without differentiation and, most importantly, to differentiate into a large variety of

The use of embryonic cells in the treatment of osteochondral defects of the knee: an ovine in vivo study

PubMed Central

MANUNTA, ANDREA FABIO; ZEDDE, PIETRO; PILICCHI, SUSANNA; ROCCA, STEFANO; POOL, ROY R.; DATTENA, MARIA; MASALA, GEROLAMO; MARA, LAURA; CASU, SARA; SANNA, DANIELA; MANUNTA, MARIA LUCIA; PASSINO, ERALDO SANNA

2016-01-01

Purpose the aim of this study was to determine whether local delivery of embryonic stem-like (ESL) cells into osteochondral defects in the femoral condyles of sheep would enhance regeneration of hyaline articular cartilage. Methods male ESL cells embedded in fibrin glue were engrafted into osteochondral defects in the medial condyles (ESL-M) of the left femur in 22 ewes. An identical defect was created in the medial condyle of the contralateral stifle joint and left untreated as a control (empty defect, ED). The ewes were divided into 5 groups. Four sheep each were euthanized at 1, 2, 6, and 12 months from surgery, and 6 ewes were euthanized 24 months post-implantation. To study the effect of varying loads on the long-term regeneration process, an identical defect was also created and ESL cell engraftment performed in the lateral condyle (ESL-L) of the left stifle joint of the animals in the 12- and 24-month groups. The evaluation of regenerated tissue was performed by biomechanical, macroscopic, histological, immunohistochemical (collagen type II) and fluorescent in situ hybridization (FISH) assays. Results no significant differences were found between treated and control sites in the biomechanical assays at any time point. ESL cell grafts showed significantly greater macroscopic evidence of regeneration as compared to controls at 24 months after surgery; significantly better histological evidence of repair in ESL-M samples versus controls was found throughout the considered period. At 24 months from surgery there was significantly improved integration of graft edges with the host tissue in the ESL-M as compared to the ESL-L samples, demonstrating that load bearing positively affects the long-term regeneration process. Conclusions ESL cells enhanced the regeneration of hyaline cartilage. FISH confirmed that the regenerative tissue originated from ESL cells. Clinical Relevance ESL cells are able to self-renew for prolonged periods without differentiation and, most

Arthroscopic Surgical Technique for an Acute Talar Dome Osteochondral Lesion in a Professional Rugby League Player.

PubMed

Sullivan, Martin; Fraser, Ethan J; Linklater, James; Harris, Craig; Morgan, Kieran

2017-06-01

Talar osteochondral lesions represent challenging clinical entities, particularly in high-demand athletes. Surgical treatment of large lesions often requires a 2-step procedure, or the use of osteotomy in the case of autologous osteochondral transfer, which can delay return to sport. A professional rugby league player underwent surgery for a complex injury to the ankle. A talar osteochondral lesion with a maximal diameter of 15 mm was treated in an arthroscopic fashion using the cartilage taken from the completely displaced osteochondral fragment. Cartilage was cut into chips and combined with bone graft product containing platelet-derived growth factor and a porous collagen scaffold. Autologous cartilage was then reimplanted arthroscopically. The patient was allowed full ankle motion from 2 weeks postoperatively, and weightbearing was commenced at 6 weeks. Follow-up imaging and functional outcomes, including return to sport, were assessed at regular intervals. The patient was able to return to professional rugby league by 23 weeks postoperatively. Magnetic resonance imaging at 16 months postoperatively showed restoration of the subchondral plate and osseous infill. At final follow-up, the patient remained pain free and was playing at preinjury level. This report describes good outcomes using a novel, 1-step cartilage repair technique to treat a large talar osteochondral lesion in a professional athlete. Level V: Expert opinion.

Studies in fat grafting: Part III. Fat grafting irradiated tissue--improved skin quality and decreased fat graft retention.

PubMed

Garza, Rebecca M; Paik, Kevin J; Chung, Michael T; Duscher, Dominik; Gurtner, Geoffrey C; Longaker, Michael T; Wan, Derrick C

2014-08-01

Following radiation therapy, skin becomes fibrotic and can present a difficult problem for reconstructive surgeons. There is an increasing belief that fat grafting under irradiated skin can reverse the damage caused by radiation. The present study evaluated the effect of fat grafting on irradiated skin, along with fat graft quality and retention rates in irradiated tissue. Nine adult Crl:NU-Foxn1 CD-1 mice underwent 30-Gy external beam irradiation of the scalp. Four weeks after irradiation, scalp skin from irradiated and nonirradiated mice was harvested and compared histologically for dermal thickness, collagen content, and vascular density. Human fat grafts were then injected in the subcutaneous plane of the scalp. Skin assessment was performed in the irradiated group at 2 and 8 weeks after grafting, and fat graft retention was measured at baseline and every 2 weeks up to 8 weeks after grafting using micro-computed tomography. Finally, fat graft samples were explanted at 8 weeks, and quality scoring was performed. Fat grafting resulted in decreased dermal thickness, decreased collagen content, and increased vascular density in irradiated skin. Computed tomographic analysis revealed significantly decreased fat graft survival in the irradiated group compared with the nonirradiated group. Histologic scoring of explanted fat grafts demonstrated no difference in quality between the irradiated and nonirradiated groups. Fat grafting attenuates dermal collagen deposition and vessel depletion characteristic of radiation fibrosis. Although fat graft retention rates are significantly lower in irradiated than in nonirradiated tissue, the quality of retained fat between the groups is similar.

[Osteochondral lesions of the talar dome: surgical treatment in a series of 30 cases].

PubMed

Jarde, O; Trinquier-Lautard, J L; Garate, F; de Lestang, M; Vives, P

2000-10-01

We reviewed 30 cases of osteochondral lesions of the astragalar vault treated surgically. Among the 30 patients, 17 participated in sports activities and 24 had a history of trauma. Mean delay to surgery was 10 months. Treatment included osteochondritis curettage and Pridie perforations. Direct access was used in 11 cases, malleolar osteotomy in 13 and arthroscopy in 6. Cancellous bone grafts were used in 6 cases. Mean follow-up was 3 years 7 months (minimum 2 years). All patients had an arthroscan at last follow-up. Evaluation of post-operative outcome was based on clinical assessment and arthroscan findings. Surgical treatment provided very good results in 75 p. 100 of cases with pain relief and improved walking distance. Our cases pointed out the important contribution of the FOG (Fracture Osteonecrosis Geode) classification to pathogenic and prognostic analysis. The Berndt and Harty classifications were not found to be useful. In case of localized necrosis, we propose arthroscopic perforation curettage. In case of bone loss, a direct cancellous graft may be used.

Comprehensive analysis of translational osteochondral repair: Focus on the histological assessment.

PubMed

Orth, Patrick; Peifer, Carolin; Goebel, Lars; Cucchiarini, Magali; Madry, Henning

2015-10-01

Articular cartilage guarantees for an optimal functioning of diarthrodial joints by providing a gliding surface for smooth articulation, weight distribution, and shock absorbing while the subchondral bone plays a crucial role in its biomechanical and nutritive support. Both tissues together form the osteochondral unit. The structural assessment of the osteochondral unit is now considered the key standard procedure for evaluating articular cartilage repair in translational animal models. The aim of this review is to give a detailed overview of the different methods for a comprehensive evaluation of osteochondral repair. The main focus is on the histological assessment as the gold standard, together with immunohistochemistry, and polarized light microscopy. Additionally, standards of macroscopic, non-destructive imaging such as high resolution MRI and micro-CT, biochemical, and molecular biological evaluations are addressed. Potential pitfalls of analysis are outlined. A second focus is to suggest recommendations for osteochondral evaluation. Copyright © 2015 Elsevier GmbH. All rights reserved.

Biological Response of Osteoblastic and Chondrogenic Cells to Graphene-Containing PCL/Bioactive Glass Bilayered Scaffolds for Osteochondral Tissue Engineering Applications.

PubMed

Deliormanlı, Aylin M; Atmaca, Harika

2018-05-25

Graphene-containing 13-93 bioactive glass and poly(ε-caprolactone)-based bilayer, electrically conductive scaffolds were prepared for osteochondral tissue repair. Biological response of osteoblastic MC3T3-E1 and chondrogenic ATDC5 cells to the composite scaffolds was assessed under mono-culture and co-culture conditions. Cytotoxicity was investigated using MTT assay, cartilage matrix production was evaluated by Alcian blue staining, and mineralization of both types of cells in the different culture systems was observed by Alizarin red S staining. Results showed that osteoblastic and chondrogenic cells utilized in the study did not show toxic response to the prepared scaffolds under mono-culture conditions and higher cell viability rates were obtained in co-culture conditions. Larger mineralized areas were determined under co-culture conditions and calcium deposition amount significantly increased compared with that in control group samples after 21 days. Additionally, the amount of glycosaminoglycans synthesized in co-culture was higher compared to mono-culture conditions. Electric stimulation applied under mono-culture conditions suppressed the viability of MC3T3-E1 cells whereas it enhanced the viability rates of ATDC5 cells. The study suggests that the designed bilayered osteochondral constructs have the potential for osteochondral defect repair.

Qualitative assessment of connective tissue graft with epithelial component. A microsurgical periodontal plastic surgical technique for soft tissue esthetics.

PubMed

Rossi, Roberto; Pilloni, Andrea; Morales, Regina Santos

2009-01-01

Connective tissue grafts have been used successfully in the treatment of gingival recession. In the mid 80s and late 90s, the periodontal literature presented various techniques such as free gingival grafts, pedicle flaps, subepithelial connective tissue grafts, acellular dermal matrix grafts, and guided tissue regeneration to cover denuded root surfaces. Currently, connective tissue grafting is a reliable treatment for esthetic root coverage. This paper presents a qualitative assessment of a surgical technique that uses a connective tissue graft, including a portion of epithelium in the shape of the defect. This procedure enhances the healing of the covered root surface, increases the thickness of the soft tissue and improves esthetics. The criteria used for evaluation were: color, volume, texture, and blending. This evaluation demonstrated encouraging results from an esthetic viewpoint.

The Long-Term Clinical Outcomes Following Autogenous Bone Grafting for Large-Volume Defects of the Knee

PubMed Central

Delano, Mark; Spector, Myron; Pittsley, Andrew; Gottschalk, Alexander

2014-01-01

Objective: We report the long-term clinical outcomes of patients who underwent autogenous bone grafting of large-volume osteochondral defects of the knee due to osteochondritis dessicans (OCD) and osteonecrosis (ON). This is the companion report to one previous published on the biological response. We hypothesized that these grafts would integrate with host bone and the articular surface would form fibrocartilage providing an enduring clinical benefit. Design: Three groups (patients/knees) were studied: OCD without a fragment (n = 12/13), OCD with a partial fragment (n = 14/16), and ON (n = 25/26). Twenty-five of 52 patients were available for clinical follow-up between 12 and 21 years. Electronic medical records provided comparison clinical information. In addition, there were plain film radiographs, MRIs, plus repeat arthroscopy and biopsy on 14 patients. Results: Autogenous bone grafts integrated with the host bone. MRI showed soft tissue covering all the grafts at long-term follow-up. Biopsy showed initial surface fibrocartilage that subsequently converted to fibrocartilage and hyaline cartilage at 20 years. OCD patients had better clinical outcomes than ON patients. No OCD patients were asymptomatic at anytime following surgery. Half of the ON patients came to total knee replacement within 10 years. Conclusions: Autogenous bone grafting provides an alternative biological matrix to fill large-volume defects in the knee as a singular solution integrating with host bone and providing an enduring articular cartilage surface. The procedure is best suited for those with OCD. The treatment for large-volume articular defects by this method remains salvage in nature and palliative in outcome. PMID:26069688

Evaluation of a press-fit osteochondral poly(ester-urethane) scaffold in a rabbit defect model.

PubMed

Dresing, Iska; Zeiter, Stephan; Auer, Jörg; Alini, Mauro; Eglin, David

2014-07-01

The purpose of this study was to evaluate the impact on osteochondral healing of press-fitted multiphasic osteochondral scaffolds consisting of poly(ester-urethane) (PUR) and hydroxyapatite into a cylindric osteochondral defect in the distal non-weight bearing femoral trochlear ridge of the rabbit. Two scaffolds were investigated, one with and one without an intermediate microporous membrane between the cartilage and the bone compartment of the scaffold. A control group without a scaffold placed into the defect was included. After 12 weeks macroscopic and histomorphological analyses were performed. The scaffold was easily press-fitted and provided a stable matrix for tissue repair. The membrane did not demonstrate a detrimental effect on tissue healing compared with the scaffold without membrane. However, the control group had statistically superior healing as reflected by histological differences in the cartilage and subchondral bone compartment between control group and each scaffold group. A more detailed analysis revealed that the difference was localized in the bone compartment healing. The present study demonstrates that an elastomeric PUR scaffold can easily be press-fitted into an osteochondral defect and provides a stable matrix for tissue repair. However, the multi-phasic scaffold did not provide a clear advantage for tissue healing. Future investigations should refine especially the bone phase of the implant to increase its stiffness, biocompatibility and osteoconductive activity. A more precise fabrication technique would be necessary for the matching of tissue organisation.

Enhancement of healing in osteochondral defects by collagen sponge implants.

PubMed

Speer, D P; Chvapil, M; Volz, R G; Holmes, M D

1979-10-01

Implants of porous, highly cross-linked collagen sponge (CS) were tested for their capacity to enhance the healing of osteochondral defects in rabbits. Comparison was made to the healing of similar defects with polyvinyl alcohol sponge (PVAS) implants and with no implants (CONT). Evaluation was carried out up to 44 weeks following implantation and included observation of host cellular response, biodegradability of implant, gross appearance of restored joint surface, collagenous architecture of repair tissue, and properties of the junctions of implants and host articular cartilage, subchondral bone, and medullary bone. Collagen sponge proved most effective in promoting healing of osteochondral defects with fibrous and fibrocartilaginous tissue over restored subchondral bone. Collagen sponge showed many desirable properties as a potential material for biologic resurfacing of damaged joints. These properties included porosity, biodegradability, biocompatability, ability to mechanically protect cells and matrix while directing cell ingrowth, and an available chemical technology for modifying its biomechanical and biological properties. Comparative analysis of results of healing of CS, PVAS, and CONT osteochondral defects suggest rational design criteria for implant materials to improve their effectiveness in restoration of articular surfaces.

Use of a porcine collagen matrix as an alternative to autogenous tissue for grafting oral soft tissue defects.

PubMed

Herford, Alan S; Akin, Lee; Cicciu, Marco; Maiorana, Carlo; Boyne, Philip J

2010-07-01

Soft tissue grafting is often required to correct intraoral mucosal deficiencies. Autogenous grafts have disadvantages including an additional harvest site with its associated pain and morbidity and, sometimes, poor quality and limited amount of the graft. Porcine collagen matrices have the potential to be helpful for grafting of soft tissue defects. Thirty consecutive patients underwent intraoral grafting to re-create missing soft tissue. Defects ranged in size from 50 to 900 mm(2). Porcine collagen matrices were used to reconstruct missing tissue. Indications included preprosthetic (22), followed by tumor removal (5), trauma (2), and release of cheek ankylosis (1). The primary efficacy parameters evaluated were the degree of lateral and/or alveolar extension and the evaluation of re-epithelialization and shrinkage of the grafted area. Overall, the percentage of shrinkage of the graft was 14% (range, 5%-20%). The amount of soft tissue extension averaged 3.4 mm (range, 2-10 mm). The secondary efficacy parameters included hemostatic effect, pain evaluation, pain and discomfort, and clinical evaluation of the grafted site. All patients reported minimal pain and swelling associated with the grafted area. No infections were noted. This porcine collagen matrix provides a biocompatible surgical material as an alternative to an autogenous transplant, thus obviating the need to harvest soft tissue autogenous grafts from other areas of the oral cavity. Copyright 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo.

PubMed

Mendes, L F; Katagiri, H; Tam, W L; Chai, Y C; Geris, L; Roberts, S J; Luyten, F P

2018-02-21

Chondrogenic mesenchymal stem cells (MSCs) have not yet been used to address the clinical demands of large osteochondral joint surface defects. In this study, self-assembling tissue intermediates (TIs) derived from human periosteum-derived stem/progenitor cells (hPDCs) were generated and validated for stable cartilage formation in vivo using two different animal models. hPDCs were aggregated and cultured in the presence of a novel growth factor (GF) cocktail comprising of transforming growth factor (TGF)-β1, bone morphogenetic protein (BMP)2, growth differentiation factor (GDF)5, BMP6, and fibroblast growth factor (FGF)2. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to study in vitro differentiation. Aggregates were then implanted ectopically in nude mice and orthotopically in critical-size osteochondral defects in nude rats and evaluated by microcomputed tomography (µCT) and immunohistochemistry. Gene expression analysis after 28 days of in vitro culture revealed the expression of early and late chondrogenic markers and a significant upregulation of NOGGIN as compared to human articular chondrocytes (hACs). Histological examination revealed a bilayered structure comprising of chondrocytes at different stages of maturity. Ectopically, TIs generated both bone and mineralized cartilage at 8 weeks after implantation. Osteochondral defects treated with TIs displayed glycosaminoglycan (GAG) production, type-II collagen, and lubricin expression. Immunostaining for human nuclei protein suggested that hPDCs contributed to both subchondral bone and articular cartilage repair. Our data indicate that in vitro derived osteochondral-like tissues can be generated from hPDCs, which are capable of producing bone and cartilage ectopically and behave orthotopically as osteochondral units.

Soft-Tissue Grafting Techniques Associated With Immediate Implant Placement.

PubMed

Bishara, Mark; Kurtzman, Gregori M; Khan, Waji; Choukroun, Joseph; Miron, Richard J

2018-02-01

Immediate implant placement often presents challenges in terms of predictably obtaining soft-tissue coverage over the implant site. While delayed implant placement offers the ability for soft tissues to grow and invade the extraction socket making their attachment around implants more predictable, immediate implant placement poses a significant risk of bacterial invasion towards the implant surface as a result of insignificant soft-tissue volume. Soft-tissue grafting techniques have often been proposed for use during immediate implant placement to augment soft-tissue deficiencies, including the use of either palatal connective tissue grafts (CTGs) or collagen-derived scaffolds. However, both of these approaches have significant drawbacks in that CTGs are harvested with high patient morbidity and collagen scaffolds remain avascular and acelluar posing a risk of infection/implant contamination. More recently, platelet-rich fibrin (PRF) has been proposed as an economical and biological means to speed soft-tissue wound healing. In combination with immediate implant placement, PRF offers an easily procurable low-cost regenerative modality that offers an efficient way to improve soft-tissue attachment around implants. Furthermore, the supra-physiological concentration of defense-fighting leukocytes in PRF, combined with a dense fibrin meshwork, is known to prevent early bacterial contamination of implant surfaces, and the biological concentrations of autologous growth factors in PRF is known to increase tissue regeneration. This article discusses soft-tissue grafting techniques associated with immediate implant placement, presents several cases demonstrating the use of PRF in routine immediate implant placement, and further discusses the biological and economic advantages of PRF for the management of soft-tissue grafting during immediate implant placement.

A Novel Esthetic Approach using Connective Tissue Graft for Soft Tissue Defect Following Surgical Excision of Gingival Fibrolipoma

PubMed Central

Parthasarathy, Harinath; Kumar, Praveenkrishna; Gajendran, Priyalochana; Appukuttan, Devapriya

2014-01-01

The aim of the present case report is to evaluate the adjunctive use of a connective tissue graft to overcome soft tissue defects following excision of a gingival fibrolipoma in the aesthetic region. Connective tissue graft has been well documented for treating defects of esthetic concern. However, the literature does not contain many reports on the esthetic clinical outcome following the use of connective tissue graft secondary to excision of soft tissue tumours. A 28-year-old male patient reported with a complaint of a recurrent growth in relation to his lower front tooth region. The lesion which was provisionally diagnosed as fibroma was treated with a complete surgical excision, following which a modified coronally advanced flap and connective tissue graft was adopted to overcome the soft tissue defect. The excised growth was diagnosed histologically as fibrolipoma. One year follow up showed no recurrence of the lesion and good esthetics.The adjunctive use of the connective tissue graft and modified coronally advanced flap predictably yields optimal soft tissue fill and excellent esthetics. Hence, routine use of this procedure may be recommended for surgical excision of soft tissue growths in esthetically sensitive areas. PMID:25584336

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

Construction of osteochondral-like tissue graft combining β-tricalcium phosphate block and scaffold-free centrifuged chondrocyte cell sheet.

PubMed

Niyama, Kouhei; Ide, Naoto; Onoue, Kaori; Okabe, Takahiro; Wakitani, Shigeyuki; Takagi, Mutsumi

2011-09-01

The combination of a β-tricalcium phosphate (βTCP) block with a scaffold-free chondrocyte sheet formed by the centrifugation of chondrocytes in a well was investigated with the aim of constructing an osteochondral-like structure. Human and porcine articular cartilage chondrocytes were respectively centrifuged in a 96-well plate or cell culture insert (0.32 cm(2)) that was set in a 24-well plate, cultivated in the respective vessel for 3 weeks, and the cell sheets were harvested. In some cases, a cylindrical βTCP block (diameter 5 mm, height 3 mm) was placed on the sheet on days 1-7. The sheet size, cell number, and sulfated glycosaminoglycan accumulation were determined. The use of a 96-well plate for not suspension but adhesion culture and the initial centrifugation of a well containing cells were crucial to obtaining a uniformly thick cell sheet. The glycosaminoglycan density of the harvested cell sheet was comparable to that of the pellet culture. An inoculum cell number of more than 31 × 10(5) cells tended to result in a curved cell sheet. Culture involving 18.6 × 10(5) cells and the 96-well plate for adhesion culture showed no curving of the cell sheet (thickness of 0.85 mm), and these were found to be the best of the culture conditions tested. The timing of the addition of a βTCP block to the cell sheet (1-7 days) markedly affected the balance between the thickness of cell sheet parts on and in the βTCP block. Centrifugation and subsequent cultivation of chondrocytes (18.6 × 10(5) cells) in a 96-well plate for adhesion culture led to the production of a scaffold-free cartilage-like cell sheet with a thickness of 0.85 mm. A combined osteochondral-like structure was produced by putting a βTCP block on the cell sheet. The thickness of the cell sheet on the βTCP block and the binding strength between the cell sheet and the βTCP block could be optimized by adjusting the inoculum cell number and timing of βTCP block addition.

Acellular dermal matrix in soft tissue reconstruction prior to bone grafting. A case report.

PubMed

Ruiz-Magaz, Vanessa; Hernández-Alfaro, Federico; Díaz-Carandell, Artur; Biosca-Gómez-de-Tejada, María-José

2010-01-01

When hard tissue augmentation is scheduled as a part of an oral rehabilitation, prior to the treatment, it is important to assess if the quality of the underlying gingiva at the recipient site can support the bone grafting procedure. The most frequent complication during autologous onlay grafts are wound dehiscences in the recipient site, so the integrity of soft tissues is a basic aspect of successful reconstructive and plastic surgical procedure. Connective tissue grafts can improve the quality and quantity of soft tissue in oral sites where a hard tissue reconstruction is going to take place. However, particularly when large grafts are harvested, the autogenous donor site can present significant postoperative morbidity, such as necrosis of the palate fibromucosa and bone exposition, pain and bleeding. Another important limitation with the use of autogenous grafts is the limited supply of donor connective tissue. If a large site needs to be grafted, more than one surgical procedure may be required. An Acellular Dermal Matrix (ADM) graft has become increasingly popular as a substitute for donor connective tissue, eliminating the disadvantages described for the autogenous donor graft. The amount of tissue harvested is unlimited, so it gives an option for treating patients that have inadequate harvestable tissue or that present a large defect to be treated. The outcome of using ADM as a matrix for soft tissue reconstruction 12 weeks before bone grafting can reduce the risk of exposure and failure of the bone graft.

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.

Hierarchical Structure of Articular Bone-Cartilage Interface and Its Potential Application for Osteochondral Tissue Engineering

NASA Astrophysics Data System (ADS)

Bian, Weiguo; Qin, Lian; Li, Dichen; Wang, Jin; Jin, Zhongmin

2010-09-01

The artificial biodegradable osteochondral construct is one of mostly promising lifetime substitute in the joint replacement. And the complex hierarchical structure of natural joint is important in developing the osteochondral construct. However, the architecture features of the interface between cartilage and bone, in particular those at the micro-and nano-structural level, remain poorly understood. This paper investigates these structural data of the cartilage-bone interface by micro computerized tomography (μCT) and Scanning Electron Microscope (SEM). The result of μCT shows that important bone parameters and the density of articular cartilage are all related to the position in the hierarchical structure. The conjunctions of bone and cartilage were defined by SEM. All of the study results would be useful for the design of osteochondral construct further manufactured by nano-tech. A three-dimensional model with gradient porous structure is constructed in the environment of Pro/ENGINEERING software.

[Double-sided juvenile osteochondritis dissecans of the lateral femoral condyle in a 15-year-old boy].

PubMed

Nordkamp, R A G; van Rensen, I H T; Sala, H A G M; van Mourik, J B A

2007-07-21

A 15-year-old boy of Turkish origin presented with a painful swollen left knee. An X-ray revealed osteochondritis dissecans of the lateral femoral condyle. Arthrotomy was performed and the fragment was fixated with tissue glue and 2 absorbable pins. Eight months later, a large recurrent osteochondral fragment of the lateral femoral condyle was seen on X-ray. The patient was re-operated, during which operation the fragment was found and fixated with three compression screws. One year after the first operation the patient developed similar complaints in the contralateral knee; this knee also contained osteochondral fragments necessitating surgery. Osteochondritis dissecans of the knee is a multifactorial disease in which part of the cartilage of the femoral condyle becomes unattached from the subchondral stratum, usually on the lateral side of the medial femoral condyle. Initially, an inflammatory reaction was thought to be the cause of osteochondritis dissecans. Because of the lack of white blood cells, a previous trauma is a better explanation for the ultimate loosening of the cartilage. The treatments that are described for osteochondritis dissecans are conservative treatment, operative fixation, with or without subsequent chondrocyte transplantation or osteochondral autograft transplantation, and finally microfracturing.

Vascular tissue engineering: towards the next generation vascular grafts.

PubMed

Naito, Yuji; Shinoka, Toshiharu; Duncan, Daniel; Hibino, Narutoshi; Solomon, Daniel; Cleary, Muriel; Rathore, Animesh; Fein, Corey; Church, Spencer; Breuer, Christopher

2011-04-30

The application of tissue engineering technology to cardiovascular surgery holds great promise for improving outcomes in patients with cardiovascular diseases. Currently used synthetic vascular grafts have several limitations including thrombogenicity, increased risk of infection, and lack of growth potential. We have completed the first clinical trial evaluating the feasibility of using tissue engineered vascular grafts (TEVG) created by seeding autologous bone marrow-derived mononuclear cells (BM-MNC) onto biodegradable tubular scaffolds. Despite an excellent safety profile, data from the clinical trial suggest that the primary graft related complication of the TEVG is stenosis, affecting approximately 16% of grafts within the first seven years after implantation. Continued investigation into the cellular and molecular mechanisms underlying vascular neotissue formation will improve our basic understanding and provide insights that will enable the rationale design of second generation TEVG. Published by Elsevier B.V.

Characterization of Mesenchymal Stem Cell-Like Cells Derived From Human iPSCs via Neural Crest Development and Their Application for Osteochondral Repair

PubMed Central

Ikeya, Makoto; Yasui, Yukihiko; Ikeda, Yasutoshi; Ebina, Kosuke; Moriguchi, Yu; Shimomura, Kazunori; Hideki, Yoshikawa

2017-01-01

Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) are a promising cell source for the repair of skeletal disorders. Recently, neural crest cells (NCCs) were reported to be effective for inducing mesenchymal progenitors, which have potential to differentiate into osteochondral lineages. Our aim was to investigate the feasibility of MSC-like cells originated from iPSCs via NCCs for osteochondral repair. Initially, MSC-like cells derived from iPSC-NCCs (iNCCs) were generated and characterized in vitro. These iNCC-derived MSC-like cells (iNCMSCs) exhibited a homogenous population and potential for osteochondral differentiation. No upregulation of pluripotent markers was detected during culture. Second, we implanted iNCMSC-derived tissue-engineered constructs into rat osteochondral defects without any preinduction for specific differentiation lineages. The implanted cells remained alive at the implanted site, whereas they failed to repair the defects, with only scarce development of osteochondral tissue in vivo. With regard to tumorigenesis, the implanted cells gradually disappeared and no malignant cells were detected throughout the 2-month follow-up. While this study did not show that iNCMSCs have efficacy for repair of osteochondral defects when implanted under undifferentiated conditions, iNCMSCs exhibited good chondrogenic potential in vitro under appropriate conditions. With further optimization, iNCMSCs may be a new source for tissue engineering of cartilage. PMID:28607560

Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

PubMed

Elomaa, Laura; Yang, Yunzhi Peter

2017-10-01

There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

Multiscale design and synthesis of biomimetic gradient protein/biosilica composites for interfacial tissue engineering.

PubMed

Guo, Jin; Li, Chunmei; Ling, Shengjie; Huang, Wenwen; Chen, Ying; Kaplan, David L

2017-11-01

Continuous gradients present at tissue interfaces such as osteochondral systems, reflect complex tissue functions and involve changes in extracellular matrix compositions, cell types and mechanical properties. New and versatile biomaterial strategies are needed to create suitable biomimetic engineered grafts for interfacial tissue engineering. Silk protein-based composites, coupled with selective peptides with mineralization domains, were utilized to mimic the soft-to-hard transition in osteochondral interfaces. The gradient composites supported tunable mineralization and mechanical properties corresponding to the spatial concentration gradient of the mineralization domains (R5 peptide). The composite system exhibited continuous transitions in terms of composition, structure and mechanical properties, as well as cytocompatibility and biodegradability. The gradient silicified silk/R5 composites promoted and regulated osteogenic differentiation of human mesenchymal stem cells in an osteoinductive environment in vitro. The cells differentiated along the composites in a manner consistent with the R5-gradient profile. This novel biomimetic gradient biomaterial design offers a useful approach to meet a broad range of needs in regenerative medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel MSC-seeded triphasic construct for the repair of osteochondral defects.

PubMed

Marquass, B; Somerson, J S; Hepp, P; Aigner, T; Schwan, S; Bader, A; Josten, C; Zscharnack, M; Schulz, R M

2010-12-01

Mesenchymal stem cells (MSC) are increasingly replacing chondrocytes in tissue engineering based research for treatment of osteochondral defects. The aim of this work was to determine whether repair of critical-size chronic osteochondral defects in an ovine model using MSC-seeded triphasic constructs would show results comparable to osteochondral autografting (OATS). Triphasic implants were engineered using a beta-tricalcium phosphate osseous phase, an intermediate activated plasma phase, and a collagen I hydrogel chondral phase. Autologous MSCs were used to seed the implants, with chondrogenic predifferentiation of the cells used in the cartilage phase. Osteochondral defects of 4.0 mm diameter were created bilaterally in ovine knees (n = 10). Six weeks later, half of the lesions were treated with OATS and half with triphasic constructs. The knees were dissected at 6 or 12 months. With the chosen study design we were not able to demonstrate significant differences between the histological scores of both groups. Subcategory analysis of O'Driscoll scores showed superior cartilage bonding in the 6-month triphasic group compared to the autograft group. The 12-month autograft group showed superior cartilage matrix morphology compared to the 12-month triphasic group. Macroscopic and biomechanical analysis showed no significant differences at 12 months. Autologous MSC-seeded triphasic implants showed comparable repair quality to osteochondral autografts in terms of histology and biomechanical testing. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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

Osteochondral Biopsy Analysis Demonstrates That BST-CarGel Treatment Improves Structural and Cellular Characteristics of Cartilage Repair Tissue Compared With Microfracture

PubMed Central

Méthot, Stéphane; Changoor, Adele; Tran-Khanh, Nicolas; Hoemann, Caroline D.; Stanish, William D.; Restrepo, Alberto; Shive, Matthew S.; Buschmann, Michael D.

2016-01-01

Objective The efficacy and safety of BST-CarGel, a chitosan-based medical device for cartilage repair, was compared with microfracture alone at 1 year during a multicenter randomized controlled trial (RCT) in the knee. The quality of repair tissue of osteochondral biopsies collected from a subset of patients was compared using blinded histological assessments. Methods The international RCT evaluated repair tissue quantity and quality by 3-dimensional quantitative magnetic resonance imaging as co-primary endpoints at 12 months. At an average of 13 months posttreatment, 21/41 BST-CarGel and 17/39 microfracture patients underwent elective second look arthroscopies as a tertiary endpoint, during which ICRS (International Cartilage Repair Society) macroscopic scoring was carried out, and osteochondral biopsies were collected. Stained histological sections were evaluated by blinded readers using ICRS I and II histological scoring systems. Collagen organization was evaluated using a polarized light microscopy score. Results BST-CarGel treatment resulted in significantly better ICRS macroscopic scores (P = 0.0002) compared with microfracture alone, indicating better filling, integration, and tissue appearance. Histologically, BST-CarGel resulted in a significant improvement of structural parameters—Surface Architecture (P = 0.007) and Surface/Superficial Assessment (P = 0.042)—as well as cellular parameters—Cell Viability (P = 0.006) and Cell Distribution (P = 0.032). No histological parameters were significantly better for the microfracture group. BST-CarGel treatment also resulted in a more organized repair tissue with collagen stratification more similar to native hyaline cartilage, as measured by polarized light microscopy scoring (P = 0.0003). Conclusion Multiple and independent analyses in this biopsy substudy demonstrated that BST-CarGel treatment results in improved structural and cellular characteristics of repair tissue at 1 year posttreatment compared with

Biphasic Scaffolds from Marine Collagens for Regeneration of Osteochondral Defects.

PubMed

Bernhardt, Anne; Paul, Birgit; Gelinsky, Michael

2018-03-13

Collagens of marine origin are applied increasingly as alternatives to mammalian collagens in tissue engineering. The aim of the present study was to develop a biphasic scaffold from exclusively marine collagens supporting both osteogenic and chondrogenic differentiation and to find a suitable setup for in vitro chondrogenic and osteogenic differentiation of human mesenchymal stroma cells (hMSC). Biphasic scaffolds from biomimetically mineralized salmon collagen and fibrillized jellyfish collagen were fabricated by joint freeze-drying and crosslinking. Different experiments were performed to analyze the influence of cell density and TGF-β on osteogenic differentiation of the cells in the scaffolds. Gene expression analysis and analysis of cartilage extracellular matrix components were performed and activity of alkaline phosphatase was determined. Furthermore, histological sections of differentiated cells in the biphasic scaffolds were analyzed. Stable biphasic scaffolds from two different marine collagens were prepared. An in vitro setup for osteochondral differentiation was developed involving (1) different seeding densities in the phases; (2) additional application of alginate hydrogel in the chondral part; (3) pre-differentiation and sequential seeding of the scaffolds and (4) osteochondral medium. Spatially separated osteogenic and chondrogenic differentiation of hMSC was achieved in this setup, while osteochondral medium in combination with the biphasic scaffolds alone was not sufficient to reach this ambition. Biphasic, but monolithic scaffolds from exclusively marine collagens are suitable for the development of osteochondral constructs.

Repair of osteochondral defects with in vitro engineered cartilage based on autologous bone marrow stromal cells in a swine model.

PubMed

He, Aijuan; Liu, Lina; Luo, Xusong; Liu, Yu; Liu, Yi; Liu, Fangjun; Wang, Xiaoyun; Zhang, Zhiyong; Zhang, Wenjie; Liu, Wei; Cao, Yilin; Zhou, Guangdong

2017-01-13

Functional reconstruction of large osteochondral defects is always a major challenge in articular surgery. Some studies have reported the feasibility of repairing articular osteochondral defects using bone marrow stromal cells (BMSCs) and biodegradable scaffolds. However, no significant breakthroughs have been achieved in clinical translation due to the instability of in vivo cartilage regeneration based on direct cell-scaffold construct implantation. To overcome the disadvantages of direct cell-scaffold construct implantation, the current study proposed an in vitro cartilage regeneration strategy, providing relatively mature cartilage-like tissue with superior mechanical properties. Our strategy involved in vitro cartilage engineering, repair of osteochondral defects, and evaluation of in vivo repair efficacy. The results demonstrated that BMSC engineered cartilage in vitro (BEC-vitro) presented a time-depended maturation process. The implantation of BEC-vitro alone could successfully realize tissue-specific repair of osteochondral defects with both cartilage and subchondral bone. Furthermore, the maturity level of BEC-vitro had significant influence on the repaired results. These results indicated that in vitro cartilage regeneration using BMSCs is a promising strategy for functional reconstruction of osteochondral defect, thus promoting the clinical translation of cartilage regeneration techniques incorporating BMSCs.

One-Step Treatment for Patellar Cartilage Defects With a Cell-Free Osteochondral Scaffold: A Prospective Clinical and MRI Evaluation.

PubMed

Perdisa, Francesco; Filardo, Giuseppe; Sessa, Andrea; Busacca, Maurizio; Zaffagnini, Stefano; Marcacci, Maurilio; Kon, Elizaveta

2017-06-01

The treatment of symptomatic cartilage defects of the patella is particularly challenging, and no gold standard is currently available. To evaluate the clinical results of a biphasic cell-free collagen-hydroxyapatite scaffold and to evaluate osteochondral tissue regeneration with magnetic resonance imaging (MRI). Case series; Level of evidence, 4. Thirty-four patients (18 men and 16 women; mean ± SD: age, 30.0 ± 10 years) were treated by scaffold implantation for knee chondral or osteochondral lesions of the patella (area, 2.1 ± 1 cm 2 ). The clinical evaluation was performed prospectively at 12 and 24 months via the IKDC (International Knee Documentation Committee; objective and subjective) and Tegner scores. MRI evaluation was performed at both follow-ups in 18 lesions through the MOCART score (magnetic resonance observation of cartilage repair tissue) and specific subchondral bone parameters. A statistically significant improvement in all the scores was observed at 12- and 24-month follow-up as compared with the basal evaluation. The IKDC subjective score improved from 39.5 ± 14.5 to 61.9 ± 14.5 at 12 months ( P > .0005) with a further increase to 67.6 ± 17.4 at 24 months of follow-up (12-24 months, P = .020). The MRI evaluation showed a stable value of the MOCART score between 12 and 24 months, with a complete filling of the cartilage in 87.0% of the lesions, complete integration of the graft in 95.7%, and intact repair tissue surface in 69.6% at final follow-up. The presence of osteophytes or more extensive bony overgrowth was documented in 47.8% of the patients of this series, but no correlation was found between MRI findings and clinical outcome. The implantation of a cell-free collagen-hydroxyapatite osteochondral scaffold provided a clinical improvement at short-term follow-up for the treatment of patellar cartilage defects. Women had lower outcomes, and the need for realignment procedures led to a slower recovery. MRI evaluation showed some abnormal

Nonlinear and Anisotropic Tensile Properties of Graft Materials used in Soft Tissue Applications

PubMed Central

Yoder, Jonathon H; Elliott, Dawn M

2010-01-01

Background The mechanical properties of extracellular matrix grafts that are intended to augment or replace soft tissues should be comparable to the native tissue. Such grafts are often used in fiber-reinforced tissue applications that undergo multi-axial loading and therefore knowledge of the anisotropic and nonlinear properties are needed, including the moduli and Poisson's ratio in two orthogonal directions within the plane of the graft. The objective of this study was to measure the tensile mechanical properties of several marketed grafts: Alloderm, Restore, CuffPatch, and OrthADAPT. Methods The degree of anisotropy and nonlinearity within each graft was evaluated from uniaxial tensile tests and compared to their native tissue. Results The Alloderm graft was anisotropic in both the toe and linear-region of the stress-strain response, was highly nonlinear, and generally had low properties. The Restore and CuffPatch grafts had similar stress-strain responses, were largely isotropic, had a linear-region modulus of 18 MPa, and were nonlinear. OrthADAPT was anisotropic in the linear region (131 vs 47 MPa) and was highly nonlinear. The Poisson ratio for all grafts was between 0.4 and 0.7, except for the parallel orientation of Restore which was greater than 1.0. Interpretation Having an informed understanding of how the available grafts perform mechanically will allow for better assessment by the physician for which graft to apply depending upon its application. PMID:20129728

Nonlinear and anisotropic tensile properties of graft materials used in soft tissue applications.

PubMed

Yoder, Jonathon H; Elliott, Dawn M

2010-05-01

The mechanical properties of extracellular matrix grafts that are intended to augment or replace soft tissues should be comparable to the native tissue. Such grafts are often used in fiber-reinforced tissue applications that undergo multi-axial loading and therefore knowledge of the anisotropic and nonlinear properties are needed, including the moduli and Poisson's ratio in two orthogonal directions within the plane of the graft. The objective of this study was to measure the tensile mechanical properties of several marketed grafts: Alloderm, Restore, CuffPatch, and OrthADAPT. The degree of anisotropy and non-linearity within each graft was evaluated from uniaxial tensile tests and compared to their native tissue. The Alloderm graft was anisotropic in both the toe- and linear-region of the stress-strain response, was highly nonlinear, and generally had low properties. The Restore and CuffPatch grafts had similar stress-strain responses, were largely isotropic, had a linear-region modulus of 18MPa, and were nonlinear. OrthADAPT was anisotropic in the linear-region (131 MPA vs 47MPa in the toe-region) and was highly nonlinear. The Poisson ratio for all grafts was between 0.4 and 0.7, except for the parallel orientation of Restore which was greater than 1.0. Having an informed understanding of how the available grafts perform mechanically will allow for better assessment by the physician for which graft to apply depending upon its application. Copyright 2010 Elsevier Ltd. All rights reserved.

Tissue-Engineered Autologous Grafts for Facial Bone Reconstruction

PubMed Central

Bhumiratana, Sarindr; Bernhard, Jonathan C.; Alfi, David M.; Yeager, Keith; Eton, Ryan E.; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M.; Lopez, Mandi J.; Eisig, Sidney B.; Vunjak-Novakovic, Gordana

2016-01-01

Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, without bone morphogenic proteins, using native bovine bone matrix and a perfusion bioreactor for the growth and transport of living grafts. The ramus-condyle unit (RCU), the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatan minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material, and crafted it into an anatomically correct shape using image-guided micromilling, to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either non-seeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. PMID:27306665

Exostosis following a subepithelial connective tissue graft.

PubMed

Corsair, A J; Iacono, V J; Moss, S S

2001-04-01

This case report describes the formation of an unusual unaesthetic gingival enlargement during a five year post operative period subsequent to a subepithelial connective tissue graft placed facial to teeth #4 and #6. Histological assessment of the enlarged tissue indicated that it consisted of viable bone and marrow. The exostosis was reduced with rotary instruments and acceptable soft tissue aesthetics were created using a carbon dioxide laser for gingivoplasty. Possible causes for this unusual enlargement are discussed.

Application of stem cells for cardiovascular grafts tissue engineering.

PubMed

Wu, Kaihong; Liu, Ying Long; Cui, Bin; Han, Zhongchao

2006-06-01

Congenital and acquired heart diseases are leading causes of morbidity and mortality world-wide. Currently, the synthetic materials or bioprosthetic replacement devices for cardiovascular surgery are imperfect and subject patients to one or more ongoing risks including thrombosis, limited durability and need for reoperations due to lack of growth in children and young adults. Suitable replacement grafts should have appropriate characteristics, including resistance to infection, low immunogenicity, good biocompatability and thromboresistance, with appropriate mechanical and physiological properties. Tissue engineering is a new scientific field aiming at fabrication of living, autologous grafts having structure or function properties that can be used to restore, maintain or improve tissue function. The use of autologous stem cells in cardiovascular tissue engineering is quite promising due to their capacity of self-renewal, high proliferation, and differentiation into specialized progeny. Progress has been made in engineering the various components of the cardiovascular system, including myocardial constructs, heart valves, and vascular patches or conduits with autologous stem cells. This paper will review the current achievements in stem cell-based cardiovascular grafts tissue engineering, with an emphasis on its clinical or possible clinical use in cardiovascular surgery.

Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model.

PubMed

Madry, H; Kaul, G; Zurakowski, D; Vunjak-Novakovic, G; Cucchiarini, M

2013-04-16

Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes overexpressing a human insulin-like growth factor I (IGF-I) gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-overexpressing chondrocytes markedly improved osteochondral repair compared with control (lacZ) constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects.

CARTILAGE CONSTRUCTS ENGINEERED FROM CHONDROCYTES OVEREXPRESSING IGF-I IMPROVE THE REPAIR OF OSTEOCHONDRAL DEFECTS IN A RABBIT MODEL

PubMed Central

Madry, Henning; Kaul, Gunter; Zurakowski, David; Vunjak-Novakovic, Gordana; Cucchiarini, Magali

2015-01-01

Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes over expressing a human insulin-like growth factor I (IGF-I) gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-over expressing chondrocytes markedly improved osteochondral repair compared with control (lacZ) constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects. PMID:23588785

Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers.

PubMed

Levato, Riccardo; Visser, Jetze; Planell, Josep A; Engel, Elisabeth; Malda, Jos; Mateos-Timoneda, Miguel A

2014-09-01

Bioprinting allows the fabrication of living constructs with custom-made architectures by spatially controlled deposition of multiple bioinks. This is important for the generation of tissue, such as osteochondral tissue, which displays a zonal composition in the cartilage domain supported by the underlying subchondral bone. Challenges in fabricating functional grafts of clinically relevant size include the incorporation of cues to guide specific cell differentiation and the generation of sufficient cells, which is hard to obtain with conventional cell culture techniques. A novel strategy to address these demands is to combine bioprinting with microcarrier technology. This technology allows for the extensive expansion of cells, while they form multi-cellular aggregates, and their phenotype can be controlled. In this work, living constructs were fabricated via bioprinting of cell-laden microcarriers. Mesenchymal stromal cell (MSC)-laden polylactic acid microcarriers, obtained via static culture or spinner flask expansion, were encapsulated in gelatin methacrylamide-gellan gum bioinks, and the printability of the composite material was studied. This bioprinting approach allowed for the fabrication of constructs with high cell concentration and viability. Microcarrier encapsulation improved the compressive modulus of the hydrogel constructs, facilitated cell adhesion, and supported osteogenic differentiation and bone matrix deposition by MSCs. Bilayered osteochondral models were fabricated using microcarrier-laden bioink for the bone compartment. These findings underscore the potential of this new microcarrier-based biofabrication approach for bone and osteochondral constructs.

Intra-oral soft tissue expansion and volume stability of onlay bone grafts.

PubMed

Abrahamsson, Peter

2011-01-01

Insufficient regeneration of missing bone and soft-tissue may present aesthetic or functional problems in patients indicated for dental implant surgery. Several techniques such as bone grafts, bone substitutes and guided tissue regeneration (GTR) have been described to rebuild a compromised alveolar ridge. Adequate soft-tissue coverage of grafted bone and titanium-mesh is important to avoid exposure which may result in loss of the bone graft. The general aim of this thesis was to evaluate use of an osmotic tissue expander for expanding intra-oral soft tissue--creating a surplus of soft tissue-- in preparation for onlay bone grafting. An experimental rabbit model was used in studies (I), (II) and (III). In (I) an osmotic soft-tissue expander was placed bilaterally on the lateral wall of the mandible via an extra-oral approach. After two weeks of expansion the rabbits were killed and specimens were collected for histology. No inflammatory reaction and no resorbtion of the cortical bone occured. The periosteum was expanded and new bone formation was seen in the edges of the expander. In (II) and (III) the expander was placed under the periosteum in the same way as in (I): bilaterally in 13 rabbits in (II) and unilaterally in 11 rabbits in (III). After two weeks of expansion the expander was identified and removed. In (II) particulated bone was placed at the recipient site protected by a titanium mesh in one site and a bio-resorbable mesh on the other site. In (III), DBBM particles and bone particles collected from the lateral border of the mandible separated by a collagen membrane was placed at the recipient site. The graft was protected by a pre-bent titanium mesh covered by a collagen membrane. After a healing period of 3 months specimens were collected for histological and SEM examination. New bone was growing in direct contact with the titanium mesh and bio resorbable mesh. The newly formed bone had the same calcium content as the mature bone in the base of the

3D printing of novel osteochondral scaffolds with graded microstructure

NASA Astrophysics Data System (ADS)

Nowicki, Margaret A.; Castro, Nathan J.; Plesniak, Michael W.; Zhang, Lijie Grace

2016-10-01

Osteochondral tissue has a complex graded structure where biological, physiological, and mechanical properties vary significantly over the full thickness spanning from the subchondral bone region beneath the joint surface to the hyaline cartilage region at the joint surface. This presents a significant challenge for tissue-engineered structures addressing osteochondral defects. Fused deposition modeling (FDM) 3D bioprinters present a unique solution to this problem. The objective of this study is to use FDM-based 3D bioprinting and nanocrystalline hydroxyapatite for improved bone marrow human mesenchymal stem cell (hMSC) adhesion, growth, and osteochondral differentiation. FDM printing parameters can be tuned through computer aided design and computer numerical control software to manipulate scaffold geometries in ways that are beneficial to mechanical performance without hindering cellular behavior. Additionally, the ability to fine-tune 3D printed scaffolds increases further through our investment casting procedure which facilitates the inclusion of nanoparticles with biochemical factors to further elicit desired hMSC differentiation. For this study, FDM was used to print investment-casting molds innovatively designed with varied pore distribution over the full thickness of the scaffold. The mechanical and biological impacts of the varied pore distributions were compared and evaluated to determine the benefits of this physical manipulation. The results indicate that both mechanical properties and cell performance improve in the graded pore structures when compared to homogeneously distributed porous and non-porous structures. Differentiation results indicated successful osteogenic and chondrogenic manipulation in engineered scaffolds.

Alveolar ridge augmentation by connective tissue grafting using a pouch method and modified connective tissue technique: A prospective study.

PubMed

Agarwal, Ashish; Gupta, Narinder Dev

2015-01-01

Localized alveolar ridge defect may create physiological and pathological problems. Developments in surgical techniques have made it simpler to change the configuration of a ridge to create a more aesthetic and more easily cleansable shape. The purpose of this study was to compare the efficacy of alveolar ridge augmentation using a subepithelial connective tissue graft in pouch and modified connective tissue graft technique. In this randomized, double blind, parallel and prospective study, 40 non-smoker individuals with 40 class III alveolar ridge defects in maxillary anterior were randomly divided in two groups. Group I received modified connective tissue graft, while group II were treated with subepithelial connective tissue graft in pouch technique. The defect size was measured in its horizontal and vertical dimension by utilizing a periodontal probe in a stone cast at base line, after 3 months, and 6 months post surgically. Analysis of variance and Bonferroni post-hoc test were used for statistical analysis. A two-tailed P < 0.05 was considered to be statistically significant. Mean values in horizontal width after 6 months were 4.70 ± 0.87 mm, and 4.05 ± 0.89 mm for group I and II, respectively. Regarding vertical heights, obtained mean values were 4.75 ± 0.97 mm and 3.70 ± 0.92 mm for group I and group II, respectively. Within the limitations of this study, connective tissue graft proposed significantly more improvement as compare to connective tissue graft in pouch.

Gradient nano-engineered in situ forming composite hydrogel for osteochondral regeneration.

PubMed

Radhakrishnan, Janani; Manigandan, Amrutha; Chinnaswamy, Prabu; Subramanian, Anuradha; Sethuraman, Swaminathan

2018-04-01

Fabrication of anisotropic osteochondral-mimetic scaffold with mineralized subchondral zone and gradient interface remains challenging. We have developed an injectable semi-interpenetrating network hydrogel construct with chondroitin sulfate nanoparticles (ChS-NPs) and nanohydroxyapatite (nHA) (∼30-90 nm) in chondral and subchondral hydrogel zones respectively. Mineralized subchondral hydrogel exhibited significantly higher osteoblast proliferation and alkaline phosphatase activity (p < 0.05). Osteochondral hydrogel exhibited interconnected porous structure and spatial variation with gradient interface of nHA and ChS-NPs. Microcomputed tomography (μCT) demonstrated nHA gradation while rheology showed predominant elastic modulus (∼930 Pa) at the interface. Co-culture of osteoblasts and chondrocytes in gradient hydrogels showed layer-specific retention of cells and cell-cell interaction at the interface. In vivo osteochondral regeneration by biphasic (nHA or ChS) and gradient (nHA + ChS) hydrogels was compared with control using rabbit osteochondral defect after 3 and 8 weeks. Complete closure of defect was observed in gradient (8 weeks) while defect remained in other groups. Histology demonstrated collagen and glycosaminoglycan deposition in neo-matrix and presence of hyaline cartilage-characteristic matrix, chondrocytes and osteoblasts. μCT showed mineralized neo-tissue formation, which was confined within the defect with higher bone mineral density in gradient (chondral: 0.42 ± 0.07 g/cc, osteal: 0.64 ± 0.08 g/cc) group. Further, biomechanical push-out studies showed significantly higher load for gradient group (378 ± 56 N) compared to others. Thus, the developed nano-engineered gradient hydrogel enhanced hyaline cartilage regeneration with subchondral bone formation and lateral host-tissue integration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Soft Tissue Grafting Around Teeth and Implants.

PubMed

Deeb, George R; Deeb, Janina Golob

2015-08-01

The presence of healthy attached tissue at the tooth and implant soft tissue interface correlates with long-term success and stability in function and esthetics. There are several soft tissue grafting procedures that increase the volume of keratinized tissue and provide coverage on both teeth and implants. Many of these techniques can be used in conjunction with implant placement, or after placement as a means of salvage. This article describes the techniques for augmentation of keratinized tissue as well as root and implant coverage. These tools should be in the armamentarium of oral and maxillofacial surgeons providing implant services. Copyright © 2015 Elsevier Inc. All rights reserved.

Point-of-care instrument for monitoring tissue health during skin graft repair

NASA Astrophysics Data System (ADS)

Gurjar, R. S.; Seetamraju, M.; Zhang, J.; Feinberg, S. E.; Wolf, D. E.

2011-06-01

We have developed the necessary theoretical framework and the basic instrumental design parameters to enable mapping of subsurface blood dynamics and tissue oxygenation for patients undergoing skin graft procedures. This analysis forms the basis for developing a simple patch geometry, which can be used to map by diffuse optical techniques blood flow velocity and tissue oxygenation as a function of depth in subsurface tissue.skin graft, diffuse correlation analysis, oxygen saturation.

Novel alginate biphasic scaffold for osteochondral regeneration: an in vivo evaluation in rabbit and sheep models.

PubMed

Filardo, Giuseppe; Perdisa, Francesco; Gelinsky, Michael; Despang, Florian; Fini, Milena; Marcacci, Maurilio; Parrilli, Anna Paola; Roffi, Alice; Salamanna, Francesca; Sartori, Maria; Schütz, Kathleen; Kon, Elizaveta

2018-05-26

Current therapeutic strategies for osteochondral restoration showed a limited regenerative potential. In fact, to promote the growth of articular cartilage and subchondral bone is a real challenge, due to the different functional and anatomical properties. To this purpose, alginate is a promising biomaterial for a scaffold-based approach, claiming optimal biocompatibility and good chondrogenic potential. A previously developed mineralized alginate scaffold was investigated in terms of the ability to support osteochondral regeneration both in a large and medium size animal model. The results were evaluated macroscopically and by microtomography, histology, histomorphometry, and immunohistochemical analysis. No evidence of adverse or inflammatory reactions was observed in both models, but limited subchondral bone formation was present, together with a slow scaffold resorption time.The implantation of this biphasic alginate scaffold provided partial osteochondral regeneration in the animal model. Further studies are needed to evaluate possible improvement in terms of osteochondral tissue regeneration for this biomaterial.

Alveolar ridge augmentation by connective tissue grafting using a pouch method and modified connective tissue technique: A prospective study

PubMed Central

Agarwal, Ashish; Gupta, Narinder Dev

2015-01-01

Background: Localized alveolar ridge defect may create physiological and pathological problems. Developments in surgical techniques have made it simpler to change the configuration of a ridge to create a more aesthetic and more easily cleansable shape. The purpose of this study was to compare the efficacy of alveolar ridge augmentation using a subepithelial connective tissue graft in pouch and modified connective tissue graft technique. Materials and Methods: In this randomized, double blind, parallel and prospective study, 40 non-smoker individuals with 40 class III alveolar ridge defects in maxillary anterior were randomly divided in two groups. Group I received modified connective tissue graft, while group II were treated with subepithelial connective tissue graft in pouch technique. The defect size was measured in its horizontal and vertical dimension by utilizing a periodontal probe in a stone cast at base line, after 3 months, and 6 months post surgically. Analysis of variance and Bonferroni post-hoc test were used for statistical analysis. A two-tailed P < 0.05 was considered to be statistically significant. Results: Mean values in horizontal width after 6 months were 4.70 ± 0.87 mm, and 4.05 ± 0.89 mm for group I and II, respectively. Regarding vertical heights, obtained mean values were 4.75 ± 0.97 mm and 3.70 ± 0.92 mm for group I and group II, respectively. Conclusion: Within the limitations of this study, connective tissue graft proposed significantly more improvement as compare to connective tissue graft in pouch. PMID:26759591

A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years.

PubMed

Kon, Elizaveta; Filardo, Giuseppe; Brittberg, Mats; Busacca, Maurizio; Condello, Vincenzo; Engebretsen, Lars; Marlovits, Stefan; Niemeyer, Philipp; Platzer, Patrik; Posthumus, Michael; Verdonk, Peter; Verdonk, Renè; Victor, Jan; van der Merwe, Willem; Widuchowski, Wojciech; Zorzi, Claudio; Marcacci, Maurilio

2017-09-14

The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen-hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions. In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness. A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups. This

Osteochondritis Dissecans

MedlinePlus

... can then break loose, causing pain and possibly hinder joint motion. Osteochondritis dissecans occurs most often in ... Adolescents participating in organized sports might benefit from education on the risks to their joints associated with ...

Soft tissue graft interference fit fixation: observations on graft insertion site healing and tunnel remodeling 2 years after ACL reconstruction in sheep.

PubMed

Hunt, Patrick; Rehm, Oliver; Weiler, Andreas

2006-12-01

Using soft tissue grafts for anterior cruciate ligament (ACL) reconstruction, insertion site healing plays a crucial role in the long-term fate of the graft. It has been shown in an experimental animal study that using a soft tissue graft and anatomic graft fixation, a direct ligamentous insertion alike the native ACL developed 24 weeks postoperatively. Yet there are no reports on the long-term insertion site healing of anatomically fixed soft tissue grafts. The objective of this study was to evaluate graft insertion site healing, the intra-tunnel fate of the graft and its osseous replacement 2 years after ACL reconstruction in sheep. The left ACLs of six sheep were replaced by an autologous flexor tendon split graft and anatomically fixed with biodegradable poly-(D, L-lactide) interference screws. Animals received polychromic sequential labeling at different points in time to determine bone apposition per period. For evaluation of the insertion site healing and intra-tunnel changes, MRI scans were taken in vivo. Following sacrifice, radiographic imaging, conventional histology and fluorescence microscopy was undertaken. Most of the specimens showed a wide direct ligamentous insertion. It showed patterns alike the direct ligament insertion seen in intact ACLs. The intra-tunnel part of the graft had completely lost its tendon-like structure and in two cases, it was separated from the graft insertion by a thick bony layer. The biodegradable interference screw was fully degraded in all specimens. Ossification of the former drill tunnels was intense, showing only partial-length tunnel remnants in one femoral and three tibial specimens. As the graft heals to the joint surface and the aperture site is closed with soft tissue, mechanical stress of the intra-tunnel part of the graft is eliminated and the bone tunnel is protected from synovial fluid, resulting in osseous bridging of the tunnel aperture site, accelerated intra-tunnel graft resorption and its osseous

Clinical Evaluation of Papilla Reconstruction Using Subepithelial Connective Tissue Graft

PubMed Central

Kaushik, Alka; PK, Pal; Chopra, Deepak; Chaurasia, Vishwajit Rampratap; Masamatti, Vinaykumar S; DK, Suresh; Babaji, Prashant

2014-01-01

Objective: The aesthetics of the patient can be improved by surgical reconstruction of interdental papilla by using an advanced papillary flap interposed with subepithelial connective tissue graft. Materials and Methods: A total of fifteen sites from ten patients having black triangles/papilla recession in the maxillary anterior region were selected and subjected to presurgical evaluation. The sites were treated with interposed subepithelial connective tissue graft placed under a coronally advance flap. The integrity of the papilla was maintained by moving the whole of gingivopapillary unit coronally. The various parameters were analysed at different intervals. Results: There was a mean decrease in the papilla presence index score and distance from contact point to gingival margin, but it was statistically not significant. Also, there is increase in the width of the keratinized gingiva which was statistically highly significant. Conclusion: Advanced papillary flap with interposed sub–epithelial connective tissue graft can offer predictable results for the reconstruction of interdental papilla. If papilla loss occurs solely due to soft-tissue damage, reconstructive techniques can completely restore it; but if due to periodontal disease involving bone loss, reconstruction is generally incomplete and multiple surgical procedures may be required. PMID:25386529

Combination of Polymeric Supports and Drug Delivery Systems for Osteochondral Regeneration.

PubMed

Rojo, Luis

2018-01-01

Musculoskeletal conditions have been defined by European National Health systems as one of the key themes which should be featured during the present decade as a consequence of the significant healthcare and social support costs. Among others, articular cartilage degeneration due to traumatic and degenerative lesion injury or other pathologies commonly results in the development of musculoskeletal disorders such as osteoarthritis and arthritis rheumatoid, eventually leading to progressive articular cartilage and joint destruction especially at osteochondral interphase, that account for more disability among the elderly than any other diseases constituting a global social challenge that needs a multidisciplinary response from the scientific community. Current treatments for damaged osteoarthritic joint cartilage include the use of disease-modifying drugs and ultimately joint arthroplasty as unavoidable surgical intervention due to the limited ability of articular cartilage to self-regenerate. However, potential future regenerative therapies based on tissue engineering strategies are likely to become more important to facilitate the recruitment of repairing cells and improve musculoskeletal metabolism. In addition, emerging bioprinting technologies in combination with implemented manufacturing techniques such electrospinning or cryogelation processes have permitted the development of new tissue substitutes with precise control of sizes and shapes to recreate the complex physiological, biomechanical and hieratical microstructure of osteochondral interphases. Thus, this chapter will provide an upgrade on the state of the art focusing the most relevant developments on polymer scaffolds and drug delivery systems for osteochondral regeneration.

Midterm results of osteochondral allograft transplantation to the humeral head.

PubMed

Riff, Andrew J; Yanke, Adam B; Shin, Jason J; Romeo, Anthony A; Cole, Brian J

2017-07-01

This study evaluated clinical outcomes of osteochondral allograft (OCA) transplantation for humeral head osteochondral defects. We hypothesized that patients with isolated humeral head disease would achieve favorable results and that patients with bipolar disease would experience inferior outcomes. We identified patients who underwent humeral head OCA transplantation. Subjective questionnaire data were obtained preoperatively and at a minimum of 2 years postoperatively. Radiographs were evaluated for graft incorporation. Failure was defined by conversion to shoulder arthroplasty, American Shoulder and Elbow Surgeons score <50, or dissatisfaction with the surgical result. Twenty patients (65% male) met inclusion criteria. Patients were an average age of 24.8 ± 8.1 years. Eleven patients underwent concomitant glenoid surgery (microfracture or meniscal allograft resurfacing). Follow-up was available for 18 patients (90%) at mean of 67 months. All grafts incorporated except 2. Four patients underwent shoulder arthroplasty at mean of 25 months postoperatively (all after pain pump chondrolysis). Eleven of the 20 patients were satisfied (all dissatisfied patients underwent glenoid surgery). Significant improvements (P < .001) were seen for the visual analog scale (from 6.1 to 1.5), Simple Shoulder Test (from 32 to 73), American Shoulder and Elbow Surgeons score (from 39 to 76), and the physical component of the 12-Item Short Form Survey (from 38 to 48). Pain pump patients who did not progress to arthroplasty experienced inferior satisfaction (40% vs. 87.5%, P = .04) and a trend toward inferior outcomes compared with the rest of the cohort. OCA transplantation is a viable option for young patients with isolated humeral chondral injury. Patients with bipolar disease or a history of intra-articular pain pump have increased failure and decreased subjective outcomes. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier

Lactated Ringer-based storage solutions are equally well suited for the storage of fresh osteochondral allografts as cell culture medium-based storage solutions.

PubMed

Harb, Afif; von Horn, Alexander; Gocalek, Kornelia; Schäck, Luisa Marilena; Clausen, Jan; Krettek, Christian; Noack, Sandra; Neunaber, Claudia

2017-07-01

Due to the rising interest in Europe to treat large cartilage defects with osteochondrale allografts, research aims to find a suitable solution for long-term storage of osteochondral allografts. This is further encouraged by the fact that legal restrictions currently limit the use of the ingredients from animal or human sources that are being used in other regions of the world (e.g. in the USA). Therefore, the aim of this study was A) to analyze if a Lactated Ringer (LR) based solution is as efficient as a Dulbecco modified Eagle's minimal essential medium (DMEM) in maintaining chondrocyte viability and B) at which storage temperature (4°C vs. 37°C) chondrocyte survival of the osteochondral allograft is optimally sustained. 300 cartilage grafts were collected from knees of ten one year-old Black Head German Sheep. The grafts were stored in four different storage solutions (one of them DMEM-based, the other three based on Lactated Ringer Solution), at two different temperatures (4 and 37°C) for 14 and 56days. At both points in time, chondrocyte survival as well as death rate, Glycosaminoglycan (GAG) content, and Hydroxyproline (HP) concentration were measured and compared between the grafts stored in the different solutions and at the different temperatures. Independent of the storage solutions tested, chondrocyte survival rates were higher when stored at 4°C compared to storage at 37°C both after short-term (14days) and long-term storage (56days). At no point in time did the DMEM-based solution show a superior chondrocyte survival compared to lactated Ringer based solution. GAG and HP content were comparable across all time points, temperatures and solutions. LR based solutions that contain only substances that are approved in Germany may be just as efficient for storing grafts as the USA DMEM-based solution gold standard. Moreover, in the present experiment storage of osteochondral allografts at 4°C was superior to storage at 37°C. Copyright © 2017

Dimensional soft tissue changes following soft tissue grafting in conjunction with implant placement or around present dental implants: a systematic review.

PubMed

Poskevicius, Lukas; Sidlauskas, Antanas; Galindo-Moreno, Pablo; Juodzbalys, Gintaras

2017-01-01

To systematically review changes in mucosal soft tissue thickness and keratinised mucosa width after soft tissue grafting around dental implants. An electronic literature search was conducted of the MEDLINE database published between 2009 and 2014. Sequential screenings at the title, abstract, and full-text levels were performed. Clinical human studies in the English language that had reported changes in soft tissue thickness or keratinised mucosa width after soft tissue grafting at implant placement or around a present implant at 6-month follow-up or longer were included. The search resulted in fourteen articles meeting the inclusion criteria: Six of them reported connective tissue grafting around present dental implants, compared to eight at the time of implant placement. Better long-term soft tissue thickness outcomes were reported for soft tissue augmentation around dental implants (0.8-1.4 mm), compared with augmentation at implant placement (-0.25-1.43 mm). Both techniques were effective in increasing keratinised tissue width: at implant placement (2.5 mm) or around present dental implants (2.33-2.57 mm). The present systematic review discovered that connective tissue grafts enhanced keratinised mucosa width and soft tissue thickness for an observation period of up to 48 months. However, some shrinkage may occur, resulting in decreases in soft tissue, mostly for the first three months. Further investigations using accurate evaluation methods need to be done to evaluate the appropriate time for grafting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Peri-Implant Tissue Findings in Bone Grafted Oral Cancer Patients Compared to non Bone Grafted Patients without Oral Cancer

PubMed Central

Agata, Hideki; Sándor, George K.; Haimi, Suvi

2011-01-01

ABSTRACT Objectives The aim of this study was to compare microbiological, histological, and mechanical findings from tissues around osseointergrated dental implants in patients who had undergone tumour resection and subsequent bone grafting with non bone grafted patients without a history of oral cancer and to develop an effective tool for the monitoring of the peri-implant tissues. A third aim was to assess and compare the masticatory function of the two patient groups after reconstruction with dental implants. Material and Methods A total of 20 patients were divided into 2 groups. The first group was edentulous and treated with dental implants without the need for bone grafting. The second edentulous group, with a history of oral cancer involving the mandible, received onlay bone grafts with concurrent placement of dental implants. Microbiological, histological, mechanical and biochemical assessment methods, crevicular fluid flow rate, hygiene-index, implant mobility, and the masticatory function were analysed and compared in both patient groups. Results The microbiological examinations showed no evidence of the three most common pathogenic bacteria: Porphyromonas gingivalis, Prevotella intermedius, Actinobacillus actinomycetencomitans. A causal relationship between specific microbes and peri-implant inflammation could not be found. All biopsies in both patient groups revealed early signs of soft tissue peri-implant inflammation. Conclusions The crevicular fluid volume and grade of gingival inflammation around the dental implants were related. Peri-implant tissue findings were similar in the two patient groups despite the history of oral cancer and the need for bone grafting at the time of dental implant placement. PMID:24421999

Enhancing integration of articular cartilage grafts via photochemical bonding.

PubMed

Arvayo, Alberto L; Wong, Ivan J; Dragoo, Jason L; Levenston, Marc E

2018-03-25

The integration of osteochondral grafts to native articular cartilage is critical as the lack of graft integration may lead to continued tissue degradation, poor load transfer and inadequate nutrient transport. Photochemical bonding promotes graft integration by activating a photosensitizer at the interface via a light source and avoids negative effects associated with other bonding techniques. We hypothesized that the bond strength depends on photosensitizer type and concentration in addition to light exposure. Photochemical bonding was evaluated using methylene blue (MB), a cationic phenothiazine photosensitizer, and two phthalocyanine photosensitizers, Al(III) phthalocyanine chloride tetrasulfonic acid (CASPc) and aluminum phthalocyanine chloride (AlPc). Exposure was altered by varying irradiation time for a fixed irradiance or by varying irradiance with a fixed irradiation time. MB was ineffective at producing bonding at the range of concentrations tested while CASPc produced a peak twofold bond strength increase over controls. AlPc produced substantial bonding at all concentrations with a peak 3.9-fold bond strength increase over controls. Parametric tests revealed that bond strength depended primarily on the total energy delivered to the bonding site rather than the rate of light delivery or light irradiance. Bond strength persisted for 1 week of in-vitro culture, which warrants further exploration for clinical applications. These studies indicate that photochemical bonding is a viable strategy for enhancing articular cartilage graft integration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Merkel cells and permanent disesthesia in the oral mucosa after soft tissue grafts.

PubMed

Aimetti, M; Romano, F; Cricenti, L; Perotto, S; Gotti, S; Panzica, G; Graziano, A

2010-07-01

Connective tissue grafts are routinely procedures in the treatment of gingival defects. The clinical success of the gingival tissue graft procedures anyway should ensure not only the aesthetic integration between the tissues but also the physiological activity of the graft in terms of sensitivity and immunity because the skin and the mucosae constitute the first natural aspecific borders against pathogens. The aim of this paper was to investigate nervous net recovery after connective graft procedure, in relation with sensorial alteration in the injured area. Results showed that there is a close link among the number of Merkel cells and the alteration of sensations. Merkel cells can be found isolated standing in the basal layer, supposed to have neuroendocrine functions in the epithelia or in larger group not associated with nerves; when found in association with nerves they are named Merkel complexes, acting as slow adapter mechanical receptor. Our data can be explained in two ways: Merkel cells increase as a consequence of tissue injury, a sort of "SOS cells" that secrete neuroendocrine signals to guide tissue healing; as an alternative the presence of the Merkel cells could be read as a derailment of tissue regeneration with the stop of cellular differentiation in the direction of an abnormal proliferation, a sort of mad stem cell. (c) 2010 Wiley-Liss, Inc.

Wistar rats immature testicular tissue vitrification and heterotopic grafting.

PubMed

Benvenutti, Larissa; Salvador, Rafael Alonso; Til, David; Senn, Alfred Paul; Tames, David Rivero; Amaral, Nicole Louise Lângaro; Amaral, Vera Lúcia Lângaro

2018-04-25

To evaluate the efficiency of two vitrification protocols for rat immature testicular tissue and heterotopic transplantation. Twenty-four pre-pubertal Wistar rats were divided into three groups (n=8). After orchiectomy, testicular fragments (3mm) from Groups 1 and 2 were vitrified with different cryoprotectant concentration solutions, using sterile inoculation loops as support. After warming up, the fragments were submitted to cell viability assessment by Trypan blue and histological evaluation. Vitrified (Groups 1 and 2) and fresh (Group 3) fragments were grafted to the animals periauricular region. After 8 weeks of grafting, the implant site was histologically analyzed. The viability recovery rate from Group 1 (72.09%) was higher (p=0.02) than that from Group 2 (59.19%). Histological analysis showed similar tubular integrity between fresh fragments from Groups 1 and 3. Group 2 samples presented lower tubular integrity. We ran histological analyses in the grafts from the Groups. In all groups, it was possible to see the implant site, however, no fragment of testicular tissue or signs of inflammation were histologically found in most samples from Groups 1 and 3. In one sample from Group 2, we found degenerated seminiferous tubules with necrosis and signs of an inflammatory process. In another sample from Group 2, we found seminiferous tubules in the implant site. The vitrification of pre-pubertal testicular tissue of rats showed little damage to cell viability through histological analysis when we used cryoprotectants in a lower concentration. Heterotopic transplantation could not preserve the structural organization of the testicular tissue.

Osteochondral lesions about the ankle.

PubMed

Naran, Ketan N; Zoga, Adam C

2008-11-01

Osteochondral lesions (OCLs) about the foot and ankle often manifest clinically as prolonged joint pain after trauma, often an ankle sprain, which is refractory to conventional, conservative therapeutic treatment. Noncontrast MR imaging is the standard of care imaging modality for diagnosing and classifying osteochondral lesions, but equivocal or difficult lesions can be assessed more specifically with direct MR arthrography or in conjunction with multidetector CT. Once an OCL has been identified, the imager should make every effort to determine whether it is stable or potentially unstable.

Connective tissue graft as a biological barrier for guided tissue regeneration in intrabony defects: a histological study in dogs.

PubMed

Ribeiro, Fernando Salimon; Pontes, Ana Emília Farias; Zuza, Elizangela Partata; da Silva, Vanessa Camila; Lia, Raphael Carlos Comelli; Marcantonio Junior, Elcio

2015-06-01

The use of the autogenous periosteal graft as biological barrier has been proposed for periodontal regeneration. The aim of this study was to evaluate the histometric findings of the subepithelial connective tissue graft as barrier in intrabony defects compared to a bioabsorbable membrane. Three-walled intrabony defects were created surgically in the mesial aspect of the right and left maxillary canines in five healthy mongrel dogs. The defects were chronified, and two types of barriers were randomly carried out for guided tissue regeneration in a split-mouth design: the test group with a subepithelial connective tissue graft and the control group with a bioabsorbable membrane. The specimens were processed for histometric analyses of the epithelium (E), connective tissue (CT), newly formed cementum (NC), new bone (NB), and total newly formed tissues (NFT). The test side showed smaller mean of NC (3.6 ± 1.2), NB (2.1 ± 0.7), and NFT (7.7 ± 0.8) than the control group (NC 7.3 ± 0.5; NB 5.3 ± 1.3; NFT 10.1 ± 2.2; P < 0.05). No statistically significant differences were verified for E (test 3.1 ± 2.0; control 2.8 ± 2.1; P > 0.05) and CT (test 2.5 ± 1.1; control 2.0 ± 0.5; P > 0.05) between groups. The bioabsorbable membrane was more effective in maintaining the space for periodontal regeneration than periosteal connective graft when used as barrier. The bioabsorbable membrane showed more favorable regenerative results in intrabony defects in dogs than the subepithelial connective tissue graft as biological barrier.

Soft Tissue Closure of Grafted Extraction Sockets in the Anterior Maxilla: A Modified Palatal Pedicle Connective Tissue Flap Technique.

PubMed

El Chaar, Edgard; Oshman, Sarah; Cicero, Giuseppe; Castano, Alejandro; Dinoi, Cinzia; Soltani, Leila; Lee, Yoonjung Nicole

Localized ridge resorption, the consequence of socket collapse, following tooth extraction in the anterior maxilla can adversely affect esthetics, function, and future implant placement. Immediate grafting of extraction sockets may help preserve natural ridge contours, but a lack of available soft tissue can compromise the final esthetic outcome. The presented modified rotated palatal pedicle connective tissue flap is a useful technique for simultaneous soft tissue coverage and augmentation of grafted sockets to improve esthetic outcome. This article delineates its advantages through the presentation of a four-case series using this new technique.

Adipose tissue-derived stem cell-seeded small intestinal submucosa for tunica albuginea grafting and reconstruction

PubMed Central

Ma, Limin; Yang, Yijun; Sikka, Suresh C.; Kadowitz, Philip J.; Ignarro, Louis J.; Abdel-Mageed, Asim B.; Hellstrom, Wayne J. G.

2012-01-01

Porcine small intestinal submucosa (SIS) has been widely used in tunica albuginea (TA) reconstructive surgery. Adipose tissue-derived stem cells (ADSCs) can repair damaged tissue, augment cellular differentiation, and stimulate release of multiple growth factors. The aim of this rat study was to assess the feasibility of seeding ADSCs onto SIS grafts for TA reconstruction. Here, we demonstrate that seeding syngeneic ADSCs onto SIS grafts (SIS-ADSC) resulted in significant cavernosal tissue preservation and maintained erectile responses, similar to controls, in a rat model of bilateral incision of TA, compared with sham-operated animals and rats grafted with SIS graft (SIS) alone. In addition to increased TGF-β1 and FGF-2 expression levels, cross-sectional studies of the rat penis with SIS and SIS-ADSC revealed mild to moderate fibrosis and an increase of 30% and 40% in mean diameter in flaccid and erectile states, respectively. SIS grafting induced transcriptional up-regulation of iNOS and down-regulation of endothelial NOS, neuronal NOS, and VEGF, an effect that was restored by seeding ADCSs on the SIS graft. Taken together, these data show that rats undergoing TA incision with autologous SIS-ADSC grafts maintained better erectile function compared with animals grafted with SIS alone. This study suggests that SIS-ADSC grafting can be successfully used for TA reconstruction procedures and can restore erectile function. PMID:22308363

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part I: Recapitulation of Native Tissue Healing and Variables for the Design of Delivery Systems

PubMed Central

Santo, Vítor E.; Mano, João F.; Reis, Rui L.

2013-01-01

The potential of growth factors to stimulate tissue healing through the enhancement of cell proliferation, migration, and differentiation is undeniable. However, critical parameters on the design of adequate carriers, such as uncontrolled spatiotemporal presence of bioactive factors, inadequate release profiles, and supraphysiological dosages of growth factors, have impaired the translation of these systems onto clinical practice. This review describes the healing cascades for bone, cartilage, and osteochondral interface, highlighting the role of specific growth factors for triggering the reactions leading to tissue regeneration. Critical criteria on the design of carriers for controlled release of bioactive factors are also reported, focusing on the need to provide a spatiotemporal control over the delivery and presentation of these molecules. PMID:23268651

Microsphere-based gradient implants for osteochondral regeneration: a long-term study in sheep

PubMed Central

Mohan, Neethu; Gupta, Vineet; Sridharan, Banu Priya; Mellott, Adam J; Easley, Jeremiah T; Palmer, Ross H; Galbraith, Richard A; Key, Vincent H; Berkland, Cory J; Detamore, Michael S

2015-01-01

Background: The microfracture technique for cartilage repair has limited ability to regenerate hyaline cartilage. Aim: The current study made a direct comparison between microfracture and an osteochondral approach with microsphere-based gradient plugs. Materials & methods: The PLGA-based scaffolds had opposing gradients of chondroitin sulfate and β-tricalcium phosphate. A 1-year repair study in sheep was conducted. Results: The repair tissues in the microfracture were mostly fibrous and had scattered fissures with degenerative changes. Cartilage regenerated with the gradient plugs had equal or superior mechanical properties; had lacunated cells and stable matrix as in hyaline cartilage. Conclusion: This first report of gradient scaffolds in a long-term, large animal, osteochondral defect demonstrated potential for equal or better cartilage repair than microfracture. PMID:26418471

Connective tissue grafts for thickening peri-implant tissues at implant placement. One-year results from an explanatory split-mouth randomised controlled clinical trial.

PubMed

Wiesner, Günter; Esposito, Marco; Worthington, Helen; Schlee, Markus

2010-01-01

Nothing to declare. To evaluate whether connective tissue grafts performed at implant placement could be effective in augmenting peri-implant soft tissues. Ten partially edentulous patients requiring at least one single implant in the premolar or molar areas of both sides of the mandible were randomised to have one side augmented at implant placement with a connective soft tissue graft harvested from the palate or no augmentation. After 3 months of submerged healing, abutments were placed and within 1 month definitive crowns were permanently cemented. Outcome measures were implant success, any complications, peri-implant marginal bone level changes, patient satisfaction and preference, thickness of the soft tissues and aesthetics (pink aesthetic score) evaluated by an independent and blinded assessor 1 year after loading. One year after loading, no patients dropped out, no implants failed and no complications occurred. Both groups lost statistically significant amounts of peri-implant bone 1 year after loading (0.8 mm in the grafted group and 0.6 mm in the non-grafted group), but there was no statistically significant difference between groups. Soft tissues at augmented sites were 1.3 mm thicker (P < 0.001) and had a significantly better pink aesthetic score (P < 0.001). Patients were highly satisfied (no statistically significant differences between treatments) though they preferred the aesthetics of the augmented sites (P = 0.031). However, five patients would not undergo the grafting procedure again and two were uncertain. Connective tissue grafts are effective in increasing soft tissue thickness, thus improving aesthetics. Longer follow-ups are needed to evaluate the stability of peri-implant tissues over time.

Tissue-engineered oral mucosa grafts for intraoral lining reconstruction of the maxilla and mandible with a fibula flap.

PubMed

Sieira Gil, Ramón; Pagés, Carles Martí; Díez, Eloy García; Llames, Sara; Fuertes, Ada Ferrer; Vilagran, Jesús Lopez

2015-01-01

Many types of soft tissue grafts have been used for grafting or prelaminating bone flaps for intraoral lining reconstruction. The best results are achieved when prelaminating free flaps with mucosal grafts. We suggest a new approach to obtain keratinized mucosa over a fibula flap using full-thickness, engineered, autologous oral mucosa. We report on a pilot study for grafting fibula flaps for mandibular and maxilla reconstruction with full-thickness tissue-engineered autologous oral mucosa. We describe 2 different techniques: prelaminating the fibula flap and second-stage grafting of the fibula after mandibular reconstruction. Preparation of the full-thickness tissue-engineered oral mucosa is also described. The clinical outcome of the tissue-engineered intraoral lining reconstruction and response after implant placement are reported. A peri-implant granulation tissue response was not observed when prelaminating the fibula, and little response was observed when intraoral grafting was performed. Tissue engineering represents an alternative method by which to obtain sufficient autologous tissue for reconstructing mucosal oral defects. The full-thickness engineered autologous oral mucosa offers definite advantages in terms of reconstruction planning, donor site morbidity, and quality of the intraoral soft tissue reconstruction, thereby restoring native tissue and avoiding peri-implant tissue complications. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Histologic evaluation of autogenous connective tissue and acellular dermal matrix grafts in humans.

PubMed

Cummings, Lewis C; Kaldahl, Wayne B; Allen, Edward P

2005-02-01

The clinical success of root coverage with autogenous connective tissue (CT) or acellular dermal matrix (ADM) has been well documented. However, limited histological results of CT grafts have been reported, and a case report of a human block section has been published documenting an ADM graft. The purpose of this study is to document the histological results of CT grafts, ADM grafts, and coronally advanced flaps to cover denuded roots in humans. This study included four patients previously treatment planned for extractions of three or more anterior teeth. Three teeth in each patient were selected and randomly designated to receive either a CT or ADM graft beneath a coronally advanced flap (tests) or coronally advanced flap alone (control). Six months postoperatively block section extractions were performed and the teeth processed for histologic evaluation with hematoxylin-eosin and Verhoeff's stains. Histologically, both the CT and ADM were well incorporated within the recipient tissues. New fibroblasts, vascular elements, and collagen were present throughout the ADM, while retention of the transplanted elastic fibers was apparent. No effect on the keratinization or connective tissue organization of the overlying alveolar mucosa was evident with either graft. For both materials, areas of cemental deposition were present within the root notches, the alveolar bone was essentially unaffected, and the attachments to the root surfaces were similar. Although CT and ADM have a slightly different histological appearance, both can successfully be used to cover denuded roots with similar attachments and no adverse healing.

Grinding and polishing instead of sectioning for the tissue samples with a graft: Implications for light and electron microscopy.

PubMed

Mukhamadiyarov, Rinat A; Sevostyanova, Victoria V; Shishkova, Daria K; Nokhrin, Andrey V; Sidorova, Olga D; Kutikhin, Anton G

2016-06-01

A broad use of the graft replacement requires a detailed investigation of the host-graft interaction, including both histological examination and electron microscopy. A high quality sectioning of the host tissue with a graft seems to be complicated; in addition, it is difficult to examine the same tissue area by both of the mentioned microscopy techniques. To solve these problems, we developed a new technique of epoxy resin embedding with the further grinding, polishing, and staining. Graft-containing tissues prepared by grinding and polishing preserved their structure; however, sectioning frequently required the explantation of the graft and led to tissue disintegration. Moreover, stained samples prepared by grinding and polishing may then be assessed by both light microscopy and backscattered scanning electron microscopy. Therefore, grinding and polishing outperform sectioning when applied to the tissues with a graft. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of a Comprehensive Osteochondral Allograft MRI Scoring System (OCAMRISS) With Histopathologic, Micro–Computed Tomography, and Biomechanical Validation

PubMed Central

Pallante-Kichura, Andrea L.; Bae, Won C.; Du, Jiang; Statum, Sheronda; Wolfson, Tanya; Gamst, Anthony C.; Cory, Esther; Amiel, David; Bugbee, William D.; Sah, Robert L.; Chung, Christine B.

2014-01-01

Objective: To describe and apply a semiquantitative MRI scoring system for multifeature analysis of cartilage defect repair in the knee by osteochondral allografts and to correlate this scoring system with histopathologic, micro–computed tomography (µCT), and biomechanical reference standards using a goat repair model. Design: Fourteen adult goats had 2 osteochondral allografts implanted into each knee: one in the medial femoral condyle and one in the lateral trochlea. At 12 months, goats were euthanized and MRI was performed. Two blinded radiologists independently rated 9 primary features for each graft, including cartilage signal, fill, edge integration, surface congruity, calcified cartilage integrity, subchondral bone plate congruity, subchondral bone marrow signal, osseous integration, and presence of cystic changes. Four ancillary features of the joint were also evaluated, including opposing cartilage, meniscal tears, synovitis, and fat-pad scarring. Comparison was made with histologic and µCT reference standards as well as biomechanical measures. Interobserver agreement and agreement with reference standards was assessed. Cohen’s κ, Spearman’s correlation, and Kruskal-Wallis tests were used as appropriate. Results: There was substantial agreement (κ > 0.6, P < 0.001) for each MRI feature and with comparison against reference standards, except for cartilage edge integration (κ = 0.6). There was a strong positive correlation between MRI and reference standard scores (ρ = 0.86, P < 0.01). Osteochondral allograft MRI scoring system was sensitive to differences in outcomes between the types of allografts. Conclusions: We have described a comprehensive MRI scoring system for osteochondral allografts and have validated this scoring system with histopathologic and µCT reference standards as well as biomechanical indentation testing. PMID:24489999

Tissue-engineered skin preserving the potential of epithelial cells to differentiate into hair after grafting.

PubMed

Larouche, Danielle; Cuffley, Kristine; Paquet, Claudie; Germain, Lucie

2011-03-01

The aim of this study was to evaluate whether tissue-engineered skin produced in vitro was able to sustain growth of hair follicles in vitro and after grafting. Different tissues were designed. Dissociated newborn mouse keratinocytes or newborn mouse hair buds (HBs) were added onto dermal constructs consisting of a tissue-engineered cell-derived matrix elaborated from either newborn mouse or adult human fibroblasts cultured with ascorbic acid. After 7-21 days of maturation at the air-liquid interface, no hair was noticed in vitro. Epidermal differentiation was observed in all tissue-engineered skin. However, human fibroblast-derived tissue-engineered dermis (hD) promoted a thicker epidermis than mouse fibroblast-derived tissue-engineered dermis (mD). In association with mD, HBs developed epithelial cyst-like inclusions presenting outer root sheath-like attributes. In contrast, epidermoid cyst-like inclusions lined by a stratified squamous epithelium were present in tissues composed of HBs and hD. After grafting, pilo-sebaceous units formed and hair grew in skin elaborated from HBs cultured 10-26 days submerged in culture medium in association with mD. However, the number of normal hair follicles decreased with longer culture time. This hair-forming capacity after grafting was not observed in tissues composed of hD overlaid with HBs. These results demonstrate that epithelial stem cells can be kept in vitro in a permissive tissue-engineered dermal environment without losing their potential to induce hair growth after grafting.

An evaluation of fibrin tissue adhesive concentration and application thickness on skin graft survival.

PubMed

O'Grady, K M; Agrawal, A; Bhattacharyya, T K; Shah, A; Toriumi, D M

2000-11-01

To examine the effects of fibrinogen concentration and application thickness of fibrin tissue adhesive on skin graft survival. Prospective controlled study. Ten domestic pigs were included in the study. A 20 x 5-cm area of skin was harvested bilaterally along the flanks of the animals using a Padgett dermatome. The harvested grafts were trimmed into four 4 x 4-cm squares. Donor sites were treated according to group assignment and the non-meshed grafts were placed on the side opposite their initial orientation and secured with staples. Both single- and multiple-donor human fibrin tissue adhesive preparations, with low and high average fibrinogen concentrations of 30 mg/mL and 60 mg/ mL, were used. Adhesive preparations were applied in either a thin layer (0.015 mL/cm2) or a thick layer (0.06 mL/cm2) using a spray applicator. A constant thrombin concentration of 10 U/mL was used in the study. No adhesive was used in the control group and grafts were stabilized with staples. No topical dressings were applied to any of the treatment sites. Animals were sacrificed 4 weeks after graft application. Based on statistical analysis, thickness of adhesive application had a significant effect on skin graft survival. Percent mean graft survival in the control and thin application groups was found to be 92% and 97.8% respectively; the mean survival rate in the thick application group was 63.1%. Fibrinogen concentration, when evaluated independently within the thin and thick application groups, was found to have no significant effect on graft survival. Independent of fibrinogen concentration, a thin layer of fibrin tissue adhesive, when applied between two opposing surfaces, does not interfere with and may support the healing process, whereas a thick layer of adhesive inhibits skin graft healing.

Delayed grafting of fetal CNS tissue into chronic compression lesions of the adult cat spinal cord.

PubMed

Anderson, D K; Reier, P J; Wirth Iii, E D; Theele, D P; Mareci, T; Brown, S A

1991-01-01

This review summarizes a series of experiments involving transplants of embryonic feline CNS tissue into chronic compression lesions of the adult cat spinal cord. Fetal spinal cord (FSC), caudal brainstem (BSt), neocortex (NCx) or a combination of either FSC/NCx or FSC/BSt was transplanted as solid pieces or as a suspension of dissociated cells into the developed cystic cavities produced by static-load compression trauma 2-10 weeks prior to grafting. All cats were immunosuppressed with cyclosporin A and their locomotor function was assessed for 6-30 weeks. Following the period of evaluation, all recipients were perfused with fixative and tissue specimens, taken at the transplantation site, were processed for general histological and/or immunocytochemical analysis. Viable graft tissue was found in all animals with the exception of two cats which showed active rejection of their transplants. All of the viable intraspinal grafts were extensively vascularized and did not show any signs of imminent or on-going tissue rejection. Fetal cat CNS grafts showed an extended maturational phase in that features of immature neural tissue (e.g. a paucity of myelination) were still seen even 6-9 weeks after transplantation. By 20-30 weeks, FSC and BSt grafts had attained a more advanced stage of maturation. Transplants in these chronic lesions were extensively blended with both the gray and white matter of the host spinal cord and could be visualized by magnetic resonance imaging (MRI). MRI could also detect regions of cavitation at the graft-host interface, as well as within some transplants. While preliminary evidence from behavioral studies suggest that the FSC and BSt grafts may improve or spare locomotor function in some recipients, a more rigorous analysis of post-grafting locomotor function is required to determine conclusively the functionality of these transplants.

Osteochondral injuries of the foot and ankle.

PubMed

Frost, Andrew; Roach, Richard

2009-06-01

Osteochondral injuries commonly affect the ankle joint and involve the dome of the talus. This article describes the etiology and pathogenesis of these injuries. Their clinical presentation is described and advice is given on how to diagnose and investigate suspected osteochondral injuries. The various treatment options currently available are briefly reviewed. There is some attempt made to give consensus on optimal treatment of this condition at the present time.

Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering.

PubMed

Henry, Jeffrey J D; Yu, Jian; Wang, Aijun; Lee, Randall; Fang, Jun; Li, Song

2017-08-17

Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

Outcome of Conventional Adipose Tissue Grafting for Contour Deformities of Face and Role of Ex Vivo Expanded Adipose Tissue-Derived Stem Cells in Treatment of Such Deformities.

PubMed

Bashir, Muhammad Mustehsan; Sohail, Muhammad; Bashir, Afzaal; Khan, Farid Ahmad; Jan, Sadia Nosheen; Imran, Muhammad; Ahmad, Fridoon Jawad; Choudhery, Mahmood S

2018-02-23

To evaluate the outcomes of conventional fat grafting for facial contour deformities and to describe clinical outcome of a patient with contour deformity of face treated with ex vivo expanded adipose tissue-derived mesenchymal stem cells (ASCs) enriched fat graft. The Department of Plastic Surgery and Tissue Engineering and Regenerative Medicine Laboratory, King Edward Medical University/Mayo Hospital, Lahore, from September 2015 to September 2017. Patients with contour deformities of face requiring soft tissue augmentation were included. Fat was harvested, processed, and injected following a standard protocol. Both subjective and objective assessments were performed and complications were also noted. Twenty-five patients underwent 51 fat-grafting sessions over a period of 24 months. Eighteen (72%) patients underwent multiple fat-grafting sessions. Mean (standard deviation) soft tissue thickness after 72 hours and 6 months of first fat graft session was 18.62 (7.2) and 12.88 (6.21) mm, respectively, which corresponds to 30.77 (13)% reduction of transplanted fat. Physician and patient assessment scores were 3.42 (0.92) and 4 (1.04), respectively. Few minor complications were observed. In the patient undergoing ex vivo expanded ASCs enriched fat graft, there was minimal decrease in soft tissue thickness of treated area (44 mm vs 42 mm) 6 months postoperatively and patient was highly satisfied with the outcome after the single session. Conventional fat grafting is safe for correction of facial contour deformities. However, procedure needs to be repeated multiple times to produce satisfactory results. Beneficial effects of ex vivo expanded ASCs enriched fat grafting have a potential to alter the current treatment paradigm of fat grafting for soft tissue reconstruction.

Surgical treatment for osteochondritis dessicans of the knee.

PubMed

Winthrop, Zachary; Pinkowsky, Gregory; Hennrikus, William

2015-12-01

Osteochondritis dissecans (OCD) of the knee is a disease of the subchondral bone with secondary injury to the overlying articular cartilage. OCD lesions are generally categorized as juvenile-growth plates open-or adult-growth plates closed. This maturity-based classification scheme has a prognostic value in that many juvenile OCD lesions will heal with conservative care while most symptomatic adult OCD lesions need surgical intervention. OCD can result in pain, knee joint effusions, loose body formation, and arthritis. Short-term treatment goals include pain and symptom resolution while the long-term goal is to minimize arthritis. Surgical options include debridement, drilling, microfracture, reduction and fixation, autograft osteochondral transplantation, autologous chondrocyte implantation, and allograft osteochondreal transplantation.

Alveolar Ridge Contouring with Free Connective Tissue Graft at Implant Placement: A 5-Year Consecutive Clinical Study.

PubMed

Hanser, Thomas; Khoury, Fouad

2016-01-01

This study evaluated volume stability after alveolar ridge contouring with free connective tissue grafts at implant placement in single-tooth gaps. A total of 52 single-tooth gaps with labial volume deficiencies in the maxilla (incisors, canines, and premolars) were consecutively treated with implants and concomitant free palatal connective tissue grafts in 46 patients between 2006 and 2009. Implants had to be covered with at least 2 mm peri-implant local bone after insertion. At implant placement, a free connective tissue graft from the palate was fixed inside a labial split-thickness flap to form an existing concave buccal alveolar ridge contour due to tissue volume deficiency into a convex shape. Standardized volumetric measurements of the labial alveolar contour using a template were evaluated before connective tissue grafting and at 2 weeks, 1 year, and 5 years after implantprosthetic incorporation. Tissue volume had increased significantly (P < .05) in all six reference points representing the outer alveolar soft tissue contour of the implant before connective tissue grafting to baseline (2 weeks after implant-prosthetic incorporation). Statistically, 50% of the reference points (P > .05) kept their volume from baseline to 1 year after prosthetic incorporation and from baseline to 5 years after prosthetic incorporation, respectively, whereas reference points located within the area of the implant sulcus showed a significant (P < .05) decrease in volume. Clinically, 5 years after prosthetic incorporation the originally concave buccal alveolar contour was still convex in all implants, leading to a continuous favorable anatomical shape and improved esthetic situation. Intraoral radiographs confirmed osseointegration and stable peri-implant parameters with a survival rate of 100% after a follow-up of approximately 5 years. Implant placement with concomitant free connective tissue grafting appears to be an appropriate long-term means to contour preexisting buccal

Electrospun Scaffolds for Tissue Engineering of Vascular Grafts

PubMed Central

Hasan, Anwarul; Memic, Adnan; Annabi, Nasim; Hossain, Monowar; Paul, Arghya; Dokmeci, Mehmet R.; Dehghani, Fariba; Khademhosseini, Ali

2013-01-01

There is a growing demand for off-the-shelf tissue engineered vascular grafts (TEVGs) for replacement or bypass of damaged arteries in various cardiovascular diseases. Scaffolds from the decellularized tissue skeletons to biopolymers and biodegradable synthetic polymers have been used for fabricating TEVGs. However, several issues have not yet been resolved, which include the inability to mimic the mechanical properties of native tissues, and the ability for long term patency and growth required for in vivo function. Electrospinning is a popular technique for the production of scaffolds that has the potential to address these issues. However, its application to human TEVGs has not yet been achieved. This review provides an overview of tubular scaffolds that have been prepared by electrospinning with potential for TEVG applications. PMID:23973391

Three dimensional socket preservation: a technique for soft tissue augmentation along with socket grafting

PubMed Central

2012-01-01

Background A cursory review of the current socket preservation literatures well depicts the necessity of further esthetic considerations through the corrective procedures of the alveolar ridge upon and post extraction. A new technique has been described here is a rotational pedicle combined epithelialized and connective tissue graft (RPC graft) adjunct with immediate guided tissue regeneration (GBR) procedure. Results We reviewed this technique through a case report and discuss it’s benefit in compare to other socket preservation procedures. Conclusion The main advantages of RPC graft would be summarized as follows: stable primary closure during bone remodeling, saving or crating sufficient vestibular depth, making adequate keratinized gingiva on the buccal surface, and being esthetically pleasant. PMID:22540920

Osteochondral Autograft Transplantation Surgery for Metacarpal Head Defects.

PubMed

Kitay, Alison; Waters, Peter M; Bae, Donald S

2016-03-01

Post-traumatic osteonecrosis of the metacarpal head is a challenging problem, particularly in younger patients in whom arthroplasty may not be a durable option. Although several osteochondral reconstructive options have been proposed, some are associated with considerable donor site morbidity and/or require the use of internal fixation. We present an application of osteochondral autograft transplantation surgery as a treatment option for focal metacarpal head lesions. An osteochondral plug from the non-weight-bearing articular surface of the knee is transferred and press-fit to resurface a focal metacarpal head defect. The technical pearls and pitfalls are reviewed, and an illustrative case is presented. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

High resolution MRI imaging at 9.4 Tesla of the osteochondral unit in a translational model of articular cartilage repair.

PubMed

Goebel, Lars; Müller, Andreas; Bücker, Arno; Madry, Henning

2015-04-16

Non-destructive structural evaluation of the osteochondral unit is challenging. Here, the capability of high-field magnetic resonance imaging (μMRI) at 9.4 Tesla (T) was explored to examine osteochondral repair ex vivo in a preclinical large animal model. A specific aim of this study was to detect recently described alterations of the subchondral bone associated with cartilage repair. Osteochondral samples of medial femoral condyles from adult ewes containing full-thickness articular cartilage defects treated with marrow stimulation were obtained after 6 month in vivo and scanned in a 9.4 T μMRI. Ex vivo imaging of small osteochondral samples (typical volume: 1-2 cm(3)) at μMRI was optimised by variation of repetition time (TR), time echo (TE), flip angle (FA), spatial resolution and number of excitations (NEX) from standard MultiSliceMultiEcho (MSME) and three-dimensional (3D) spoiled GradientEcho (SGE) sequences. A 3D SGE sequence with the parameters: TR = 10 ms, TE = 3 ms, FA = 10°, voxel size = 120 × 120 × 120 μm(3) and NEX = 10 resulted in the best fitting for sample size, image quality, scanning time and artifacts. An isovolumetric voxel shape allowed for multiplanar reconstructions. Within the osteochondral unit articular cartilage, cartilaginous repair tissue and bone marrow could clearly be distinguished from the subchondral bone plate and subarticular spongiosa. Specific alterations of the osteochondral unit associated with cartilage repair such as persistent drill holes, subchondral bone cysts, sclerosis of the subchondral bone plate and of the subarticular spongiosa and intralesional osteophytes were precisely detected. High resolution, non-destructive ex vivo analysis of the entire osteochondral unit in a preclinical large animal model that is sufficient for further analyses is possible using μMRI at 9.4 T. In particular, 9.4 T is capable of accurately depicting alterations of the subchondral bone that are associated with

Current Concepts: Osteochondritis Dissecans of the Capitellum and the Role of Osteochondral Autograft Transplantation.

PubMed

Kirsch, Jacob M; Thomas, Jared; Bedi, Asheesh; Lawton, Jeffrey N

2016-12-01

Background: Osteochondritis dissecans (OCD) of the capitellum is a painful condition, which often affects young throwing athletes. Our current understanding regarding the etiology, risks factors, diagnosis, and efficacy of the available treatment options has expanded over recent years, however remains suboptimal. Recent data on patient-reported outcomes following osteochondral autograft transplantation (OAT) for the treatment of large osteochondral lesions of the capitellum have been promising but limited. This review seeks to critically analyze and summarize the available literature on the etiology, diagnosis, and reported outcomes associated with OCD of the capitellum and the use of OAT for its treatment. Methods: A comprehensive literature search was conducted. Unique and customized search strategies were formulated in PubMed, Embase, Scopus, Web of Science, and CENTRAL. Combinations of keywords and controlled vocabulary terms were utilized in order to cast a broad net. Relevant clinical, biomechanical, anatomic and imaging studies were reviewed along with recent review articles, and case series. Results: Forty-three articles from our initial literature search were found to be relevant for this review. The majority of these articles were either review articles, clinical studies, anatomic or imaging studies or biomechanical studies. Conclusions: Current evidence suggests that OAT may lead to better and more consistent outcomes than previously described methods for treating large OCD lesions of the capitellum.

Intraoral Grafting of Tissue-Engineered Human Oral Mucosa

PubMed Central

Izumi, Kenji; Neiva, Rodrigo F.; Feinberg, Stephen E.

2014-01-01

Purpose The primary objective of this study was to evaluate the safety of a tissue-engineered human ex vivo–produced oral mucosa equivalent (EVPOME) in intraoral grafting procedures. The secondary objective was to assess the efficacy of the grafted EVPOME in producing a keratinized mucosal surface epithelium. Materials and Methods Five patients who met the inclusion criteria of having one mucogingival defect or a lack of keratinized gingiva on a nonmolar tooth, along with radiographic evidence of sufficient interdental bone height, were recruited as subjects to increase the width of keratinized gingiva at the defect site. A punch biopsy specimen of the hard palate was taken to acquire oral keratinocytes, which were expanded, seeded, and cultured on an acellular dermal matrix for fabrication of an EVPOME. EVPOME grafts were applied directly over an intact periosteal bed and secured in place. At baseline (biopsy specimen retrieval) and at 7, 14, 30, 90, and 180 days postsurgery, Plaque Index and Gingival Index were recorded for each subject. In addition, probing depths, keratinized gingival width, and keratinized gingival thickness were recorded at baseline, 30, 90, and 180 days. Results No complications or adverse reactions to EVPOME were observed in any subjects during the study. The mean gain in keratinized gingival width was 3 mm (range, 3 to 4 mm). The mean gain in keratinized gingival thickness was 1 mm (range, 1 to 2 mm). No significant changes in probing depths were observed. Conclusion Based on these findings, it can be concluded that EVPOME is safe for intraoral use and has the ability to augment keratinized tissue around teeth. Future clinical trials are needed to further explore this potential. PMID:24066347

Surgical option for the correction of Peyronie's disease: an autologous tissue-engineered endothelialized graft.

PubMed

Imbeault, Annie; Bernard, Geneviève; Ouellet, Gabrielle; Bouhout, Sara; Carrier, Serge; Bolduc, Stéphane

2011-11-01

Surgical treatment is indicated in severe cases of Peyronie's disease. Incision of the plaque with subsequent graft material implantation is the option of choice. Ideal graft tissue is not yet available. To evaluate the use of an autologous tissue-engineered endothelialized graft by the self-assembly method, for tunica albuginea (TA) reconstruction in Peyronie's disease. Two TA models were created. Human fibroblasts were isolated from a skin biopsy and cultured in vitro until formation of fibroblast sheets. After 4 weeks of maturation, human umbilical vein endothelial cells (HUVEC) were seeded on fibroblasts sheets and wrapped around a tubular support to form a cylinder of about 10 layers. After 21 days of tube maturation, HUVEC were seeded into the lumen of the fibroblast tubes for the endothelialized tunica albuginea (ETA). No HUVEC were seeded into the lumen for the TA model. Both constructs were placed under perfusion in a bioreactor for 1 week. Histology, immunohistochemistry, and burst pressure were performed to characterize mature tubular graft. Animal manipulations were also performed to demonstrate the impact of endothelial cells in vivo. Histology showed uniform multilayered fibroblasts. Extracellular matrix, produced entirely by fibroblasts, presented a good staining for collagen 1. Some elastin fibers were also present. For the TA model, anti-human von Willebrand antibody revealed the endothelial cells forming capillary-like structures. TA model reached a burst pressure of 584 mm Hg and ETA model obtained a burst pressure of 719 mm Hg. This tissue-engineered endothelialized tubular graft is structurally similar to normal TA and presents an adequate mechanical resistance. The self-assembly method used and the autologous property of this model could represent an advantage comparatively to other available grafts. Further evaluation including functional testing will be necessary to characterize in vivo implantation and behavior of the graft. © 2011

Validity of T2 mapping in characterization of the regeneration tissue by bone marrow derived cell transplantation in osteochondral lesions of the ankle.

PubMed

Battaglia, M; Rimondi, E; Monti, C; Guaraldi, F; Sant'Andrea, A; Buda, R; Cavallo, M; Giannini, S; Vannini, F

2011-11-01

Bone marrow derived cell transplantation (BMDCT) has been recently suggested as a possible surgical technique to repair osteochondral lesions. To date, no qualitative MRI studies have evaluated its efficacy. The aim of our study is to investigate the validity of MRI T2-mapping sequence in characterizing the reparative tissue obtained and its ability to correlate with clinical results. 20 patients with an osteochondral lesion of the talus underwent BMDCT and were evaluated at 2 years follow up using MRI T2-mapping sequence. 20 healthy volunteers were recruited as controls. MRI images were acquired using a protocol suggested by the International Cartilage Repair Society, MOCART scoring system and T2 mapping. Results were then correlated with AOFAS clinical score. AOFAS score increased from 66.8±14.5 pre-operatively to 91.2±8.3 (p<0.0005) at 2 years follow-up. T2-relaxation time value of 35-45 ms was derived from healthy ankles evaluation and assumed as normal hyaline cartilage value and used as a control. Regenerated tissue with a T2-relaxation time value comparable to hyaline cartilage was found in all the cases treated, covering a mean of 78% of the repaired lesion area. A high clinical score was related directly to isointense signal in DPFSE fat sat (p=0.05), and percentage of regenerated hyaline cartilage (p=0.05), inversely to the percentage of regenerated fibrocartilage. Lesion's depth negatively related to the integrity of the repaired tissue's surface (tau=-0.523, p=0.007), and to the percentage of regenerated hyaline cartilage (rho=-0.546, p=0.013). Because of its ability to detect cartilage's quality and to correlate to the clinical score, MRI T2-mapping sequence integrated with Mocart score represent a valid, non-invasive technique for qualitative cartilage assessment after regenerative surgical procedures. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Subperiosteal and intraosseous connective tissue grafts for pocket reduction: a 9- to 13-year retrospective case series report.

PubMed

Nelson, S W

2001-10-01

Recent histological evidence has documented that grafted palatal connective tissue is capable of forming a new attachment to previously exposed roots in the treatment of gingival recession. No clinical studies have tested the ability of connective tissue that has been implanted beneath the periosteum into periodontal osseous defects to reduce probing depth and increase clinical attachment levels. This study reports the long-term clinical effect of subperiosteal and intraosseous connective tissue grafts on deep periodontal pockets. Connective tissue (CT) grafts were placed in 32 periodontal pockets on 27 patients. Grafts were classified into 3 groups. Type I grafts had 50% or more vascular surface contact and were < or = 2.5 mm thick. Type II grafts had 50% or more contact but were > 2.5 mm thick, and Type III grafts had less than 50% vascular contact regardless of thickness. Twelve of 14 Type I sites, 9 of 15 Type II sites, and 3 of 3 Type III sites were analyzed 9 to 13 years following treatment. Clinical attachment level change differed significantly between the graft types on survivor teeth (P < 0.05): Type III had 2 mm loss (95% confidence interval [CI]: 0.4 to 3.6), while Type II and Type I grafts had a 2.7 mm gain (95% CI: 2.0 to 3.4) and 4.3 mm gain (95% CI: 3.3 to 5.2), respectively. Similar substantial differences were presented for changes in probing depth and recession. This long-term (9 to 13 years) retrospective case-series analysis suggests substantial improvements in periodontal clinical measures for Type I CT grafts in deep periodontal pockets. Randomized trials are required to evaluate this promising procedure.

[Experimental study on loading naringin composite scaffolds for repairing rabbit osteochondral defects].

PubMed

Huang, Junbo; Wang, Shiyong; Zhang, Xiaomin; Li, Gen; Ji, Puzhong; Zhao, Hongbin

2017-04-01

cartilage, and new cartilage well integrated with the adjacent cartilage in group D. The results of histological staining revealed that defects were filled with a small amount of fibrous tissue in groups A and B, and a small amount of new cartilage in groups C and D at 3 months after repair; new cartilage of groups C and D was similar to normal cartilage, but defects were filled with a large amount of fibrous tissue in groups A and B at 6 months after repair. The expression of collagen type II in groups C and D was significantly higher than that in groups A and B ( P <0.05), but no significant difference was found between groups C and D ( P >0.05). Loading naringin composite scaffolds have good biocompatibility and effect in repair of rabbit articular osteochondral defects.

Post-traumatic osteochondral ''loose body'' of the olecranon fossa

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

Bassett, L.W.; Mirra, J.M.; Forrester, D.M.

1981-12-01

Three cases of intra-articular osteochondral bodies with the olecranon fossa are reported. All patients had had severe trauma to the elbow, and in each case an osteochondral fragment, nourished by the synovial fluid, became enlarged and finally lodged within the fossa. The radiological and pathological features and presumed pathogenesis are described.

Preliminary study of coconut water for graft tissues preservation in transplantation.

PubMed

César, Jorge Miguel Schettino; Petroianu, Andy; Vasconcelos, Leonardo de Souza; Cardoso, Valbert Nascimento; Mota, Luciene das Graças; Barbosa, Alfredo José Afonso; Soares, Cristina Duarte Vianna; de Oliveira, Amanda Lima

2015-01-01

to verify the effectiveness of coconut water in preserving tissues for transplant. Fifty male Wistar rats were randomly distributed in five groups, according to the following preservation solutions for tissue grafts: Group 1: Lactated Ringer; Group 2: Belzer solution; Group 3: mature coconut water; Group 4: green coconut water; Group 5: modified coconut water. In Group 5, the green coconut water has been modified like the Belzer solution. From each animal we harvested the spleen, ovaries and skin of the back segment. These tissues were preserved for six hours in one of the solutions. Then, the grafts were reimplanted. The recovery of the function of the implanted tissues was assessed 90 days after surgery, by splenic scintigraphy and blood exam. The implanted tissues were collected for histopathological examination. The serum levels did not differ among groups, except for the animals in Group 5, which showed higher levels of IgG than Group 1, and differences in relation to FSH between groups 1 and 2 (p <0.001), 4 and 2 (p = 0.03) and 5 and 2 (p = 0.01). The splenic scintigraphy was not different between groups. The ovarian tissue was better preserved in mature coconut water (p <0.007). the coconut water-based solutions preserves spleen, ovary, and rat skin for six hours, maintaining their normal function.

[Comparative study on graft of autogeneic iliac bone and tissue engineered bone].

PubMed

Shen, Bing; Xie, Fu-lin; Xie, Qing-fang

2002-11-01

To compare the clinical results of repairing bone defect of limbs with tissue engineering technique and with autogeneic iliac bone graft. From July 1999 to September 2001, 52 cases of bone fracture were randomly divided into two groups (group A and B). Open reduction and internal fixation were performed in all cases as routine operation technique. Autogeneic iliac bone was implanted in group A, while tissue engineered bone was implanted in group B. Routine postoperative treatment in orthopedic surgery was taken. The operation time, bleeding volume, wound healing and drainage volume were compared. The bone union was observed by the X-ray 1, 2, 3, and 5 months after operation. The sex, age and disease type had no obvious difference between groups A and B. all the wounds healed with first intention. The swelling degree of wound and drainage volume had no obvious difference. The operation time in group A was longer than that in group B (25 minutes on average) and bleeding volume in group A was larger than that in group B (150 ml on average). Bone union completed within 3 to 7 months in both groups. But there were 2 cases of delayed union in group A and 1 case in group B. Repair of bone defect with tissue engineered bone has as good clinical results as that with autogeneic iliac bone graft. In aspect of operation time and bleeding volume, tissue engineered bone graft is superior to autogeneic iliac bone.

Return to sports after autogenous osteochondral mosaicplasty of the femoral condyles: 25 cases at a mean follow-up of 9 years.

PubMed

Cognault, J; Seurat, O; Chaussard, C; Ionescu, S; Saragaglia, D

2015-05-01

Autogenous osteochondral mosaicplasty is the most common cartilage restoration technique in standard clinical practice. The purpose of this study was to evaluate the return to sports 9 years after mosaicplasty of the femoral condyles. The long-term results of an osteochondral autograft show that patients can regain their pre-injury activity level. This study is based on a series of 25 patients with a mean age of 28.9 years (range, 16-44 years) who had stage 3 or 4 chondral lesions of the femoral condyles (according to the ICRS or ICRS-OCD scores). The origin of the lesion was osteochondritis dissecans (13 knees), osteochondral fracture sequelae (ten knees), or aseptic osteonecrosis (two knees). The average size of the lesion was 2.11 ± 0.9 cm(2). Ten patients (40%) had an associated procedure during the osteochondral autograft. The patients were assessed clinically (IKDC and Lysholm-Tegner scores) and radiographically by a reviewer independent of the team of operators. All patients were re-examined at a mean follow-up of 9 years (range, 6-15 years), with 84% satisfied or very satisfied with the procedure. The average IKDC was 74.5 ± 18.5 points. The average Lysholm score was 87.3 ± 11.6 points. The average Tegner score ranged from 6.35 ± 1.53 points prior to surgery to 5.60 ± 1.64 points after surgery (P = 0.001). The average loss was 0.64 points for patients whose presurgery Tegner score was greater than or equal to 7 (P = 0.019) and 0.3 points if lower than 7. The radiologic evaluation of 21 patients showed complete osteointegration of the grafts in 90% of cases. The results of the femoral condyle mosaic autografts are satisfactory, a mean of 9 years after surgery. The most active patients lowered their activity level while the more sedentary did not have to adapt their lifestyle. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Focal Defects of the Knee Articular Surface: Evidence of a Regenerative Potential Pattern in Osteochondritis Dissecans and Degenerative Lesions

PubMed Central

Gabusi, Elena; Manferdini, Cristina; Paolella, Francesca; Gambari, Laura; Mariani, Erminia

2017-01-01

The surgical treatment of knee articular focal lesions may offer heterogeneous clinical results. Osteochondritis dissecans (OCD) lesions showed to heal better than degenerative lesions (DL) but the underlying biological reasons are unknown. We evaluated the basal histological and immunohistochemical characteristics of these lesions analyzing a series of osteochondral fragments from young patients with similar age but presenting different etiology. Osteochondral tissue samples were stained with Safranin O and graded using a histological score. Markers of mesenchymal progenitor cells (CD146), osteoclasts (tartrate-resistant acid phosphatase, TRAP), and vessels (CD34) were evaluated. Histological score showed a higher degeneration of both cartilage and bone compartments in OCD compared to DL fragments. Only CD146-positive cells were found at the same percentage in cartilage compartment of both DL and OCD patients. By contrast, in the bone compartment a significantly higher percentage of CD146, TRAP, and CD34 markers was found in OCD compared to DL patients. These data showed distinct histological characteristics of osteochondral focal lesions located in the same anatomical region but having a different etiology. The higher percentages of these markers in OCD than in DL, mainly associated with a high bone turnover, could help to explain the higher clinical healing potential of OCD patients. PMID:28770227

Differences in joint morphology between the knee and ankle affect the repair of osteochondral defects in a rabbit model.

PubMed

Makitsubo, Manami; Adachi, Nobuo; Nakasa, Tomoyuki; Kato, Tomohiro; Shimizu, Ryo; Ochi, Mitsuo

2016-10-04

Although differences in the results of the bone marrow stimulation technique between the knee and ankle have been reported, a detailed mechanism for those differences has not been clarified. The purpose of this study was to examine whether morphological differences between the knee and ankle joint affect the results of drilling as treatment for osteochondral defects in a rabbit model. Osteochondral defects were created at the knee and ankle joint in the rabbit. In the knee, osteochondral defects were created at the medial femoral condyle (MFC) and patellar groove (PG). At the ankle, defects were created in the talus at either a covered or uncovered area by the tibial plafond. After creating the osteochondral defect, drilling was performed. At 4, 8, and 12 weeks after surgery, repair of the osteochondral defects were evaluated histologically. The proliferation of rabbit chondrocytes and proteoglycan release of cartilage tissue in response to IL-1β were analyzed in vitro in both joints. At 8 weeks after surgery, hyaline cartilage repair was observed in defects at the covered area of the talus and the MFC. At 12 weeks, hyaline cartilage with a normal thickness was observed for the defect at the covered area of the talus, but not for the defect at the MFC. At 12 weeks, subchondral bone formation progressed and a normal contour of subchondral bone was observed on CT in the defect at the covered area of the talus. No significant differences in chondrocyte proliferation rate and proteoglycan release were detected between the knee and ankle in vitro. Our results demonstrate that the covered areas of the talus show early and sufficient osteochondral repair compared to that of the knee and the uncovered areas of the talus. These results suggest that the congruent joint shows better subchondral repair prior to cartilage repair compared to that of the incongruent joint.

Recent Advances in Cartilage Tissue Engineering: From the Choice of Cell Sources to the Use of Bioreactors

NASA Astrophysics Data System (ADS)

Martin, Ivan; Démarteau, Olivier; Braccini, Alessandra

Grafting engineered cartilage tissues represents a promising approach for the repair of joint injuries. Recent animal experiments have demonstrated that tissues engineered by culturing chondrocytes on 3D scaffolds in bioreactors provide functional templates for orderly repair of large osteochondral lesions. To date, however, a reproducible generation of uniform cartilage tissues of predefined size starting from adult human cells has not been achieved. In this paper we review some of the recent advances and challenges ahead in the identification of appropriate (i) cell sources, (ii) bioactive factors, (iii) 3D scaffolds and (iv) bioreactors for human cartilage tissue engineering. We also present an example of how integrated efforts in these different areas can help addressing fundamental questions and advancing the field of cartilage tissue engineering towards clinical use. The presented experiment demonstrates that human nasal chondrocytes are responsive to dynamic loading and thus could be further investigated as a cell source for implantation in a joint environment.

Cell culture-based tissue engineering as an alternative to bone grafts in implant dentistry: a literature review.

PubMed

Boeckel, Daniel Gonçalves; Shinkai, Rosemary Sadami Arai; Grossi, Márcio Lima; Teixeira, Eduardo Rolim

2012-09-01

Several biomaterials and techniques for bone grafting have been described in the literature for atresic bone tissue replacement caused by edentulism, surgical resectioning, and traumas. A new technique involves tissue engineering, a promising option to replace bone tissue and solve problems associated with morbidity of autogenous grafting. This literature review aims to describe tissue-engineering techniques using ex vivo cell culture as an alternative to repair bone maxillary atresias and discuss the concepts and potentials of bone regeneration through cell culture techniques as an option for restorative maxillofacial surgery.

Stage-two surgery using collagen soft tissue grafts: clinical cases and ultrastructural analysis.

PubMed

Fischer, Kai R; Fickl, Stefan; Mardas, Nikos; Bozec, Laurent; Donos, Nikolaos

2014-01-01

To present the application of two different soft tissue grafts around dental implants during stage-two surgery. Furthermore, the ultrastructure of these materials is shown and discussed using scanning electron microscopy (SEM). Although soft tissue autografts may be currently regarded as the gold standard, harvesting of these grafts might lead to higher morbidity, longer chair time, and intra-/postoperative complications at the donor site. New developments in collagen scaff olds have provided an alternative to successfully replace autologous grafts in clinical practice. The SEM pictures clearly show the different composition of a bilayer scaff old (collagen matrix, CM) and a porcine acellular dermal matrix (ADM). These distinctive properties lead to different possible indications. Within the presented cases, ADM was used to augment the ridge contour and was placed into a buccal pouch to achieve complete coverage and an uneventful closed healing. On the other side, CM was left exposed to the oral cavity to successfully gain keratinized mucosa around and between two dental implants.

Bacterial adherence to graft tissues in static and flow conditions.

PubMed

Veloso, Tiago Rafael; Claes, Jorien; Van Kerckhoven, Soetkin; Ditkowski, Bartosz; Hurtado-Aguilar, Luis G; Jockenhoevel, Stefan; Mela, Petra; Jashari, Ramadan; Gewillig, Marc; Hoylaerts, Marc F; Meyns, Bart; Heying, Ruth

2018-01-01

Various conduits and stent-mounted valves are used as pulmonary valve graft tissues for right ventricular outflow tract reconstruction with good hemodynamic results. Valve replacement carries an increased risk of infective endocarditis (IE). Recent observations have increased awareness of the risk of IE after transcatheter implantation of a stent-mounted bovine jugular vein valve. This study focused on the susceptibility of graft tissue surfaces to bacterial adherence as a potential risk factor for subsequent IE. Adhesion of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus sanguinis to bovine pericardium (BP) patch, bovine jugular vein (BJV), and cryopreserved homograft (CH) tissues was quantified under static and shear stress conditions. Microscopic analysis and histology were performed to evaluate bacterial adhesion to matrix components. In general, similar bacteria numbers were recovered from CH and BJV tissue surfaces for all strains, especially in flow conditions. Static bacterial adhesion to the CH wall was lower for S sanguinis adhesion (P < .05 vs BP patch). Adhesion to the BJV wall, CH wall, and leaflet was decreased for S epidermidis in static conditions (P < .05 vs BP patch). Bacterial adhesion under shear stress indicated similar bacterial adhesion to all tissues, except for lower adhesion to the BJV wall after S sanguinis incubation. Microscopic analysis showed the importance of matrix component exposure for bacterial adherence to CH. Our data provide evidence that the surface composition of BJV and CH tissues themselves, bacterial surface proteins, and shear forces per se are not the prime determinants of bacterial adherence. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Changes of the peri-implant soft tissue thickness after grafting with a collagen matrix.

PubMed

Zafiropoulos, Gregory-George; Deli, Giorgio; Hoffmann, Oliver; John, Gordon

2016-01-01

The aim of this study was to determine the treatment outcome of the use of a porcine monolayer collagen matrix (mCM) to increase soft-tissue volume as a part of implant site development. Implants were placed in single sites in 27 patients. In the test group, mCM was used for soft-tissue augmentation. No graft was placed in the control group. Soft-tissue thickness (STTh) was measured at the time of surgery (T0) and 6 months postoperatively (T1) at two sites (STTh 1, 1 mm below the gingival margin; STTh 2, 3 mm below the mucogingival margin). Significant increases ( P < 0.001) in STTh (STTh 1 = 1.06 mm, 117%; STTh 2 = 0.89 mm, 81%) were observed in the test group. Biopsy results showed angiogenesis and mature connective tissue covered by keratinized epithelium. Within the limitations of this study, it could be concluded that mCM leads to a significant increase of peri-implant soft-tissue thickness, with good histological integration and replacement by soft tissue and may serve as an alternative to connective tissue grafting.

How I Manage Osteochondritis Dissecans.

ERIC Educational Resources Information Center

DiStefano, Vincent J.

1986-01-01

Osteochondritis dissecans, a lesion found most often on the femur at the knee joint, occurs most frequently in active adolescents. This article describes treatment for preadolescents, adolescents, and adults. Osteochondritus dissecans of the patella is also presented. (MT)

The influence of different soft-tissue grafting procedures at single implant placement on esthetics: A randomized controlled trial.

PubMed

Zuiderveld, Elise G; Meijer, Henny J A; Vissink, Arjan; Raghoebar, Gerry M

2018-05-13

Soft tissue grafting to thicken the soft tissue around dental implants was proposed to ameliorate the esthetic outcome. Traditionally, connective tissue is used as a grafting material, but a xenogeneic collagen matrix was introduced as an alternative to reduce patient morbidity. Sixty patients randomly received either no graft (n = 20, NG group), a connective tissue graft (n = 20, CTG group) or a xenogeneic collagen matrix (n = 20, XCM group) when placing an implant in a preserved alveolar ridge. Changes in mid-buccal mucosal level (MBML) at one (T 1 ) and twelve (T 12 ) months after final implant crown placement were compared to the pre-extraction situation. Additionally, esthetics, marginal bone level, clinical peri-implant parameters and patient satisfaction were assessed. At T 12 , mean changes in MBML were -0.48±1.5 mm, -0.04±1.1 mm and -0.17±1.3 mm in the NG, CTG and XCM groups (p = 0.56), respectively. Regarding the other outcome variables, no significant inter-group differences were observed. Soft tissue grafting at single implant placement in preserved alveolar ridges does not result in a better esthetic outcome or in better peri-implant health and should not be considered as a standard procedure. This article is protected by copyright. All rights reserved. © 2018 American Academy of Periodontology.

Influence of insulin-like growth factor-I (IGF-I) on nerve autografts and tissue-engineered nerve grafts.

PubMed

Fansa, Hisham; Schneider, Wolfgang; Wolf, Gerald; Keilhoff, Gerburg

2002-07-01

To overcome the problems of limited donor nerves for nerve reconstruction, we established nerve grafts made from cultured Schwann cells and basal lamina from acellular muscle and used them to bridge a 2-cm defect of the rat sciatic nerve. Due to their basal lamina and to viable Schwann cells, these grafts allow regeneration that is comparable to autologous nerve grafts. In order to enhance regeneration, insulin-like growth factor (IGF-I) was locally applied via osmotic pumps. Autologous nerve grafts with and without IGF-I served as controls. Muscle weight ratio was significantly increased in the autograft group treated with IGF-I compared to the group with no treatment; no effect was evident in the tissue-engineered grafts. Autografts with IGF-I application revealed a significantly increased axon count and an improved g-ratio as indicator for "maturity" of axons compared to autografts without IGF-I. IGF-I application to the engineered grafts resulted in a decreased axon count compared to grafts without IGF-I. The g-ratio, however, revealed no significant difference between the groups. Local administration of IGF-I improves axonal regeneration in regular nerve grafts, but not in tissue-engineered grafts. Seemingly, in these grafts the interactive feedback mechanisms of neuron, glial cell, and extracellular matrix are not established, and IGF-I cannot exert its action as a pleiotrophic signal. Copyright 2002 Wiley Periodicals, Inc.

Acute Delamination of Commercially Available Decellularized Osteochondral Allograft Plugs

PubMed Central

Degen, Ryan M.; Tetreault, Danielle; Mahony, Greg T.; Williams, Riley J.

2016-01-01

Articular cartilage injuries, and corresponding surgical procedures, are occurring with increasing frequency as identified by a review of recent surgical trends. Concerns have grown in recent years regarding the longevity of results following microfracture, with a shift toward cartilage restoration procedures in recent years. This case report describes 2 cases of acute failure following the use of commercially available osteochondral allograft plugs used for the treatment of osteochondral defects of the distal femur. In both cases the chondral surface of the plug delaminated from the underlying cancellous bone, resulting in persistent pain and swelling requiring reoperation and removal of the loose fragments. Caution should be employed when considering use of these plugs for the treatment of osteochondral lesions, as similar outcomes have not been noted with other cartilage restoration techniques. PMID:27688840

Treatment of Articular Cartilage Defects in the Goat with Frozen Versus Fresh Osteochondral Allografts: Effects on Cartilage Stiffness, Zonal Composition, and Structure at Six Months

PubMed Central

Pallante, Andrea L.; Görtz, Simon; Chen, Albert C.; Healey, Robert M.; Chase, Derek C.; Ball, Scott T.; Amiel, David; Sah, Robert L.; Bugbee, William D.

2012-01-01

Background: Understanding the effectiveness of frozen as compared with fresh osteochondral allografts at six months after surgery and the resultant consequences of traditional freezing may facilitate in vivo maintenance of cartilage integrity. Our hypothesis was that the state of the allograft at implantation affects its performance after six months in vivo. Methods: The effect of frozen as compared with fresh storage on in vivo allograft performance was determined for osteochondral allografts that were transplanted into seven recipient goats and analyzed at six months. Allograft performance was assessed by examining osteochondral structure (cartilage thickness, fill, surface location, surface degeneration, and bone-cartilage interface location), zonal cartilage composition (cellularity, matrix content), and cartilage biomechanical function (stiffness). Relationships between cartilage stiffness or cartilage composition and surface degeneration were assessed with use of linear regression. Results: Fresh allografts maintained cartilage load-bearing function, while also maintaining zonal organization of cartilage cellularity and matrix content, compared with frozen allografts. Overall, allograft performance was similar between fresh allografts and nonoperative controls. However, cartilage stiffness was approximately 80% lower (95% confidence interval [CI], 73% to 87%) in the frozen allografts than in the nonoperative controls or fresh allografts. Concomitantly, in frozen allografts, matrix content and cellularity were approximately 55% (95% CI, 22% to 92%) and approximately 96% (95% CI, 94% to 99%) lower, respectively, than those in the nonoperative controls and fresh allografts. Cartilage stiffness correlated positively with cartilage cellularity and matrix content, and negatively with surface degeneration. Conclusions: Maintenance of cartilage load-bearing function in allografts is associated with zonal maintenance of cartilage cellularity and matrix content. In

Dimensional changes in soft tissues around dental implants following free gingival grafting: an experimental study in dogs.

PubMed

Bengazi, Franco; Lang, Niklaus P; Caroprese, Marino; Urbizo Velez, Joaquin; Favero, Vittorio; Botticelli, Daniele

2015-02-01

To study the buccal dimensional tissue changes at oral implants following free gingival grafting, with or without including the keratin layer, performed at the time of implant installation into alveolar mucosa. The mandibular premolars and first molars were extracted bilaterally in six Beagle dogs. In the right side of the mandible (Test), flaps were first elevated, and the buccal as well as part of the lingual masticatory mucosa was removed. An incision of the periosteum at the buccal aspect was performed to allow the flap to be coronally repositioned. Primary wound closure was obtained. In the left side, the masticatory (keratinized) mucosa was left in situ, and no sutures were applied (Control). After 3 months of healing, absence of keratinized mucosa was confirmed at the test sites. Two recipient sites were prepared at each side of the mandible in the region of the third and fourth premolars. All implants were installed with the shoulder placed flush with the buccal alveolar bony crest, and abutments were connected to allow a non-submerged healing. Two free gingival mucosal grafts were harvested from the buccal region of the maxillary canines. One graft was left intact (gingival mucosal graft), while for the second, the epithelial layer was removed (gingival connective tissue graft). Subsequently, the grafts were fixed around the test implants in position of the third and fourth premolars, respectively. After 3 months, the animals were euthanized and ground sections obtained. Similar bony crest resorption and coronal extension of osseointegration were found at test and control sites. Moreover, similar dimensions of the peri-implant soft tissues were obtained at test and control sites. The increase in the alveolar mucosal thickness by means of a gingival graft affected the peri-implant marginal bone resorption and soft tissue recession around implants. This resulted in outcomes that were similar to those at implants surrounded by masticatory mucosa, indicating

Success Rates and Immunologic Responses of Autogenic, Allogenic, and Xenogenic Treatments to Repair Articular Cartilage Defects

PubMed Central

Revell, Christopher M.

2009-01-01

This review examines current approaches available for articular cartilage repair, not only in terms of their regeneration potential, but also as a function of immunologic response. Autogenic repair techniques, including osteochondral plug transplantation, chondrocyte implantation, and microfracture, are the most widely accepted clinical treatment options due to the lack of immunogenic reactions, but only moderate graft success rates have been reported. Although suspended allogenic chondrocytes are shown to evoke an immune response upon implantation, allogenic osteochondral plugs and tissue-engineered grafts using allogenic chondrocytes exhibit a tolerable immunogenic response. Additionally, these repair techniques produce neotissue with success rates approaching those of currently available autogenic repair techniques, while simultaneously obviating their major hindrance of donor tissue scarcity. To date, limited research has been performed with xenogenic tissue, although several studies demonstrate the potential for its long-term success. This article focuses on the various treatment options for cartilage repair and their associated success rates and immunologic responses. PMID:19063664

In vitro skin models and tissue engineering protocols for skin graft applications.

PubMed

Naves, Lucas B; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram

2016-11-30

In this review, we present a brief introduction of the skin structure, a concise compilation of skin-related disorders, and a thorough discussion of different in vitro skin models, artificial skin substitutes, skin grafts, and dermal tissue engineering protocols. The advantages of the development of in vitro skin disorder models, such as UV radiation and the prototype model, melanoma model, wound healing model, psoriasis model, and full-thickness model are also discussed. Different types of skin grafts including allografts, autografts, allogeneic, and xenogeneic are described in detail with their associated applications. We also discuss different tissue engineering protocols for the design of various types of skin substitutes and their commercial outcomes. Brief highlights are given of the new generation three-dimensional printed scaffolds for tissue regeneration applications. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

A novel aragonite-based scaffold for osteochondral regeneration: early experience on human implants and technical developments.

PubMed

Kon, Elizaveta; Robinson, Dror; Verdonk, Peter; Drobnic, Matej; Patrascu, Jenel Mariano; Dulic, Oliver; Gavrilovic, Gordon; Filardo, Giuseppe

2016-12-01

Chondral and osteochondral lesions represent a debilitating disease. Untreated lesions remain a risk factor for more extensive joint damage. The objective of this clinical study is to evaluate safety and early results of an aragonite-based scaffold used for osteochondral unit repair, by analysing both clinical outcome and MRI results, as well as the benefits of the procedure optimization through novel tapered shaped implants. A crystalline aragonite bi-phasic scaffold was implanted in patients affected by focal chondral-osteochondral knee lesions of the condyle and trochlea. Twenty-one patients (17 men, 4 women with a mean age of 31.0 ± 8.6 years) without severe OA received tapered shaped implants for the treatment of 2.5 ±1.7 cm 2 sized defects. The control group consisted of 76 patients selected according to the same criteria from a database of patients who previously underwent implantation of cylindrical-shaped implants. The clinical outcome of all patients was evaluated with the IKDC subjective score, the Lysholm score, and all 5 KOOS subscales administered preoperatively and at 6 and 12 months after surgery, while MRI evaluation was performed at the 12 month follow-up. A statistically significant improvement in all clinical scores was documented both in the tapered implants and the cylindrical group. No difference could be detected in the comparison between the improvement obtained with the two implant types, neither in the clinical nor in imaging evaluations. A difference could be detected instead in terms of revision rate, which was lower in the tapered implant group with no implant removal - 0% vs 8/76-10.5% failures in the cylindrical implants. This study highlighted both safety and potential of a novel aragonite-based scaffold for the treatment of chondral and osteochondral lesions in humans. A tapered shape relative to the cylindrical shaped implant design, improved the scaffold's safety profile. Tapered scaffolds maintain the clinical improvement

Clinical Comparison of Full and Partial Double Pedicle Flaps with Connective Tissue Grafts for Treatment of Gingival Recession

PubMed Central

Ranjbari, Ardeshir; Gholami, Gholam Ali; Amid, Reza; Kadkhodazadeh, Mahdi; Youssefi, Navid; Mehdizadeh, Amir Reza; Aghaloo, Maryam

2016-01-01

Statement of the Problem Gingival recession has been considered as the most challenging issue in the field of periodontal plastic surgery. Purpose The purpose of this study was to evaluate the clinical efficacy of root coverage procedures by using partial thickness double pedicle graft and compare it with full thickness double pedicle graft. Materials and Method Eight patients, aged 15 to 58 years including 6 females and 2 males with 20 paired (mirror image) defects with class I and II gingival recession were randomly assigned into two groups. Clinical parameters such as recession depth, recession width, clinical attachment level, probing depth, and width of keratinized tissue were measured at the baseline and 6 months post-surgery. A mucosal double papillary flap was elevated and the respective root was thoroughly planed. The connective tissue graft was harvested from the palate, and then adapted over the root. The pedicle flap was secured over the connective tissue graft and sutured. The surgical technique was similar in the control group except for the prepared double pedicle graft which was full thickness. Results The mean root coverage was 88.14% (2.83 mm) in the test group and 85.7% (2.75 mm) in the control group. No statistical differences were found in the mean reduction of vertical recession, width of recession, or probing depth between the test and control groups. In both procedures, the width of keratinized tissue increased after three months and the difference between the two groups was not statistically significant in this respect. Conclusion Connective tissue with partial and full thickness double pedicle grafts can be successfully used for treatment of marginal gingival recession. PMID:27602394

Clinical evaluation of subepithelial connective tissue graft and guided tissue regeneration for treatment of Miller’s class 1 gingival recession (comparative, split mouth, six months study)

PubMed Central

Bhavsar, Neeta-V.; Dulani, Kirti; Trivedi, Rahul

2014-01-01

Objectives: The present study aims to clinically compare and evaluate subepithelial connective tissue graft and the GTR based root coverage in treatment of Miller’s Class I gingival recession. Study Design: 30 patients with at least one pair of Miller’s Class I gingival recession were treated either with Subepithelial connective tissue graft (Group A) or Guided tissue regeneration (Group B). Clinical parameters monitored included recession RD, width of keratinized gingiva (KG), probing depth (PD), clinical attachment level (CAL), attached gingiva (AG), residual probing depth (RPD) and % of Root coverage(%RC). Measurements were taken at baseline, three months and six months. A standard surgical procedure was used for both Group A and Group B. Data were recorded and statistical analysis was done for both intergroup and intragroup. Results: At end of six months % RC obtained were 84.47% (Group A) and 81.67% (Group B). Both treatments resulted in statistically significant improvement in clinical parameters. When compared, no statistically significant difference was found between both groups except in RPD, where it was significantly greater in Group A. Conclusions: GTR technique has advantages over subepithelial connective tissue graft for shallow Miller’s Class I defects and this procedure can be used to avoid patient discomfort and reduce treatment time. Key words:Collagen membrane, comparative split mouth study, gingival recession, subepithelial connective tissue graft, guided tissue regeneration (GTR). PMID:25136420

A novel double-network hydrogel induces spontaneous articular cartilage regeneration in vivo in a large osteochondral defect.

PubMed

Yasuda, Kazunori; Kitamura, Nobuto; Gong, Jian Ping; Arakaki, Kazunobu; Kwon, Hyuck Joon; Onodera, Shin; Chen, Yong Mei; Kurokawa, Takayuki; Kanaya, Fuminori; Ohmiya, Yoshihiro; Osada, Yoshihito

2009-04-08

We have developed a novel method to induce spontaneous hyaline cartilage regeneration in vivo for a large osteochondral defect by implanting a plug made from a double-network hydrogel composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethylacrylamide) at the bottom of the defect, leaving the cavity vacant. In cells regenerated in the treated defect, type-2 collagen, Aggrican, and SOX9 mRNAs were highly expressed and the regenerated matrix was rich in proteoglycan and type-2 collagen at 4 weeks. This fact gave a significant modification to the commonly established concept that hyaline cartilage tissue cannot regenerate in vivo. This study prompted an innovative strategy in the field of joint surgery to repair an osteochondral defect using an advanced, high-function hydrogel.

Connective tissue graft vs. emdogain: A new approach to compare the outcomes.

PubMed

Sayar, Ferena; Akhundi, Nasrin; Gholami, Sanaz

2013-01-01

The aim of this clinical trial study was to clinically evaluate the use of enamel matrix protein derivative combined with the coronally positioned flap to treat gingival recession compared to the subepithelial connective tissue graft by a new method to obtain denuded root surface area. Thirteen patients, each with two or more similar bilateral Miller class I or II gingival recession (40 recessions) were randomly assigned to the test (enamel matrix protein derivative + coronally positioned flap) or control group (subepithelial connective tissue graft). Recession depth, width, probing depth, keratinized gingival, and plaque index were recorded at baseline and at one, three, and six months after treatment. A stent was used to measure the denuded root surface area at each examination session. Results were analyzed using Kolmogorov-Smirnov, Wilcoxon, Friedman, paired-sample t test. The average percentages of root coverage for control and test groups were 63.3% and 55%, respectively. Both groups showed significant keratinized gingival increase (P < 0.05). Recession depth decreased significantly in both groups. Root surface area was improved significantly from baseline with no significant difference between the two study groups (P > 0.05). The results of Friedman test were significant for clinical indices (P < 0.05), except for probing depth in control group (P = 0.166). Enamel matrix protein derivative showed the same results as subepithelial connective tissue graft with relatively easy procedure to perform and low patient morbidity.

Immediate placement and provisionalization of maxillary anterior single implant with guided bone regeneration, connective tissue graft, and coronally positioned flap procedures.

PubMed

Waki, Tomonori; Kan, Joseph Y K

2016-01-01

Immediate implant placement and provisionalization in the esthetic zone have been documented with success. The benefit of immediate implant placement and provisionalization is the preservation of papillary mucosa. However, in cases with osseous defects presenting on the facial bony plate, immediate implant placement procedures have resulted in facial gingival recession. Subepithelial connective tissue grafts for immediate implant placement and provisionalization procedures have been reported with a good esthetic outcome. Biotype conversion around implants with subepithelial connective tissue grafts have been advocated, and the resulting tissues appear to be more resistant to recession. The dimensions of peri-implant mucosa in a thick biotype were significantly greater than in a thin biotype. Connective tissue graft with coronally positioned flap procedures on natural teeth has also been documented with success. This article describes a technique combining immediate implant placement, provisionalization, guided bone regeneration (GBR), connective tissue graft, and a coronally positioned flap in order to achieve more stable peri-implant tissue in facial osseous defect situations.

Changes of the peri-implant soft tissue thickness after grafting with a collagen matrix

PubMed Central

Zafiropoulos, Gregory-George; Deli, Giorgio; Hoffmann, Oliver; John, Gordon

2016-01-01

Background: The aim of this study was to determine the treatment outcome of the use of a porcine monolayer collagen matrix (mCM) to increase soft-tissue volume as a part of implant site development. Materials and Methods: Implants were placed in single sites in 27 patients. In the test group, mCM was used for soft-tissue augmentation. No graft was placed in the control group. Soft-tissue thickness (STTh) was measured at the time of surgery (T0) and 6 months postoperatively (T1) at two sites (STTh 1, 1 mm below the gingival margin; STTh 2, 3 mm below the mucogingival margin). Results: Significant increases (P < 0.001) in STTh (STTh 1 = 1.06 mm, 117%; STTh 2 = 0.89 mm, 81%) were observed in the test group. Biopsy results showed angiogenesis and mature connective tissue covered by keratinized epithelium. Conclusions: Within the limitations of this study, it could be concluded that mCM leads to a significant increase of peri-implant soft-tissue thickness, with good histological integration and replacement by soft tissue and may serve as an alternative to connective tissue grafting. PMID:28298828

Xenogeneic Collagen Matrix Versus Connective Tissue Graft: Case Series of Various Gingival Recession Treatments.

PubMed

Chevalier, Grégoire; Cherkaoui, Selma; Kruk, Hanna; Bensaïd, Xavier; Danan, Marc

A xenogeneic collagen matrix recently has been suggested as an alternative to connective tissue graft for the treatment of gingival recession. The matrix avoids the second surgical site, and as a consequence could decrease surgical morbidity. This new matrix was used in various clinical situations and compared to connective tissue graft (CTG) in a split-mouth design case series. A total of 17 recessions were treated with a coronally advanced flap, 9 with CTG, and 8 with the matrix. Mean recession reduction was 2.00 mm with the CTG and 2.00 mm with the matrix. No significant statistical differences between the techniques were observed in this case report.

Xenogeneic Collagen Matrix Versus Connective Tissue Graft: Case Series of Various Gingival Recession Treatments.

PubMed

Chevalier, Grégoire; Cherkaoui, Selma; Kruk, Hanna; Bensaïd, Xavier; Danan, Marc

2016-08-24

A xenogeneic collagen matrix recently has been suggested as an alternative to connective tissue graft for the treatment of gingival recession. The matrix avoids the second surgical site, and as a consequence could decrease surgical morbidity. This new matrix was used in various clinical situations and compared to connective tissue graft (CTG) in a split-mouth design case series. A total of 17 recessions were treated with a coronally advanced flap, 9 with CTG, and 8 with the matrix. Mean recession reduction was 2.00 mm with the CTG and 2.00 mm with the matrix. No significant statistical differences between the techniques were observed in this case report.

Refixation of Osteochondral Fractures by an Ultrasound-Activated Pin System - An Ovine In Vivo Examination Using CT and Scanning Electron Microscope.

PubMed

H, Neumann; A P, Schulz; S, Breer; A, Unger; B, Kienast

2015-01-01

Osteochondral injuries, if not treated appropriately, often lead to severe osteoarthritis of the affected joint. Without refixation of the osteochondral fragment, human cartilage only repairs these defects imperfectly. All existing refixation systems for chondral defects have disadvantages, for instance bad MRI quality in the postoperative follow-up or low anchoring forces. To address the problem of reduced stability in resorbable implants, ultrasound-activated pins were developed. By ultrasound-activated melting of the tip of these implants a higher anchoring is assumed. Aim of the study was to investigate, if ultrasound-activated pins can provide a secure refixation of osteochondral fractures comparing to conventional screw and conventional, resorbable pin osteosynthesis. CT scans and scanning electron microscopy should proovegood refixation results with no further tissue damage by the melting of the ultrasound-activated pins in comparison to conventional osteosynthesis. Femoral osteochondral fragments in sheep were refixated with ultrasound-activated pins (SonicPin™), Ethipins(®) and screws (Asnis™). The quality of the refixated fragments was examined after three month of full weight bearing by CT scans and scanning electron microscopy of the cartilage surface. The CT examination found almost no statistically significant difference in the quality of refixation between the three different implants used. Concerning the CT morphology, ultrasound-activated pins demonstrated at least the same quality in refixation of osteochondral fragments as conventional resorbable pins or screws. The scanning electron microscopy showed no major surface damage by the three implants, especially any postulated cartilage damage induced by the heat of the ultrasound-activated pin. The screws protruded above the cartilage surface, which may affect the opposingtibial surface. Using CT scans and scanning electron microscopy, the SonicPin™, the Ethipin(®) and screws were at least

The use of a cartilage decellularized matrix scaffold for the repair of osteochondral defects: the importance of long-term studies in a large animal model.

PubMed

Vindas Bolaños, R A; Cokelaere, S M; Estrada McDermott, J M; Benders, K E M; Gbureck, U; Plomp, S G M; Weinans, H; Groll, J; van Weeren, P R; Malda, J

2017-03-01

To investigate the effect of decellularized cartilage-derived matrix (CDM) scaffolds, by itself and as a composite scaffold with a calcium phosphate (CaP) base, for the repair of osteochondral defects. It was hypothesized that the chondral defects would heal with fibrocartilaginous tissue and that the composite scaffold would result in better bone formation. After an 8-week pilot experiment in a single horse, scaffolds were implanted in eight healthy horses in osteochondral defects on the medial trochlear ridge of the femur. In one joint a composite CDM-CaP scaffold was implanted (+P), in the contralateral joint a CDM only (-P) scaffold. After euthanasia at 6 months, tissues were analysed by histology, immunohistochemistry, micro-CT, biochemistry and biomechanical evaluation. The 8-week pilot showed encouraging formation of bone and cartilage, but incomplete defect filling. At 6 months, micro-CT and histology showed much more limited filling of the defect, but the CaP component of the +P scaffolds was well integrated with the surrounding bone. The repair tissue was fibrotic with high collagen type I and low type II content and with no differences between the groups. There were also no biochemical differences between the groups and repair tissue was much less stiff than normal tissue (P < 0.0001). The implants failed to produce reasonable repair tissue in this osteochondral defect model, although the CaP base in the -P group integrated well with the recipient bone. The study stresses the importance of long-term in vivo studies to assess the efficacy of cartilage repair techniques. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

An update-tissue engineered nerve grafts for the repair of peripheral nerve injuries.

PubMed

Patel, Nitesh P; Lyon, Kristopher A; Huang, Jason H

2018-05-01

Peripheral nerve injuries (PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts (ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts (TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems (DDS), co-administration of platelet-rich plasma (PRP), and pretreatment with chondroitinase ABC (Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix (ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia (DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.

A Missense Mutation in the Aggrecan C-type Lectin Domain Disrupts Extracellular Matrix Interactions and Causes Dominant Familial Osteochondritis Dissecans

PubMed Central

Stattin, Eva-Lena; Wiklund, Fredrik; Lindblom, Karin; Önnerfjord, Patrik; Jonsson, Björn-Anders; Tegner, Yelverton; Sasaki, Takako; Struglics, André; Lohmander, Stefan; Dahl, Niklas; Heinegård, Dick; Aspberg, Anders

2010-01-01

Osteochondritis dissecans is a disorder in which fragments of articular cartilage and subchondral bone dislodge from the joint surface. We analyzed a five-generation family in which affected members had autosomal-dominant familial osteochondritis dissecans. A genome-wide linkage analysis identified aggrecan (ACAN) as a prime candidate gene for the disorder. Sequence analysis of ACAN revealed heterozygosity for a missense mutation (c.6907G > A) in affected individuals, resulting in a p.V2303M amino acid substitution in the aggrecan G3 domain C-type lectin, which mediates interactions with other proteins in the cartilage extracellular matrix. Binding studies with recombinant mutated and wild-type G3 proteins showed loss of fibulin-1, fibulin-2, and tenascin-R interactions for the V2303M protein. Mass spectrometric analyses of aggrecan purified from patient cartilage verified that V2303M aggrecan is produced and present in the tissue. Our results provide a molecular mechanism for the etiology of familial osteochondritis dissecans and show the importance of the aggrecan C-type lectin interactions for cartilage function in vivo. PMID:20137779

Standardizing Descemet Membrane Endothelial Keratoplasty Graft Preparation Method in the Eye Bank-Experience of 527 Descemet Membrane Endothelial Keratoplasty Tissues.

PubMed

Parekh, Mohit; Baruzzo, Mattia; Favaro, Elisa; Borroni, Davide; Ferrari, Stefano; Ponzin, Diego; Ruzza, Alessandro

2017-12-01

To share the experience and provide a standardized protocol for Descemet membrane endothelial keratoplasty (DMEK) graft preparation. A retrospective study based on 527 prestripped DMEK tissues that were prepared between 2014 and 2017. The experience of using different instruments and techniques has been described, and a standardized technique for preparing DMEK grafts has been identified. The tissues in general were prepared by superficially tapping the endothelial side with a Moria trephine (9.5 mm diameter). The plane of cleavage was identified using a cleavage hook, and the DMEK graft was deadhered from the trephined site throughout the circumference for ease of excising the graft. The DMEK graft was peeled using either one or multiple quadrant methods depending on the challenges faced during excision. The graft was finally marked with the letter "F" to identify the orientation during surgery. Data on endothelial cell loss (ECL) and challenging cases were observed, monitored, and recorded during this period. Less than 1 percent trypan blue-positive cells with tissue wastage of <6% was observed during the study period. Our standardized stripping technique has resulted in an overall ECL of 4.6%. Marking Descemet membrane showed 0.5% cell mortality. Standardizing DMEK technique using specific tools and simple techniques would help new surgeons to decide the instruments and improve their tissue preparation skills also in challenging cases such as previous cataract incisions or horseshoe-shaped tears, further reducing ECL or tissue wastage.

Refixation of Osteochondral Fractures by an Ultrasound-Activated Pin System – An Ovine In Vivo Examination Using CT and Scanning Electron Microscope

PubMed Central

H, Neumann; A.P, Schulz; S, Breer; A, Unger; B, Kienast

2015-01-01

Background: Osteochondral injuries, if not treated appropriately, often lead to severe osteoarthritis of the affected joint. Without refixation of the osteochondral fragment, human cartilage only repairs these defects imperfectly. All existing refixation systems for chondral defects have disadvantages, for instance bad MRI quality in the postoperative follow-up or low anchoring forces. To address the problem of reduced stability in resorbable implants, ultrasound-activated pins were developed. By ultrasound-activated melting of the tip of these implants a higher anchoring is assumed. Aim of the study was to investigate, if ultrasound-activated pins can provide a secure refixation of osteochondral fractures comparing to conventional screw and conventional, resorbable pin osteosynthesis. CT scans and scanning electron microscopy should proovegood refixation results with no further tissue damage by the melting of the ultrasound-activated pins in comparison to conventional osteosynthesis. Methods: Femoral osteochondral fragments in sheep were refixated with ultrasound-activated pins (SonicPin™), Ethipins® and screws (Asnis™). The quality of the refixated fragments was examined after three month of full weight bearing by CT scans and scanning electron microscopy of the cartilage surface. Results: The CT examination found almost no statistically significant difference in the quality of refixation between the three different implants used. Concerning the CT morphology, ultrasound-activated pins demonstrated at least the same quality in refixation of osteochondral fragments as conventional resorbable pins or screws. The scanning electron microscopy showed no major surface damage by the three implants, especially any postulated cartilage damage induced by the heat of the ultrasound-activated pin. The screws protruded above the cartilage surface, which may affect the opposingtibial surface. Conclusion: Using CT scans and scanning electron microscopy, the Sonic

Porcine small intestine submucosal grafts improve remucosalization and progenitor cell recruitment to sites of upper airway tissue remodeling.

PubMed

Nayak, Jayakar V; Rathor, Aakanksha; Grayson, Jessica W; Bravo, Dawn T; Velasquez, Nathalia; Noel, Julia; Beswick, Daniel M; Riley, Kristen O; Patel, Zara M; Cho, Do-Yeon; Dodd, Robert L; Thamboo, Andrew; Choby, Garret W; Walgama, Evan; Harsh, Griffith R; Hwang, Peter H; Clemons, Lisa; Lowman, Deborah; Richman, Joshua S; Woodworth, Bradford A

2018-06-01

To better understand upper airway tissue regeneration, the exposed cartilage and bone at donor sites of tissue flaps may serve as in vivo "Petri dishes" for active wound healing. The pedicled nasoseptal flap (NSF) for skull-base reconstruction creates an exposed donor site within the nasal airway. The objective of this study is to evaluate whether grafting the donor site with a sinonasal repair cover graft is effective in promoting wound healing. In this multicenter, prospective trial, subjects were randomized to intervention (graft) or control (no graft) intraoperatively after NSF elevation. Individuals were evaluated at 2, 6, and 12 weeks postintervention with endoscopic recordings. Videos were graded (Likert scale) by 3 otolaryngologists blinded to intervention on remucosalization, crusting, and edema. Scores were analyzed for interrater reliability and cohorts compared. Biopsy and immunohistochemistry at the leading edge of wound healing was performed in select cases. Twenty-one patients were randomized to intervention and 26 to control. Subjects receiving the graft had significantly greater overall remucosalization (p = 0.01) than controls over 12 weeks. Although crusting was less in the small intestine submucosa (SIS) group, this was not statistically significant (p = 0.08). There was no overall effect on nasal edema (p = 0.2). Immunohistochemistry demonstrated abundant upper airway basal cell progenitors in 2 intervention samples, suggesting that covering grafts may facilitate tissue proliferation via progenitor cell expansion. This prospective, randomized, controlled trial indicates that a porcine SIS graft placed on exposed cartilage and bone within the upper airway confers improved remucosalization compared to current practice standards. © 2018 ARS-AAOA, LLC.

Genetics Home Reference: familial osteochondritis dissecans

MedlinePlus

... Familial osteochondritis dissecans Seattle Children's TeensHealth from Nemours: Knee Injuries University of Connecticut Health Center Patient Support and Advocacy Resources (1 link) American College of Rheumatology: Osteoarthritis ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles ...

Osteochondral Diseases and Fibrodysplasia Ossificans Progressiva

PubMed Central

Kaplan, Frederick S.

2016-01-01

Osteochondrodysplasias like thanatophoric dysplasia, osteogenesis imperfecta, achondroplasia, and other genetic skeletal disorders like fibrodysplasia ossificans progressiva are infrequently seen in clinical practice. In cases of sporadic achondroplasia as well as in fibrodysplasia ossificans progressiva, there is a strong association with paternal age, a relationship that is less evident in other genetic osteochondral diseases. No other constitutional or environmental factor has proven to be associated with these disorders. The use of prenatal ultrasonography as a routine component of prenatal care is crucial in the early suspicion of osteochondrodysplasias whereas definitive diagnosis is usually obtained by pre-natal molecular analysis. In the case of fibrodysplasia ossificans progressiva, recognition of congenital great toe malformations associated with rapidly–appearing soft tissue swelling is sufficient to make the proper clinical diagnosis, which can be confirmed by genetic testing. Large regional centres will improve diagnosis performance, provide accurate genetic counselling, and ensure an integral assistance for these often severe and incapacitating conditions. PMID:20824454

Tissue-engineered tracheal reconstruction using three-dimensionally printed artificial tracheal graft: preliminary report.

PubMed

Chang, Jae Won; Park, Su A; Park, Ju-Kyeong; Choi, Jae Won; Kim, Yoo-Suk; Shin, Yoo Seob; Kim, Chul-Ho

2014-06-01

Three-dimensional printing has come into the spotlight in the realm of tissue engineering. We intended to evaluate the plausibility of 3D-printed (3DP) scaffold coated with mesenchymal stem cells (MSCs) seeded in fibrin for the repair of partial tracheal defects. MSCs from rabbit bone marrow were expanded and cultured. A half-pipe-shaped 3DP polycaprolactone scaffold was coated with the MSCs seeded in fibrin. The half-pipe tracheal graft was implanted on a 10 × 10-mm artificial tracheal defect in four rabbits. Four and eight weeks after the operation, the reconstructed sites were evaluated bronchoscopically, radiologically, histologically, and functionally. None of the four rabbits showed any sign of respiratory distress. Endoscopic examination and computed tomography showed successful reconstruction of trachea without any collapse or blockage. The replaced tracheas were completely covered with regenerated respiratory mucosa. Histologic analysis showed that the implanted 3DP tracheal grafts were successfully integrated with the adjacent trachea without disruption or granulation tissue formation. Neo-cartilage formation inside the implanted graft was sufficient to maintain the patency of the reconstructed trachea. Scanning electron microscope examination confirmed the regeneration of the cilia, and beating frequency of regenerated cilia was not different from those of the normal adjacent mucosa. The shape and function of reconstructed trachea using 3DP scaffold coated with MSCs seeded in fibrin were restored successfully without any graft rejection. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Repair Mechanism of Osteochondral Defect Promoted by Bioengineered Chondrocyte Sheet

PubMed Central

Kamei, Naosuke; Adachi, Nobuo; Hamanishi, Michio; Kamei, Goki; Mahmoud, Elhussein Elbadry; Nakano, Tomohiro; Iwata, Takanori; Yamato, Masayuki; Okano, Teruo; Ochi, Mitsuo

2015-01-01

Cell sheet engineering has developed as a remarkable method for cell transplantation. In the field of cartilage regeneration, several studies previously reported that cartilage defects could be regenerated by transplantation of a chondrocyte sheet using cell sheet engineering. However, it remains unclear how such a thin cell sheet could repair a deep cartilage defect. We, therefore, focused on the mechanism of cartilage repair using cell sheet engineering in this study. Chondrocyte sheets and synovial cell sheets were fabricated using cell sheet engineering, and these allogenic cell sheets were transplanted to cover an osteochondral defect in a rat model. Macroscopic and histological evaluation was performed at 4 and 12 weeks after transplantation. Analysis of the gene expression of each cell sheet and of the regenerated tissue at 1 week after transplantation was performed. In addition, green fluorescent protein (GFP) transgenic rats were used as donors (transplanted chondrocyte sheets) or recipients (osteochondral defect models) to identify the cell origin of regenerated cartilage. Cartilage repair was significantly better in the group implanted with a chondrocyte sheet than in that with a synovial cell sheet. The results of gene expression analysis suggest that the possible factor contributing to cartilage repair might be TGFβ1. Cell tracking experiments using GFP transgenic rats showed that the regenerated cartilage was largely composed of cells derived from the transplanted chondrocyte sheets. PMID:25396711

Insulin-like Growth Factor-I and Slow, Bi-directional Perfusion Enhance the Formation of Tissue-Engineered Cardiac Grafts

PubMed Central

Cheng, Mingyu; Moretti, Matteo; Engelmayr, George C.

2009-01-01

Biochemical and mechanical signals enabling cardiac regeneration can be elucidated using in vitro tissue-engineering models. We hypothesized that insulin-like growth factor-I (IGF) and slow, bi-directional perfusion could act independently and interactively to enhance the survival, differentiation, and contractile performance of tissue-engineered cardiac grafts. Heart cells were cultured on three-dimensional porous scaffolds in medium with or without supplemental IGF and in the presence or absence of slow, bi-directional perfusion that enhanced transport and provided shear stress. Structural, molecular, and electrophysiologic properties of the resulting grafts were quantified on culture day 8. IGF had independent, beneficial effects on apoptosis (p < 0.01), cellular viability (p < 0.01), contractile amplitude (p < 0.01), and excitation threshold (p < 0.01). Perfusion independently affected the four aforementioned parameters and also increased amounts of cardiac troponin-I (p < 0.01), connexin-43 (p < 0.05), and total protein (p < 0.01) in the grafts. Interactive effects of IGF and perfusion on apoptosis were also present (p < 0.01). Myofibrillogenesis and spontaneous contractility were present only in grafts cultured with perfusion, although contractility was inducible by electrical field stimulation of grafts from all groups. Our findings demonstrate that multi-factorial stimulation of tissue-engineered cardiac grafts using IGF and perfusion resulted in independent and interactive effects on heart cell survival, differentiation, and contractility. PMID:18759675

Fresh osteochondral allografts in the knee: comparison of primary transplantation versus transplantation after failure of previous subchondral marrow stimulation.

PubMed

Gracitelli, Guilherme C; Meric, Gokhan; Briggs, Dustin T; Pulido, Pamela A; McCauley, Julie C; Belloti, João Carlos; Bugbee, William D

2015-04-01

In most treatment algorithms, osteochondral allograft (OCA) transplantation is regarded as an alternative salvage procedure when other, previous reparative treatments have failed. To compare the outcomes of a retrospective matched-pair cohort of (1) primary OCA transplantation and (2) OCA transplantation after failure of previous subchondral marrow stimulation. Cohort study; Level of evidence, 3. An OCA database was used to identify 46 knees that had OCA transplantation performed as a primary treatment (group 1) and 46 knees that underwent OCA transplantation after failure of previous subchondral marrow stimulation (group 2). All patients had a minimum of 2 years' follow-up. Patients in each group were matched for age (±5 years), diagnosis (osteochondral lesion, degenerative chondral lesion, traumatic chondral injury), and graft size (small, <5 cm2; medium, 5-10 cm2; large, >10 cm2). The groups had similar body mass indexes, sex distributions, and graft locations (femoral condyle, patella, and trochlea. The number and type of further surgeries after the OCA transplantation were assessed; failure was defined as any reoperation resulting in removal of the graft. Functional outcomes were evaluated by use of the modified Merle d'Aubigné-Postel (18-point) scale, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Knee injury and Osteoarthritis Outcomes Score (KOOS), and the Knee Society function (KS-F) scale. Patient satisfaction, according to a 5-point scale from "extremely satisfied" to "dissatisfied," was recorded at the latest follow-up. Eleven of 46 knees (24%) in group 1 had reoperations, compared with 20 of 46 knees (44%) in group 2 (P = .04). The OCA was classified as a failure in 5 knees (11%) in group 1 and 7 knees (15%) in group 2 (P = .53). At 10 years of follow-up, survivorship of the graft was 87.4% and 86% in groups 1 and 2, respectively. Both groups showed improvement in pain and function on all subjective scores from

Meniscal root entrapment of an osteochondritis dissecans loose body.

PubMed

Jones, Christopher R; McMonagle, Joseph S; Garrett, William E

2014-09-01

Loose bodies are relatively common in the knee. On radiographs they can often be seen in the medial and lateral gutters, intercondylar notch, and the posterior compartment. At times an apparent loose body is not free to move in the knee because it has been covered by synovium and is no longer mobile. It is uncommon for an osteochondral loose body to become incorporated into meniscal tissue. We report a case of an apparent loose body becoming incorporated into the posterior horn and root of the medial meniscus. We are not aware that this condition has been previously reported. Because removing the entire loose body would have destabilized the posterior root of the medial meniscus, it is important to be aware of this potential occurrence.

Altering the architecture of tissue engineered hypertrophic cartilaginous grafts facilitates vascularisation and accelerates mineralisation.

PubMed

Sheehy, Eamon J; Vinardell, Tatiana; Toner, Mary E; Buckley, Conor T; Kelly, Daniel J

2014-01-01

Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) can be leveraged to generate bone in vivo by executing an endochondral program, leading to increased interest in the use of such hypertrophic grafts for the regeneration of osseous defects. During normal skeletogenesis, canals within the developing hypertrophic cartilage play a key role in facilitating endochondral ossification. Inspired by this developmental feature, the objective of this study was to promote endochondral ossification of an engineered cartilaginous construct through modification of scaffold architecture. Our hypothesis was that the introduction of channels into MSC-seeded hydrogels would firstly facilitate the in vitro development of scaled-up hypertrophic cartilaginous tissues, and secondly would accelerate vascularisation and mineralisation of the graft in vivo. MSCs were encapsulated into hydrogels containing either an array of micro-channels, or into non-channelled 'solid' controls, and maintained in culture conditions known to promote a hypertrophic cartilaginous phenotype. Solid constructs accumulated significantly more sGAG and collagen in vitro, while channelled constructs accumulated significantly more calcium. In vivo, the channels acted as conduits for vascularisation and accelerated mineralisation of the engineered graft. Cartilaginous tissue within the channels underwent endochondral ossification, producing lamellar bone surrounding a hematopoietic marrow component. This study highlights the potential of utilising engineering methodologies, inspired by developmental skeletal processes, in order to enhance endochondral bone regeneration strategies.

Altering the Architecture of Tissue Engineered Hypertrophic Cartilaginous Grafts Facilitates Vascularisation and Accelerates Mineralisation

PubMed Central

Sheehy, Eamon J.; Vinardell, Tatiana; Toner, Mary E.; Buckley, Conor T.; Kelly, Daniel J.

2014-01-01

Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) can be leveraged to generate bone in vivo by executing an endochondral program, leading to increased interest in the use of such hypertrophic grafts for the regeneration of osseous defects. During normal skeletogenesis, canals within the developing hypertrophic cartilage play a key role in facilitating endochondral ossification. Inspired by this developmental feature, the objective of this study was to promote endochondral ossification of an engineered cartilaginous construct through modification of scaffold architecture. Our hypothesis was that the introduction of channels into MSC-seeded hydrogels would firstly facilitate the in vitro development of scaled-up hypertrophic cartilaginous tissues, and secondly would accelerate vascularisation and mineralisation of the graft in vivo. MSCs were encapsulated into hydrogels containing either an array of micro-channels, or into non-channelled ‘solid’ controls, and maintained in culture conditions known to promote a hypertrophic cartilaginous phenotype. Solid constructs accumulated significantly more sGAG and collagen in vitro, while channelled constructs accumulated significantly more calcium. In vivo, the channels acted as conduits for vascularisation and accelerated mineralisation of the engineered graft. Cartilaginous tissue within the channels underwent endochondral ossification, producing lamellar bone surrounding a hematopoietic marrow component. This study highlights the potential of utilising engineering methodologies, inspired by developmental skeletal processes, in order to enhance endochondral bone regeneration strategies. PMID:24595316

Vascularization after treatment of gingival recession defects with platelet-rich fibrin or connective tissue graft.

PubMed

Eren, Gülnihal; Kantarcı, Alpdoğan; Sculean, Anton; Atilla, Gül

2016-11-01

The aim of this study was to evaluate histologically the following treatment of bilateral localized gingival recessions with coronally advanced flap (CAF) combined with platelet-rich fibrin (PRF) or subepithelial connective tissue graft (SCTG). Tissue samples were harvested from 14 subjects either 1 or 6 months after the surgeries. The 2-mm punch biopsies were obtained from the mid-portion of the grafted sites. Neutral buffered formalin fixed, paraffin-embedded 5-μm thick tissue sections were stained with hematoxylin eosin and Masson's trichrome in order to analyze the collagen framework, epithelium thickness and rete-peg length. Multiple sequential sections were cut from paraffin-embedded blocks of tissue and immunohistochemically prepared for detection of vascular endothelial growth factor, CD31 and CD34, for the assessment of vascularization. Rete peg formation was significantly increased in the sites treated with PRF compared to the SCTG group after 6 months (p < 0.05). On the contrary, the number of vessels was increased in the SCTG group compared to the PRF group after 6 months (p < 0.05). No statistically significant differences were observed in the collagen density. Staining intensity of CD31 increased in submucosal area of PRF group than SCTG group after 1 month. Higher staining intensity of CD34 was observed in the submucosal area of PRF group compared with SCTG group after 6 months. The results of the present study suggest that in histological evaluation because of its biological compounds, PRF results earlier vessel formation and tissue maturation compared to connective tissue graft. PRF regulated the vascular response associated with an earlier wound healing.

Repair of articular osteochondral defects of the knee joint using a composite lamellar scaffold.

PubMed

Lv, Y M; Yu, Q S

2015-04-01

The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility. The bone-cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid-hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated. After 12 weeks of implantation, defects in the experimental group were filled with white semi-translucent tissue, protruding slightly over the peripheral cartilage surface. After 24 weeks, the defect space in the experimental group was filled with new cartilage tissues, finely integrated into surrounding normal cartilage. The lamellar scaffold of ß-TCP/col I/col II was gradually degraded and absorbed, while new cartilage tissue formed. In the control group, the defects were not repaired. This method can be used as a suitable scaffold material for the tissue-engineered repair of articular cartilage defects. Cite this article: Bone Joint Res 2015;4:56-64. ©2015 The British Editorial Society of Bone & Joint Surgery.

The use of osteochondral allograft with bone marrow-derived mesenchymal cells and hinge joint distraction in the treatment of post-collapse stage of osteonecrosis of the femoral head.

PubMed

Gagala, J; Tarczynska, M; Gaweda, K; Matuszewski, L

2014-09-01

Osteonecrosis of the femoral head is an entity which occurs mainly in young and active patients aged between 20 and 50. The success of hip joint preserving treatments ranges from 15% to 50% depending on the stage and amount of osteonecrotic lesion. Total hip replacement is indicated in late post-collapse hips but it has unsatisfactory survival because of the wear and osteolysis in young and active patients. Osteochondral allografts have been reported in the treatment of large articular lesions with defects in underlying bone in knee, talus and shoulder. By combining osteoconductive properties of osteochondral allograft with osteogenic abilities of bone marrow-derived mesenchymal cells it has a potential to be an alternative to an autologous graft. The adjunct of hinged joint distraction should minimize stresses in subchondral bone to promote creeping substitution and prevent femoral head collapse. Unlike current treatment modalities, it would provide both structural support and allow bony and articular substitution. Copyright © 2014 Elsevier Ltd. All rights reserved.

Spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect created in the femoral condyle using a novel double-network hydrogel.

PubMed

Yokota, Masashi; Yasuda, Kazunori; Kitamura, Nobuto; Arakaki, Kazunobu; Onodera, Shin; Kurokawa, Takayuki; Gong, Jian-Ping

2011-02-22

Functional repair of articular osteochondral defects remains a major challenge not only in the field of knee surgery but also in tissue regeneration medicine. The purpose is to clarify whether the spontaneous hyaline cartilage regeneration can be induced in a large osteochondral defect created in the femoral condyle by means of implanting a novel double-network (DN) gel at the bottom of the defect. Twenty-five mature rabbits were used in this study. In the bilateral knees of each animal, we created an osteochondral defect having a diameter of 2.4-mm in the medial condyle. Then, in 21 rabbits, we implanted a DN gel plug into a right knee defect so that a vacant space of 1.5-mm depth (in Group I), 2.5-mm depth (in Group II), or 3.5-mm depth (in Group III) was left. In the left knee, we did not apply any treatment to the defect to obtain the control data. All the rabbits were sacrificed at 4 weeks, and the gross and histological evaluations were performed. The remaining 4 rabbits underwent the same treatment as used in Group II, and real-time PCR analysis was performed at 4 weeks. The defect in Group II was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen. The Wayne's gross appearance and histology scores showed that Group II was significantly greater than Group I, III, and Control (p < 0.012). The relative expression level of type-2 collagen, aggrecan, and SOX9 mRNAs was significantly greater in Group II than in the control group (p < 0.023). This study demonstrated that spontaneous hyaline cartilage regeneration can be induced in vivo in an osteochondral defect created in the femoral condyle by means of implanting the DN gel plug at the bottom of the defect so that an approximately 2-mm deep vacant space was intentionally left in the defect. This fact has prompted us to propose an innovative strategy without cell culture to repair osteochondral lesions in the femoral condyle.

Tissue engineering of peripheral nerves: Epineurial grafts with application of cultured Schwann cells.

PubMed

Fansa, H; Dodic, T; Wolf, G; Schneider, W; Keilhoff, G

2003-01-01

After a simple nerve lesion, primary microsurgical suture is the treatment of choice. A nerve gap has to be bridged, with a nerve graft sacrificing a functioning nerve. Alternatively, tissue engineering of nerve grafts has become a subject of experimental research. It is evident that nerve regeneration requires not only an autologous, allogenous, or biodegradable scaffold, but additional interactions with regeneration-promoting Schwann cells. In this study, we compared epineurial and acellularized epineurial tubes with and without application of cultured Schwann cells as alternative grafts in a rat sciatic nerve model. Autologous nerve grafts served as controls. Evaluation was performed after 6 weeks; afterwards, sections of the graft and distal nerve were harvested for histological and morphometrical analysis. Compared to controls, all groups showed a significantly lower number of axons, less well-shaped remyelinizated axons, and a delay in clinical recovery (e.g., toe spread). The presented technique with application of Schwann cells into epineurial tubes did not offer any major advantages for nerve regeneration. Thus, in this applied model, neither the implantation of untreated nor the implantation of acellularized epineurial tubes with cultured Schwann cells to bridge nerve defects was capable of presenting a serious alternative to the present gold standard of conventional nerve grafts for bridging nerve defects in this model. Copyright 2003 Wiley-Liss, Inc.

Tissue-engineered vascularized bone grafts: basic science and clinical relevance to trauma and reconstructive microsurgery.

PubMed

Johnson, Elizabeth O; Troupis, Theodore; Soucacos, Panayotis N

2011-03-01

Bone grafts are an important part of orthopaedic surgeon's armamentarium. Despite well-established bone-grafting techniques, large bone defects still represent a challenge. Efforts have therefore been made to develop osteoconductive, osteoinductive, and osteogenic bone-replacement systems. The long-term clinical goal in bone tissue engineering is to reconstruct bony tissue in an anatomically functional three-dimensional morphology. Current bone tissue engineering strategies take into account that bone is known for its ability to regenerate following injury, and for its intrinsic capability to re-establish a complex hierarchical structure during regeneration. Although the tissue engineering of bone for the reconstruction of small to moderate sized bone defects technically feasible, the reconstruction of large defects remains a daunting challenge. The essential steps towards optimized clinical application of tissue-engineered bone are dependent upon recent advances in the area of neovascularization of the engineered construct. Despite these recent advances, however, a gap from bench to bedside remains; this may ultimately be bridged by a closer collaboration between basic scientists and reconstructive surgeons. The aim of this review is to introduce the basic principles of tissue engineering of bone, outline the relevant bone physiology, and discuss the recent concepts for the induction of vascularization in engineered bone tissue. Copyright © 2011 Wiley-Liss, Inc.

New description of gradual substitution of graft by bone tissue including biomechanical and structural effects, nutrients supply and consumption

NASA Astrophysics Data System (ADS)

Lu, Yanfei; Lekszycki, Tomasz

2018-03-01

A new description of graft substitution by bone tissue is proposed in this work. The studied domain is considered as a continuum model consisting of a mixture of the bone tissue and the graft material. Densities of both components evolve in time as a result of cellular activity and biodegradation. The proposed model focuses on the interaction between the bone cell activity, mechanical stimuli, nutrients supply and scaffold microstructure. Different combinations of degradation rate and stiffness of the graft material were examined by numerical simulation. It follows from the calculations that the degradation rate of the scaffold should be tuned to the synthesis/resorption rate of the tissue, which are dependent among the others on scaffold porosity changes. Simulation results imply potential criteria to choose proper bone substitute material in consideration of degradation rate, initial porosity and mechanical characteristics.

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

PubMed Central

Santo, Vítor E.; Mano, João F.; Reis, Rui L.

2013-01-01

The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors. PMID:23249320

Soft tissue volume alterations after connective tissue grafting at teeth: the subepithelial autologous connective tissue graft versus a porcine collagen matrix - a pre-clinical volumetric analysis.

PubMed

Schmitt, Christian M; Matta, Ragai E; Moest, Tobias; Humann, Julia; Gammel, Lisa; Neukam, Friedrich W; Schlegel, Karl A

2016-07-01

This study evaluates a porcine collagen matrix (CM) for soft tissue thickening in comparison to the subepithelial connective tissue graft (SCTG). In eight beagle dogs, soft tissue thickening was performed at the buccal aspects of the upper canines (SCTG and CM). Impressions were taken before augmentation (i1), after surgery (i2), after one (i3), three (i4) and ten month (i5). Casts were optically scanned with a 3D scanner and each augmented region (unit of analysis) evaluated (primary outcome variable: volume increase in mm(3) ; secondary outcome variables: volume increase in percent, mean and maximum thickness increases in mm). 3D tissue measurements after surgery revealed a significant higher volume increase in the CM (86.37 mm(3)  ± 35.16 mm(3) ) than in the SCTG group (47.65 mm(3)  ± 17.90 mm(3) ). After 10 months, volume increase was non-significant between groups (SCTG:11.36 mm(3)  ± 9.26 mm(3) ; CM: 8.67 mm(3)  ± 13.67 mm(3) ). Maximum soft tissue thickness increase (i1-i5) was 0.66 mm ± 0.29 mm (SCTG) and 0.79 mm ± 0.37 mm (CM) with no significant difference. Ten months after soft tissue thickening, the CM is statistically non-inferior to the SCTG in terms of soft tissue volume and thickness increase. Further 3D studies are needed to confirm the data. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Osteochondral Repair Using Porous Three-dimensional Nanocomposite Scaffolds in a Rabbit Model

PubMed Central

ŻYLIŃSKA, BEATA; STODOLAK-ZYCH, EWA; SOBCZYŃSKA-RAK, ALEKSANDRA; SZPONDER, TOMASZ; SILMANOWICZ, PIOTR; ŁAŃCUT, MIROSŁAW; JAROSZ, ŁUKASZ; RÓŻAŃSKI, PAWEŁ; POLKOWSKA, IZABELA

2017-01-01

Aim: To evaluate the utility of a novel nanocomposite biomaterial consisting of poly-L/D-lactide, and hydroxyapatite bioceramics, enriched with sodium alginate in articular cartilage defect treatment. Materials and Methods: The biomaterial was prepared using the method of solvent casting and particle leaching. The study was conducted on 20 New Zealand White rabbits. Experimental osteochondral defects were created in the femoral trochlear grooves and filled with biomaterials. In control groups, the defects were left to spontaneously heal. The quality of newly-formed tissue was evaluated on the basis of macroscopic and histological assessment. Additionally the level of osteogenic and cartilage degradation markers were measured. Results: The majority of the defects from the treatment group were covered with tissue similar in structure and colour to healthy cartilage, whereas in the control group, tissue was uneven, and not integrated into the surrounding cartilage. Conclusion: The results obtained validate the choice of biomaterial used in this study as well as the method of its application. PMID:28882956

Femoral osteochondral fracture--a non-contact injury in martial arts? A case report.

PubMed Central

Mbubaegbu, C E; Percy, A J

1994-01-01

A report of a case of osteochondral fracture of the lateral femoral condyle in a patient doing a karate kick. The problems related to fixation of osteochondral fragments with protruding screws are highlighted and the suitability of Herbert screw fixation noted. Images Figure 1 Figure 2 Figure 3 PMID:8000822

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

Connective tissue changes in a mouse model of vein graft disease.

PubMed

Schachner, T; Heiss, S; Mayr, T; Steger, C; Zipponi, D; Reisinger, P; Bonaros, N; Laufer, G; Bonatti, J

2008-04-01

The extracellular matrix plays an important physiological role in the architecture of the vascular wall. In arterialized vein grafts severe early changes, such as thrombosis and neointimal hyperplasia occur. Paclitaxel is in clinical use as antiproliferative coating of coronary stents. We aimed to investigate the early connective tissue changes in arterialized vein grafts and the influence of perivascular paclitaxel treatment in an in vivo model. C57 black mice underwent interposition of the vena cava into the carotid artery. Neointimal hyperplasia, thrombosis, acid mucopolysaccharides (Alcian), collagen fibers (trichrome Masson), elastic fibers, and apoptosis rate (TUNEL) were quantified in paclitaxel treated veins and controls. In both, controls and paclitaxel treated vein grafts acid mucopolysaccharides and elastic fibers were found predominantly in the neointima, whereas collagen fibers were found mainly in the media and adventitia. At 4 weeks postoperatively the neointimal thickness in controls was 52 (13-130) microm, whereas in 0.6 mg/mL l paclitaxel treated veins it was 103 (43-318) microm (P=0.094). At 8 weeks postoperatively paclitaxel treated veins showed a significantly increased neointimal thickness of 136 (87-199) microm compared with 79 (62-146) microm in controls (P=0.032). There was no difference in apoptosis rate between the two groups (P=NS). Even with the lowest concentration of 0.008 mg/mL paclitaxel veins showed a neointimal thickness of 67 (46-205) microm at 4 weeks postoperatively (P=NS vs controls). Early vein graft disease is characterised by an accumulation of acid mucopolysaccharides and elastic fibers in the thickened neointima. Paclitaxel treatment increases the neointimal hyperplasia in mouse vein grafts in vivo.

Osteointegration of soft tissue grafts within the bone tunnels in anterior cruciate ligament reconstruction can be enhanced.

PubMed

Kuang, Guan-Ming; Yau, W P; Lu, William W; Chiu, K Y

2010-08-01

Anterior cruciate ligament reconstruction with a soft tissue autograft (hamstring autograft) has grown in popularity in the last 10 years. However, the issues of a relatively long healing time and an inferior histological healing result in terms of Sharpey-like fibers connection in soft tissue grafts are still unsolved. To obtain a promising outcome in the long run, prompt osteointegration of the tendon graft within the bone tunnel is essential. In recent decades, numerous methods have been reported to enhance osteointegration of soft tissue graft in the bone tunnel. In this article, we review the current literature in this research area, mainly focusing on strategies applied to the local bone tunnel environment. Biological strategies such as stem cell and gene transfer technology, as well as the local application of specific growth factors have been reported to yield exciting results. The use of biological bone substitute and physical stimulation also obtained promising results. Artificially engineered tissue has promise as a solution to the problem of donor site morbidity. Despite these encouraging results, the current available evidence is still experimental. Further clinical studies in terms of randomized control trial in the future should be conducted to extrapolate these basic science study findings into clinical practice.

Novel application and serial evaluation of tissue-engineered portal vein grafts in a murine model.

PubMed

Maxfield, Mark W; Stacy, Mitchel R; Kurobe, Hirotsugu; Tara, Shuhei; Yi, Tai; Cleary, Muriel A; Zhuang, Zhen W; Rodriguez-Davalos, Manuel I; Emre, Sukru H; Iwakiri, Yasuko; Shinoka, Toshiharu; Breuer, Christopher K

2017-12-01

Surgical management of pediatric extrahepatic portal vein obstruction requires meso-Rex bypass using autologous or synthetic grafts. Tissue-engineered vascular grafts (TEVGs) provide an alternative, but no validated animal models using portal TEVGs exist. Herein, we preclinically assess TEVGs as portal vein bypass grafts. TEVGs were implanted as portal vein interposition conduits in SCID-beige mice, monitored by ultrasound and micro-computed tomography, and histologically assessed postmortem at 12 months. TEVGs remained patent for 12 months. Histologic analysis demonstrated formation of neovessels that resembled native portal veins, with similar content of smooth muscle cells, collagen type III and elastin. TEVGs are feasible portal vein conduits in a murine model. Further preclinical evaluation of TEVGs may facilitate pediatric clinical translation.

Synthesis of electroactive tetraaniline grafted polyethylenimine for tissue engineering

NASA Astrophysics Data System (ADS)

Dong, Shilei; Han, Lu; Cai, Muhang; Li, Luhai; Wei, Yan

2015-07-01

Tetraaniline grafted polyethylenimine (AT-PEI) was successfully synthesized in this study. Proton Nuclear Magnetic Resonance (1H NMR) Spectroscopy was used to determine the structure of carboxyl-capped aniline tetramer (AT-COOH) and AT-PEI. UV-Vis spectroscopy and Fourier transform infrared (FT-IR) spectroscopy were employed to characterize the absorption spectrum of the obtained AT-PEI samples. The morphology of AT-PEI copolymers in aqueous solution was determined by Scanning electron microscope (SEM). Moreover, AT-PEI copolymers demonstrated excellent solubility in aqueous solution and possessed electroactivity by cyclic voltammogram (CV) curves, which showed its potential application in the field of tissue engineering.

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.

Transplantation of dedifferentiated fat cell-derived micromass pellets contributed to cartilage repair in the rat osteochondral defect model.

PubMed

Shimizu, Manabu; Matsumoto, Taro; Kikuta, Shinsuke; Ohtaki, Munenori; Kano, Koichiro; Taniguchi, Hiroaki; Saito, Shu; Nagaoka, Masahiro; Tokuhashi, Yasuaki

2018-03-20

Mature adipocyte-derived dedifferentiated fat (DFAT) cells possesses the ability to proliferate effectively and the potential to differentiate into multiple linages of mesenchymal tissue; similar to adipose-derived stem cells (ASCs). The purpose of this study is to examine the effects of DFAT cell transplantation on cartilage repair in a rat model of osteochondral defects. Full-thickness osteochondral defects were created in the knees of Sprague-Dawley rats bilaterally. Cartilage-like micromass pellets were prepared from green fluorescent protein (GFP)-labeled rat DFAT cells and subsequently transplanted into the affected right knee of these rats. Defects in the left knee were used as a control. Macroscopic and microscopic changes of treated and control defects were evaluated up to 12 weeks post-treatment with DFAT cells. To observe the transplanted cells, sectioned femurs were immunostained for GFP and type II collagen. DFAT cells formed micromass pellets expressing characteristics of immature cartilage in vitro. In the DFAT cell-transplanted limbs, the defects were completely filled with white micromass pellets as early as 2 weeks post-treatment. These limbs became smooth at 4 weeks. Conversely, the defects in the control limbs were still not repaired by 4 weeks. Macroscopic ICRS scores at 2 and 4 weeks were significantly higher in the DFAT cells-transplanted limbs compared to those of the control limbs. The modified O'Driscol histological scores for the DFAT cell-transplanted limbs were significantly higher than those of the control limbs at corresponding time points. GFP-positive DAFT cells were detected in the transplanted area at 2 weeks but hardly visible at 12 weeks post-operation. Transplantation of DFAT cell-derived micromass pellets contribute to cartilage repair in a rat osteochondral defect model. DFAT cell transplantation may be a viable therapeutic strategy for the repair of osteochondral injuries. Copyright © 2018 The Authors. Published by

Osteochondritis dissecans of the knee in a subadult from a medieval (ninth century A.D.) site in Croatia.

PubMed

Slaus, Mario; Cicvara-Pećina, Tatjana; Lucijanić, Ivica; Pećina, Marko; Stilinović, Davor

2010-06-01

Although osteochondritis dissecans of the knee has been known for a long time, we still do not fully understand why it develops. This prompted us to present and describe an example of osteochondritis dissecans identified in the Osteological Collection of the Croatian Academy of Sciences and Arts. The case of osteochondritis dissecans described in this report was recovered from the Gluvine kuće cemetery in the Dalmatian hinterland, approximately 28 km north-east of Split. A total of 77 graves were excavated and the individual exhibiting osteochondritis dissecans was recovered from grave number 16 that belongs to the younger phase of the cemetery that lasted during the second half of the 9th century A.D. Osteochondritis dissecans was noted in a subadult individual. The pathological changes consistent with osteochondritis dissecans are present on both medial femoral condyles. The lesion on the right femoral condyle is an oval crater-like defect with well defined margins and a porous floor of rough trabecular bone. The lesion on the left femoral condyle is basically, with two small provisions, identical to the one on the right side. The first is that it is slightly smaller, while the second is that unlike its antimere, it has a well preserved bone fragment that fits perfectly into the ostechondritic pit. Radiographic analyses of the femoral condyles support a diagnosis of osteochondritis dissecans and show a well-demarcated radiolucent defect in the articular surfaces of both joints surrounded by a thin sclerotic repair zone. According to the classification systems this degree of change corresponds to stage 3 or grade 3 osteochondritis dissecans--a detached but non-displaced fragment. Returning, for a second, to the opinion that prompted us to present this case, it is clear that during the last 1100 years there have been no significant morphological or radiological changes in the characteristics of osteochondritis dissecans.

Reconstruction of attached soft tissue around dental implants by acelluar dermal matrix grafts and resin splint

PubMed Central

Liu, Changying; Su, Yucheng; Tan, Baosheng; Ma, Pan; Wu, Gaoyi; Li, Jun; Geng, Wei

2014-01-01

Objectives: The purpose of this study was to recommend a new method using acellular dermal matrix graft and resin splint to reconstruct the attached soft tissue around dental implants in patients with maxillofacial defects. Materials and methods: Total 8 patients (3 male and 5 female patients) diagnosed with maxillofacial defects and dentition defects caused by tumors, fractures or edentulous jaw, were selected for this study. Dental implants were routinely implanted at the edentulous area. Acellular dermal matrix heterografts and resin splint were used to increase the attached soft tissue. The width of attached gingiva in the labial or buccal surface at edentulous area was measured before surgical procedures and after the completion of superstructures. Paired t-test was applied to assess the change of quantitative variables. All tests were 2-tailed, and P < 0.05 was considered statistically significant. Results: The dense connective tissue around implants could be reconstructed one month after the completion of surgical procedures, and the epithelial cuff around the implant neck established very well. The width of attached gingival tissue in the patients increased significantly from a mean of 0.61 ± 0.75 mm to 6.25 ± 1.04 mm. The patients were fully satisfied with the esthetic and functional results achieved. Conclusions: The acellular dermal matrix graft could be used to increase the attached gingiva around dental implants in these patients with maxillofacial defects. The resin splint could facilitate the healing of graft. PMID:25663964

Greater magnitude tibiofemoral contact forces are associated with reduced prevalence of osteochondral pathologies 2-3 years following anterior cruciate ligament reconstruction.

PubMed

Saxby, David John; Bryant, Adam L; Van Ginckel, Ans; Wang, Yuanyuan; Wang, Xinyang; Modenese, Luca; Gerus, Pauline; Konrath, Jason M; Fortin, Karine; Wrigley, Tim V; Bennell, Kim L; Cicuttini, Flavia M; Vertullo, Christopher; Feller, Julian A; Whitehead, Tim; Gallie, Price; Lloyd, David G

2018-06-07

External loading of osteoarthritic and healthy knees correlates with current and future osteochondral tissue state. These relationships have not been examined following anterior cruciate ligament reconstruction. We hypothesised greater magnitude tibiofemoral contact forces were related to increased prevalence of osteochondral pathologies, and these relationships were exacerbated by concomitant meniscal injury. This was a cross-sectional study of 100 individuals (29.7 ± 6.5 years, 78.1 ± 14.4 kg) examined 2-3 years following hamstring tendon anterior cruciate ligament reconstruction. Thirty-eight participants had concurrent meniscal pathology (30.6 ± 6.6 years, 83.3 ± 14.3 kg), which included treated and untreated meniscal injury, and 62 participants (29.8 ± 6.4 years, 74.9 ± 13.3 kg) were free of meniscal pathology. Magnetic resonance imaging of reconstructed knees was used to assess prevalence of tibiofemoral osteochondral pathologies (i.e., cartilage defects and bone marrow lesions). A calibrated electromyogram-driven neuromusculoskeletal model was used to predict medial and lateral tibiofemoral compartment contact forces from gait analysis data. Relationships between contact forces and osteochondral pathology prevalence were assessed using logistic regression models. In patients with reconstructed knees free from meniscal pathology, greater medial contact forces were related to reduced prevalence of medial cartilage defects (odds ratio (OR) = 0.7, Wald χ 2 (2) = 7.9, 95% confidence interval (CI) = 0.50-95, p = 0.02) and medial bone marrow lesions (OR = 0.8, Wald χ 2 (2) = 4.2, 95% CI = 0.7-0.99, p = 0.04). No significant relationships were found in lateral compartments. In reconstructed knees with concurrent meniscal pathology, no relationships were found between contact forces and osteochondral pathologies. In patients with reconstructed knees free from meniscal pathology, increased

Repair of articular cartilage defects in the knee with autologous iliac crest cartilage in a rabbit model.

PubMed

Jing, Lizhong; Zhang, Jiying; Leng, Huijie; Guo, Qinwei; Hu, Yuelin

2015-04-01

To demonstrate that iliac crest cartilage may be used to repair articular cartilage defects in the knees of rabbits. Full-thickness cartilage defects were created in the medial femoral condyle on both knees of 36 New Zealand white rabbits. The 72 defects were randomly assigned to be repaired with ipsilateral iliac crest cartilage (Group I), osteochondral tissues removed at defect creation (Group II), or no treatment (negative control, Group III). Animals were killed at 6, 12, and 24 weeks post-operatively. The repaired tissues were harvested for magnetic resonance imaging (MRI), histological studies (haematoxylin and eosin and immunohistochemical staining), and mechanical testing. At 6 weeks, the iliac crest cartilage graft was not yet well integrated with the surrounding articular cartilage, but at 12 weeks, the graft deep zone had partial ossification. By 24 weeks, the hyaline cartilage-like tissue was completely integrated with the surrounding articular cartilage. Osteochondral autografts showed more rapid healing than Group I at 6 weeks and complete healing at 12 weeks. Untreated defects were concave or partly filled with fibrous tissue throughout the study. MRI showed that Group I had slower integration with surrounding normal cartilage compared with Group II. The mechanical properties of Group I were significantly lower than those of Group II at 12 weeks, but this difference was not significant at 24 weeks. Iliac crest cartilage autografts were able to repair knee cartilage defects with hyaline cartilage and showed comparable results with osteochondral autografts in the rabbit model.

Biomaterials for Tissue Engineering

PubMed Central

Lee, Esther J.; Kasper, F. Kurtis; Mikos, Antonios G.

2013-01-01

Biomaterials serve as an integral component of tissue engineering. They are designed to provide architectural framework reminiscent of native extracellular matrix in order to encourage cell growth and eventual tissue regeneration. Bone and cartilage represent two distinct tissues with varying compositional and mechanical properties. Despite these differences, both meet at the osteochondral interface. This article presents an overview of current biomaterials employed in bone and cartilage applications, discusses some design considerations, and alludes to future prospects within this field of research. PMID:23820768

Development of a Sterile Amniotic Membrane Tissue Graft Using Supercritical Carbon Dioxide

DTIC Science & Technology

2015-03-04

production of acellular dermal matrices for clinical use . Wound Repair Regen 12, 276, 2004. 40. Movasaghi, Z., Rehman, S., and Rehman, I.U. Fourier...Development of a Sterile Amniotic Membrane Tissue Graft Using Supercritical Carbon Dioxide Jennifer L. Wehmeyer, PhD, Shanmugasundaram Natesan, PhD...and Robert J. Christy, PhD Numerous techniques have been reported for preparing and sterilizing amniotic membrane (AM) for use in clinical

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.

A comparative clinical study of the efficacy of subepithelial connective tissue graft and acellular dermal matrix graft in root coverage: 6-month follow-up observation

PubMed Central

Thomas, Libby John; Emmadi, Pamela; Thyagarajan, Ramakrishnan; Namasivayam, Ambalavanan

2013-01-01

Aims: The purpose of this study was to compare the clinical efficacy of subepithelial connective tissue graft and acellular dermal matrix graft associated with coronally repositioned flap in the treatment of Miller's class I and II gingival recession, 6 months postoperatively. Settings and Design: Ten patients with bilateral Miller's class I or class II gingival recession were randomly divided into two groups using a split-mouth study design. Materials and Methods: Group I (10 sites) was treated with subepithelial connective tissue graft along with coronally repositioned flap and Group II (10 sites) treated with acellular dermal matrix graft along with coronally repositioned flap. Clinical parameters like recession height and width, probing pocket depth, clinical attachment level, and width of keratinized gingiva were evaluated at baseline, 90th day, and 180th day for both groups. The percentage of root coverage was calculated based on the comparison of the recession height from 0 to 180th day in both Groups I and II. Statistical Analysis Used: Intragroup parameters at different time points were measured using the Wilcoxon signed rank test and Mann–Whitney U test was employed to analyze the differences between test and control groups. Results: There was no statistically significant difference in recession height and width, gain in CAL, and increase in the width of keratinized gingiva between the two groups on the 180th day. Both procedures showed clinically and statistically significant root coverage (Group I 96%, Group II 89.1%) on the 180th day. Conclusions: The results indicate that coverage of denuded root with both subepithelial connective tissue autograft and acellular dermal matrix allograft are very predictable procedures, which were stable for 6 months postoperatively. PMID:24174728

Evaluation of Small Intestine Grafts Decellularization Methods for Corneal Tissue Engineering

PubMed Central

Oliveira, Ana Celeste; Garzón, Ingrid; Ionescu, Ana Maria; Carriel, Victor; Cardona, Juan de la Cruz; González-Andrades, Miguel; Pérez, María del Mar; Alaminos, Miguel; Campos, Antonio

2013-01-01

Advances in the development of cornea substitutes by tissue engineering techniques have focused on the use of decellularized tissue scaffolds. In this work, we evaluated different chemical and physical decellularization methods on small intestine tissues to determine the most appropriate decellularization protocols for corneal applications. Our results revealed that the most efficient decellularization agents were the SDS and triton X-100 detergents, which were able to efficiently remove most cell nuclei and residual DNA. Histological and histochemical analyses revealed that collagen fibers were preserved upon decellularization with triton X-100, NaCl and sonication, whereas reticular fibers were properly preserved by decellularization with UV exposure. Extracellular matrix glycoproteins were preserved after decellularization with SDS, triton X-100 and sonication, whereas proteoglycans were not affected by any of the decellularization protocols. Tissue transparency was significantly higher than control non-decellularized tissues for all protocols, although the best light transmittance results were found in tissues decellularized with SDS and triton X-100. In conclusion, our results suggest that decellularized intestinal grafts could be used as biological scaffolds for cornea tissue engineering. Decellularization with triton X-100 was able to efficiently remove all cells from the tissues while preserving tissue structure and most fibrillar and non-fibrillar extracellular matrix components, suggesting that this specific decellularization agent could be safely used for efficient decellularization of SI tissues for cornea TE applications. PMID:23799114

Two Patients with Osteochondral Injury of the Weight-Bearing Portion of the Lateral Femoral Condyle Associated with Lateral Dislocation of the Patella

PubMed Central

Inoue, Hiroaki; Atsumi, Satoru; Ichimaru, Shohei; Fujiwara, Hiroyoshi; Kubo, Toshikazu

2014-01-01

Complications of patellar dislocation include osteochondral injury of the lateral femoral condyle and patella. Most cases of osteochondral injury occur in the anterior region, which is the non-weight-bearing portion of the lateral femoral condyle. We describe two patients with osteochondral injury of the weight-bearing surface of the lateral femoral condyle associated with lateral dislocation of the patella. The patients were 18- and 11-year-old females. Osteochondral injury occurred on the weight-bearing surface distal to the lateral femoral condyle. The presence of a free osteochondral fragment and osteochondral injury of the lateral femoral condyle was confirmed on MRI and reconstruction CT scan. Treatment consisted of osteochondral fragment fixation or microfracture, as well as patellar stabilization. Osteochondral injury was present in the weight-bearing portion of the lateral femoral condyle in both patients, suggesting that the injury was caused by friction between the patella and lateral femoral condyle when the patella was dislocated or reduced at about 90° flexion of the knee joint. These findings indicate that patellar dislocation may occur and osteochondral injury may extend to the weight-bearing portion of the femur even in deep flexion, when the patella is stabilized on the bones of the femoral groove. PMID:25506015

Osteochondritis Dessicans- Primary Fixation using Bioabsorbable Implants

PubMed Central

Galagali, Anand; Rao, Muralidhar

2012-01-01

Introduction: Osteochondritis dessicans (OCD) is a localized condition where a section of articular cartilage and underlying subchondral bone separate from the joint surface. It is important to diagnose unstable OCD early and fix the fragments primarily as the results of any surgical management at late presentations are guarded. Use of bioabsorbable implants for fixing OCD is recent and we report one such case in grade IV OCD. Case Report: We present a 14 year old girl who came with a history of acute pain, swelling, inability to bear weight on the right knee following a dance practice. MRI showed stage IV osteochondral fragment measuring 20x 8mm lying free. This was primarily fixed with bioabsorbable implants. 10 months follow up showed excellent clinical and functional results. Conclusion: This case highlights the advantages of early primary fixation whenever possible. By far, to our knowledge, this is the first case of successful treatment of stage IV OCD using bioabsorbable implants. PMID:27298854

Perfusion-decellularization of human ear grafts enables ECM-based scaffolds for auricular vascularized composite tissue engineering.

PubMed

Duisit, Jérôme; Amiel, Hadrien; Wüthrich, Tsering; Taddeo, Adriano; Dedriche, Adeline; Destoop, Vincent; Pardoen, Thomas; Bouzin, Caroline; Joris, Virginie; Magee, Derek; Vögelin, Esther; Harriman, David; Dessy, Chantal; Orlando, Giuseppe; Behets, Catherine; Rieben, Robert; Gianello, Pierre; Lengelé, Benoît

2018-06-01

Human ear reconstruction is recognized as the emblematic enterprise in tissue engineering. Up to now, it has failed to reach human applications requiring appropriate tissue complexity along with an accessible vascular tree. We hereby propose a new method to process human auricles in order to provide a poorly immunogenic, complex and vascularized ear graft scaffold. 12 human ears with their vascular pedicles were procured. Perfusion-decellularization was applied using a SDS/polar solvent protocol. Cell and antigen removal was examined by histology and DNA was quantified. Preservation of the extracellular matrix (ECM) was assessed by conventional and 3D-histology, proteins and cytokines quantifications. Biocompatibility was assessed by implantation in rats for up to 60 days. Adipose-derived stem cells seeding was conducted on scaffold samples and with human aortic endothelial cells whole graft seeding in a perfusion-bioreactor. Histology confirmed cell and antigen clearance. DNA reduction was 97.3%. ECM structure and composition were preserved. Implanted scaffolds were tolerated in vivo, with acceptable inflammation, remodeling, and anti-donor antibody formation. Seeding experiments demonstrated cell engraftment and viability. Vascularized and complex auricular scaffolds can be obtained from human source to provide a platform for further functional auricular tissue engineered constructs, hence providing an ideal road to the vascularized composite tissue engineering approach. The ear is emblematic in the biofabrication of tissues and organs. Current regenerative medicine strategies, with matrix from donor tissues or 3D-printed, didn't reach any application for reconstruction, because critically missing a vascular tree for perfusion and transplantation. We previously described the production of vascularized and cell-compatible scaffolds, from porcine ear grafts. In this study, we ---- applied findings directly to human auricles harvested from postmortem donors

Osteochondral Repair Using Porous Three-dimensional Nanocomposite Scaffolds in a Rabbit Model.

PubMed

Żylińska, Beata; Stodolak-Zych, Ewa; Sobczyńska-Rak, Aleksandra; Szponder, Tomasz; Silmanowicz, Piotr; Łańcut, Mirosław; Jarosz, Łukasz; Różański, Paweł; Polkowska, Izabela

2017-01-01

To evaluate the utility of a novel nanocomposite biomaterial consisting of poly-L/D-lactide, and hydroxyapatite bioceramics, enriched with sodium alginate in articular cartilage defect treatment. The biomaterial was prepared using the method of solvent casting and particle leaching. The study was conducted on 20 New Zealand White rabbits. Experimental osteochondral defects were created in the femoral trochlear grooves and filled with biomaterials. In control groups, the defects were left to spontaneously heal. The quality of newly-formed tissue was evaluated on the basis of macroscopic and histological assessment. Additionally the level of osteogenic and cartilage degradation markers were measured. The majority of the defects from the treatment group were covered with tissue similar in structure and colour to healthy cartilage, whereas in the control group, tissue was uneven, and not integrated into the surrounding cartilage. The results obtained validate the choice of biomaterial used in this study as well as the method of its application. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Harnessing cell–biomaterial interactions for osteochondral tissue regeneration.

PubMed

Kim, Kyobum; Yoon, Diana M; Mikos, Antonios; Kasper, F Kurtis

2012-01-01

Articular cartilage that is damaged or diseased often requires surgical intervention to repair the tissue; therefore, tissue engineering strategies have been developed to aid in cartilage regeneration. Tissue engineering approaches often require the integration of cells, biomaterials, and growth factors to direct and support tissue formation. A variety of cell types have been isolated from adipose, bone marrow, muscle, and skin tissue to promote cartilage regeneration. The interaction of cells with each other and with their surrounding environment has been shown to play a key role in cartilage engineering. In tissue engineering approaches, biomaterials are commonly used to provide an initial framework for cell recruitment and proliferation and tissue formation. Modifications of the properties of biomaterials, such as creating sites for cell binding, altering their physicochemical characteristics, and regulating the delivery of growth factors, can have a significant influence on chondrogenesis. Overall, the goal is to completely restore healthy cartilage within an articular cartilage defect. This chapter aims to provide information about the importance of cell–biomaterial interactions for the chondrogenic differentiation of various cell populations that can eventually produce functional cartilage matrix that is indicative of healthy cartilage tissue.

Arthroscopic retrograde osteochondral autologous transplantation to chondral lesion in femoral head.

PubMed

Cetinkaya, Sarper; Toker, Berkin; Taser, Omer

2014-06-01

This report describes the treatment of 2 cases of full-thickness cartilage defect of the femoral head. The authors performed osteochondral autologous transplantation with a different technique that has not been reported to date. One patient was 37 years old, and the other was 42 years old. Both presented with hip pain. In both patients, radiograph and magnetic resonance imaging scan showed a focal chondral defect on the weight-bearing area of the femoral head and acetabular impingement. A retrograde osteochondral autologous transplantation technique combined with hip arthroscopy and arthroscopic impingement treatment was performed. After a 2-month recovery period, the symptoms were resolved. In the first year of follow-up, Harris Hip scores improved significantly (case 1, 56.6 to 87.6; case 2, 58.6 to 90). The technique described yielded good short- and midterm clinical and radiologic outcomes. To the authors' knowledge, this report is the first to describe a retrograde osteochondral transplantation technique performed with hip arthroscopy in the femoral head. Copyright 2014, SLACK Incorporated.

Nonexpansive immediate breast reconstruction using human acellular tissue matrix graft (AlloDerm).

PubMed

Salzberg, C Andrew

2006-07-01

Immediate breast reconstruction has become a standard of care following mastectomy for cancer, largely due to improved esthetic and psychologic outcomes achieved with this technique. However, the current historical standards--transverse rectus abdominis myocutaneous flap reconstruction and expander--implant surgery-still have limitations as regards patient morbidity, short-term body-image improvements, and even cost. To address these shortcomings, we employ a novel concept of human tissue replacement to enhance breast shape and provide total coverage, enabling immediate mound reconstruction without the need for breast expansion prior to permanent implant placement. AlloDerm (human acellular tissue matrix) is a human-derived graft tissue with extensive experience in various settings of skin and soft tissue replacement surgery. This report describes the success using acellular tissue matrix to provide total coverage over the prosthesis in immediate reconstruction, with limited muscle dissection. In this population, 49 patients (76 breasts) successfully underwent the acellular tissue matrix-based immediate reconstruction, resulting in durable breast reconstruction with good symmetry. These findings may predict that acellular tissue matrix-supplemented immediate breast reconstruction will become a new technique for the immediate reconstruction of the postmastectomy breast.

Osteochondritis Dissecans of the Glenoid in a Major League Baseball Prospect: A Case Report.

PubMed

Grau, Luis Carlos; Jose, Jean; Sama, Andrew Joseph; Baraga, Michael Gerald

2016-01-01

A 16-year-old Major League Baseball prospect presented with persistent shoulder pain associated with throwing. Magnetic resonance imaging (MRI) demonstrated a large osteochondritis dissecans lesion in the posterosuperior aspect of the glenoid. The patient was restricted from throwing and underwent therapy to improve range of motion and throwing mechanics. Eight months after initiating nonoperative treatment, an MRI arthrogram demonstrated a healed lesion. At follow-up 2 years after treatment, full relief of symptoms had persisted. Osteochondritis dissecans lesions of the glenoid are extremely rare, but have the potential to heal in overhead-throwing athletes. To our knowledge, this is the only case reported in the literature that demonstrates a healed osteochondritis dissecans lesion of the glenoid following nonoperative treatment.

Fabrication and preliminary study of a biomimetic tri-layer tubular graft based on fibers and fiber yarns for vascular tissue engineering.

PubMed

Wu, Tong; Zhang, Jialing; Wang, Yuanfei; Li, Dandan; Sun, Binbin; El-Hamshary, Hany; Yin, Meng; Mo, Xiumei

2018-01-01

Designing a biomimetic and functional tissue-engineered vascular graft has been urgently needed for repairing and regenerating defected vascular tissues. Utilizing a multi-layered vascular scaffold is commonly considered an effective way, because multi-layered scaffolds can easily simulate the structure and function of natural blood vessels. Herein, we developed a novel tri-layer tubular graft consisted of Poly(L-lactide-co-caprolactone)/collagen (PLCL/COL) fibers and Poly(lactide-co-glycolide)/silk fibroin (PLGA/SF) yarns via a three-step electrospinning method. The tri-layer vascular graft consisted of PLCL/COL aligned fibers in inner layer, PLGA/SF yarns in middle layer, and PLCL/COL random fibers in outer layer. Each layer possessed tensile mechanical strength and elongation, and the entire tubular structure provided tensile and compressive supports. Furthermore, the human umbilical vein endothelial cells (HUVECs) and smooth muscle cells (SMCs) proliferated well on the materials. Fluorescence staining images demonstrated that the axially aligned PLCL/COL fibers prearranged endothelium morphology in lumen and the circumferential oriented PLGA/SF yarns regulated SMCs organization along the single yarns. The outside PLCL/COL random fibers performed as the fixed layer to hold the entire tubular structure. The in vivo results showed that the tri-layer vascular graft supported cell infiltration, scaffold biodegradation and abundant collagen production after subcutaneous implantation for 10weeks, revealing the optimal biocompatibility and tissue regenerative capability of the tri-layer graft. Therefore, the specially designed tri-layer vascular graft will be beneficial to vascular reconstruction. Copyright © 2017. Published by Elsevier B.V.

Effect of Low-Intensity Pulsed Ultrasound after Mesenchymal Stromal Cell Injection to Treat Osteochondral Defects: An In Vivo Study.

PubMed

Yamaguchi, Shoki; Aoyama, Tomoki; Ito, Akira; Nagai, Momoko; Iijima, Hirotaka; Tajino, Junichi; Zhang, Xiangkai; Wataru, Kiyan; Kuroki, Hiroshi

2016-12-01

We investigated the effect of low-intensity pulsed ultrasound (LIPUS) treatment combined with mesenchymal stromal cell (MSC) injection for cartilage repair and subchondral bone reconstitution for treatment of osteochondral defects. An osteochondral defect was created on both femur grooves of Wistar rats. Four weeks later, bone marrow MSCs were injected into the right knee joint. The rats were divided into two intervention groups: without or with LIPUS irradiation. Cartilage repair was evaluated histologically based on the Wakitani cartilage repair score. Subchondral bone reconstitution was evaluated as bone volume (BV)/tissue volume (TV) by micro-computed tomography analysis. MSC injection improved the cartilage repair score, and LIPUS irradiation improved BV/TV. Combination treatment promoted both cartilage repair and BV/TV improvement. Thus, MSC injection combined with LIPUS irradiation is more effective than either treatment alone in promoting concurrent cartilage repair and subchondral reconstitution. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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.

Characterization of evolving biomechanical properties of tissue engineered vascular grafts in the arterial circulation.

PubMed

Udelsman, Brooks V; Khosravi, Ramak; Miller, Kristin S; Dean, Ethan W; Bersi, Matthew R; Rocco, Kevin; Yi, Tai; Humphrey, Jay D; Breuer, Christopher K

2014-06-27

We used a murine model to assess the evolving biomechanical properties of tissue engineered vascular grafts (TEVGs) implanted in the arterial circulation. The initial polymeric tubular scaffold was fabricated from poly(lactic acid)(PLA) and coated with a 50:50 copolymer of poly(caprolactone) and poly(lactic acid)(P[PC/LA]). Following seeding with syngeneic bone marrow derived mononuclear cells, TEVGs (n=50) were implanted as aortic interposition grafts in wild-type mice and monitored serially using ultrasound. A custom biaxial mechanical testing device was used to quantify the in vitro circumferential and axial mechanical properties of grafts explanted at 3 or 7 months. At both times, TEVGs were much stiffer than native tissue in both directions. Repeated mechanical testing of some TEVGs treated with elastase or collagenase suggested that elastin did not contribute significantly to the overall stiffness whereas collagen did contribute. Traditional histology and immunostaining revealed smooth muscle cell layers, significant collagen deposition, and increasing elastin production in addition to considerable scaffold at both 3 and 7 months, which likely dominated the high stiffness seen in mechanical testing. These results suggest that PLA has inadequate in vivo degradation, which impairs cell-mediated development of vascular neotissue having properties closer to native arteries. Assessing contributions of individual components, such as elastin and collagen, to the developing neovessel is needed to guide computational modeling that may help to optimize the design of the TEVG. Copyright © 2014 Elsevier Ltd. All rights reserved.

Osteochondral transplantation of the talus: long-term clinical and magnetic resonance imaging evaluation.

PubMed

Imhoff, Andreas B; Paul, Jochen; Ottinger, Benjamin; Wörtler, Klaus; Lämmle, Lena; Spang, Jeffrey; Hinterwimmer, Stefan

2011-07-01

Osteochondral lesions of the ankle are a common injury after ankle sprains, especially in young and active patients. The Osteochondral Autograft Transfer System (OATS) is the only 1-step surgical technique designed to replace the entire osteochondral unit. This study was conducted to evaluate the long-term clinical and radiographic outcomes of the OATS procedure for the talus and compare the results of patients who have had prior surgical interventions with patients for whom OATS represents the primary surgical treatment. Case series; Level of evidence, 4. The authors retrospectively analyzed 26 talus OATS procedures (25 patients) with an average follow-up of 84 months (range, 53-124 months); 9 patients had OATS as a second surgical intervention. The patients completed the American Orthopaedic Foot & Ankle Society (AOFAS) and Tegner scores plus the visual analog scale (VAS) preoperatively and at follow-up. Magnetic resonance imaging examinations were conducted on a 1.5-T whole-body magnet that assessed transplant congruency, adjacent surface of the talus, the corresponding distal tibia, and joint effusion. The authors found significant increases for the AOFAS score (50 to 78 points, P < .01) and the Tegner score (3.1 to 3.7, P < .05) and a significant decrease for the VAS (7.8 to 1.5, P < .01) from preoperative to postoperative. Patients with normal integration or minor incongruity of the transplant on magnetic resonance imaging (81%) had significantly better AOFAS scores (P = .03). Other magnetic resonance imaging criteria did not predict clinical results. Patients for whom OATS represented a second procedure had significantly worse clinical AOFAS and Tegner scores plus a higher VAS. Long-term clinical and magnetic resonance imaging results after osteochondral transplantation are good and patients significantly benefit from this surgery. Magnetic resonance imaging should not be a routine control but appears to be indicated when clinical symptoms persist after

* A Rat Model for the In Vivo Assessment of Biological and Tissue-Engineered Valvular and Vascular Grafts.

PubMed

Sugimura, Yukiharu; Schmidt, Anna Kathrin; Lichtenberg, Artur; Assmann, Alexander; Akhyari, Payam

2017-12-01

The demand for an improvement of the biocompatibility and durability of vascular and valvular implants requires translational animal models to study the in vivo fate of cardiovascular grafts. In the present article, a review on the development and application of a microsurgical rat model of infrarenal implantation of aortic grafts and aortic valved conduits is provided. By refinement of surgical techniques and inclusion of hemodynamic considerations, a functional model has been created, which provides a modular platform for the in vivo assessment of biological and tissue-engineered grafts. Through optional addition of procalcific diets, disease-inducing agents, and genetic modifications, complex multimorbidity scenarios mimicking the clinical reality in cardiovascular patients can be simulated. Applying this model, crucial aspects of the biocompatibility, biofunctionality and degeneration of vascular and valvular implants in dependency on graft preparation, and modification as well as systemic antidegenerative treatment of the recipient have been and will be addressed.

Impact of storage conditions on electromechanical, histological and histochemical properties of osteochondral allografts.

PubMed

Mickevicius, Tomas; Pockevicius, Alius; Kucinskas, Audrius; Gudas, Rimtautas; Maciulaitis, Justinas; Noreikaite, Aurelija; Usas, Arvydas

2015-10-23

Osteochondral allograft transplantation has a good clinical outcome, however, there is still debate on optimization of allograft storage protocol. Storage temperature and nutrient medium composition are the most critical factors for sustained biological activity of grafts before implantation. In this study, we performed a time-dependent in vitro experiment to investigate the effect of various storage conditions on electromechanical, histological and histochemical properties of articular cartilage. Osteochondral grafts derived from goat femoral condyles were frozen at -70 °C or stored at 4 °C and 37 °C in the medium supplemented with or without insulin-like growth factor-1 (IGF-1). After 14 and 28 days the cartilage samples were quantitatively analysed for electromechanical properties, glycosaminoglycan distribution, histological structure, chondrocyte viability and apoptosis. The results were compared between the experimental groups and correlations among different evaluation methods were determined. Storage at -70 °C and 37 °C significantly deteriorated cartilage electromechanical, histological and histochemical properties. Storage at 4 °C maintained the electromechanical quantitative parameter (QP) and glycosaminoglycan expression near the normal levels for 14 days. Although hypothermic storage revealed reduced chondrocyte viability and increased apoptosis, these parameters were superior compared with the storage at -70 °C and 37 °C. IGF-1 supplementation improved the electromechanical QP, chondrocyte viability and histological properties at 37 °C, but the effect lasted only 14 days. Electromechanical properties correlated with the histological grading score (r = 0.673, p < 0.001), chondrocyte viability (r = -0.654, p < 0.001) and apoptosis (r = 0.416, p < 0.02). In addition, apoptosis correlated with glycosaminoglycan distribution (r = -0.644, p < 0.001) and the histological grading score (r = 0.493, p�

Stem Cells for Osteochondral Regeneration.

PubMed

Canadas, Raphaël F; Pirraco, Rogério P; Oliveira, J Miguel; Reis, Rui L; Marques, Alexandra P

2018-01-01

Stem cell research plays a central role in the future of medicine, which is mainly dependent on the advances on regenerative medicine (RM), specifically in the disciplines of tissue engineering (TE) and cellular therapeutics. All RM strategies depend upon the harnessing, stimulation, or guidance of endogenous developmental or repair processes in which cells have an important role. Among the most clinically challenging disorders, cartilage degeneration, which also affects subchondral bone becoming an osteochondral (OC) defect, is one of the most demanding. Although primary cells have been clinically applied, stem cells are currently seen as the promising tool of RM-related research because of its availability, in vitro proliferation ability, pluri- or multipotency, and immunosuppressive features. Being the OC unit, a transition from the bone to cartilage, mesenchymal stem cells (MSCs) are the main focus for OC regeneration. Promising alternatives, which can also be obtained from the patient or at banks and have great differentiation potential toward a wide range of specific cell types, have been reported. Still, ethical concerns and tumorigenic risk are currently under discussion and assessment. In this book chapter, we revise the existing stem cell-based approaches for engineering bone and cartilage, focusing on cell therapy and TE. Furthermore, 3D OC composites based on cell co-cultures are described. Finally, future directions and challenges still to be faced are critically discussed.

Fresh Osteochondral Allograft Transplantation for Fractures of the Knee.

PubMed

Gracitelli, Guilherme C; Tirico, Luis Eduardo Passarelli; McCauley, Julie C; Pulido, Pamela A; Bugbee, William D

2017-04-01

Objective The purpose of this study was to evaluate functional outcomes and allograft survivorship among patients with knee fracture who underwent fresh osteochondral allograft (OCA) transplantation as a salvage treatment option. Design Retrospective analysis of prospectively collected data. Setting Department of Orthopaedic Surgery at one hospital. Patients Fresh OCAs were implanted for osteochondral lesions after knee fracture in 24 males and 15 females with an average age of 34 years. Twenty-nine lesions (74%) were tibial plateau fractures, 6 (15%) were femoral condyle fractures, and 4 (10%) were patella fractures. Main Outcome Measurements Clinical evaluation included modified Merle d'Aubigné-Postel (18-point), International Knee Documentation Committee, and Knee Society function scores, and patient satisfaction. Failure of OCA was defined as revision OCA or conversion to total knee arthroplasty (TKA). Results Nineteen of 39 knees (49%) had further surgery. Ten knees (26%) were considered OCA failures (3 OCA revisions, 6 TKA, and 1 patellectomy). Survivorship of the OCA was 82.6% at 5 years and 69.6% at 10 years. Among the 29 knees (74%) that had the OCA still in situ, median follow-up was 6.6 years. Pain and function improved from preoperative to latest follow-up; 83% of patients reported satisfaction with OCA results. Conclusion OCA transplantation is a useful salvage treatment option for osteochondral lesions caused by knee fracture. Although the reoperation rate was high, successful outcome was associated with significant clinical improvement.

Chemical and morphological gradient scaffolds to mimic hierarchically complex tissues: From theoretical modeling to their fabrication.

PubMed

Marrella, Alessandra; Aiello, Maurizio; Quarto, Rodolfo; Scaglione, Silvia

2016-10-01

Porous multiphase scaffolds have been proposed in different tissue engineering applications because of their potential to artificially recreate the heterogeneous structure of hierarchically complex tissues. Recently, graded scaffolds have been also realized, offering a continuum at the interface among different phases for an enhanced structural stability of the scaffold. However, their internal architecture is often obtained empirically and the architectural parameters rarely predetermined. The aim of this work is to offer a theoretical model as tool for the design and fabrication of functional and structural complex graded scaffolds with predicted morphological and chemical features, to overcome the time-consuming trial and error experimental method. This developed mathematical model uses laws of motions, Stokes equations, and viscosity laws to describe the dependence between centrifugation speed and fiber/particles sedimentation velocity over time, which finally affects the fiber packing, and thus the total porosity of the 3D scaffolds. The efficacy of the theoretical model was tested by realizing engineered graded grafts for osteochondral tissue engineering applications. The procedure, based on combined centrifugation and freeze-drying technique, was applied on both polycaprolactone (PCL) and collagen-type-I (COL) to test the versatility of the entire process. A functional gradient was combined to the morphological one by adding hydroxyapatite (HA) powders, to mimic the bone mineral phase. Results show that 3D bioactive morphologically and chemically graded grafts can be properly designed and realized in agreement with the theoretical model. Biotechnol. Bioeng. 2016;113: 2286-2297. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Phase II Clinical Trial of Intraoral Grafting of Human Tissue Engineered Oral Mucosa

DTIC Science & Technology

2017-10-01

experimental arm subject in the small defect study. A protocol amendment in early 2017revised the study inclusionary criteria to include all non ...construed as an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE...group phase II study to assess the safety and efficacy for use of human EVPOME for soft tissue intraoral grafting procedures compared to the “gold

Analysis of the in vitro degradation and the in vivo tissue response to bi-layered 3D-printed scaffolds combining PLA and biphasic PLA/bioglass components - Guidance of the inflammatory response as basis for osteochondral regeneration.

PubMed

Barbeck, Mike; Serra, Tiziano; Booms, Patrick; Stojanovic, Sanja; Najman, Stevo; Engel, Elisabeth; Sader, Robert; Kirkpatrick, Charles James; Navarro, Melba; Ghanaati, Shahram

2017-12-01

The aim of the present study was the in vitro and in vivo analysis of a bi-layered 3D-printed scaffold combining a PLA layer and a biphasic PLA/bioglass G5 layer for regeneration of osteochondral defects in vivo Focus of the in vitro analysis was on the (molecular) weight loss and the morphological and mechanical variations after immersion in SBF. The in vivo study focused on analysis of the tissue reactions and differences in the implant bed vascularization using an established subcutaneous implantation model in CD-1 mice and established histological and histomorphometrical methods. Both scaffold parts kept their structural integrity, while changes in morphology were observed, especially for the PLA/G5 scaffold. Mechanical properties decreased with progressive degradation, while the PLA/G5 scaffolds presented higher compressive modulus than PLA scaffolds. The tissue reaction to PLA included low numbers of BMGCs and minimal vascularization of its implant beds, while the addition of G5 lead to higher numbers of BMGCs and a higher implant bed vascularization. Analysis revealed that the use of a bi-layered scaffold shows the ability to observe distinct in vivo response despite the physical proximity of PLA and PLA/G5 layers. Altogether, the results showed that the addition of G5 enables to reduce scaffold weight loss and to increase mechanical strength. Furthermore, the addition of G5 lead to a higher vascularization of the implant bed required as basis for bone tissue regeneration mediated by higher numbers of BMGCs, while within the PLA parts a significantly lower vascularization was found optimally for chondral regeneration. Thus, this data show that the analyzed bi-layered scaffold may serve as an ideal basis for the regeneration of osteochondral tissue defects. Additionally, the results show that it might be able to reduce the number of experimental animals required as it may be possible to analyze the tissue response to more than one implant in one

Rational design of an improved tissue-engineered vascular graft: determining the optimal cell dose and incubation time.

PubMed

Lee, Yong-Ung; Mahler, Nathan; Best, Cameron A; Tara, Shuhei; Sugiura, Tadahisa; Lee, Avione Y; Yi, Tai; Hibino, Narutoshi; Shinoka, Toshiharu; Breuer, Christopher

2016-03-01

We investigated the effect of cell seeding dose and incubation time on tissue-engineered vascular graft (TEVG) patency. Various doses of bone marrow-derived mononuclear cells (BM-MNCs) were seeded onto TEVGs, incubated for 0 or 12 h, and implanted in C57BL/6 mice. Different doses of human BM-MNCs were seeded onto TEVGs and measured for cell attachment. The incubation time showed no significant effect on TEVG patency. However, TEVG patency was significantly increased in a dose-dependent manner. In the human graft, more bone marrow used for seeding resulted in increased cell attachment in a dose-dependent manner. Increasing the BM-MNC dose and reducing incubation time is a viable strategy for improving the performance and utility of the graft.

Effects of Autogenous Bone Marrow Aspirate Concentrate on Radiographic Integration of Femoral Condylar Osteochondral Allografts.

PubMed

Oladeji, Lasun O; Stannard, James P; Cook, Cristi R; Kfuri, Mauricio; Crist, Brett D; Smith, Matthew J; Cook, James L

2017-10-01

Transplantation of fresh osteochondral allografts (OCAs) is an attractive treatment option for symptomatic articular cartilage lesions in young, healthy patients. Because the lack of OCA bone integration can be a cause of treatment failure, methods for speeding and enhancing OCA bone integration to mitigate this potential complication are highly desirable. To determine if autogenous bone marrow aspirate concentrate (BMC) treatment of large femoral condylar OCAs would be associated with superior radiographic OCA bone integration compared with nontreated allografts during the critical first 6 months after surgery. Cohort study; Level of evidence, 3. A review of patients enrolled in a prospective registry who were treated with transplantation of large OCAs to one or both femoral condyles at our institution from March 12, 2013 to March 14, 2016 was performed. Patients were stratified into 2 groups based on BMC treatment versus no BMC treatment; the treatment was nonrandomized and was rooted in a shift in practice and a continuing effort to optimize OCA transplantation at our institution. Patients were excluded if they did not have orthogonal view radiographs performed at 6 weeks, 3 months, and 6 months postoperatively. Each condyle undergoing OCA transplantation was assessed individually by an independent musculoskeletal radiologist, who was blinded to the treatment group and time point. OCAs were assessed with respect to graft integration (0%-100%; 0 = no integration, 100 = complete integration) and degree of sclerosis (0-3; 0 = normal, 1 = mild sclerosis, 2 = moderate sclerosis, and 3 = severe sclerosis) of the graft at each time point. This study identified 17 condyles in 15 patients who underwent OCA transplantation without BMC and 29 condyles in 22 patients who underwent OCA transplantation with BMC. The BMC group had significantly ( P = .033) higher graft integration scores at 6 weeks, 3 months, and 6 months after surgery. Graft sclerosis was significantly ( P

Optimization of Soft Tissue Management, Spacer Design, and Grafting Strategies for Large Segmental Bone Defects using the Chronic Caprine Tibial Defect Model

DTIC Science & Technology

2014-10-01

histology, and microCT analysis. In the current phase of work he will receive more specialized ` training and orientation to microCT analysis...fibrous connective tissue. • Performed histology on goat autogenous bone graft which demonstrated that the quantity and quality of cancellous bone graft

Combination therapy with intra-articular injection of mesenchymal stem cells and articulated joint distraction for repair of a chronic osteochondral defect in the rabbit.

PubMed

Harada, Yohei; Nakasa, Tomoyuki; Mahmoud, Elhussein Elbadry; Kamei, Goki; Adachi, Nobuo; Deie, Masataka; Ochi, Mitsuo

2015-10-01

The present study investigated intra-articular injection of bone-marrow-derived mesenchymal stem cells (MSCs) combined with articulated joint distraction as treatment for osteochondral defects. Large osteochondral defects were created in the weight-bearing area of the medial femoral condyle in rabbit knees. Four weeks after defect creation, rabbits were divided into six groups: control group, MSC group, distraction group, distraction + MSC group, temporary distraction group, and temporary distraction + MSC group. Groups with MSC received intra-articular injection of MSCs. Groups with distraction underwent articulated distraction arthroplasty. Groups with temporary distraction discontinued the distraction after 4 weeks. The rabbits were euthanized at 4, 8, and 12 weeks after treatment except temporary distraction groups which were euthanized at only 12 weeks. Histological scores in the distraction + MSC group were significantly better than in the control, MSC group or distraction group at 4 and 8 weeks, but showed no further improvement. At 12 weeks, the temporary distraction + MSC group showed the best results, demonstrating hyaline cartilage repair with regeneration of the osteochondral junction. In conclusion, joint distraction with intra-articular injection of MSCs promotes early cartilage repair, and compressive loading of the repair tissue after temporary distraction stimulates articular cartilage regeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Clinical Outcomes of Comparing Soft Tissue Alternatives to Free Gingival Graft: A Systematic Review and Meta-Analysis
.

PubMed

Dragan, Irina F; Hotlzman, Lucrezia Paterno; Karimbux, Nadeem Y; Morin, Rebecca A; Bassir, Seyed Hossein

2017-12-01

This systematic review and meta-analysis aimed to compare clinical outcomes and width of keratinized tissue (KT) around teeth, following the soft tissue alter- natives and free gingival graft (FGG) procedures. The specific graft materials that were explored were extracellular matrix membrane, bilayer collagen membrane, living cellular construct, and acellular dermal matrix. Four different databases were queried to identify human controlled clinical trials and randomized controlled clinical trials that fulfilled the eligibility criteria. Relevant studies were identified by 3 independent reviewers, compiling the results of the electronic and handsearches. Studies identified through electronic and handsearches were reviewed by title, abstract, and full text using Covidence Software. Primary outcome in the present study was change in the width of KT. Results of the included studies were pooled to estimate the effect size, expressed as weighted mean differences and 95% confidence interval. A random-effects model was used to perform the meta-analyses. Six hundred thirty-eight articles were screened by title, 55 articles were screened by abstracts, and 34 full-text articles were reviewed. Data on quantitative changes in width of KT were provided in 7 studies. Quantitative analyses revealed a significant difference in changes in width of KT between patients treated with soft tissue alternatives and patients treated with FGGs (P < .001). The weighted mean difference of changes in the width of KT was 21.39 (95% confidence interval: 21.82 to 20.96; heterogeneity I 5 70.89%), indicating patients who were treated with soft tissue alternatives gained 1.39 mm less KT width compared with the patients who received free gingival graft. Based on the clinical outcomes, the results of this systematic review and meta-analysis showed that soft tissue alternatives result in an increased width of KT. Patients in the soft tissue alternatives group obtained 1.39 mm less KT compared with

Biomechanical Comparison of an Intramedullary and Extramedullary Free-Tissue Graft Reconstruction of the Acromioclavicular Joint Complex

PubMed Central

Garg, Rishi; Javidan, Pooya; Lee, Thay Q.

2013-01-01

Background Several different surgical techniques have been described to address the coracoclavicular (CC) ligaments in acromioclavicular (AC) joint injuries. However, very few techniques focus on reconstructing the AC ligaments, despite its importance in providing stability. The purpose of our study was to compare the biomechanical properties of two free-tissue graft techniques that reconstruct both the AC and CC ligaments in cadaveric shoulders, one with an extramedullary AC reconstruction and the other with an intramedullary AC reconstruction. We hypothesized intramedullary AC reconstruction will provide greater anteroposterior translational stability and improved load to failure characteristics than an extramedullary technique. Methods Six matched cadaveric shoulders underwent translational testing at 10 N and 15 N in the anteroposterior and superoinferior directions, under AC joint compression loads of 10 N, 20 N, and 30 N. After the AC and CC ligaments were transected, one of the specimens was randomly assigned the intramedullary free-tissue graft reconstruction while its matched pair received the extramedullary graft reconstruction. Both reconstructed specimens then underwent repeat translational testing, followed by load to failure testing, via superior clavicle distraction, at a rate of 50 mm/min. Results Intramedullary reconstruction provided significantly greater translational stability in the anteroposterior direction than the extramedullary technique for four of six loading conditions (p < 0.05). There were no significant differences in translational stability in the superoinferior direction for any loading condition. The intramedullary reconstructed specimens demonstrated improved load to failure characteristics with the intramedullary reconstruction having a lower deformation at yield and a higher ultimate load than the extramedullary reconstruction (p < 0.05). Conclusions Intramedullary reconstruction of the AC joint provides greater stability in the

Polyphenol-Stabilized Tubular Elastin Scaffolds for Tissue Engineered Vascular Grafts

PubMed Central

Chuang, Ting-Hsien; Stabler, Christopher; Simionescu, Agneta

2009-01-01

Tissue-engineered vascular grafts require elastic, acellular porous scaffolds with controlled biodegradability and properties matching those of natural arteries. Elastin would be a desirable component for such applications, but elastin does not easily regenerate experimentally. Our approach is to develop tubular elastin scaffolds using decellularization and removal of collagen from porcine carotid arteries (∼5 mm diameter) using alkaline extraction. Because elastin is susceptible to rapid degeneration after implantation, scaffolds were further treated with penta-galloyl glucose (PGG), an established polyphenolic elastin-stabilizing agent. Scaffolds were compared in vitro with detergent-decellularized arteries for structure, composition, resistance to degradation, mechanical properties, and cytotoxicity and in vivo for cell infiltration and remodeling potential. Results showed effective decellularization and almost complete collagen removal by alkaline extraction. PGG-treated elastin scaffolds proved to be resistant to elastase digestion in vitro, maintained their cylindrical shapes, showed high resistance to burst pressures, and supported growth of endothelial cells and fibroblasts. In vivo results showed that PGG treatment reduced the rate of elastin biodegradation and controlled cell infiltration but did not hamper new collagen and proteoglycan deposition and secretion of matrix-degrading proteases. Alkali-purified, PGG-treated tubular arterial elastin scaffolds exhibit many desirable properties to be recommended for clinical applications as vascular grafts. PMID:19254115

Effects of osteochondral defect size on cartilage regeneration using a double-network hydrogel.

PubMed

Higa, Kotaro; Kitamura, Nobuto; Goto, Keiko; Kurokawa, Takayuki; Gong, Jian Ping; Kanaya, Fuminori; Yasuda, Kazunori

2017-05-22

There has been increased interest in one-step cell-free procedures to avoid the problems related to cell manipulation and its inherent disadvantages. We have studied the chondrogenic induction ability of a PAMPS/PDMAAm double-network (DN) gel and found it to induce chondrogenesis in animal osteochondral defect models. The purpose of this study was to investigate whether the healing process and the degree of cartilage regeneration induced by the cell-free method using DN gel are influenced by the size of osteochondral defects. A total of 63 mature female Japanese white rabbits were used in this study, randomly divided into 3 groups of 21 rabbits each. A 2.5-mm diameter osteochondral defect was created in the femoral trochlea of the patellofemoral joint of bilateral knees in Group I, a 4.3-mm osteochondral defect in Group II, and a 5.8-mm osteochondral defect in Group III. In the right knee of each animal, a DN gel plug was implanted so that a vacant space of 2-mm depth was left above the plug. In the left knee, we did not conduct any treatment to obtain control data. Animals were sacrificed at 2, 4, and 12 weeks after surgery, and gross and histological evaluations were made. The present study demonstrated that all sizes of the DN gel implanted defects as well as the 2.5mm untreated defects showed cartilage regeneration at 4 and 12 weeks. The 4.3-mm and 5.8-mm untreated defects did not show cartilage regeneration during the 12-week period. The quantitative score reported by O'Driscoll et al. was significantly higher in the 4.3-mm and 5.8-mm DN gel-implanted defects than the untreated defects at 4 and 12 weeks (p < 0.05). The 2.5-mm and 4.3-mm DN gel implanted defects maintained relatively high macroscopic and histological scores for the 12-week implantation period, while the histological score of the 5.8-mm DN gel implanted defect had decreased somewhat but statistically significantly at 12 weeks (p = 0.0057). The DN gel induced cartilage regeneration in

Combined osteochondral allograft and meniscal allograft transplantation: a survivorship analysis.

PubMed

Getgood, Alan; Gelber, Jonathon; Gortz, Simon; De Young, Alison; Bugbee, William

2015-04-01

The efficacy of meniscal allograft transplantation (MAT) and osteochondral allografting (OCA) as individual treatment modalities for select applications is well established. MAT and OCA are considered symbiotic procedures due to a complementary spectrum of indications and reciprocal contraindications. However, few outcomes of concomitant MAT and OCA have been reported. This study is a retrospective review of patients who received simultaneous MAT and OCA between 1983 and 2011. Forty-eight (twenty-nine male: nineteen female) patients with a median age of 35.8 years (15-66) received combined MAT and OCA procedures between 1983 and 2011. Forty-three patients had received previous surgery with a median of 3 procedures (1-11 procedures). The underlying diagnosis was trauma (tibial plateau fracture) in 33 % with osteoarthritis predominating in 54.2 % of cases. Thirty-one patients received a lateral meniscus, 16 received a medial meniscus and one patient received bilateral MAT. The median number of OCAs was two per patient (1-5 grafts), with a median graft area of 15 cm(2) (0.7-41 cm(2)). There were 21 unipolar, 24 bipolar (tibiofemoral) and three multifocal lesions. Thirty-six MATs constituted a compound tibial plateau OCA with native meniscus attached. At follow-up, failure was defined as any procedure resulting in removal or revision of one or more of the grafts. Patients completed the modified Merle d'Aubigné and Postel (18-point) scale, Knee Society Function (KS-F) score, and subjective International Knee Documentation Committee (IKDC) scores. Patient satisfaction was also captured. Twenty-six of 48 patients (54.2 %) required reoperation, but only 11 patients (22.9 %) were noted to have failed (10 MAT and 11 OCA). The mean time to failure was 3.2 years (95 % CI 1.5-4.9 years) and 2.7 years (95 % CI 1.3-4.2 years) for MAT and OCA, respectively. The 5-year survivorship was 78 and 73 % for MAT and OCA respectively, and 69 and 68 % at 10 years. Six of

Cryopreserved and frozen hyaline cartilage imaged by environmental scanning electron microscope. An experimental and prospective study.

PubMed

Sastre, Sergi; Suso, Santiago; Segur, Josep-Maria; Bori, Guillem; Carbonell, José-Antonio; Agustí, Elba; Nuñez, Montse

2008-08-01

To obtain images of the articular surface of osteochondral grafts (fresh, frozen, and cryopreserved in RPMI) using an environmental scanning electron microscope (ESEM). To evaluate and compare the main morphological aspects of the chondral surface of the fresh, frozen, and cryopreserved grafts as visualized via ESEM. The study was based on osteochondral fragments from the internal condyle of the knee joint of New Zealand rabbits, corresponding to the chondral surface from fresh, frozen, and cryopreserved samples. One hundred ESEM images were obtained from each group and then classified according to a validated system. The kappa index and the corresponding concordance index were calculated, and the groups were compared by Pearson's chi-squared test (p < 0.05). The articular surface of cryopreserved osteochondral grafts had fewer even surfaces and filled lacunae and a higher number of empty lacunae as compared to fresh samples; these differences correspond to images of cell membrane lesions that lead to destruction of the chondrocyte. Frozen grafts showed more hillocky and knobby surfaces than did fresh grafts; they also had a greater number of empty chondrocyte lacunae. ESEM is useful for obtaining images of the surface of osteochondral grafts. When compared to fresh samples, cryopreservation in RPMI medium produces changes in the surface of hyaline cartilage, but to a lesser extent than those produced by freezing.

Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds.

PubMed

Solchaga, Luis A; Temenoff, Johnna S; Gao, Jizong; Mikos, Antonios G; Caplan, Arnold I; Goldberg, Victor M

2005-04-01

The natural repair of osteochondral defects can be enhanced with biocompatible, biodegradable materials that support the repair process. It is our hypothesis that hyaluronan-based scaffolds are superior to synthetic scaffolds because they provide biological cues. We tested this thesis by comparing two hyaluronan-based scaffolds [auto cross-linked polysaccharide polymer (ACP) and HYAFF-11] to polyester-based scaffolds [poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA)] with similar pore size, porosity and degradation times. Fifty-four rabbits received bilateral osteochondral defects. One defect received a hyaluronan-based scaffold and the contralateral defect received the corresponding polyester-based scaffold. Rabbits were euthanized 4, 12 and 20 weeks after surgery and the condyles dissected and processed for histology. Only ACP-treated defects presented bone at the base of the defect at 4 weeks. At 12 weeks, only defects treated with rapidly dissolving implants (ACP and PLGA) presented bone reconstitution consistently, while bone was present in only one third of those treated with slowly dissolving scaffolds (HYAFF-11 and PLLA). After 20 weeks, the articular surface of PLGA-treated defects presented fibrillation more frequently than in ACP-treated defects. The surface of defects treated with slowly dissolving scaffolds presented more cracks and fissures. The degradation rate of the scaffolds is critical for the repair process. Slowly dissolving scaffolds sustain thicker cartilage at the surface but, it frequently presents cracks and discontinuities. These scaffolds also delay bone formation at the base of the defects. Hyaluronan-based scaffolds appear to allow faster cell infiltration leading to faster tissue formation. The degradation of ACP leads to rapid bone formation while the slow degradation of HYAFF-11 prolongs the presence of cartilage and delays endochondral bone formation.

Matrilin-3 codelivery with adipose-derived mesenchymal stem cells promotes articular cartilage regeneration in a rat osteochondral defect model.

PubMed

Muttigi, Manjunatha S; Kim, Byoung Ju; Choi, Bogyu; Yoshie, Arai; Kumar, Hemant; Han, Inbo; Park, Hansoo; Lee, Soo-Hong

2018-03-01

Matrilin-3 is an essential extracellular matrix component present only in cartilaginous tissues. Matrilin-3 exerts chondroprotective effects by regulating an anti-inflammatory function and extracellular matrix components. We hypothesized that the codelivery of matrilin-3 with infrapatellar adipose-tissue-derived mesenchymal stem cells (Ad-MSCs) may enhance articular cartilage regeneration. Matrilin-3 treatment of Ad-MSCs in serum-free media induced collagen II and aggrecan expression, and matrilin-3 in chondrogenic media also enhanced in vitro chondrogenic differentiation. Next, the in vivo effect of matrilin-3 codelivery with Ad-MSCs on cartilage regeneration was assessed in an osteochondral defect model in Sprague Dawley rats: Ad-MSCs and hyaluronic acid were implanted at the defect site with or without matrilin-3 (140, 280, and 700 ng). Safranin O staining revealed that matrilin-3 (140 and 280 ng) treatment significantly improved cartilage regeneration and glycosaminoglycan accumulation. In the animals treated with 140-ng matrilin-3, in particular, the defect site exhibited complete integration with surrounding tissue and a smooth glistening surface. The International Cartilage Repair Society macroscopic and O'Driscoll microscopic scores for regenerated cartilage were furthermore shown to be considerably higher for this group (matrilin-3; 140 ng) compared with the other groups. Furthermore, the defects treated with 140-ng matrilin-3 revealed significant hyaline-like cartilage regeneration in the osteochondral defect model; in contrast, the defects treated with 700-ng matrilin-3 exhibited drastically reduced cartilage regeneration with mixed hyaline-fibrocartilage morphology. Codelivery of matrilin-3 with Ad-MSCs significantly influenced articular cartilage regeneration, supporting the potential use of this tissue-specific protein for a cartilage-targeted stem cell therapy. Copyright © 2017 John Wiley & Sons, Ltd.

Glenoid dysplasia and osteochondritis dissecans in a cat

PubMed Central

Schwarze, Rebecca A.; Tano, Cheryl A.; Carroll, Vincent W.

2015-01-01

A 2-year-old Maine coon cat was presented for a right forelimb lameness. Computed tomography of the shoulder revealed a shallow glenoid, osteophyte deposition at the caudal humeral head and medial glenoid, and an intra-articular osseous body. This cat had glenoid dysplasia and osteochondritis dissecans of the glenoid. PMID:26130839

Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration.

PubMed

Zhang, S; Chu, W C; Lai, R C; Lim, S K; Hui, J H P; Toh, W S

2016-12-01

Clinical and animal studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapies in cartilage repair. As the efficacy of many MSC-based therapies has been attributed to paracrine secretion, particularly extracellular vesicles/exosomes, we determine here if weekly intra-articular injections of human embryonic MSC-derived exosomes would repair and regenerate osteochondral defects in a rat model. In this study, osteochondral defects were created on the trochlear grooves of both distal femurs in 12 adult rats. In each animal, one defect was treated with 100 μg exosomes and the contralateral defect treated with phosphate buffered saline (PBS). Intra-articular injections of exosomes or PBS were administered after surgery and thereafter weekly for a period of 12 weeks. Three unoperated age-matched animals served as native controls. Analyses were performed by histology, immunohistochemistry, and scoring at 6 and 12 weeks after surgery. Generally, exosome-treated defects showed enhanced gross appearance and improved histological scores than the contralateral PBS-treated defects. By 12 weeks, exosome-treated defects displayed complete restoration of cartilage and subchondral bone with characteristic features including a hyaline cartilage with good surface regularity, complete bonding to adjacent cartilage, and extracellular matrix deposition that closely resemble that of age-matched unoperated control. In contrast, there were only fibrous repair tissues found in the contralateral PBS-treated defects. This study demonstrates for the first time the efficacy of human embryonic MSC exosomes in cartilage repair, and the utility of MSC exosomes as a ready-to-use and 'cell-free' therapeutic alternative to cell-based MSC therapy. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Evolution of Autologous Chondrocyte Repair and Comparison to Other Cartilage Repair Techniques

PubMed Central

Dewan, Ashvin K.; Gibson, Matthew A.; Elisseeff, Jennifer H.; Trice, Michael E.

2014-01-01

Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques. Methods. We searched PubMed from 1949 to 2014 for the keywords “autologous chondrocyte implantation” (ACI) and “cartilage repair” in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks. Results. Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells) and associated scaffolds (natural or synthetic, hydrogels or membranes). ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient's knee as evaluated by multiple clinical indices and the quality of regenerated tissue. Conclusion. Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients. PMID:25210707

Management of Osteochondritis Dissecans of the Femoral Condyle.

PubMed

Shea, Kevin G; Carey, James L; Brown, Gregory A; Murray, Jayson N; Pezold, Ryan; Sevarino, Kaitlyn S

2016-09-01

The American Academy of Orthopaedic Surgeons has developed the Appropriate Use Criteria (AUC) document Management of Osteochondritis Dissecans of the Femoral Condyle. Evidence-based information, in conjunction with the clinical expertise of physicians, was used to develop the criteria to improve patient care and obtain the best outcomes while considering the subtleties and distinctions necessary in making clinical decisions. The AUC clinical patient scenarios were derived from patient indications that generally accompany osteochondritis dissecans of the femoral condyle, as well as from current evidence-based clinical practice guidelines and supporting literature. The 64 patient scenarios and 12 treatments were developed by the Writing Panel, a group of clinicians who are specialists in this AUC topic. Lastly, a separate, multidisciplinary Voting Panel (made up of specialists and nonspecialists) rated the appropriateness of treatment of each patient scenario using a 9-point scale to designate a treatment as Appropriate (median rating, 7 to 9), May Be Appropriate (median rating, 4 to 6), or Rarely Appropriate (median rating, 1 to 3).

Computationally Optimizing the Compliance of a Biopolymer Based Tissue Engineered Vascular Graft

PubMed Central

Harrison, Scott; Tamimi, Ehab; Uhlorn, Josh; Leach, Tim; Vande Geest, Jonathan P.

2016-01-01

Coronary heart disease is a leading cause of death among Americans for which coronary artery bypass graft (CABG) surgery is a standard surgical treatment. The success of CABG surgery is impaired by a compliance mismatch between vascular grafts and native vessels. Tissue engineered vascular grafts (TEVGs) have the potential to be compliance matched and thereby reduce the risk of graft failure. Glutaraldehyde (GLUT) vapor-crosslinked gelatin/fibrinogen constructs were fabricated and mechanically tested in a previous study by our research group at 2, 8, and 24 hrs of GLUT vapor exposure. The current study details a computational method that was developed to predict the material properties of our constructs for crosslinking times between 2 and 24 hrs by interpolating the 2, 8, and 24 hrs crosslinking time data. matlab and abaqus were used to determine the optimal combination of fabrication parameters to produce a compliance matched construct. The validity of the method was tested by creating a 16-hr crosslinked construct of 130 μm thickness and comparing its compliance to that predicted by the optimization algorithm. The predicted compliance of the 16-hr construct was 0.00059 mm Hg−1 while the experimentally determined compliance was 0.00065 mm Hg−1, a relative difference of 9.2%. Prior data in our laboratory has shown the compliance of the left anterior descending porcine coronary (LADC) artery to be 0.00071 ± 0.0003 mm Hg−1. Our optimization algorithm predicts that a 258-μm-thick construct that is GLUT vapor crosslinked for 8.1 hrs would match LADC compliance. This result is consistent with our previous work demonstrating that an 8-hr GLUT vapor crosslinked construct produces a compliance that is not significantly different from a porcine coronary LADC. PMID:26593773

Fresh osteochondral allograft transplantation for osteochondritis dissecans of the capitellum in baseball players.

PubMed

Mirzayan, Raffy; Lim, Michael J

2016-11-01

Osteochondritis dissecans (OCD) of the capitellum is a rare yet debilitating injury seen in young athletes. This is the first report in the literature describing fresh osteochondral allograft transplantation (FOCAT) to treat OCD of the capitellum. Nine male baseball players (mean age, 15.3; range, 14-18 years), with OCD of the capitellum were treated with FOCAT. There were 6 pitchers and 3 position players. A ligament-sparing, mini-open approach was used. A fresh femoral hemicondyle was used as a donor source. Of the 9 patients, 7 required 1 plug and 2 required 2 plugs. The average plug diameter was 11 mm (range, 8-18 mm). Five plugs were press fit, and 4 required additional fixation. Clinical outcomes were evaluated at a mean follow-up of 48.4 months (range, 11-90 months). Preoperative and postoperative outcome scores were calculated using the paired t test. The Mayo Elbow Performance score improved from an average 57.8 to 98.9 (P < .01). The Oxford Elbow Score improved from 22.4 to 44.8 (P < .01). The Disabilities of the Arm, Shoulder and Hand score improved from 35.2 to 5.4 (P < .01). The visual analog scale score improved from 7.8 to 0.5 (P < .01). The Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow score improved from 32.6 to 82.5 (P < .01). All patients returned to throwing and were still active in their sport or played at least 2 years of baseball before leaving the sport unrelated to the elbow. FOCAT for OCD of the capitellum in properly selected cases is a viable treatment with significant functional improvement and pain reduction in throwers. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Bone cysts after osteochondral allograft repair of cartilage defects in goats suggest abnormal interaction between subchondral bone and overlying synovial joint tissues.

PubMed

Pallante-Kichura, Andrea L; Cory, Esther; Bugbee, William D; Sah, Robert L

2013-11-01

The efficacy of osteochondral allografts (OCAs) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12months in vivo. The objectives of this study were to further analyze OCAs and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral bone (ScB) and trabecular bone (TB) structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCAs was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCAs was lower than Non-Op and other OCAs. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCAs did not vary compared to Non-Op, but BS/TV was lower. (2) OCAs contained "basal" cysts, localized to deeper regions, some "subchondral" cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These

Bone Cysts After Osteochondral Allograft Repair of Cartilage Defects in Goats Suggest Abnormal Interaction Between Subchondral Bone and Overlying Synovial Joint Tissues

PubMed Central

Pallante-Kichura, Andrea L.; Cory, Esther; Bugbee, William D.; Sah, Robert L.

2013-01-01

The efficacy of osteochondral allografts (OCA) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12 months in vivo. The objectives of this study were to further analyze OCA and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral (ScB) and trabecular (TB) bone structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCA was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCA was lower than Non-Op and other OCA. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCA did not vary compared to Non-Op, but BS/TV was lower. (2) OCA contained “basal” cysts, localized to deeper regions, some “subchondral” cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These

Anatomic feature of deltoid ligament attachment in posteromedial osteochondral lesion of talar dome.

PubMed

Nakasa, Tomoyuki; Sawa, Mikiya; Ikuta, Yasunari; Yoshikawa, Masahiro; Tsuyuguchi, Yusuke; Adachi, Nobuo

2018-03-01

Osteochondral lesions of the talus (OLT) are recognized as being commonly associated with trauma. However, the etiology of OLT remains unclear. In the case of a posteromedial lesion of OLT (medial OLT), the deep layer of the deltoid ligament is located close to the medial OLT, and this relationship between a medial lesion and deltoid ligament could be a risk factor for medial OLT. The purpose of this study is to investigate the unique anatomic feature of the deep deltoid attachment to the talus in patients with medial OLT compared with patients with non-medial OLT. Forty ankles with medial OLT and 40 ankles without medial OLT were retrospectively reviewed in this study. On the coronal images of MRI, the attachment of deltoid ligament was measured. The continuity of the osteochondral fragment and its bed was evaluated on MRI and arthroscopic findings. Coronal MRI images showed that the attachment of the deep deltoid ligament to the medial OLT was broader and located more proximally than in non-medial OLT. The continuity of fibers from the insertion site of deltoid ligament to the talus to the osteochondral fragment was observed (76.7%). In the arthroscopic findings, the osteochondral fragment was obviously connected to the talus at the medial site in 85.2% of feet. The location of the deep deltoid ligament attachment to the medial OLT was more proximal and there was the possibility of these anatomic feature might contribute to the pathogenesis of medial OLT. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Graft Product for Autologous Peripheral Blood Stem Cell Transplantation Enhances Thrombin Generation and Expresses Procoagulant Microparticles and Tissue Factor.

PubMed

Sidibe, Fatoumata; Spanoudaki, Anastasia; Vanneaux, Valerie; Mbemba, Elisabeth; Larghero, Jerome; Van Dreden, Patrick; Lotz, Jean-Pierre; Elalamy, Ismail; Larsen, Annette K; Gerotziafas, Grigoris T

2018-05-01

The beneficial effect of autologous peripheral blood stem cell transplantation (APBSCT) may be compromised by acute vascular complications related to hypercoagulability. We studied the impact of graft product on thrombin generation of normal plasma and the expression of tissue factor (TF) and procoagulant platelet-derived procoagulant microparticles (Pd-MPs) in samples of graft products. Graft products from 10 patients eligible for APBSCT were mixed with platelet-poor plasma (PPP) or platelet-rich plasma (PRP) from healthy volunteers and assessed for in vitro thrombin generation. In control experiments, thrombin generation was assessed in (1) PPP and PRP without any exogenous TF and/or procoagulant phospholipids, (2) PPP with the addition of TF (5 pM) and procoagulant phospholipids (4 μM), (3) in PRP with the addition of TF (5 pM). Graft products were assessed with Western blot assay for TF expression, with a specific clotting assay for TF activity and with flow cytometry assay for Pd-MPs. The graft product enhanced thrombin generation and its procoagulant activity was related to the presence of Pd-MPs and TF. The concentration of Pd-MPs in the graft product was characterized by a significant interindividual variability. The present study reveals the need for a thorough quality control of the graft products regarding their procoagulant potential.

Biologically engineered protein-graft-poly(ethylene glycol) hydrogels: A cell-adhesive and plasmin-degradable biosynthetic material for tissue repair

NASA Astrophysics Data System (ADS)

Halstenberg, Sven

2002-01-01

The goal of the research presented in this dissertation was to create a biomimetic artificial material that exhibits functions of extracellular matrix relevant for improved nerve regeneration. Neural adhesion peptides were photoimmobilized on highly crosslinked poly(ethylene glycol)-based substrates that were otherwise non-adhesive. Neurons adhered in two-dimensional patterns for eleven hours, but no neurites extended. To enable neurite extension and nerve regeneration in three dimensions, and to address the need for specifically cell adhesive and cell degradable materials for clinical applications in tissue repair in general, an artificial protein was recombinantly expressed and purified that consisted of a repeating amino acid sequence based on fibrinogen and anti-thrombin III. The recombinant protein contained integrin-binding RGD sites, plasmin degradation sites, heparin binding sites, and six thiol-containing cysteine residues as grafting sites for poly(ethylene glycol) diacrylate via Michael-type conjugate addition. The resulting protein-graft-poly(ethylene glycol)acrylates were crosslinked by photopolymerization to form hydrogels. Although three-dimensional, RGD mediated and serine protease-dependent ingrowth of human fibroblasts into protein-graft-poly(ethylene glycol) hydrogels occurred, only surface neurite outgrowth was observed from chick dorsal root ganglia. Axonal outgrowth depended on the concentration of matrix-bound heparin, suggesting that improved mechanical strength of the hydrogels and possible immobilization of neuroactive factors due to the presence of heparin promoted neurite outgrowth. Together, the above results show that specific biological functions can be harnessed by protein-graft-poly(ethylene glycol) hydrogels to serve as matrices for tissue repair and regeneration. In particular, the two design objectives, specific cell adhesion and degradability by cell-associated proteases, were fulfilled by the material. In the future, this and

Clinical evaluation of expanded mesh connective tissue graft in the treatment for multiple adjacent gingival recessions in the esthetic zone

PubMed Central

Shanmugam, M.; Shivakumar, B.; Meenapriya, B.; Anitha, V.; Ashwath, B.

2015-01-01

Background: Multiple approaches have been used to replace lost, damaged or diseased gingival tissues. The connective tissue graft (CTG) procedure is the golden standard method for root coverage. Although multiple sites often need grafting, the palatal mucosa supplies only a limited area of grafting material. To overcome this limitation, expanded mesh graft provides a method whereby a graft can be stretched to cover a large area. The aim of this study was to evaluate the effectiveness and the predictability of expanded mesh CTG (e-MCTG) in the treatment of adjacent multiple gingival recessions. Materials and Methods: Sixteen patients aged 20–50 years contributed to 55 sites, each site falling into at least three adjacent Miller's Class 1 or Class 2 gingival recession. The CTG obtained from the palatal mucosa was expanded to cover the recipient bed, which was 1.5 times larger than the graft. Clinical measurements were recorded at baseline and 3 months, 12 months postoperatively. Results: A mean coverage of 1.96 mm ± 0.66 mm and 2.22 mm ± 0.68 mm was obtained at the end of 3rd and 12th month, respectively. Twelve months after surgery a statistically significant increase in CAL (2.2 mm ± 0.68 mm, P < 0.001) and increasing WKT (1.75 ± 0.78, P < 0.001) were obtained. In 80% of the treated sites, 100% root coverage was achieved (mean 93.5%). Conclusions: The results of this study demonstrated that multiple adjacent recessions were treated by using e-MCTG technique can be applied and highly predictable root coverage can be achieved. PMID:26321829

Nanofat grafting under a split-thickness skin graft for problematic wound management.

PubMed

Kemaloğlu, Cemal Alper

2016-01-01

Obesity and certain medical disorders make the reconstruction of skin defects challenging. Different kind of procedure can be used for these defect, besides, skin grafting is one of the most common and simplest procedure. Fat grafting and stem cells which are located in the adipose tissue have been commonly used in plastic surgery for regeneration and rejuvenation purposes. To decrease graft failure rate we performed nanofat grafting under an autologous split-thickness skin graft in our patient who had a problematic wound. The case of a 35-year-old female patient with a traumatic skin defect on her left anterior crural region is described herein. After subsequent flap reconstruction, the result was disappointing and the defect size was widened. The defect was treated with combined grafting (nanofat grafting under an autologous split-thickness skin graft). At the 6 months follow-up assessment after combined grafting, the integrity of the skin graft was good with excellent pliability. Combined grafting for problematic wounds seems to be a useful technique for cases requiring reconstruction. The potential existence of stem cells may be responsible for the successful result in our patient.

In Vivo Tracking of Mesechymal Stem Cells Using Fluorescent Nanoparticles in an Osteochondral Repair Model

PubMed Central

Lee, Jong Min; Kim, Byung-Soo; Lee, Haeshin; Im, Gun-Il

2012-01-01

We devised and tested an in vivo system to monitor the migration of mesenchymal stem cells (MSCs) within the marrow cavity. In vitro studies confirmed that platelet-derived growth factor (PDGF)-AA had the most potent chemotactic effect of the tested factors, and possessed the greatest number of receptors in MSCs. MSCs were labeled with fluorescent nanoparticles and injected into the marrow cavity of nude rats through osteochondral defects created in the distal femur. The defects were sealed with HCF (heparin-conjugated fibrin) or PDGF-AA-loaded HCF. In the HCF-only group, the nanoparticle-labeled MSCs dispersed outside the marrow cavity within 3 days after injection. In the PDGF-AA-loaded HCF group, the labeled cells moved time-dependently for 14 days toward the osteochondral defect. HCF-PDGF in low dose (LD; 8.5 ng/µl) was more effective than HCF-PDGF in high dose (HD; 17 ng/µl) in recruiting the MSCs to the osteochondral defect. After 21 days, the defects treated with PDGF and transforming growth factor (TGF)-β1-loaded HCF showed excellent cartilage repair compared with other groups. Further studies confirmed that this in vivo osteochondral MSCs tracking system (IOMTS) worked for other chemoattractants (chemokine (C-C motif) ligand 2 (CCL2) and PDGF-BB). IOMTS can provide a useful tool to examine the effect of growth factors or chemokines on endogenous cartilage repair. PMID:22491215

From natural bone grafts to tissue engineering therapeutics: Brainstorming on pharmaceutical formulative requirements and challenges.

PubMed

Baroli, Biancamaria

2009-04-01

Tissue engineering is an emerging multidisciplinary field of investigation focused on the regeneration of diseased or injured tissues through the delivery of appropriate molecular and mechanical signals. Therefore, bone tissue engineering covers all the attempts to reestablish a normal physiology or to speed up healing of bone in all musculoskeletal disorders and injuries that are lashing modern societies. This article attempts to give a pharmaceutical perspective on the production of engineered man-made bone grafts that are described as implantable tissue engineering therapeutics, and to highlight the importance of understanding bone composition and structure, as well as osteogenesis and bone healing processes, to improve the design and development of such implants. In addition, special emphasis is given to pharmaceutical aspects that are frequently minimized, but that, instead, may be useful for formulation developments and in vitro/in vivo correlations.

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

In vitro characterization of design and compressive properties of 3D-biofabricated/decellularized hybrid grafts for tracheal tissue engineering.

PubMed

Johnson, Christopher; Sheshadri, Priyanka; Ketchum, Jessica M; Narayanan, Lokesh K; Weinberger, Paul M; Shirwaiker, Rohan A

2016-06-01

Infection or damage to the trachea, a thin walled and cartilage reinforced conduit that connects the pharynx and larynx to the lungs, leads to serious respiratory medical conditions which can often prove fatal. Current clinical strategies for complex tracheal reconstruction are of limited availability and efficacy, but tissue engineering and regenerative medicine approaches may provide viable alternatives. In this study, we have developed a new "hybrid graft" approach that utilizes decellularized tracheal tissue along with a resorbable polymer scaffold, and holds promise for potential clinical applications. First, we evaluated the effect of our decellularization process on the compression properties of porcine tracheal segments, and noted approximately 63% decrease in resistance to compression following decellularization. Next we developed four C-shape scaffold designs by varying the base geometry and thickness, and fabricated polycaprolactone scaffolds using a combination of 3D-Bioplotting and thermally-assisted forming. All scaffolds designs were evaluated in vitro under three different environmental testing conditions to determine the design that offered the best resistance to compression. These were further studied to determine the effect of gamma radiation sterilization and cyclic compression loading. Finally, hybrid grafts were developed by securing these optimal design scaffolds to decellularized tracheal segments and evaluated in vitro under physiological testing conditions. Results show that the resistance to compression offered by the hybrid grafts created using gamma radiation sterilized scaffolds was comparable to that of fresh tracheal segments. Given that current clinical attempts at tracheal transplantation using decellularized tissue have been fraught with luminal collapse and complications, our data support the possibility that future embodiments using a hybrid graft approach may reduce the need for intraluminal stenting in tracheal transplant

Tissue-engineered vascular grafts for use in the treatment of congenital heart disease: from the bench to the clinic and back again.

PubMed

Patterson, Joseph T; Gilliland, Thomas; Maxfield, Mark W; Church, Spencer; Naito, Yuji; Shinoka, Toshiharu; Breuer, Christopher K

2012-05-01

Since the first tissue-engineered vascular graft (TEVG) was implanted in a child over a decade ago, growth in the field of vascular tissue engineering has been driven by clinical demand for improved vascular prostheses with performance and durability similar to an autologous blood vessel. Great strides were made in pediatric congenital heart surgery using the classical tissue engineering paradigm, and cell seeding of scaffolds in vitro remained the cornerstone of neotissue formation. Our second-generation bone marrow cell-seeded TEVG diverged from tissue engineering dogma with a design that induces the recipient to regenerate vascular tissue in situ. New insights suggest that neovessel development is guided by cell signals derived from both seeded cells and host inflammatory cells that infiltrate the graft. The identification of these signals and the regulatory interactions that influence cell migration, phenotype and extracellular matrix deposition during TEVG remodeling are yielding a next-generation TEVG engineered to guide neotissue regeneration without the use of seeded cells. These developments represent steady progress towards our goal of an off-the-shelf tissue-engineered vascular conduit for pediatric congenital heart surgery.

Laser-assisted fibrinogen bonding of umbilical vein grafts.

PubMed

Oz, M C; Williams, M R; Souza, J E; Dardik, H; Treat, M R; Bass, L S; Nowygrod, R

1993-06-01

Despite success with autologous tissue welding, laser welding of synthetic vascular prostheses has not been possible. The graft material appears inert and fails to allow the collagen breakdown and electrostatic bonding that results in tissue welding. To develop a laser welding system for graft material, we repaired glutaraldehyde-tanned human umbilical cord vein graft incisions using laser-assisted fibrinogen bonding (LAFB) technology. Modified umbilical vein graft was incised transversely (1.2 cm). Incisions were repaired using sutures, laser energy alone, or LAFB. For LAFB, indocyanine green dye was mixed with human fibrinogen and the compound applied with forceps onto the weld site prior to exposure to 808 nm diode laser energy (power density 4.8 W/cm 2). Bursting pressures for sutured repairs (126.6 +/- 23.4 mm Hg) were similar to LAFB anastomoses (111.6 +/- 55.0 mm Hg). No evidence of collateral thermal injury to the graft material was noted. In vivo evaluation of umbilical graft bonding with canine arteries demonstrates that LAFB can reliably reinforce sutured anastomoses. The described system for bonding graft material with laser exposed fibrinogen may allow creation or reinforcement of vascular anastomoses in procedures where use of autologous tissue is not feasible.

Esthetic assessment of immediately restored implants combined with GBR and free connective tissue graft.

PubMed

Kolerman, Roni; Nissan, Joseph; Mijiritsky, Eitan; Hamoudi, Nasreen; Mangano, Carlo; Tal, Haim

2016-11-01

Esthetic assessment of immediately restored implants combined with GBR and free connective tissue (CT) graft METHODS: A case-control, retrospective study involving 34 patients treated with maxillary anterior single implants, immediately placed and restored. Clinical and esthetic results were analyzed using standard clinical examination and a comprehensive index, comprising pink esthetic and white esthetic scores (PES/WES). The height of the implant crown and the corresponding height of the contralateral tooth crown were measured to identify mucosal recessions. The distance from the mucosal margin to the implant shoulder (DIM) was measured on the master model. Thirty of 34 implants fulfilled the strict success criteria set for dental implants with regard to osseointegration. Success was defined as implants with bone loss not exceeding 1.5 mm during the first year and loosing not more than 0.2 for each successive year. The other four implants were stable but did not meet the bone loss criteria mentioned above and defined as survived implants. Mean PES/WES was 14.44 ± 2.34 (range: 9-20). Mean PES was 7.12 ± 1.89 (range: 1-10). The highest mean values were achieved for the variable of root convexity/soft tissue color and texture (1.71 ± 0.46) whereas the mesial papilla (1.09 ± 0.62) proved to be the least pleasing. The mean WES was 7.32 ± 1.25 (range: 5-10). The difference between IC and contralateral TC was 0.54 mm. The mean value for the facial DIM was 3.82 ± 0.87 mm. An evaluation of soft and hard tissue augmentation in immediately restored immediate implant procedures was employed to obtain stable hard and soft tissues. The combined GBR and CT graft procedure achieved favorable peri-implant soft tissue condition and esthetic results. However, recession and incomplete papillas were frequently observed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High Rate of Osteoarthritis After Osteochondritis Dissecans Fragment Excision Compared With Surgical Restoration at a Mean 16-Year Follow-up.

PubMed

Sanders, Thomas L; Pareek, Ayoosh; Obey, Mitchel R; Johnson, Nicholas R; Carey, James L; Stuart, Michael J; Krych, Aaron J

2017-07-01

Osteochondritis dissecans (OCD) is a disorder of subchondral bone that causes adverse effects on the overlying cartilage and commonly affects the knee. The incidence of OCD and its long-term effect on the knee joint are controversial. Hypothesis/Purpose: The purpose of this study was to (1) evaluate the rate of osteoarthritis and knee arthroplasty in a population-based cohort of patients with OCD lesions treated operatively and (2) evaluate factors that may predispose patients to knee osteoarthritis and arthroplasty. The investigators hypothesized that OCD lesions diagnosed after skeletal maturity and treatment with fragment excision would be predictive of a diagnosis of osteoarthritis. Cohort study; Level of evidence, 3. The investigators identified 221 patients (mean ± SD age, 26.1 ± 13.6 years) with OCD lesions treated operatively between 1976 and 2010 and followed for 16.3 ± 11.4 years (mean ± SD) from diagnosis. Information related to the diagnosis, laterality of lesion, details of treatment, and progression to osteoarthritis was obtained from the medical record. Surgical treatment was classified as fragment excision, fragment preservation (lesion drilling and/or fragment fixation), or chondral defect grafting (osteochondral allograft or autograft). Factors predictive of osteoarthritis and arthroplasty were examined. There were 134 patients in the fragment excision group, 78 patients in the fragment preservation group, and 9 patients in the chondral defect grafting group. In the fragment excision group, the cumulative incidence of osteoarthritis was 12.0% at 5 years, 17.0% at 10 years, 26.0% at 15 years, 39.0% at 20 years, and 70% at 30 years. The cumulative incidence of arthroplasty was 2.0% at 5 years, 4.0% at 10 years, 4.0% at 15 years, 10.0% at 20 years, and 32.0% at 30 years. In the fragment preservation group, the cumulative incidence of osteoarthritis was 3.0% at 5 years, 7.0% at 10 years, 16.0% at 15 years, 25.0% at 20 years, and 51% at 30 years

A critical role for macrophages in neovessel formation and the development of stenosis in tissue-engineered vascular grafts

PubMed Central

Hibino, Narutoshi; Yi, Tai; Duncan, Daniel R.; Rathore, Animesh; Dean, Ethan; Naito, Yuji; Dardik, Alan; Kyriakides, Themis; Madri, Joseph; Pober, Jordan S.; Shinoka, Toshiharu; Breuer, Christopher K.

2011-01-01

The primary graft-related complication during the first clinical trial evaluating the use of tissue-engineered vascular grafts (TEVGs) was stenosis. We investigated the role of macrophages in the formation of TEVG stenosis in a murine model. We analyzed the natural history of TEVG macrophage infiltration at critical time points and evaluated the role of cell seeding on neovessel formation. To assess the function of infiltrating macrophages, we implanted TEVGs into mice that had been macrophage depleted using clodronate liposomes. To confirm this, we used a CD11b-diphtheria toxin-receptor (DTR) transgenic mouse model. Monocytes infiltrated the scaffold within the first few days and initially transformed into M1 macrophages. As the scaffold degraded, the macrophage infiltrate disappeared. Cell seeding decreased the incidence of stenosis (32% seeded, 64% unseeded, P=0.024) and the degree of macrophage infiltration at 2 wk. Unseeded TEVGs demonstrated conversion from M1 to M2 phenotype, whereas seeded grafts did not. Clodronate and DTR inhibited macrophage infiltration and decreased stenosis but blocked formation of vascular neotissue, evidenced by the absence of endothelial and smooth muscle cells and collagen. These findings suggest that macrophage infiltration is critical for neovessel formation and provides a strategy for predicting, detecting, and inhibiting stenosis in TEVGs.—Hibino, N., Yi, T., Duncan, D. R., Rathore, A., Dean, E., Naito, Y., Dardik, A., Kyriakides, T., Madri, J., Pober, J. S., Shinoka, T., Breuer, C. K. A critical role for macrophages in neovessel formation and the development of stenosis in tissue-engineered vascular grafts. PMID:21865316

Fresh osteochondral allograft transplantation for isolated patellar cartilage injury.

PubMed

Gracitelli, Guilherme C; Meric, Gokhan; Pulido, Pamela A; Görtz, Simon; De Young, Allison J; Bugbee, William D

2015-04-01

The treatment of patellofemoral cartilage injuries can be challenging. Osteochondral allograft (OCA) transplantation has been used as a treatment option for a range of cartilage disorders. To evaluate functional outcomes and survivorship of the grafts among patients who underwent OCA for patellar cartilage injuries. Case series; Level of evidence, 4. An institutional review board-approved OCA database was used to identify 27 patients (28 knees) who underwent isolated OCA transplantation of the patella between 1983 and 2010. All patients had a minimum 2-year follow-up. The mean age of the patients was 33.7 years (range, 14-64 years); 54% were female. Twenty-six (92.9%) knees had previous surgery (mean, 3.2 procedures; range, 1-10 procedures). The mean allograft area was 10.1 cm(2) (range, 4.0-18.0 cm(2)). Patients returned for clinical evaluation or were contacted via telephone for follow-up. The number and type of reoperations were assessed. Any reoperation resulting in removal of the allograft was considered a failure of the OCA transplantation. Patients were evaluated pre- and postoperatively using the modified Merle d'Aubigné-Postel (18-point) scale, the International Knee Documentation Committee (IKDC) pain, function, and total scores, and the Knee Society function (KS-F) score. Patient satisfaction was assessed at latest follow-up. Seventeen of the 28 knees (60.7%) had further surgery after the OCA transplantation; 8 of the 28 knees (28.6%) were considered OCA failures (4 conversions to total knee arthroplasty, 2 conversions to patellofemoral knee arthroplasty, 1 revision OCA, 1 patellectomy). Patellar allografting survivorship was 78.1% at 5 and 10 years and 55.8% at 15 years. Among the 20 knees (71.4%) with grafts in situ, the mean follow-up duration was 9.7 years (range, 1.8-30.1 years). Pain and function improved from the preoperative visit to latest follow-up, and 89% of patients were extremely satisfied or satisfied with the results of the OCA

Sinus grafting using recombinant human tissue factor, platelet-rich plasma gel, autologous bone, and anorganic bovine bone mineral xenograft: histologic analysis and case reports.

PubMed

Philippart, Pierre; Daubie, Valéry; Pochet, Roland

2005-01-01

The purpose of this study was to analyze healthy bone formation by means of histology and immunohistochemistry after grafting with a mixture of autologous ground calvarial bone, inorganic xenograft, platelet-rich plasma (PRP), and recombinant human tissue factor (rhTF). Maxillary sinus floor augmentation was performed on 3 patients by grafting with 5 to 10 mL of a paste consisting of autologous powder from calvarial bone (diameter < 1 mm), 50% v/v anorganic bovine bone mineral xenograft (PepGen P-15, a new tissue-engineered bone replacement graft material), PRP (1.8 x 10(6) platelets/mm3 plasma), and about 1 microg rhTF. Six and 10 months after grafting, bone cores were extracted for implant fixation and analyzed. Histology demonstrated a high degree of inorganic xenograft integration and natural bone regeneration. Both the xenograft and newly synthesized bone were colonized with osteocytes and surrounded by osteoblasts. Six-month-old bone cores demonstrated a ratio of synthesized bone to xenograft particles ratio of 0.5, whereas 10-month-old cores demonstrated a ratio of 2. A low degree of inflammation could also be observed using S100A8 immunohistochemistry. Autologous grafting in edentulous patients is a complex procedure; the successful substitution of synthetic analogs for ground bone is a major challenge. In this investigation, it was shown that inorganic xenograft in the harvested bone paste could be safe for patients and had high bone regeneration capacity over time. The sinus graft showed intense bone formation 6 months after grafting and a further increase in bone growth 10 months after grafting.

Complications of harvesting a connective tissue graft from the palate. A retrospective study and description of a new technique

PubMed Central

Aguirre-Zorzano, Luis-Antonio; Estefanía-Fresco, Ruth; Marichalar-Mendía, Xabier

2017-01-01

Background Connective tissue graft (CTG) is considered as the gold standard for the treatment of gingival recessions (GR). There are few studies assessing the complications that can arise in the donor site when harvesting a connective tissue graft (CTG) and how the harvesting technique can influence those complications. Material and Methods A retrospective clinical study was carried out in order to compare the complications observed in 40 patients with Miller class I, II and III GR ≥ 3 mm, after using the trap-door technique (TD) in the control group and a newly described technique, the “UPV/EHU technique”, in the test group. Patients were consecutively allocated to each treatment group. Patients were monitored 14 days after surgery in order to evaluate post-operative complications in the donor site: presence of pain (P), bleeding (B), infection (I) and necrosis > 30%. Results Although morbidity was observed in both groups, it was less important in the test group (no pain and minimal pain in 30% and 35% of the cases, respectively, and absence of bleeding or infection and necrosis >30% in only 5% of the cases). Conclusions Within the limits of this study, this newly described “UPV/EHU technique” should be considered as a treatment option when harvesting a CTG, with minimal morbidity for patients. Key words:Connective tissue graft, pain, gingival recessions, wound healing, cosmetic periodontal plastic surgery, trap-door technique, “UPV/EHU technique”. PMID:29410760

Intraoperative extracorporeal autogenous irradiated tendon grafts for functional limb salvage surgery of soft tissue sarcomas of the wrist and hand.

PubMed

Omori, Shinsuke; Hamada, Kenichiro; Outani, Hidetatsu; Oshima, Kazuya; Joyama, Susumu; Tomita, Yasuhiko; Naka, Norifumi; Araki, Nobuhito; Yoshikawa, Hideki

2015-05-12

In patients with soft tissue sarcoma of the wrist and hand, limb salvage operation is extremely challenging for surgeons in attempting a complete tumor resection with negative surgical margins. In this study, we report four patients with soft tissue sarcoma of the wrist and hand treated by limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts. The patients were all male, and the mean age at the time of surgery was 45 years. Histological diagnoses included clear cell sarcoma in two patients, synovial sarcoma in one, and angiosarcoma in one. All four patients had high grade tumors, wherein three had American Joint Committee on Cancer (AJCC) stage III disease and one with AJCC stage IV disease. The tumors were resected en bloc with involved tendons. The tendons were isolated from the resected tissues, irradiated ex vivo, and re-implanted into the host tendons. In one patient, the bone was resected additionally because of tumor invasion to the bone. Hand function was evaluated using Musculoskeletal Tumor Society (MSTS) rating system. Of the four patients, three died of distant metastatic disease. The remaining patient lives and remains disease-free. The mean follow-up period was 33 months. One patient had local recurrence outside the irradiated graft at 20 months after surgery. The functional rating was 22. Lower scores were seen in patients with reconstruction of flexor tendons than extensor tendons. Limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts is an acceptable method in selected patients with soft tissue sarcoma of the wrist and hand.

Acellular dermal matrix and subepithelial connective tissue grafts for root coverage: A systematic review

PubMed Central

Gallagher, Sarah Ivy; Matthews, Debora Candace

2017-01-01

Background: The aim of this systematic review was to evaluate whether patients with gingival recession would benefit from an acellular dermal matrix graft (ADMG) in ways that are comparable to the gold standard of the subepithelial connective tissue graft (SCTG). Materials and Methods: A systematic review and meta-analysis comparing ADMG to SCTG for the treatment of Miller Class I and II recession defects was conducted according to PRISMA guidelines. PubMed, Excerpta Medica Database, and Cochrane Central Register of Controlled Trials databases were searched up to March 2016 for controlled trials with minimum 6 months duration. The primary outcome was root coverage; secondary outcomes included attachment level change, keratinized tissue (KT) change, and patient-based outcomes. Both authors independently assessed the quality of each included trial and extracted the relevant data. Results: From 158 potential titles, 17 controlled trials were included in the meta-analysis. There were no differences between ADMG and SCTG for mean root coverage, percent root coverage, and clinical attachment level gain. ADMG was statistically better than SCTG for gain in width of KT (−0.43 mm; 95% confidence interval: −0.72, −0.15). Only one study compared patient-based outcomes. Conclusion: This review found that an ADMG would be a suitable root coverage substitute for an SCTG when avoidance of the second surgical site is preferred. PMID:29551861

Soft tissue engineering with micronized-gingival connective tissues.

PubMed

Noda, Sawako; Sumita, Yoshinori; Ohba, Seigo; Yamamoto, Hideyuki; Asahina, Izumi

2018-01-01

The free gingival graft (FGG) and connective tissue graft (CTG) are currently considered to be the gold standards for keratinized gingival tissue reconstruction and augmentation. However, these procedures have some disadvantages in harvesting large grafts, such as donor-site morbidity as well as insufficient gingival width and thickness at the recipient site post-treatment. To solve these problems, we focused on an alternative strategy using micronized tissue transplantation (micro-graft). In this study, we first investigated whether transplantation of micronized gingival connective tissues (MGCTs) promotes skin wound healing. MGCTs (≤100 µm) were obtained by mincing a small piece (8 mm 3 ) of porcine keratinized gingiva using the RIGENERA system. The MGCTs were then transplanted to a full skin defect (5 mm in diameter) on the dorsal surface of immunodeficient mice after seeding to an atelocollagen matrix. Transplantations of atelocollagen matrixes with and without micronized dermis were employed as experimental controls. The results indicated that MGCTs markedly promote the vascularization and epithelialization of the defect area 14 days after transplantation compared to the experimental controls. After 21 days, complete wound closure with low contraction was obtained only in the MGCT grafts. Tracking analysis of transplanted MGCTs revealed that some mesenchymal cells derived from MGCTs can survive during healing and may function to assist in wound healing. We propose here that micro-grafting with MGCTs represents an alternative strategy for keratinized tissue reconstruction that is characterized by low morbidity and ready availability. © 2017 Wiley Periodicals, Inc.

Is retrograde drilling really useful for osteochondral lesion of talus with subchondral cyst?: A case report.

PubMed

Jeong, Seong-Yup; Kim, Jong-Kil; Lee, Kwang-Bok

2016-12-01

Retrograde drilling is a well accepted procedure for osteochondral lesion of the talus and subchondral cyst with intact overlying cartilage. It has good results in most reports. Compared to anterograde drilling, retrograde drilling can protect the integrity of the articular cartilage. The purpose of this study was to evaluate the suitability of using retrograde drilling for osteochondral lesion with subchondral cyst and discuss the mechanism involved in the development of subchondral cyst. We report a 53-year-old man who had complained left ankle pain that lasted over 6 months which was exacerbated by walking. We diagnosed it as osteochondral lesion of the talus with subchondral cyst. Plain X-ray, computed tomography, and magnetic resonance imaging (MRI) of the ankle. He undertook retrograde drilling without debridement of cartilage. After the surgery, the pain had been subsided for 1 year, although arthritic change had progressed. However, after 5 years of retrograde drilling, he revisited our hospital due to severe ankle pain. Plain X-ray and MRI showed arthritic change of the ankle and multiple cystic formation of talus. Retrograde drilling has some problem because this procedure is not theoretically correct when the development of a subchondral cyst in osteochondral lesion of the talus is considered. In addition, retrograde drilling may impair uninjured bone marrow of the talus, resulting in the development of multiple cystic formations.

Fabrication of Custom-Shaped Grafts for Cartilage Regeneration

PubMed Central

Koo, Seungbum; Hargreaves, Brian A.; Gold, Garry E.; Dragoo, Jason L.

2011-01-01

Transplantation of engineered cartilage grafts is a promising method to treat diseased articular cartilage. The interfacial areas between the graft and the native tissues play an important role in the successful integration of the graft to adjacent native tissues. The purposes of the study were to create a custom shaped graft through 3D tissue shape reconstruction and rapid-prototype molding methods using MRI data, and to test the accuracy of the custom shaped graft against the original anatomical defect. An iatrogenic defect on the distal femur was identified with a 1.5 Tesla MRI and its shape was reconstructed into a three-dimensional (3D) computer model by processing the 3D MRI data. First, the accuracy of the MRI-derived 3D model was tested against a laser-scan based 3D model of the defect. A custom-shaped polyurethane graft was fabricated from the laser-scan based 3D model by creating custom molds through computer aided design and rapid-prototyping methods. The polyurethane tissue was laser-scanned again to calculate the accuracy of this process compared to the original defect. The volumes of the defect models from MRI and laser-scan were 537 mm3 and 405 mm3, respectively, implying that the MRI model was 33% larger than the laser-scan model. The average (±SD) distance deviation of the exterior surface of the MRI model from the laser-scan model was 0.4±0.4 mm. The custom-shaped tissue created from the molds was qualitatively very similar to the original shape of the defect. The volume of the custom-shaped cartilage tissue was 463 mm3 which was 15% larger than the laser-scan model. The average (±SD) distance deviation between the two models was 0.04±0.19 mm. Custom-shaped engineered grafts can be fabricated from standard sequence 3-D MRI data with the use of CAD and rapid-prototyping technology, which may help solve the interfacial problem between native cartilage and graft, if the grafts are custom made for the specific defect. The major source of error in

The Effect of Remnant Tissue Preservation in Anatomic Double-Bundle ACL Reconstruction on Knee Stability and Graft Maturation.

PubMed

Takahashi, Tsuneari; Kimura, Masashi; Hagiwara, Keiichi; Ohsawa, Takashi; Takeshita, Katsushi

2018-06-13

Several investigators have developed anterior cruciate ligament reconstructions (ACLR) with remnant tissue preservation (RTP) and have reported better clinical outcomes. However, the effects of RTP remain controversial. To date, no reports have compared both clinical and radiological outcomes of anatomic double-bundle ACLR using the hamstring tendon and outside-in technique with/without RTP. This article evaluates the effectiveness of RTP in ACLR on knee stability and graft maturation. In total, 75 patients with unilateral ACL injury who had undergone anatomic double-bundle ACLR using autografted hamstring tendon either with RTP (Group P, n  = 43) or without (Group N, n  = 32) were enrolled. Clinical scores, pre- and postoperative side-to-side differences (SSDs) obtained using Telos, radiological evaluations of the grafted tendon using the signal/noise quotient (SNQ) measured using magnetic resonance imaging, and arthroscopic evaluations of the grafted tendon were retrospectively compared between the groups. Postoperative SSDs were smaller in the Group P (0.78 ± 1.90 mm) than in the Group N (1.29 ± 2.18 mm); however, this difference was not significant. Comparing two subgroups of the Group P, the SSD was significantly smaller in those with sufficient remnant coverage (-0.56 ± 1.38 mm) than in those without (1.48 ± 1.77 mm) ( p  = 0.019), as well as in the Group N patients ( p  = 0.019). The degree of synovial coverage of the anteromedial ( p  = 0.0064) and posterolateral ( p  = 0.032) bundle grafted tendon at the time of second-look arthroscopy was significantly better in the Group P than in the Group N. SNQ values of ACL grafted tendon at proximal ( p  = 0.049), middle, and distal ( p  = 0.039) one-third in Group P were better than those in Group N. RTP may enhance synovial coverage and maturation of the grafted tendon. Sufficient remnant tissue coverage may contribute to better knee stability. This is a Level

In vitro and in vivo assessment of oral autologous artificial connective tissue characteristics that influence its performance as a graft.

PubMed

Fontanilla, Marta Raquel; Espinosa, Lady Giovanna

2012-09-01

Several studies have evaluated proteins secreted by fibroblasts comprising skin substitutes, finding that they are secreted in combinations and concentrations that promote wound healing. However, assessment of proteins secreted by oral fibroblasts forming a part of oral substitutes is scarce. In our previous work, collagen type-I scaffolds (CSs) and autologous artificial connective tissue (AACT) were produced and implanted in rabbit oral lesions, evidencing that AACT outperforms CS. The present work determined the secreted factor profile of AACT in the time of grafting as well as that of the AACT embedded in the clot. It also evaluated the proliferation and viability of AACT fibroblasts to establish the dwell time of these cells in the grafted area. Finally, it assessed whether CS, AACT, and clot-embedded AACT increase fibroblast recruitment induced by a fibrin clot, because the cell migratory response has been associated with the wound-healing outcome. We found that some of the factors secreted by AACT fibroblasts are significantly different from those secreted by clot-embedded AACT fibroblasts. Also, that the profile of proteins secreted by AACT fibroblasts and clot-embedded AACT fibroblasts is different from already reported protein secretion profiles of other engineered tissues used in treating oral mucosa wounds. It was also found that AACT fibroblasts are viable when grafted and remain in the treated area for almost 2 weeks, and that the migratory response of fibroblasts to tissue-substitute stimulus is significantly less than the migratory response induced by the clot alone. Overall, data suggest that AACT secretion of proteins is modulated by three-dimensionality and environment factors. This bioactivity and the fact that AACT does not increase fibroblast migration can be held accountable for AACT's good performance as a graft.

Tissue engineering in urethral reconstruction—an update

PubMed Central

Mangera, Altaf; Chapple, Christopher R

2013-01-01

The field of tissue engineering is rapidly progressing. Much work has gone into developing a tissue engineered urethral graft. Current grafts, when long, can create initial donor site morbidity. In this article, we evaluate the progress made in finding a tissue engineered substitute for the human urethra. Researchers have investigated cell-free and cell-seeded grafts. We discuss different approaches to developing these grafts and review their reported successes in human studies. With further work, tissue engineered grafts may facilitate the management of lengthy urethral strictures requiring oral mucosa substitution urethroplasty. PMID:23042444

Free Gingival Graft versus Mucograft: Histological Evaluation

PubMed Central

Menceva, Zaklina; Dimitrovski, Oliver; Popovska, Mirjana; Spasovski, Spiro; Spirov, Vancho; Petrushevska, Gordana

2018-01-01

INTRODUCTION: The correction of the gingival recession is of esthetical and functional significance, but the tissue regeneration can only be confirmed by a histological examination. AIM: This study aims to make a comparison between the free gingival graft and the autograft. MATERIAL AND METHODS: This study included 24 patients with single and multiple gingival recessions. Twelve patients were treated with a free gingival graft and the other twelve with a micrograft. Six months after the surgical procedure, a micro-punch biopsy of the transplantation area was performed. The tissue was histologically evaluated, graded in 4 categories: immature, mature, fragmented and edematous collagen tissue. The elastic fibres were also examined and graded in three categories: with a normal structure, fragmented rare and fragmented multiplied. RESULTS: Regarding the type of collagen tissue that was present, there was a significant difference between the two groups of patients, with a larger number of patients treated with a micrograft showing a presence of mature tissue, compared to the patients treated with a free gingival graft. A larger number of patients in both of the groups displayed elastic fibres with a rare fragmented structure; 33.3% of the patients showed a normal structure; 50% demonstrated a normal structure. CONCLUSION: The patients treated with a free gingival graft showed a larger presence of fragmented collagen tissue and fragmented elastic fibres, whereas a mature tissue was predominantly present in the surgical area where a Geistlich Mucograft was placed. PMID:29731940

Tissue Engineering at the Blood-Contacting Surface: A Review of Challenges and Strategies in Vascular Graft Development.

PubMed

Radke, Daniel; Jia, Wenkai; Sharma, Dhavan; Fena, Kemin; Wang, Guifang; Goldman, Jeremy; Zhao, Feng

2018-05-07

Tissue engineered vascular grafts (TEVGs) are beginning to achieve clinical success and hold promise as a source of grafting material when donor grafts are unsuitable or unavailable. Significant technological advances have generated small-diameter TEVGs that are mechanically stable and promote functional remodeling by regenerating host cells. However, developing a biocompatible blood-contacting surface remains a major challenge. The TEVG luminal surface must avoid negative inflammatory responses and thrombogenesis immediately upon implantation and promote endothelialization. The surface has therefore become a primary focus for research and development efforts. The current state of TEVGs is herein reviewed with an emphasis on the blood-contacting surface. General vascular physiology and developmental challenges and strategies are briefly described, followed by an overview of the materials currently employed in TEVGs. The use of biodegradable materials and stem cells requires careful control of graft composition, degradation behavior, and cell recruitment ability to ensure that a physiologically relevant vessel structure is ultimately achieved. The establishment of a stable monolayer of endothelial cells and the quiescence of smooth muscle cells are critical to the maintenance of patency. Several strategies to modify blood-contacting surfaces to resist thrombosis and control cellular recruitment are reviewed, including coatings of biomimetic peptides and heparin. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modeling conduction in host-graft interactions between stem cell grafts and cardiomyocytes.

PubMed

Chen, Michael Q; Yu, Jin; Whittington, R Hollis; Wu, Joseph C; Kovacs, Gregory T A; Giovangrandi, Laurent

2009-01-01

Cell therapy has recently made great strides towards aiding heart failure. However, while transplanted cells may electromechanically integrate into host tissue, there may not be a uniform propagation of a depolarization wave between the heterogeneous tissue boundaries. A model using microelectrode array technology that maps the electrical interactions between host and graft tissues in co-culture is presented and sheds light on the effects of having a mismatch of conduction properties at the boundary. Skeletal myoblasts co-cultured with cardiomyocytes demonstrated that conduction velocity significantly decreases at the boundary despite electromechanical coupling. In an attempt to improve the uniformity of conduction with host cells, differentiating human embryonic stem cells (hESC) were used in co-culture. Over the course of four to seven days, synchronous electrical activity was observed at the hESC boundary, implying differentiation and integration. Activity did not extend far past the boundary, and conduction velocity was significantly greater than that of the host tissue, implying the need for other external measures to properly match the conduction properties between host and graft tissue.

Evidence-based alternatives for autogenous grafts around teeth: outcomes, attachment, and stability.

PubMed

McGuire, Michael K

2014-06-01

Although the use of autogenous harvested tissues has proven to be the gold standard for soft tissue augmentation procedures involving root coverage or generation of keratinized tissue, harvest site morbidity and limited supply have prompted clinicians to seek graft alternatives. Using a hierarchy of evidence, the author reviews both clinical and patient-reported results for harvest graft substitutes and, considering his own research experience, reviews autogenous graft substitute outcomes, attachment, and stability over time. Overall, when the goal is keratinized-tissue generation, living cellular constructs and xenogeneic collagen matrices have provided acceptable clinical results, but with better esthetics and patient preference than autogenous free gingival grafts. For root coverage therapy, enamel matrix derivatives, platelet-derived growth factors, and xenogeneic collagen matrices have provided acceptable results with equivalent esthetics to autogenous connective tissue grafts, while also being preferred by patients. Longterm results for enamel matrix derivatives, platelet-derived growth factors, and xenogeneic collagen matrices indicate root coverage can be maintained over time. In the author's hands, xenogeneic collagen matrices have been the only harvest graft alternatives that can be used either covered or uncovered by soft tissue.

Multimodal imaging of vascular grafts using time-resolved fluorescence and ultrasound

NASA Astrophysics Data System (ADS)

Fatakdawala, Hussain; Griffiths, Leigh G.; Wong, Maelene L.; Humphrey, Sterling; Marcu, Laura

2015-02-01

The translation of engineered tissues into clinic requires robust monitoring of tissue development, both in vitro and in vivo. Traditional methods for the same are destructive, inefficient in time and cost and do not allow time-lapse measurements from the same sample or animal. This study reports on the ability of time-resolved fluorescence and ultrasound measurements for non-destructive characterization of explanted tissue engineered vascular grafts. Results show that TRFS and FLIm are able to assess alterations in luminal composition namely elastin, collagen and cellular (hyperplasia) content via changes in fluorescence lifetime values between normal and grafted tissue. These observations are complemented by structural changes observed in UBM pertaining to graft integration and intimal thickness over the grafted region. These results encourage the future application of a catheter-based technique that combines these imaging modalities for non-destructive characterization of vascular grafts in vivo.

Xenogeneic collagen matrix versus connective tissue graft for buccal soft tissue augmentation at implant site. A randomized, controlled clinical trial.

PubMed

Cairo, Francesco; Barbato, Luigi; Tonelli, Paolo; Batalocco, Guido; Pagavino, Gabriella; Nieri, Michele

2017-07-01

Peri-implant soft tissue may be critical to prevent inflammation and promote gingival margin stability. The purpose of this randomized clinical trial (RCT) is to compare xenogeneic collagen matrix (XCM) versus connective tissue graft (CTG) to increase buccal soft tissue thickness at implant site. Soft tissue augmentation with XCM (test) or CTG (control) was performed at 60 implants in 60 patients at the time of implant uncovering. Measurements were performed by a blinded examiner at baseline, 3 and 6 months. Outcome measures included buccal soft tissue thickness (GT), apico-coronal keratinized tissue (KT), chair time and post-operative discomfort. Visual Analogue Scale (VAS) was used to evaluate patient satisfaction. After 6 months, the final GT increase was 0.9 ± 0.2 in the XCM group and 1.2 ± 0.3 mm in the CTG group, with a significant difference favouring the control group (0.3 mm; p = .0001). Both procedures resulted in similar final KT amount with no significant difference between treatments. XCM was associated with significant less chair-time (p < .0001), less post-operative pain (p < .0001), painkillers intake (p < .0001) and higher final satisfaction than CTG (p = .0195). CTG was more effective than XCM to increase buccal peri-implant soft tissue thickness. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

3D Printing and Biofabrication for Load Bearing Tissue Engineering.

PubMed

Jeong, Claire G; Atala, Anthony

2015-01-01

Cell-based direct biofabrication and 3D bioprinting is becoming a dominant technological platform and is suggested as a new paradigm for twenty-first century tissue engineering. These techniques may be our next step in surpassing the hurdles and limitations of conventional scaffold-based tissue engineering, and may offer the industrial potential of tissue engineered products especially for load bearing tissues. Here we present a topically focused review regarding the fundamental concepts, state of the art, and perspectives of this new technology and field of biofabrication and 3D bioprinting, specifically focused on tissue engineering of load bearing tissues such as bone, cartilage, osteochondral and dental tissue engineering.

Osteochondral Allograft Transplantation of the Knee in Patients with an Elevated Body Mass Index.

PubMed

Wang, Dean; Rebolledo, Brian J; Dare, David M; Pais, Mollyann D; Cohn, Matthew R; Jones, Kristofer J; Williams, Riley J

2018-02-01

Objective To characterize the graft survivorship and clinical outcomes of osteochondral allograft transplantation (OCA) of the knee in patients with an elevated body mass index (BMI). Design Prospective data on 38 consecutive patients with a BMI ≥30 kg/m 2 treated with OCA from 2000 to 2015 were reviewed. Complications, reoperations, and patient responses to validated outcome measures were examined. Failures were defined by any removal/revision of the allograft or conversion to arthroplasty. Results Thirty-one knees in 31 patients (mean age, 35.4 years [range, 17-61 years]; 87% male) met the inclusion criteria. Mean BMI was 32.9 kg/m 2 (range, 30-39 kg/m 2 ). Mean chondral defect size was 6.4 cm 2 (range, 1.0-15.3 cm 2 ). Prior to OCA, 23 patients (74%) had undergone previous surgery to the ipsilateral knee. Mean duration of follow-up was 4.1 years (range, 2-11 years). After OCA, 5 knees (13%) underwent conversion to unicompartmental (1) or total (4) knee arthroplasty. Two- and 5-year graft survivorship were 87% and 83%, respectively. At final follow-up, clinically significant improvements were noted in the pain (49.3-72.6) and physical functioning (52.9-81.3) subscales of the Short Form-36 ( P ≤ 0.001), International Knee Documentation Committee subjective form (43.5-67.0; P = 0.002), Knee Outcome Survey-Activities of Daily Living (58.2-80.4; P = 0.002), and overall condition subscale of the Cincinnati Knee Rating System (4.7-6.9; P = 0.046). Conclusions OCA can be a successful midterm treatment option for focal cartilage defects of the knee in select patients with a BMI ≥30 kg/m 2 .

The effect of partially exposed connective tissue graft on root-coverage outcomes: a systematic review and meta-analysis.

PubMed

Dodge, Austin; Garcia, Jeffrey; Luepke, Paul; Lai, Yu-Lin; Kassab, Moawia; Lin, Guo-Hao

2018-04-01

The aim of this systematic review was to compare the root-coverage outcomes of using a partially exposed connective tissue graft (CTG) technique with a fully covered CTG technique for root coverage. An electronic search up to February 28 th , 2017, was performed to identify human clinical studies with data comparing outcomes of root coverage using CTG, with and without a partially exposed graft. Five clinical studies were selected for inclusion in this review. For each study, the gain of keratinized gingiva, reduction of recession depth, number of surgical sites achieving complete root coverage, percentage of root coverage, gain of tissue thickness, and changes of probing depth and clinical attachment level were recorded. Meta-analysis for the comparison of complete root coverage between the two techniques presented no statistically significant differences. A statistically significant gain of keratinized tissue in favor of the sites with an exposed CTG and a tendency of greater reduction in recession depth were seen at the sites with a fully covered CTG. Based on the results, the use of a partially exposed CTG in root-coverage procedures could achieve greater gain in keratinized gingiva, while a fully covered CTG might be indicated for procedures aiming to reduce recession depth. © 2018 Eur J Oral Sci.

Osteochondral lesions in developing rats intoxicated with thallium twenty four hours after birth.

PubMed

Barroso-Moguel, R; Villeda-Hernández, J; Méndez-Armenta, M; Ríos, C; Galván-Arzate, S

1992-01-01

An i.p. injection of a solution of thallium acetate in deionized water at a dose of 32 mg/kg, in 24-h-old rats, produces morphological and biochemical alterations in both cartilaginous and osseous tissues. From the beginning, there are alterations in the cartilaginous cell as well as in chrondrine, osteoblasts, osseous tissue and bone marrow. Rats were sacrificed at 24, 48, and 72 h and also at 7 days. Two animals survived for 50 days. One showed total irreversible alopecia while the other one had partial alopecia with discrete recovery. Both showed a low weight and a size of 8 cm. Microscopically, degenerative changes were produced consisting of alteration and death of many cartilaginous cells, uneven metachromasia and the chondrine and decrease of the growth cartilage, scanty bone trabeculae with few osteoblasts. The bone marrow showed few myeloblasts and megakaryocytes. Progressive cellular damage throughout the 50 days of survival represents a response of the thallium ionic accumulation and recycling in cellular mitochondria of all the body's cells. This appeared in our study as irreversible and progressive osteochondral alterations with atrophy of the skin and its adnexa, hyalinization of elastic and collagenous fibers with intense interstitial edema.

Chemical hydrogels based on a hyaluronic acid-graft-α-elastin derivative as potential scaffolds for tissue engineering.

PubMed

Palumbo, Fabio Salvatore; Pitarresi, Giovanna; Fiorica, Calogero; Rigogliuso, Salvatrice; Ghersi, Giulio; Giammona, Gaetano

2013-07-01

In this work hyaluronic acid (HA) functionalized with ethylenediamine (EDA) has been employed to graft α-elastin. In particular a HA-EDA derivative bearing 50 mol% of pendant amino groups has been successfully employed to produce the copolymer HA-EDA-g-α-elastin containing 32% w/w of protein. After grafting with α-elastin, remaining free amino groups reacted with ethylene glycol diglycidyl ether (EGDGE) for producing chemical hydrogels, proposed as scaffolds for tissue engineering. Swelling degree, resistance to chemical and enzymatic hydrolysis, as well as preliminary biological properties of HA-EDA-g-α-elastin/EGDGE scaffold have been evaluated and compared with a HA-EDA/EGDGE scaffold. The presence of α-elastin grafted to HA-EDA improves attachment, viability and proliferation of primary rat dermal fibroblasts and human umbilical artery smooth muscle cells. Biological performance of HA-EDA-g-α-elastin/EGDGE scaffold resulted comparable to that of a commercial collagen type I sponge (Antema®), chosen as a positive control. Copyright © 2013 Elsevier B.V. All rights reserved.

Can subepithelial connective tissue grafts be considered the gold standard procedure in the treatment of Miller Class I and II recession-type defects?

PubMed

Chambrone, Leandro; Chambrone, Daniela; Pustiglioni, Francisco E; Chambrone, Luiz A; Lima, Luiz A

2008-09-01

The objective of this systematic review was to answer the following question: 'Can subepithelial connective tissue grafts (SCTG) be considered the gold standard procedure in the treatment of recession-type defects?' DATA AND SOURCE: An electronic search (MEDLIINE, EMBASE and CENTRAL) for randomized controlled clinical trials with at least 6 months' follow-up comparing SCTG with other procedures for the treatment of gingival recession was performed up to December 2007. To be eligible to this review patients had to present a diagnosis of gingival recession with the following characteristics: (a) recession areas selected for treatment classified as Miller [Miller Jr PD. A classification of marginal tissue recession. International Journal of Periodontics & Restorative Dentistry 1985;5:8-13.] Class I or Class II of at least 2mm; (b) recession areas containing teeth with no caries or restorations; and (c) at least 10 participants per group at final examination. From a total of 568 references, 23 studies were considered relevant. The results indicated a statistically significant greater reduction in gingival recession for SCTG, when compared to acellular dermal matrix grafts and guided tissue regeneration with resorbable membranes (GTR rm). For clinical attachment level changes, differences between all groups were not significant. For changes in the keratinized tissue (KT), the results showed a statistically significant gain in the width of KT for SCTG when compared to GTR rm. The results of this review show that subepithelial connective tissue grafts provided significant root coverage, clinical attachment and keratinized tissue gain. Overall comparisons allow us to consider it as the 'gold standard' procedure in the treatment of recession-type defects.

Composite scaffolds for osteochondral repair obtained by combination of additive manufacturing, leaching processes and hMSC-CM functionalization.

PubMed

Díaz Lantada, Andrés; Alarcón Iniesta, Hernán; García-Ruíz, Josefa Predestinación

2016-02-01

Articular repair is a relevant and challenging area for the emerging fields of tissue engineering and biofabrication. The need of significant gradients of properties, for the promotion of osteochondral repair, has led to the development of several families of composite biomaterials and scaffolds, using different effective approaches, although a perfect solution has not yet been found. In this study we present the design, modeling, rapid manufacturing and in vitro testing of a composite scaffold aimed at osteochondral repair. The presented composite scaffold stands out for having a functional gradient of density and stiffness in the bony phase, obtained in titanium by means of computer-aided design combined with additive manufacture using selective laser sintering. The chondral phase is obtained by sugar leaching, using a PDMS matrix and sugar as porogen, and is joined to the bony phase during the polymerization of PDMS, therefore avoiding the use of supporting adhesives or additional intermediate layers. The mechanical performance of the construct is biomimetic and the stiffness values of the bony and chondral phases can be tuned to the desired applications, by means of controlled modifications of different parameters. A human mesenchymal stem cell (h-MSC) conditioned medium (CM) is used for improving scaffold response. Cell culture results provide relevant information regarding the viability of the composite scaffolds used. Copyright © 2015 Elsevier B.V. All rights reserved.

Production of sperm from porcine fetal testicular tissue after cryopreservation and grafting into nude mice.

PubMed

Kaneko, Hiroyuki; Kikuchi, Kazuhiro; Men, Nguyen Thi; Nakai, Michiko; Noguchi, Junko; Kashiwazaki, Naomi; Ito, Junya

2017-03-15

A major goal of testicular xenografting is to salvage germ cells from immature animals that cannot be used for reproduction and generate their offspring. In this study, we investigated whether porcine fetal testicular tissue would acquire the ability to produce sperm with full developmental competence after they had been cryopreserved and grafted into nude mice. Testicular fragments from fetuses at 35, 55 and 90 days postartificial insemination (dpi) were vitrified and stored in liquid nitrogen. Immediately after warming, testicular fragments at each fetal stage were transplanted under the back skin of castrated nude mice (Crlj:CD1-Foxn1 nu ) (35-, 55- and 90-dpi groups, respectively) (day 0 = grafting). Before grafting, the testicular fragments contained seminiferous cords consisting of only gonocytes and Sertoli cells. Histological analyses of the testicular grafts revealed that the differentiation of seminiferous tubules was largely dependent on the time after grafting, and not on donor age. On day 180 in each group, 10-20% of the total number of tubule/cord cross-sections examined had germ cells that had progressed beyond the spermatogonial stage. Fewer than 5% of tubule cross-sections contained elongated spermatids or sperm. Between days 360 and 420, tubule differentiation advanced further, until more than 45% of the tubule cross-sections contained elongated spermatids or sperm. Sperm were recovered for the first time from a single mouse in the 55-dpi group on day 180, although on days 360-420 sperm were recovered from most mice in all of the groups. Serum concentrations of inhibin and testosterone in host mice in all of the groups were higher than those in castrated mice that had received no testicular grafts. Single sperm collected from mice in each group on day 300 or later were injected into individual in vitro-matured oocytes, and these sperm-injected oocytes were transferred to the oviducts of 2 or 3 estrus-synchronized recipient gilts. None of the

Contact-free monitoring of vessel graft stiffness - proof of concept as a tool for vascular tissue engineering.

PubMed

Hoenicka, Markus; Kaspar, Marcel; Schmid, Christof; Liebold, Andreas; Schrammel, Siegfried

2017-10-01

Tissue-engineered vessel grafts have to mimic the biomechanical properties of native blood vessels. Manufacturing processes often condition grafts to adapt them to the target flow conditions. Graft stiffness is influenced by material properties and dimensions and determines graft compliance. This proof-of-concept study evaluated a contact-free method to monitor biomechanical properties without compromising sterility. Forced vibration response analysis was performed on human umbilical vein (HUV) segments mounted in a buffer-filled tubing system. A linear motor and a dynamic signal analyser were used to excite the fluid by white noise (0-200 Hz). Vein responses were read out by laser triangulation and analysed by fast Fourier transformation. Modal analysis was performed by monitoring multiple positions of the vessel surface. As an inverse model of graft stiffening during conditioning, HUV were digested proteolytically, and the course of natural frequencies (NFs) was monitored over 120 min. Human umbilical vein showed up to five modes with NFs in the range of 5-100 Hz. The first natural frequencies of HUV did not alter over time while incubated in buffer (p = 0.555), whereas both collagenase (-35%, p = 0.0061) and elastase (-45%, p < 0.001) treatments caused significant decreases of NF within 120 min. Decellularized HUV showed similar results, indicating that changes of the extracellular matrix were responsible for the observed shift in NF. Performing vibration response analysis on vessel grafts is feasible without compromising sterility or integrity of the samples. This technique allows direct measurement of stiffness as an important biomechanical property, obviating the need to monitor surrogate parameters. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Long-term Follow-up of Revision Osteochondral Allograft Transplantation of the Ankle.

PubMed

Gaul, Florian; Tírico, Luís E P; McCauley, Julie C; Bugbee, William D

2018-05-01

Osteochondral allograft (OCA) transplantation is a useful alternative for treatment of posttraumatic ankle arthritis in young patients but has a relatively high failure rate and further procedures are often required. The purpose of this study was to evaluate outcomes of patients who underwent revision OCA transplantation of the ankle after failed primary OCA transplantation. Twenty patients underwent revision OCA transplantation of the ankle between 1988 and 2015. Mean age was 44 years, 55% (11 of 20) were female. The mean time from primary to revision OCA was 3.0 ± 1.7 years. All patients had a minimum follow-up of 2 years. Outcomes included the American Academy of Orthopaedic Surgeons Foot and Ankle Module (AAOS-FAM) and questionnaires evaluating pain and satisfaction. Failure of the revision OCA was defined as a conversion to arthroplasty, arthrodesis, or amputation. Ten of 20 ankles required further surgery, of which 30% (6 of 20) were considered OCA revision failures (4 arthrodeses, 1 arthroplasty, and 1 amputation). The mean time to failure was 6.7 (range, 0.6-13.1) years. Survivorship of the revision OCA was 84% at 5 years and 65% at 10 years. The 14 patients with grafts remaining in situ had an average follow-up of 10.3 years; mean AAOS-FAM Core Score was 70.5 (range, 42.3-99). Of the patients who answered the follow-up questions, 4 of 7 reported moderate to severe pain, and 5 of 12 were satisfied with the results of the procedure. Although the results of revision ankle OCA transplantation are not inferior to primary OCA transplantation, the high rates of persistent pain, further surgery, and graft failure suggest that the indications for OCA as a revision procedure should be carefully evaluated, with proper patient selection. Considering the treatment alternatives, revising a failed OCA transplantation can be a useful treatment option, especially for young and active patients who wish to avoid arthrodesis or arthroplasty. Level IV, case series.

Randomized controlled clinical study evaluating effectiveness and safety of a volume-stable collagen matrix compared to autogenous connective tissue grafts for soft tissue augmentation at implant sites.

PubMed

Thoma, Daniel S; Zeltner, Marco; Hilbe, Monika; Hämmerle, Christoph H F; Hüsler, Jürg; Jung, Ronald E

2016-10-01

To test whether or not the use of a collagen matrix (VCMX) results in short-term soft tissue volume increase at implant sites non-inferior to an autogenous subepithelial connective tissue graft (SCTG), and to evaluate safety and tissue integration of VCMX and SCTG. In 20 patients with a volume deficiency at single-tooth implant sites, soft tissue volume augmentation was performed randomly allocating VCMX or SCTG. Soft tissue thickness, patient-reported outcome measures (PROMs), and safety were assessed up to 90 days (FU-90). At FU-90 (abutment connection), tissue samples were obtained for histological analysis. Descriptive analysis was computed for both groups. Non-parametric tests were applied to test non-inferiority for the gain in soft tissue thickness at the occlusal site. Median soft tissue thickness increased between BL and FU-90 by 1.8 mm (Q1:0.5; Q3:2.0) (VCMX) (p = 0.018) and 0.5 mm (-1.0; 2.0) (SCTG) (p = 0.395) (occlusal) and by 1.0 mm (0.5; 2.0) (VCMX) (p = 0.074) and 1.5 mm (-2.0; 2.0) (SCTG) (p = 0.563) (buccal). Non-inferiority with a non-inferiority margin of 1 mm could be demonstrated (p = 0.020); the difference between the two group medians (1.3 mm) for occlusal sites indicated no relevant, but not significant superiority of VCMX versus SCTG (primary endpoint). Pain medication consumption and pain perceived were non-significantly higher in group SCTG up to day 3. Median physical pain (OHIP-14) at day 7 was 100% higher for SCTG than for VCMX. The histological analysis revealed well-integrated grafts. Soft tissue augmentation at implant sites resulted in a similar or higher soft tissue volume increase after 90 days for VCMX versus SCTG. PROMs did not reveal relevant differences between the two groups. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Engineering Orthopedic Tissue Interfaces

PubMed Central

Yang, Peter J.

2009-01-01

While a wide variety of approaches to engineering orthopedic tissues have been proposed, less attention has been paid to the interfaces, the specialized areas that connect two tissues of different biochemical and mechanical properties. The interface tissue plays an important role in transitioning mechanical load between disparate tissues. Thus, the relatively new field of interfacial tissue engineering presents new challenges—to not only consider the regeneration of individual orthopedic tissues, but also to design the biochemical and cellular composition of the linking tissue. Approaches to interfacial tissue engineering may be distinguished based on if the goal is to recreate the interface itself, or generate an entire integrated tissue unit (such as an osteochondral plug). As background for future efforts in engineering orthopedic interfaces, a brief review of the biology and mechanics of each interface (cartilage–bone, ligament–bone, meniscus–bone, and muscle–tendon) is presented, followed by an overview of the state-of-the-art in engineering each tissue, including advances and challenges specific to regenerating the interfaces. PMID:19231983

Initial evaluation of the use of USPIO cell labeling and noninvasive MR monitoring of human tissue-engineered vascular grafts in vivo.

PubMed

Nelson, G N; Roh, J D; Mirensky, T L; Wang, Y; Yi, T; Tellides, G; Pober, J S; Shkarin, P; Shapiro, E M; Saltzman, W M; Papademetris, X; Fahmy, T M; Breuer, C K

2008-11-01

This pilot study examines noninvasive MR monitoring of tissue-engineered vascular grafts (TEVGs) in vivo using cells labeled with iron oxide nanoparticles. Human aortic smooth muscle cells (hASMCs) were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. The labeled hASMCs, along with human aortic endothelial cells, were incorporated into eight TEVGs and were then surgically implanted as aortic interposition grafts in a C.B-17 SCID/bg mouse host. USPIO-labeled hASMCs persisted in the grafts throughout a 3 wk observation period and allowed noninvasive MR imaging of the human TEVGs for real-time, serial monitoring of hASMC retention. This study demonstrates the feasibility of applying noninvasive imaging techniques for evaluation of in vivo TEVG performance.

Fixation of osteochondral fractures in rabbit knees. A comparison of Kirschner wires, fibrin sealant, and polydioxanone pins.

PubMed

Plaga, B R; Royster, R M; Donigian, A M; Wright, G B; Caskey, P M

1992-03-01

We compared fibrin sealant, polydioxanone (PDS) pins and Kirschner wires in the fixation of osteochondral fractures in rabbit knees. Standardised osteochondral fractures of the right medial femoral condyle were made in 56 adult New Zealand white rabbits. There were equal groups of control knees, and those which had Kirschner-wire, fibrin-sealant or PDS-pin fixation. No external immobilisation was used. One animal from each group was killed at two, three and four weeks. The remaining rabbits were killed at six weeks. A fracture which healed with less than 1 mm of displacement was considered a success. There was successful healing in 29% of the control group, in all of the Kirschner-wire group, in 50% of the fibrin-sealant group, and in 86% of the PDS-pin group. The use of PDS pins appears to be a reliable alternative to the use of metal in the fixation of osteochondral fractures in rabbits.

[Free tissue transfers with lengthening of vascular pedicle using interpositional vein grafts. About 10 cases].

PubMed

Yeo, S; Perrot, P; Duteille, F

2010-04-01

The realization of free flaps with lack of reliable vessels nearby the loss of substance is a difficult problem for plastic surgeons. We report 10 cases of free tissue transfers with a one-stage technique lengthening the vascular pedicle of the free flap with interpositional vein grafts. Taking into consideration the good results and the low rate of morbidity, the authors emphasize the use of this technique rather than a two-stage procedure. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Tissue engineering-based cartilage repair with mesenchymal stem cells in a porcine model.

PubMed

Chang, Chih-Hung; Kuo, Tzong-Fu; Lin, Feng-Huei; Wang, Jyh-Horng; Hsu, Yuan-Ming; Huang, Huei-Ting; Loo, Shiao-Tung; Fang, Hsu-Wei; Liu, Hwa-Chang; Wang, Wen-Chih

2011-12-01

This in vivo pilot study explored the use of mesenchymal stem cell (MSC) containing tissue engineering constructs in repair of osteochondral defects. Osteochondral defects were created in the medial condyles of both knees of 16 miniature pigs. One joint received a cell/collagen tissue engineering construct with or without pretreatment with transforming growth factor β (TGF-β) and the other joint from the same pig received no treatment or the gel scaffold only. Six months after surgery, in knees with no treatment, all defects showed contracted craters; in those treated with the gel scaffold alone, six showed a smooth gross surface, one a hypertrophic surface, and one a contracted crater; in those with undifferentiated MSCs, five defects had smooth, fully repaired surfaces or partially repaired surfaces, and one defect poor repair; in those with TGF-β-induced differentiated MSCs, seven defects had smooth, fully repaired surfaces or partially repaired surfaces, and three defects showed poor repair. In Pineda score grading, the group with undifferentiated MSC, but not the group with TGF-β-induced differentiated MSCs, had significantly lower subchondral, cell morphology, and total scores than the groups with no or gel-only treatment. The compressive stiffness was larger in cartilage without surgical treatment than the treated area within each group. In conclusion, this preliminary pilot study suggests that using undifferentiated MSCs might be a better approach than using TGF-β-induced differentiated MSCs for in vivo tissue engineered treatment of osteochondral defects. Copyright © 2011 Orthopaedic Research Society.

Athymic Rat Model for Evaluation of Engineered Anterior Cruciate Ligament Grafts

PubMed Central

Leong, Natalie L.; Kabir, Nima; Arshi, Armin; Nazemi, Azadeh; Wu, Ben M.; McAllister, David R.; Petrigliano, Frank A.

2015-01-01

Anterior cruciate ligament (ACL) rupture is a common ligamentous injury that often requires surgery because the ACL does not heal well without intervention. Current treatment strategies include ligament reconstruction with either autograft or allograft, which each have their associated limitations. Thus, there is interest in designing a tissue-engineered graft for use in ACL reconstruction. We describe the fabrication of an electrospun polymer graft for use in ACL tissue engineering. This polycaprolactone graft is biocompatible, biodegradable, porous, and is comprised of aligned fibers. Because an animal model is necessary to evaluate such a graft, this paper describes an intra-articular athymic rat model of ACL reconstruction that can be used to evaluate engineered grafts, including those seeded with xenogeneic cells. Representative histology and biomechanical testing results at 16 weeks postoperatively are presented, with grafts tested immediately post-implantation and contralateral native ACLs serving as controls. The present study provides a reproducible animal model with which to evaluate tissue engineered ACL grafts, and demonstrates the potential of a regenerative medicine approach to treatment of ACL rupture. PMID:25867958

Biological, biochemical and biomechanical characterisation of articular cartilage from the porcine, bovine and ovine hip and knee.

PubMed

Fermor, H L; McLure, S W D; Taylor, S D; Russell, S L; Williams, S; Fisher, J; Ingham, E

2015-01-01

This study aimed to determine the optimal starting material for the development of an acellular osteochondral graft. Osteochondral tissues from three different species were characterised; pig (6 months), cow (18 months) and two ages of sheep (8-12 months and >4 year old). Tissues from the acetabulum and femoral head of the hip, and the groove, medial and lateral condyles and tibial plateau of the knee were assessed. Histological analysis of each tissue allowed for qualification of cartilage histoarchitecture, glycosaminoglycan (GAG) distribution, assessment of cellularity and cartilage thickness. Collagen and GAG content were quantified and cartilage water content was defined. Following biomechanical testing, the percentage deformation, permeability and equilibrium elastic modulus was determined. Results showed that porcine cartilage had the highest concentration of sulphated proteoglycans and that the condyles and groove of the knee showed higher GAG content than other joint areas. Cartilage from younger tissues (porcine and young ovine) had higher cell content and was thicker, reflecting the effects of age on cartilage structure. Cartilage from older sheep had a much higher elastic modulus and was less permeable than other species.

Multiple Osteochondral Allograft Transplantation with Concomitant Tibial Tubercle Osteotomy for Multifocal Chondral Disease of the Knee.

PubMed

Cotter, Eric J; Waterman, Brian R; Kelly, Mick P; Wang, Kevin C; Frank, Rachel M; Cole, Brian J

2017-08-01

Symptomatic patellofemoral chondral lesions are a challenging clinical entity, as these defects may result from persistent lateral patellar maltracking or repetitive microtrauma. Anteromedializing tibial tubercle osteotomy has been shown to be an effective strategy for primary and adjunctive treatment of focal or diffuse patellofemoral disease to improve the biomechanical loading environment. Similarly, osteochondral allograft transplantation has proven efficacy in physiologically young, high-demand patients with condylar or patellofemoral lesions, particularly without early arthritic progression. The authors present the surgical management of a young athlete with symptomatic tricompartmental focal chondral defects with fresh osteochondral allograft transplantation and anteromedializing tibial tubercle osteotomy.

Calculations for reproducible autologous skin cell-spray grafting.

PubMed

Esteban-Vives, Roger; Young, Matthew T; Zhu, Toby; Beiriger, Justin; Pekor, Chris; Ziembicki, Jenny; Corcos, Alain; Rubin, Peter; Gerlach, Jörg C

2016-12-01

Non-cultured, autologous cell-spray grafting is an alternative to mesh grafting for larger partial- and deep partial-thickness burn wounds. The treatment uses a suspension of isolated cells, from a patient's donor site skin tissue, and cell-spray deposition onto the wound that facilitates re-epithelialization. Existing protocols for therapeutic autologous skin cell isolation and cell-spray grafting have defined the donor site area to treatment area ratio of 1:80, substantially exceeding the coverage of conventional mesh grafting. However, ratios of 1:100 are possible by maximizing the wound treatment area with harvested cells from a given donor site skin tissue according to a given burn area. Although cell isolation methods are very well described in the literature, a rational approach addressing critical aspects of these techniques are of interest in planning clinical study protocols. We considered in an experimental study the cell yield as a function of the donor site skin tissue, the cell density for spray grafting, the liquid spray volume, the sprayed distribution area, and the percentage of surface coverage. The experimental data was then used for the development of constants and mathematical equations to give a rationale for the cell isolation and cell-spray grafting processes and in planning for clinical studies. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Repair of massively defected hemi-joints using demineralized osteoarticular allografts with protected cartilage.

PubMed

Li, Siming; Yang, Xiaohong; Tang, Shenghui; Zhang, Xunmeng; Feng, Zhencheng; Cui, Shuliang

2015-08-01

Surgical replacement of massively defected joints necessarily relies on osteochondral grafts effective to both of bone and cartilage. Demineralized bone matrix (DBM) retains the osteoconductivity but destroys viable chondrocytes in the cartilage portion essential for successful restoration of defected joints. This study prepared osteochondral grafts of DBM with protected cartilage. Protected cartilage portions was characterized by cellular and molecular biology and the grafts were allogenically used for grafting. Protected cartilage showed similar histomorphological structure and protected proteins estimated by total proteins and cartilage specific proteins as in those of fresh controls when DBMs were generated in bone portions. Such grafts were successfully used for simultaneously repair of bone and cartilage in massively defected osteoarticular joints within 16 weeks post-surgery. These results present an allograft with clinical potential for simultaneous restoration of bone and cartilage in defected joints.

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

Technical Report: Correlation Between the Repair of Cartilage and Subchondral Bone in an Osteochondral Defect Using Bilayered, Biodegradable Hydrogel Composites.

PubMed

Lu, Steven; Lam, Johnny; Trachtenberg, Jordan E; Lee, Esther J; Seyednejad, Hajar; van den Beucken, Jeroen J J P; Tabata, Yasuhiko; Kasper, F Kurtis; Scott, David W; Wong, Mark E; Jansen, John A; Mikos, Antonios G

2015-12-01

The present work investigated correlations between cartilage and subchondral bone repair, facilitated by a growth factor-delivering scaffold, in a rabbit osteochondral defect model. Histological scoring indices and microcomputed tomography morphological parameters were used to evaluate cartilage and bone repair, respectively, at 6 and 12 weeks. Correlation analysis revealed significant associations between specific cartilage indices and subchondral bone parameters that varied with location in the defect (cortical vs. trabecular region), time point (6 vs. 12 weeks), and experimental group (insulin-like growth factor-1 only, bone morphogenetic protein-2 only, or both growth factors). In particular, significant correlations consistently existed between cartilage surface regularity and bone quantity parameters. Overall, correlation analysis between cartilage and bone repair provided a fuller understanding of osteochondral repair and can help drive informed studies for future osteochondral regeneration strategies.

Postextraction socket preservation using epithelial connective tissue graft vs porcine collagen matrix. 1-year results of a randomised controlled trial.

PubMed

Meloni, Silvio Mario; Tallarico, Marco; Lolli, Francesco Maria; Deledda, Alessandro; Pisano, Milena; Jovanovic, Sascha A

2015-01-01

To compare epithelial connective tissue graft vs porcine collagen matrix for sealing postextraction sockets grafted with deproteinised bovine bone. A total of 30 patients, who needed a maxillary tooth to be extracted between their premolars and required a delayed, fixed, single implant-supported restoration, had their teeth atraumatically extracted and their sockets grafted with deproteinised bovine bone. Patients were randomised according to a parallel group design into two arms: socket sealing with epithelial connective tissue graft (group A) vs porcine collagen matrix (group B). Outcome measures were: implant success and survival rate, complications, horizontal and vertical alveolar bone dimensional changes measured on Cone Beam computed tomography (CBCT) scans at three levels localised 1, 3, and 5 mm below the most coronal aspect of the bone crest (levels A, B, and C); and between the palatal and buccal wall peaks (level D); and peri-implant marginal bone level changes measured on periapical radiographs. 15 patients were randomised to group A and 15 to group B. No patients dropped out. No failed implants or complications were reported 1 year after implant placement. Five months after tooth extraction there were no statistically significant differences between the 2 groups for both horizontal and vertical alveolar bone dimensional changes. At level A the difference was 0.13 ± 0.18; 95% CI 0.04 to 0.26 mm (P = 0.34), at level B it was 0.08 ± 0.23; 95% CI -0.14 to 0.14 (P = 0.61), at level C it was 0.05 ± 0.25; 95% CI -0.01 to 0.31 mm (P = 0.55) and at level D it was 0.13 ± 0.27; 95% CI -0.02 to 0.32 mm (P = 0.67). One year after implant placement there were no statistically significant differences between the 2 groups for peri-implant marginal bone level changes (difference: 0.07 ± 0.11 mm; 95% CI -0.02 to 0.16; P = 0.41). When teeth extractions were performed atraumatically and sockets were filled with deproteinised bovine bone, sealing the socket with a

Effects of Proud Large Osteochondral Plugs on Contact Forces and Knee Kinematics: A Robotic Study.

PubMed

Du, Peter Z; Markolf, Keith L; Boguszewski, Daniel V; Yamaguchi, Kent T; Lama, Christopher J; McAllister, David R; Jones, Kristofer J

2018-05-01

Osteochondral allograft (OCA) transplantation is used to treat large focal femoral condylar articular cartilage defects. A proud plug could affect graft survival by altering contact forces (CFs) and knee kinematics. A proud OCA plug will significantly increase CF and significantly alter knee kinematics throughout controlled knee flexion. Controlled laboratory study. Human cadaver knees had miniature load cells, each with a 20-mm-diameter cylinder of native bone/cartilage attached at its exact anatomic position, installed in both femoral condyles at standardized locations representative of clinical defects. Spacers were inserted to create proud plug conditions of +0.5, +1.0, and +1.5 mm. CFs and knee kinematics were recorded as a robot flexed the knee continuously from 0° to 50° under 1000 N of tibiofemoral compression. CFs were increased significantly (vs flush) for all proudness conditions between 0° and 45° of flexion (medial) and 0° to 50° of flexion (lateral). At 20°, the average increases in medial CF for +0.5-mm, +1-mm, and +1.5-mm proudness were +80 N (+36%), +155 N (+70%), and +193 N (+87%), respectively. Corresponding increases with proud lateral plugs were +44 N (+14%), +90 N (+29%), and +118 N (+38%). CF increases for medial plugs at 20° of flexion were significantly greater than those for lateral plugs at all proudness conditions. At 50°, a 1-mm proud lateral plug significantly decreased internal tibial rotation by 15.4° and decreased valgus rotation by 2.5°. A proud medial or lateral plug significantly increased CF between 0° and 45° of flexion. Our results suggest that a medial plug at 20° may be more sensitive to graft incongruity than a lateral plug. The changes in rotational kinematics with proud lateral plugs were attributed to earlier contact between the proud plug's surface and the lateral meniscus, leading to rim impingement with decreased tibial rotation. Increased CF and altered knee kinematics from a proud femoral plug could

Hamstring Graft Technique for Stabilization of Canine Cranial Cruciate Ligament Deficient Stifles

PubMed Central

LOPEZ, MANDI J.; MARKEL, MARK D.; KALSCHEUR, VICKI; LU, YAN; MANLEY, PAUL A.

2007-01-01

Objective To investigate the harvest and application of hamstring grafts for canine cranial cruciate ligament (CrCL) reconstruction. Study Design Experimental study. Animals Four adult female hounds, weighing 26.3 ± 1.6 kg (mean ± SEM). Methods One stifle in each dog was randomly chosen for hamstring graft CrCL reconstruction after native CrCL transection. Arthroscopy was performed to evaluate graft integrity at 12 weeks. Gait analysis and stifle radiographs were performed preoperatively and up to 52 weeks after graft placement. Dogs were killed 12 (n = 2) or 52 weeks (n = 2) after CrCL reconstruction. Tissues were evaluated grossly and with light and confocal laser microscopy. Results Hamstring grafts were intact in all stifles at 12 weeks (n = 4) and 52 weeks (n = 2). Grossly, there was no osteoarthritis in stifles at 12 weeks and only chondrophytes along the trochlear ridges at 52 weeks. Minimal radiographic evidence of osteoarthritis developed in stifles with grafts during the study. Lameness in limbs with grafts resolved by 52 weeks. Graft tissue was highly vascular, ligamentized, and undergoing active remodeling at 12 weeks. Fifty-two weeks after graft placement, intraarticular graft tissue was well vascularized, mature, and encapsulated by synovium, and graft-bone interfaces were characterized by Sharpey’s fiber insertions. There was no evidence of graft necrosis using confocal laser microscopy at either time point. Conclusions The hamstring graft technique may be a viable method of canine CrCL reconstruction. Clinical Relevance Hamstring grafts may be an alternative technique for canine CrCL reconstruction. Further study is needed before clinical application. PMID:12866003

Osteochondral repair in hemophilic ankle arthropathy: from current options to future perspectives

PubMed Central

BUDA, ROBERTO; CAVALLO, MARCO; CASTAGNINI, FRANCESCO; FERRANTI, ENRICO; NATALI, SIMONE; GIANNINI, SANDRO

2015-01-01

Young hemophilic patients are frequently affected by ankle arthropathy. At the end stage of the disease, the current treatments are arthrodesis and arthroplasty, which have significant drawbacks. Validated procedures capable of slowing down or even arresting the progression towards the end stage are currently lacking. This review aims to discuss the rationale for and feasibility of applying, in mild hemophilic ankle arthropathy, the main techniques currently used to treat osteochondral defects, focusing in particular on ankle distraction, chondrocyte implantation, mesenchymal stem cell transplantation, allograft transplantation and the use of growth factors. To date, ankle distraction is the only procedure that has been successfully used in hemophilic ankle arthropathy. The use of mesenchymal stem cells have recently been evaluated as feasible for osteochondral repair in hemophilic patients. There may be a rationale for the use of growth factors if they are combined with the previous techniques, which could be useful to arrest the progression of the degeneration or delay end-stage procedures. PMID:26904526

Diabetes mellitus increases risk of unsuccessful graft preparation in Descemet membrane endothelial keratoplasty: a multicenter study.

PubMed

Greiner, Mark A; Rixen, Jordan J; Wagoner, Michael D; Schmidt, Gregory A; Stoeger, Christopher G; Straiko, Michael D; Zimmerman, M Bridget; Kitzmann, Anna S; Goins, Kenneth M

2014-11-01

The aim of this study was to evaluate preparation outcomes of tissue prepared for Descemet membrane endothelial keratoplasty (DMEK) from diabetic and nondiabetic donors. In this nonrandomized, consecutive case series, DMEK grafts were prepared from diabetic and nondiabetic donors by experienced technicians in 2 eye banks using slightly different, modified submerged manual preparation techniques to achieve "prestripped" graft tissue. Graft preparation results were analyzed retrospectively. The main outcome measure was the rate of unsuccessful (failed) DMEK graft preparations, defined as tears through the graft area that prevent tissue use. A total of 359 corneas prepared from 290 donors (114 diabetic and 245 nondiabetic) were included in the statistical analysis of graft preparation failure. There were no significant differences between diabetic and nondiabetic donor tissue characteristics with respect to donor age, death to preservation time, death to preparation time, endothelial cell density, percent hexagonality, or coefficient of variation. DMEK tissue preparation was unsuccessful in 19 (5.3%) cases. There was a significant difference in the site-adjusted rate of DMEK preparation failure between diabetic [15.3%; 95% confidence interval (CI), 9.0-25.0] and nondiabetic donors (1.9%; 95% CI, 0.8-4.8), and the corresponding site-adjusted odds ratio of DMEK graft preparation failure in diabetic donor tissue versus nondiabetic donor tissue was 9.20 (95% CI, 2.89-29.32; P = 0.001). Diabetes may be a risk factor for unsuccessful preparation of donor tissue for DMEK. We recommend caution in the use of diabetic tissue for DMEK graft preparation. Further study is needed to identify what subset of diabetic donors is at risk for unsuccessful DMEK graft preparation.

Comparative evaluation of a bioabsorbable collagen membrane and connective tissue graft in the treatment of localized gingival recession: A clinical study

PubMed Central

Babu, Harsha Mysore; Gujjari, Sheela Kumar; Prasad, Deepak; Sehgal, Praveen Kumar; Srinivasan, Aishwarya

2011-01-01

Background: Gingival recession (GR) can result in root sensitivity, esthetic concern to the patient, and predilection to root caries. The purpose of this randomized clinical study was to evaluate (1) the effect of guided tissue regeneration (GTR) procedure using a bioabsorbable collagen membrane, in comparison to autogenous subepithelial connective tissue graft (SCTG) for root coverage in localized gingival recession defects; and (2) the change in width of keratinized gingiva following these two procedures. Materials and Methods: A total of 10 cases, showing at least two localized Miller's Class I or Class II gingival recession, participated in this study. In a split mouth design, the pairs of defects were randomly assigned for treatment with either SCTG (SCTG Group) or GTR-based collagen membrane (GTRC Group). Both the grafts were covered with coronally advanced flap. Recession depth (RD), recession width (RW), width of keratinized gingiva (KG), probing depth (PD), relative attachment level (RAL), plaque index (PI), and gingival index (GI) were recorded at baseline, 3 and 6 months postoperatively. Results: Six months following root coverage procedures, the mean root coverage was found to be 84.84% ± 16.81% and 84.0% ± 15.19% in SCTG Group and GTRC Group, respectively. The mean keratinized gingival width increase was 1.50 ± 0.70 mm and 2.30 ± 0.67 mm in the SCTG and GTRC group, respectively, which was not statistically significant. Conclusion: It may be concluded that resorbable collagen membrane can be a reliable alternative to autogenous connective tissue graft in the treatment of gingival recession. PMID:22368359

Osteochondral lesions of the ankle joint in professional soccer players: treatment with autologous matrix-induced chondrogenesis.

PubMed

Valderrabano, Victor; Barg, Alexej; Alattar, Abdulhameed; Wiewiorski, Martin

2014-12-01

Acute and recurrent ankle sprains and other trauma to the ankle joint are common injuries in soccer and can be accompanied by or result in osteochondral lesions of the ankle joint, majorly of the talus. Conservative treatment frequently fails. Several operative treatment techniques exist; however, the choice of the right procedure is difficult due to lack of literature with a high level of evidence. We present our treatment method for acute and chronic ankle osteochondral lesions with cystic formation approached by a new surgical technique combining bone plasty and a collagen matrix (autologous matrix-induced chondrogenesis). Therapeutic, Level IV: Case series. © 2014 The Author(s).

Angiogenesis in healing autogenous flexor-tendon grafts.

PubMed

Gelberman, R H; Chu, C R; Williams, C S; Seiler, J G; Amiel, D

1992-09-01

On the basis of recent evidence that flexor tendon grafts may heal without the ingrowth of vascular adhesions, eighteen autogenous donor tendons of intrasynovial and extrasynovial origin were transferred to the synovial sheaths in the forepaws of nine dogs, and controlled passive mobilization was instituted early in the postoperative period. The angiogenic responses of the tendon grafts were determined with perfusion studies with India ink followed by cleaing of the tissues with the Spalteholz technique at two, four, and six weeks. A consistent pattern of neovascularization was noted in the donor tendons of extrasynovial origin. Vascular adhesions arising from the flexor digitorum superficialis and the tendon sheath enveloped the tendon grafts by two weeks. By six weeks, the vascularity of the tendon grafts of extrasynovial origin appeared completely integrated with that of the surrounding tissues. Examination of cross sections revealed that the segments of tendon had been completely vascularized by obliquely oriented intratendinous vessels. In contrast, the flexor tendon grafts of intrasynovial origin healed without ingrowth of vascular adhesions. Primary intrinsic neovascularization took place from the proximal and, to a lesser extent, distal sites of the sutures. Examination of cross sections revealed vessels extending through the surface layer of the tendon graft, with small vessels penetrating the interior of the tendons at regular intervals.

Tissue-Engineered Nanofibrous Nerve Grafts for Enhancing the Rate of Nerve Regeneration

DTIC Science & Technology

2015-10-01

structured nanofibrous biodegradable nerve graft system that present ECM protein, neurotrophic factor, and pre-seeded with bone marrow stromal cells in...nanofibrous biodegradable nerve graft system that present extracellular matrix (ECM) protein, nerve growth factor, and pre-seeded with bone marrow stromal...proposed novel structured nanofibrous biodegradable grafts will provide the micro environment, bioactivity, transport features and mechanics ideal for

Storage and qualification of viable intact human amniotic graft and technology transfer to a tissue bank.

PubMed

Laurent, Romain; Nallet, Aurélie; Obert, Laurent; Nicod, Laurence; Gindraux, Florelle

2014-06-01

Human amniotic membrane (hAM) is known to have good potential to help the regeneration of tissue. It has been used for over 100 years in many medical disciplines because of its properties, namely a scaffold containing stem cells and growth factors, with low immunogenicity and anti-microbial, anti-inflammatory, anti-fibrotic and analgesic properties. In order to use this "boosted membrane" as an advanced therapeutic medicinal product for bone repair, we aimed to observe the influence of tissue culture and/or cryopreservation on cell viability and tissue structure, and secondly, to adapt to a tissue bank, identify easy processes to store hAM containing viable cells and to verify the quality of the graft before its release for use. To this end, we tested different published culture or cryopreservation storage conditions and cell viability assays. Tissue structure was evaluated by Giemsa staining and was compared to histological analysis. Preliminary results show no dramatic decrease in cell viability in cultured hAM as compared to cryopreserved hAM, but tissue structure alterations were observed with both storage conditions. Histological and immunohistochemical data highlight that tissue damage was associated with significantly modified protein expression, which could lead to a possible loss of differentiation potential. Finally, we report that trypan blue and Giemsa staining could constitute controls that are "materially and easily transferable" to a tissue bank.

Osteochondral microdamage from valgus bending of the human knee.

PubMed

Meyer, Eric G; Villwock, Mark R; Haut, Roger C

2009-08-01

Valgus bending of the knee is promoted as an anterior cruciate ligament injury mechanism and is associated with a characteristic "footprint" of bone bruising. The hypothesis of this study was that during ligamentous failure caused by valgus bending of the knee, high tibiofemoral contact pressures induce acute osteochondral microdamage. Four knee pairs were loaded in valgus bending until gross injury with or without a tibiofemoral compression pre-load. The peak valgus moment and resultant motions of the knee joint were recorded. Pressure sensitive film documented the magnitude and location of tibiofemoral contact. Cartilage fissures were documented on the tibial plateau, and microcracks in subchondral bone were documented from micro-computed tomography scans. Injuries were to the anterior cruciate ligament in three knees and the medial collateral ligament in seven knees. The mean (standard deviation) peak bending moment at failure was 107 (64)Nm. Valgus bending produced regions of contact on the lateral tibial plateau with average maximum pressures of approximately 30 (8)MPa. Cartilage fissures and subchondral bone microcracks were observed in these regions of high contact pressure. Combined valgus bending and tibiofemoral compression produce slightly higher contact pressures, but do not alter the gross injury pattern from isolated valgus bending experiments. Athletes who sustain a severe valgus knee bending moment, may be at risk of acute osteochondral damage especially if the loading mechanism occurs with a significant tibiofemoral compression component.

Immunoexpression of PPAR-γ and osteocalcin proteins for bone repair of critical-size defects treated with fragmented autogenous abdominal adipose tissue graft.

PubMed

Deliberador, Tatiana Miranda; Giovanini, Allan Fernando; Lopes, Tertuliano Ricardo; Zielak, João César; Moro, Alexandre; Baratto Filho, Flares; Santos, Felipe Rychuv; Storrer, Carmen L Mueller

2014-01-01

Immunoexpression of PPAR-γ and osteocalcin proteins was evaluated for bone repair of critical-size defects (CSDs), created in rat calvaria (n=42) and treated with fragmented abdominal autogenous adipose tissue graft. Three groups (n=14) were formed: C (control - blood clot), AB (autogenous bone) and AT (fragmented adipose tissue). The groups were divided into subgroups (n=7) for euthanasia at 30 and 90 days. Histological and immunohistochemical analyses were performed. Data were subjected to descriptive statistics (mode). A complete bone closure was observed in Group AB 90 days after surgery. In Group C, repair was achieved by the formation of collagen fiber bundles oriented parallel to the wound surface at both post-surgery periods. In Group AT the type of healing was characterized by dense connective tissue containing collagen fiber bundles arranged amidst the remaining adipose tissue, with rare heterotopic bone formation associated with fibrosis and different types of tissue necrosis. Immunostaining of PPAR-γ was not observed in any specimen from Groups C and AB. In Group AT, the immunostaining of PPAR-γ was more evident 30 days after surgery. Immunostaining of osteocalcin was present in all groups and at both postoperative periods. The fragmented autogenous abdominal adipose tissue graft did not favor the repair of critical-size bone defects created surgically in rat calvaria as evidenced by the positive immunostaining of PPAR-γ protein and the negative immunostaining of osteocalcin in the osteoblast-like cells and bone matrix.

Transplantation of free tibial periosteal grafts for the repair of articular cartilage defect: An experimental study

PubMed Central

Singh, Ravijot; Chauhan, Vijendra; Chauhan, Neena; Sharma, Sansar

2009-01-01

Background: Articular chondrocytes have got a long lifespan but rarely divides after maturity. Thus, an articular cartilage has a limited capacity for repair. Periosteal grafts have chondrogenic potential and have been used to repair defects in the articular cartilage. The purpose of the present study is to investigate the differentiation of free periosteal grafts in the patellofemoral joint where the cambium layer faces the subchondral bone and to investigate the applicability of periosteal grafts in the reconstruction of articular surfaces. Materials and Methods: The study was carried out over a period of 1 year on 25 adult, male Indian rabbits after obtaining permission from the institutional animal ethical committee. A full-thickness osteochondral defect was created by shaving off the whole articular cartilage of the patella of the left knee. The defect thus created was grafted with free periosteal graft. The patella of the right knee was taken as a control where no grafting was done after shaving off the articular cartilage. The first animal was used to study the normal histology of the patellar articular cartilage and periosteum obtained from the medial surface of tibial condyle. Rest 24 animals were subjected to patellectomy, 4 each at serial intervals of 2, 4, 8, 16, 32 and 48 weeks and the patellar articular surfaces were examined macroscopically and histologically. Results: The grafts got adherent to the underlying patellar articular surface at the end of 4 weeks. Microscopically, graft incorporation could be appreciated at 4 weeks. Mesenchymal cells of the cambium layer were seen differentiating into chondrocytes by the end of 4 weeks in four grafts (100%) and they were arranged in a haphazard manner. Till the end of 8 weeks, the cellular arrangement was mostly wooly. At 16 weeks, one graft (25%) had wooly arrangement of chondrocytes and three grafts (75%) had columnar formation of cells. Same percentage was maintained at 32 weeks. Four grafts (100%) at

[Autologous fat grafting in children].

PubMed

Baptista, C; Bertrand, B; Philandrianos, C; Degardin, N; Casanova, D

2016-10-01

Lipofilling or fat grafting transfer is defined as a technique of filling soft tissue by autologous fat grafting. The basic principle of lipofilling is based on a harvest of adipose tissue, followed by a reinjection after treatment. Lipofilling main objective is a volume defect filling, but also improving cutaneous trophicity. Lipofilling specificities among children is mainly based on these indications. Complications of autologous fat grafting among children are the same as those in adults: we distinguish short-term complications (intraoperative and perioperative) and the medium and long-term complications. The harvesting of fat tissue is the main limiting factor of the technique, due to low percentage of body fat of children. Indications of lipofilling among children may be specific or similar to those in adults. There are two types of indications: cosmetic, in which the aim of lipofilling is correcting a defect density, acquired (iatrogenic, post-traumatic scar) or malformation (otomandibular dysplasia, craniosynostosis, Parry Romberg syndrom, Poland syndrom, pectus excavatum…). The aim of functional indications is correcting a velar insufficiency or lagophthalmos. In the paediatric sector, lipofilling has become an alternative to the conventional techniques, by its reliability, safety, reproducibility, and good results. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The role of plant hormones during grafting.

PubMed

Nanda, Amrit K; Melnyk, Charles W

2018-01-01

For millennia, people have cut and joined different plant tissues together through a process known as grafting. By creating a chimeric organism, desirable properties from two plants combine to enhance disease resistance, abiotic stress tolerance, vigour or facilitate the asexual propagation of plants. In addition, grafting has been extremely informative in science for studying and identifying the long-distance movement of molecules. Despite its increasing use in horticulture and science, how plants undertake the process of grafting remains elusive. Here, we discuss specifically the role of eight major plant hormones during the wound healing and vascular formation process, two phenomena involved in grafting. We furthermore present the roles of these hormones during graft formation and highlight knowledge gaps and future areas of interest for the field of grafting biology.

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.

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

Protective constriction of coronary vein grafts with knitted nitinol

PubMed Central

Moodley, Loven; Franz, Thomas; Human, Paul; Wolf, Michael F.; Bezuidenhout, Deon; Scherman, Jacques; Zilla, Peter

2013-01-01

OBJECTIVES Different flow patterns and shear forces were shown to cause significantly more luminal narrowing and neointimal tissue proliferation in coronary than in infrainguinal vein grafts. As constrictive external mesh support of vein grafts led to the complete suppression of intimal hyperplasia (IH) in infrainguinal grafts, we investigated whether mesh constriction is equally effective in the coronary position. METHODS Eighteen senescent Chacma baboons (28.8 ± 3.6 kg) received aorto-coronary bypass grafts to the left anterior descending artery (LAD). Three groups of saphenous vein grafts were compared: untreated controls (CO); fibrin sealant-sprayed controls (CO + FS) and nitinol mesh-constricted grafts (ME + FS). Meshes consisted of pulse-compliant, knitted nitinol (eight needles; 50 μm wire thickness; 3.4 mm resting inner diameter, ID) spray attached to the vein grafts with FS. After 180 days of implantation, luminal dimensions and IH were analysed using post-explant angiography and macroscopic and histological image analysis. RESULTS At implantation, the calibre mismatch between control grafts and the LAD expressed as cross-sectional quotient (Qc) was pronounced [Qc = 0.21 ± 0.07 (CO) and 0.18 ± 0.05 (CO + FS)]. Mesh constriction resulted in a 29 ± 7% reduction of the outer diameter of the vein grafts from 5.23 ± 0.51 to 3.68 ± 0 mm, significantly reducing the calibre discrepancy to a Qc of 0.41 ± 0.17 (P < 0.02). After 6 months of implantation, explant angiography showed distinct luminal irregularities in control grafts (ID difference between widest and narrowest segment 74 ± 45%), while diameter variations were mild in mesh-constricted grafts. In all control grafts, thick neointimal tissue was present [600 ± 63 μm (CO); 627 ± 204 μm (CO + FS)] as opposed to thin, eccentric layers of 249 ± 83 μm in mesh-constricted grafts (ME + FS; P < 0.002). The total wall thickness had increased by 363 ± 39% (P < 0.00001) in CO and 312 ± 61% (P < 0

A comparative evaluation of subepithelial connective tissue graft (SCTG) versus platelet concentrate graft (PCG) in the treatment of gingival recession using coronally advanced flap technique: A 12-month study

PubMed Central

Kumar, G. Naveen Vital; Murthy, K. Raja Venkatesh

2013-01-01

Objective: The objective of this study was to clinically evaluate and compare the efficacy of platelet concentrate graft (PCG) with that of subepithelial connective tissue graft (SCTG) using a coronally advanced flap technique in the treatment of gingival recession. Materials and Methods: Twelve patients with a total of 24 gingival recession defects were selected and randomly assigned either to experimental site-A (SCTG) or experimental site-B (PCG). The clinical parameters were recorded at baseline up to 12 months post-operatively and compared. Results: The mean vertical recession depth (VRD) statistically significantly decreased from 2.50 ± 0.48 mm to 0.54 ± 0.50 mm with PCG and from 2.75 ± 0.58 mm to 0.54 ± 0.45 mm with SCTG at 12 months. No statistically significant differences between the treatments were found for VRD and clinical attachment level (CAL), while keratinized tissue width (KTW) gain was statistically significant. Conclusion: Both the SCTG and the PCG group resulted in a significant amount of root coverage. The PCG technique was less invasive and required minimal time and clinical maneuver. It resulted in superior aesthetic outcome and lower post-surgical discomfort at the 12 months follow-up. PMID:24554889

Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: gross morphology and histology.

PubMed

Sánchez, Mikel; Anitua, Eduardo; Azofra, Juan; Prado, Roberto; Muruzabal, Francisco; Andia, Isabel

2010-04-01

To investigate whether the application of a particular platelet-rich plasma preparation rich in growth factors (PRGF) during anterior cruciate ligament (ACL) surgery gives a potential advantage for better tendon graft ligamentization. This study included 37 volunteers who underwent either conventional (control group, n = 15) or PRGF-assisted (n = 22) ACL reconstruction with an autogenous hamstring and required second-look arthroscopy to remove hardware or loose bodies, treat meniscal tears or plica syndrome, or resect cyclops lesions at 6 to 24 months after ACL surgery. The gross morphologies of the grafts were evaluated on second-look arthroscopy by use of the full arthroscopic score (0 to 4 points) to evaluate graft thickness and apparent tension (0 to 2 points) plus synovial coverage (0 to 2 points). At the same time, biopsy specimens were harvested uniformly from the grafted tendons. In these specimens the histologic transformation of the tendon graft to ACL-like tissue was evaluated by use of the Ligament Tissue Maturity Index, and a score to assess the progression of new connective tissue enveloping the graft was created by use of 3 criteria previously used to characterize changes during ligament healing: cellularity, vascularity, and collagen properties. The overall arthroscopic evaluation of PRGF-treated grafts showed an excellent rating in 57.1% of the knees (score of 4) and a fair rating in 42.9% (score of 2 or 3). In contrast, evaluation of untreated grafts showed an excellent rating in 33.3% of the knees, a fair rating in 46.7%, and a poor rating in 20% (score of 0 or 1). Overall, arthroscopic evaluations were not statistically different between PRGF and control groups (P = .051). PRGF treatment influenced the histologic characteristics of the tendon graft, resulting in tissue that was more mature than in controls (P = .024). Histologically evident newly formed connective tissue enveloping the graft was present in 77.3% of PRGF-treated grafts and 40% of

Survival of Skin Graft between Transgenic Cloned Dogs and Non-Transgenic Cloned Dogs

PubMed Central

Kim, Geon A; Oh, Hyun Ju; Kim, Min Jung; Jo, Young Kwang; Choi, Jin; Park, Jung Eun; Park, Eun Jung; Lim, Sang Hyun; Yoon, Byung Il; Kang, Sung Keun; Jang, Goo; Lee, Byeong Chun

2014-01-01

Whereas it has been assumed that genetically modified tissues or cells derived from somatic cell nuclear transfer (SCNT) should be accepted by a host of the same species, their immune compatibility has not been extensively explored. To identify acceptance of SCNT-derived cells or tissues, skin grafts were performed between cloned dogs that were identical except for their mitochondrial DNA (mtDNA) haplotypes and foreign gene. We showed here that differences in mtDNA haplotypes and genetic modification did not elicit immune responses in these dogs: 1) skin tissues from genetically-modified cloned dogs were successfully transplanted into genetically-modified cloned dogs with different mtDNA haplotype under three successive grafts over 63 days; and 2) non-transgenic cloned tissues were accepted into transgenic cloned syngeneic recipients with different mtDNA haplotypes and vice versa under two successive grafts over 63 days. In addition, expression of the inserted gene was maintained, being functional without eliciting graft rejection. In conclusion, these results show that transplanting genetically-modified tissues into normal, syngeneic or genetically-modified recipient dogs with different mtDNA haplotypes do not elicit skin graft rejection or affect expression of the inserted gene. Therefore, therapeutically valuable tissue derived from SCNT with genetic modification might be used safely in clinical applications for patients with diseased tissues. PMID:25372489

Osteochondral lesion of the talus in a recreational athlete: a case report

PubMed Central

deGraauw, Chris

1999-01-01

A 23-year-old recreational male athlete presented with intermittent pain of three weeks duration, localized to the left ankle. Pain was aggravated by walking, although his symptoms had not affected the patient’s jogging activity which was performed three times per week. Past history revealed an inversion sprain of the left ankle, sustained fifteen months previously. Examination showed mild swelling anterior to the ankle mortise joint while other tests including range of motion, strength and motion palpation of specific joints of the ankle were noted to be unremarkable. Radiographic findings revealed a defect in the medial aspect of the talus. An orthopaedic referral was made for further evaluation. Tomography revealed a Grade III osteochondral lesion of the talus. It was determined that follow-up views be taken in three months to demonstrate if the lesion was progressing or healing. Within the three month period, activity modifications and modalities for pain control were indicated. Surgery was considered a reasonable option should conservative measures fail. The present case illustrates an osteochondral lesion of the talus, a condition which has not previously been reported in the chiropractic literature. A review of the pertinent orthopaedic literature has indicated an average delay of three years in diagnosing the existence of this lesion. Although considered rare, the diagnostic frequency of the condition appears to be on the rise due to increased awareness and the use of bone and CT scans. The osteochondral lesion of the talus deserves particular consideration by practitioners working with athletes due to its higher incidence within this group. This diagnosis should be considered in patients presenting with chronic ankle pain particularly when a history of an inversion sprain exists. The purpose of this report is to increase awareness of this condition, and review diagnosis and management strategies. ImagesFigure 1Figure 2

Steroid-induced femoral head osteonecrosis in immune thrombocytopenia treatment with osteochondral autograft transplantation.

PubMed

Fotopoulos, Vasileios Ch; Mouzopoulos, George; Floros, Themistoklis; Tzurbakis, Matthaios

2015-09-01

Osteonecrosis of the femoral head is a devastating complication of steroid administration and has rarely been observed in the treatment of immune thrombocytopenia. The treatment of osteochondral defects in advanced stages of avascular necrosis (AVN), characterized by collapse of the subchondral bone, remains an unsolved burden in orthopedic surgery. In this report, we present a case of a 19-year-old female that was admitted in the Emergency Department with walking disability and painful hip joint movement due to steroid-induced femoral head osteonecrosis. Two years before she was diagnosed with immune thrombocytopenia, for which she received pulse steroid therapy with high dose of dexamethasone and underwent a splenectomy. This case report is the first to describe the use of osteochondral autograft transplantation as a treatment of steroid-induced AVN of the femoral head due to immune thrombocytopenia at the age of 19 years with very good clinical and radiological results 3 years postoperatively.

Eye Bank-Prepared Femtosecond Laser-Assisted Automated Descemet Membrane Endothelial Grafts.

PubMed

Jardine, Griffin J; Holiman, Jeffrey D; Galloway, Joshua D; Stoeger, Christopher G; Chamberlain, Winston D

2015-07-01

The aim of this study was to investigate the use of a femtosecond laser (FL) in the eye bank preparation of corneas for Descemet membrane (DM) automated endothelial keratoplasty (fDMAEK) and to compare endothelial cell death in graft preparations between fDMAEK, Descemet stripping endothelial keratoplasty (DSEK), and DM endothelial keratoplasty (DMEK). Twenty cadaveric tissues were used to test the fDMAEK method. A 9.0-mm-diameter lamellar incision was made using the FL with a 6.0-mm perpendicular anterior ring cut that enabled a stromal rim by acting as a venting incision for bubble expansion. DM was pneumodissected off the central 6.0 mm of the tissue. The fDMAEK grafts were trephined and stained with a viability dye, calcein AM. The entire stained endothelial surface was digitally captured and the endothelial cell loss (ECL) was calculated using trainable segmentation software. For comparison, a series of 6 DSEK grafts and 8 DMEK grafts were created and analyzed. Six of 20 tissues (30%) were lost during fDMAEK preparation. In the 14 successful tissues, the average ECL was 30.4% [95% confidence interval (CI), 25.3-35.6] compared with 21.1% (95% CI, 13.2-28.9, P = 0.09) in the 6 DSEK grafts and 22.5% (95% CI, 18.0-27.0, P = 0.04) in the 8 DMEK grafts. FLs are useful in preparing DMAEK tissue at the eye bank and may promote predictable and precise big bubbles and stromal rims. The fDMAEK preparation success improved with experience and laser adjustments. In fDMAEK, the ECL is higher than was previously reported in DMEK and DSEK, likely due to greater tissue manipulation, although not significantly higher than DSEK controls.

Acellular vascular matrix grafts from human placenta chorion: Impact of ECM preservation on graft characteristics, protein composition and in vivo performance.

PubMed

Schneider, Karl H; Enayati, Marjan; Grasl, Christian; Walter, Ingrid; Budinsky, Lubos; Zebic, Gabriel; Kaun, Christoph; Wagner, Anja; Kratochwill, Klaus; Redl, Heinz; Teuschl, Andreas H; Podesser, Bruno K; Bergmeister, Helga

2018-05-29

Small diameter vascular grafts from human placenta, decellularized with either Triton X-100 (Triton) or SDS and crosslinked with heparin were constructed and characterized. Graft biochemical properties, residual DNA, and protein composition were evaluated to compare the effect of the two detergents on graft matrix composition and structural alterations. Biocompatibility was tested in vitro by culturing the grafts with primary human macrophages and in vivo by subcutaneous implantation of graft conduits (n = 7 per group) into the flanks of nude rats. Subsequently, graft performance was evaluated using an aortic implantation model in Sprague Dawley rats (one month, n = 14). In situ graft imaging was performed using MRI angiography. Retrieved specimens were analyzed by electromyography, scanning electron microscopy, histology and immunohistochemistry to evaluate cell migration and the degree of functional tissue remodeling. Both decellularization methods resulted in grafts of excellent biocompatibility in vitro and in vivo, with low immunogenic potential. Proteomic data revealed removal of cytoplasmic proteins with relative enrichment of ECM proteins in decelluarized specimens of both groups. Noteworthy, LC-Mass Spectrometry analysis revealed that 16 proteins were exclusively preserved in Triton decellularized specimens in comparison to SDS-treated specimens. Aortic grafts showed high patency rates, no signs of thrombus formation, aneurysms or rupture. Conduits of both groups revealed tissue-specific cell migration indicative of functional remodeling. This study strongly suggests that decellularized allogenic grafts from the human placenta have the potential to be used as vascular replacement materials. Both detergents produced grafts with low residual immunogenicity and appropriate mechanical properties. Observed differences in graft characteristics due to preservation method had no impact on successful in vivo performance in the rodent model. Copyright �

Neointimal hyperplasia on a cell-seeded polytetrafluoroethylene graft is promoted by transfer of tissue plasminogen activator gene and inhibited by transfer of nitric oxide synthase gene.

PubMed

Yu, Hong; Dai, Wangde; Yang, Zhe; Romaguera, Rita L; Kirkman, Paul; Rowe, Vincent L

2005-01-01

The objective of this study was to examine the effect of tissue plasminogen activator (tPA) and endothelial nitric oxide synthase (eNOS) on thrombosis and neointimal hyperplasia on a polytetrafluoroethylene (PTFE) graft seeded with smooth muscle cells (SMCs). SMCs retrovirally transduced with tPA and eNOS genes were seeded on PTFE grafts and then implanted into the infrarenal rabbit aorta. Thrombosis and neointimal hyperplasia on the grafts were examined after 30 and 100 days of implantation. At 30 days of implantation, thrombus was observed on the luminal surface of both unseeded and SMC seeded control grafts, whereas grafts seeded with SMCs secreting tPA were nearly free of thrombus. At 100 days, the neointima on grafts seeded with tPA transduced SMCs was significantly thicker (925 +/- 150 microm, n = 5) than neointima on the other grafts (range, 132 to 374 microm; P < .001). Neointima thickness on grafts seeded with eNOS transduced SMCs (154 +/- 27 microm) was similar to that of unseeded grafts (132 +/- 16 microm, P > .05); both were thinner than those on grafts seeded with SMCs transduced with only lacZ gene (287 +/- 35 microm). The ratio of seeded cells in the neointima was significantly higher on SMC/tPA grafts (46% +/- 8%) than SMC/NOS grafts (21% +/- 6%, P < .05), indicating tPA transduced cells proliferated more than eNOS transduced cells. Engineered tPA expression in seeded SMCs causes significantly more neointimal hyperplasia, despite the favorable inhibition of luminal thrombus. eNOS expression in the seeded cells inhibits neointimal hyperplasia.

Percutaneous CT-Guided Treatment of Osteochondritis Dissecans of the Sacroiliac Joint

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

Becce, Fabio, E-mail: fabio.becce@chuv.ch; Mouhsine, Elyazid; Mosimann, Pascal John

2012-08-15

Osteochondritis dissecans (OCD) is a joint disorder that affects the articular cartilage and subchondral bone, most commonly at the knee. OCD of the sacroiliac joint is extremely rare. Management of OCD remains controversial, and surgery is often needed, especially when conservative treatment fails. We present a rare case of OCD involving the left sacroiliac joint successfully treated by percutaneous computed tomography-guided retrograde drilling and debridement.

Subpedicle connective tissue graft versus guided tissue regeneration with bioabsorbable membrane in the treatment of human gingival recession defects.

PubMed

Trombelli, L; Scabbia, A; Tatakis, D N; Calura, G

1998-11-01

The purpose of the present clinical study was to evaluate the effect of guided tissue regeneration (GTR) in comparison to subpedicle connective tissue graft (SCTG) in the treatment of gingival recession defects. A total of 12 patients, each contributing a pair of Miller's Class I or II buccal gingival recessions, was treated. According to a randomization list, one defect in each patient received a polyglycolide/lactide bioabsorbable membrane, while the paired defect received a SCTG. Treatment effect was evaluated 6 months postsurgery. Clinical recordings included full-mouth and defect-specific oral hygiene standards and gingival health, recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), and keratinized tissue width (KT). Mean RD significantly decreased from 3.1 mm presurgery to 1.5 mm at 6 months postsurgery for the GTR group (48% root coverage), and from 3.0 mm to 0.5 mm for the SCTG group (81% root coverage). RD reduction and root coverage were significantly greater in SCTG group compared to GTR group. Mean CAL gain amounted to 1.7 mm for the GTR group, and 2.3 mm in the SCTG group. No significant differences in PD changes were observed within and between groups. KT increased significantly from presurgery for both treatment groups, however gingival augmentation was significantly greater in the SCTG group compared to GTR group. Results indicate that: 1) treatment of human gingival recession defects by means of both GTR and SCTG procedures results in clinically and statistically significant improvement of the soft tissue conditions of the defect; and 2) treatment outcome was significantly better following SCTG compared to GTR in terms of recession depth reduction, root coverage, and keratinized tissue increase.

Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

PubMed Central

van Bergen, Christiaan JA; Blankevoort, Leendert; de Haan, Rob J; Sierevelt, Inger N; Meuffels, Duncan E; d'Hooghe, Pieter RN; Krips, Rover; van Damme, Geert; van Dijk, C Niek

2009-01-01

Background Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society – Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration Netherlands Trial Register (NTR1636) PMID:19591674

Osteochondral lesions in distal tarsal joints of Icelandic horses reveal strong associations between hyaline and calcified cartilage abnormalities.

PubMed

Ley, C J; Ekman, S; Hansson, K; Björnsdóttir, S; Boyde, A

2014-03-25

Osteochondral lesions in the joints of the distal tarsal region of young Icelandic horses provide a natural model for the early stages of osteoarthritis (OA) in low-motion joints. We describe and characterise mineralised and non-mineralised osteochondral lesions in left distal tarsal region joint specimens from twenty-two 30 ±1 month-old Icelandic horses. Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including, importantly, iodine staining) and three-dimensional microcomputed tomography were used on specimens obtained with guidance from clinical imaging. Lesion-types were described and classified into groups according to morphological features. Their locations in the hyaline articular cartilage (HAC), articular calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues were identified and their frequency in the joints recorded. Associations and correlations between lesion-types were investigated for centrodistal joints only. In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advance had significant associations and strong correlations. These lesion-types had moderate to high frequency in centrodistal joints but low frequencies in tarsometatarsal and talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant associations with other lesion-types in the centrodistal joints but high frequency in both the centrodistal and tarsometatarsal joints. The frequency of SCB lesion-types in all joints was low. Hypermineralised infill phase lesion-types were detected. Our results emphasise close associations between HAC and ACC lesions in equine centrodistal joints and the importance of ACC lesions in the development of OA in low-motion compression-loaded equine joints.

Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting

PubMed Central

Alexander, Robert W; Harrell, David B

2013-01-01

Objectives Provide background for use of acquiring autologous adipose tissue as a tissue graft and source of adult progenitor cells for use in cosmetic plastic surgery. Discuss the background and mechanisms of action of closed syringe vacuum lipoaspiration, with emphasis on accessing adipose-derived mesenchymal/stromal cells and the stromal vascular fraction (SVF) for use in aesthetic, structural reconstruction and regenerative applications. Explain a proven protocol for acquiring high-quality autologous fat grafts (AFG) with use of disposable, microcannula systems. Design Explain the components and advantage of use of the patented super luer-lock and microcannulas system for use with the closed-syringe system. A sequential explanation of equipment selection for minimally traumatic lipoaspiration in small volumes is presented, including use of blunt injection cannulas to reduce risk of embolism. Results Thousands of AFG have proven safe and efficacious for lipoaspiration techniques for large and small structural fat grafting procedures. The importance and advantages of gentle harvesting of the adipose tissue complex has become very clear in the past 5 years. The closed-syringe system offers a minimally invasive, gentle system with which to mobilize subdermal fat tissues in a suspension form. Resulting total nuclear counting of undifferentiated cells of the adipose-derived -SVF suggests that the yield achieved is better than use of always-on, constant mechanical pump applied vacuum systems. Conclusion Use of a closed-syringe lipoaspiration system featuring disposable microcannulas offers a safe and effective means of harvesting small volumes of nonmanipulated adipose tissues and its accompanying progenitor cells within the SVF. Closed syringes and microcannulas are available as safe, sterile, disposable, compact systems for acquiring high-quality AFG. Presented is a detailed, step-by-step, proven protocol for performing quality autologous structural adipose

Three-dimensional polycaprolactone-hydroxyapatite scaffolds combined with bone marrow cells for cartilage tissue engineering.

PubMed

Wei, Bo; Yao, Qingqiang; Guo, Yang; Mao, Fengyong; Liu, Shuai; Xu, Yan; Wang, Liming

2015-08-01

The goal of this study was to investigate the chondrogenic potential of three-dimensional polycaprolactone-hydroxyapatite (PCL-HA) scaffolds loaded with bone marrow cells in vitro and the effect of PCL-HA scaffolds on osteochondral repair in vivo. Here, bone marrow was added to the prepared PCL-HA scaffolds and cultured in chondrogenic medium for 10 weeks. Osteochondral defects were created in the trochlear groove of 29 knees in 17 New Zealand white rabbits, which were then divided into four groups that underwent: implantation of PCL-HA scaffolds (left knee, n = 17; Group 1), microfracture (right knee, n = 6; Group 2), autologous osteochondral transplantation (right knee, n = 6; Group 3), and no treatment (right knee, n = 5; Control). Extracellular matrix produced by bone marrow cells covered the surface and filled the pores of PCL-HA scaffolds after 10 weeks in culture. Moreover, many cell-laden cartilage lacunae were observed, and cartilage matrix was concentrated in the PCL-HA scaffolds. After a 12-week repair period, Group 1 showed excellent vertical and lateral integration with host bone, but incomplete cartilage regeneration and matrix accumulation. An uneven surface of regenerated cartilage and reduced distribution of cartilage matrix were observed in Group 2. In addition, abnormal bone growth and unstable integration between repaired and host tissues were detected. For Group 3, the integration between transplanted and host cartilage was interrupted. Our findings indicate that the PCL-HA scaffolds loaded with bone marrow cells improved chondrogenesis in vitro and implantation of PCL-HA scaffolds for osteochondral repairenhanced integration with host bone. However, cartilage regeneration remained unsatisfactory. The addition of trophic factors or the use of precultured cell-PCL-HA constructs for accelerated osteochondral repair requires further investigation. © The Author(s) 2015.

Utility of Cartilage Grafts Wrapped With Amniotic Membrane in Dorsal Nasal Augmentation.

PubMed

Atespare, Altay; Kara, Hakan; Ilter, Erdin; Boyaci, Zerrin; Çelik, Öner; Midi, Ahmet

2016-06-01

The success of rhinoplasty may be compromised with postoperative problems like rough and rigid nasal dorsum. Biological grafts or alloplastic materials are required to hurdle and correct nasal dorsal deformities and also irregularities. The purpose of this experimental study was to compare pure cartilage graft, cartilage graft wrapped in amniotic membrane, and diced cartilage grafts wrapped in amniotic membrane for soft tissue augmentation. All grafts were transplanted through a subcutaneous tunnel created in the nasal dorsum of 18 rats, 6 in each group. After 3 months follow-up, the histopathological changes in all groups were evaluated by light microscopy and volumetric measurements. With regard to cartilage viability, cartilage wrapped in amniotic membrane had a higher success rate than pure cartilage graft. Also, a further increased success rate was found in the diced group. In the soft tissue augmentation after rhinoplasty surgery, especially diced cartilage wrapped in amniotic membrane keeps the graft viable and adjoined.

Plant grafting: new mechanisms, evolutionary implications.

PubMed

Goldschmidt, Eliezer E

2014-01-01

Grafting, an old plant propagation practice, is still widely used with fruit trees and in recent decades also with vegetables. Taxonomic proximity is a general prerequisite for successful graft-take and long-term survival of the grafted, composite plant. However, the mechanisms underlying interspecific graft incompatibility are as yet insufficiently understood. Hormonal signals, auxin in particular, are believed to play an important role in the wound healing and vascular regeneration within the graft union zone. Incomplete and convoluted vascular connections impede the vital upward and downward whole plant transfer routes. Long-distance protein, mRNA and small RNA graft-transmissible signals currently emerge as novel mechanisms which regulate nutritional and developmental root/top relations and may play a pivotal role in grafting physiology. Grafting also has significant pathogenic projections. On one hand, stock to scion mechanical contact enables the spread of diseases, even without a complete graft union. But, on the other hand, grafting onto resistant rootstocks serves as a principal tool in the management of fruit tree plagues and vegetable soil-borne diseases. The 'graft hybrid' historic controversy has not yet been resolved. Recent evidence suggests that epigenetic modification of DNA-methylation patterns may account for certain graft-transformation phenomena. Root grafting is a wide spread natural phenomenon; both intraspecific and interspecific root grafts have been recorded. Root grafts have an evolutionary role in the survival of storm-hit forest stands as well as in the spread of devastating diseases. A more fundamental evolutionary role is hinted by recent findings that demonstrate plastid and nuclear genome transfer between distinct Nicotiana species in the graft union zone, within a tissue culture system. This has led to the formation of alloploid cells that, under laboratory conditions, gave rise to a novel, alloploid Nicotiana species, indicating

Plant grafting: new mechanisms, evolutionary implications

PubMed Central

Goldschmidt, Eliezer E.

2014-01-01

Grafting, an old plant propagation practice, is still widely used with fruit trees and in recent decades also with vegetables. Taxonomic proximity is a general prerequisite for successful graft-take and long-term survival of the grafted, composite plant. However, the mechanisms underlying interspecific graft incompatibility are as yet insufficiently understood. Hormonal signals, auxin in particular, are believed to play an important role in the wound healing and vascular regeneration within the graft union zone. Incomplete and convoluted vascular connections impede the vital upward and downward whole plant transfer routes. Long-distance protein, mRNA and small RNA graft-transmissible signals currently emerge as novel mechanisms which regulate nutritional and developmental root/top relations and may play a pivotal role in grafting physiology. Grafting also has significant pathogenic projections. On one hand, stock to scion mechanical contact enables the spread of diseases, even without a complete graft union. But, on the other hand, grafting onto resistant rootstocks serves as a principal tool in the management of fruit tree plagues and vegetable soil-borne diseases. The ‘graft hybrid’ historic controversy has not yet been resolved. Recent evidence suggests that epigenetic modification of DNA-methylation patterns may account for certain graft-transformation phenomena. Root grafting is a wide spread natural phenomenon; both intraspecific and interspecific root grafts have been recorded. Root grafts have an evolutionary role in the survival of storm-hit forest stands as well as in the spread of devastating diseases. A more fundamental evolutionary role is hinted by recent findings that demonstrate plastid and nuclear genome transfer between distinct Nicotiana species in the graft union zone, within a tissue culture system. This has led to the formation of alloploid cells that, under laboratory conditions, gave rise to a novel, alloploid Nicotiana species

A Ringed Fascia Lata Graft Without Peritendinous Areolar Tissue Encircling the Levator Veli Palatini and Superior Pharyngeal Constrictor Muscles Gradually Shrinks to Reduce Velopharyngeal Incompetence, Functioning as an Intravelar Palatal Lift

PubMed Central

Fujita, Kenya; Matsuo, Kiyoshi; Yuzuriha, Shunsuke

2013-01-01

Introduction: We have previously reported that fascia lata grafts with peritendinous areolar tissue used to treat severe congenital blepharoptosis gradually shrink within 6 weeks postoperatively and maintain long-term shrinkage of 15.5% on average. Accordingly, it seemed possible that a fascia lata graft without peritendinous areolar tissue would shrink more than the one with peritendinous areolar tissue in a clinical setting. We evaluated this possibility in a patient with Klippel-Feil syndrome having postoperative deep atonic nasopharynx. Methods: In combination with intravelar veloplasty and palatal lengthening with modified bilateral buccinator sandwich pushback, a ringed fascia lata without peritendinous areolar tissue encircling the levator veli palatini and superior constrictor muscles was grafted to cure severe velopharyngeal incompetence. Results: Obstructive sleep apnea did not occur following surgery. Pharyngoscopy, videofluoroscopy, and nasometry showed no amelioration of velopharyngeal incompetence at 1 month postoperatively, but marked velopharyngeal incompetence reduction was evident at 4 months and 2 years after surgery. Conclusions: The extended recovery period suggests that the anticipated postoperative shrinkage of the ringed fascia lata without peritendinous areolar tissue played a more prominent role than intravelar veloplasty and palatal lengthening, which posteroinferiorly elongated the atonic soft palate. Although the pharyngeal flap procedure is the most popular technique for treatment of velopharyngeal incompetence, it is sometimes accompanied by respiratory complications. Thus, the gradual postoperative shrinkage of a ringed fascia lata graft encircling the velopharyngeal muscles functions as an intravelar palatal lift and may be an additional surgical method with less respiratory complications to narrow atonic nasopharyngeal port. PMID:23814637

A ringed fascia lata graft without peritendinous areolar tissue encircling the levator veli palatini and superior pharyngeal constrictor muscles gradually shrinks to reduce velopharyngeal incompetence, functioning as an intravelar palatal lift.

PubMed

Fujita, Kenya; Matsuo, Kiyoshi; Yuzuriha, Shunsuke

2013-01-01

We have previously reported that fascia lata grafts with peritendinous areolar tissue used to treat severe congenital blepharoptosis gradually shrink within 6 weeks postoperatively and maintain long-term shrinkage of 15.5% on average. Accordingly, it seemed possible that a fascia lata graft without peritendinous areolar tissue would shrink more than the one with peritendinous areolar tissue in a clinical setting. We evaluated this possibility in a patient with Klippel-Feil syndrome having postoperative deep atonic nasopharynx. In combination with intravelar veloplasty and palatal lengthening with modified bilateral buccinator sandwich pushback, a ringed fascia lata without peritendinous areolar tissue encircling the levator veli palatini and superior constrictor muscles was grafted to cure severe velopharyngeal incompetence. Obstructive sleep apnea did not occur following surgery. Pharyngoscopy, videofluoroscopy, and nasometry showed no amelioration of velopharyngeal incompetence at 1 month postoperatively, but marked velopharyngeal incompetence reduction was evident at 4 months and 2 years after surgery. The extended recovery period suggests that the anticipated postoperative shrinkage of the ringed fascia lata without peritendinous areolar tissue played a more prominent role than intravelar veloplasty and palatal lengthening, which posteroinferiorly elongated the atonic soft palate. Although the pharyngeal flap procedure is the most popular technique for treatment of velopharyngeal incompetence, it is sometimes accompanied by respiratory complications. Thus, the gradual postoperative shrinkage of a ringed fascia lata graft encircling the velopharyngeal muscles functions as an intravelar palatal lift and may be an additional surgical method with less respiratory complications to narrow atonic nasopharyngeal port.

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

Fabrication of custom-shaped grafts for cartilage regeneration.

PubMed

Koo, Seungbum; Hargreaves, Brian A; Gold, Garry E; Dragoo, Jason L

2010-10-01

to create a custom-shaped graft through 3D tissue shape reconstruction and rapid-prototype molding methods using MRI data, and to test the accuracy of the custom-shaped graft against the original anatomical defect. An iatrogenic defect on the distal femur was identified with a 1.5 Tesla MRI and its shape was reconstructed into a three-dimensional (3D) computer model by processing the 3D MRI data. First, the accuracy of the MRI-derived 3D model was tested against a laser-scan based 3D model of the defect. A custom-shaped polyurethane graft was fabricated from the laser-scan based 3D model by creating custom molds through computer aided design and rapid-prototyping methods. The polyurethane tissue was laser-scanned again to calculate the accuracy of this process compared to the original defect. The volumes of the defect models from MRI and laser-scan were 537 mm3 and 405 mm3, respectively, implying that the MRI model was 33% larger than the laser-scan model. The average (±SD) distance deviation of the exterior surface of the MRI model from the laser-scan model was 0.4 ± 0.4 mm. The custom-shaped tissue created from the molds was qualitatively very similar to the original shape of the defect. The volume of the custom-shaped cartilage tissue was 463 mm3 which was 15% larger than the laser-scan model. The average (±SD) distance deviation between the two models was 0.04 ± 0.19 mm. This investigation proves the concept that custom-shaped engineered grafts can be fabricated from standard sequence 3-D MRI data with the use of CAD and rapid-prototyping technology. The accuracy of this technology may help solve the interfacial problem between native cartilage and graft, if the grafts are custom made for the specific defect. The major source of error in fabricating a 3D custom-shaped cartilage graft appears to be the accuracy of a MRI data itself; however, the precision of the model is expected to increase by the utilization of advanced MR sequences with higher magnet

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

Indications and results of omental pedicle grafts in oncology

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

Petit, J.Y.; Lacour, J.; Margulis, A.

1979-12-01

Sixty omental grafts were performed in our department. Sixty-two percent concerned breast cancer patients. Other grafts were undertaken for other cancers: head and neck, gynecologic urologic and intestinal, skin and soft tissue tumors. These grafts were indicated for radionecrosis or chemonecrosis in 33 cases and for cancer recurrence in 26 cases (among whom 24 were previously irradiated). Only one graft was performed for lymphoedema treatment. Overall, fifty four patients (83.5%) had successful grafts, and six (16.5%) had graft failures. According to the treated lesion we obtained 82% of successful treatment among patients treated for radio or chemonecrosis, and 92% formore » patients treated for recurrences.« less

Foreskin-isolated keratinocytes provide successful extemporaneous autologous paediatric skin grafts.

PubMed

Mcheik, Jiad N; Barrault, Christine; Pedretti, Nathalie; Garnier, Julien; Juchaux, Franck; Levard, Guillaume; Morel, Franck; Lecron, Jean-Claude; Bernard, François-Xavier

2016-03-01

Severe burns in children are conventionally treated with split-thickness skin autografts or epidermal sheets. However, neither early complete healing nor quality of epithelialization is satisfactory. An alternative approach is to graft isolated keratinocytes. We evaluated paediatric foreskin and auricular skin as donor sources, autologous keratinocyte transplantation, and compared the graft efficiency to the in vitro capacities of isolated keratinocytes to divide and reconstitute epidermal tissue. Keratinocytes were isolated from surgical samples by enzymatic digestion. Living cell recovery, in vitro proliferation and epidermal reconstruction capacities were evaluated. Differentiation status was analysed, using qRT-PCR and immunolabelling. Eleven children were grafted with foreskin-derived (boys) or auricular (girls) keratinocyte suspensions dripped onto deep severe burns. The aesthetic and functional quality of epithelialization was monitored in a standardized way. Foreskin keratinocyte graft in male children provides for the re-epithelialization of partial deep severe burns and accelerates wound healing, thus allowing successful wound closure, and improves the quality of scars. In accordance, in vitro studies have revealed a high yield of living keratinocyte recovery from foreskin and their potential in terms of regeneration and differentiation. We report a successful method for grafting paediatric males presenting large severe burns through direct spreading of autologous foreskin keratinocytes. This alternative method is easy to implement, improves the quality of skin and minimizes associated donor site morbidity. In vitro studies have highlighted the potential of foreskin tissue for graft applications and could help in tissue selection with the prospect of grafting burns for girls. Copyright © 2013 John Wiley & Sons, Ltd.

Excellent Aesthetic and Functional Outcome After Fractionated Carbon Dioxide Laser Skin Graft Revision Surgery: Case Report and Review of Laser Skin Graft Revision Techniques.

PubMed

Ho, Derek; Jagdeo, Jared

2015-11-01

Skin grafts are utilized in dermatology to reconstruct a defect secondary to surgery or trauma of the skin. Common indications for skin grafts include surgical removal of cutaneous malignancies, replacement of tissue after burns or lacerations, and hair transplantation in alopecia. Skin grafts may be cosmetically displeasing, functionally limiting, and significantly impact patient's quality-of-life. There is limited published data regarding skin graft revision to enhance aesthetics and function. Here, we present a case demonstrating excellent aesthetic and functional outcome after fractionated carbon dioxide (CO2) laser skin graft revision surgery and review of the medical literature on laser skin graft revision techniques.

Bioactive and metal uptake studies of carboxymethyl chitosan-graft-D-glucuronic acid membranes for tissue engineering and environmental applications.

PubMed

Jayakumar, R; Rajkumar, M; Freitas, H; Sudheesh Kumar, P T; Nair, S V; Furuike, T; Tamura, H

2009-08-01

Carboxymethyl chitosan-graft-D-glucuronic acid (CMCS-g-D-GA) was prepared by grafting D-GA onto CMCS in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and then the membranes were made from it. In this work, the bioactivity studies of CMCS-g-D-GA membranes were carried out and then characterized by SEM, CLSM, XRD and FT-IR. The CMCS-g-D-GA membranes were found to be bioactive. The adsorption of Ni2+, Zn2+ and Cu2+ ions onto CMCS-g-D-GA membranes has also been investigated. The maximum adsorption capacity of CMCS-g-D-GA for Ni2+, Zn2+ and Cu2+ was found to be 57, 56.4 and 70.2 mg/g, respectively. Hence, these membranes were useful for tissue engineering, environmental and water purification applications.

Cartilage Morphological and Histological Findings After Reconstruction of the Glenoid With an Iliac Crest Bone Graft.

PubMed

Auffarth, Alexander; Resch, Herbert; Matis, Nicholas; Hudelmaier, Martin; Wirth, Wolfgang; Forstner, Rosemarie; Neureiter, Daniel; Traweger, Andreas; Moroder, Philipp

2018-04-01

The J-bone graft is presumably representative of iliac crest bone grafts in general and allows anatomic glenoid reconstruction in cases of bone defects due to recurrent traumatic anterior shoulder dislocations. As a side effect, these grafts have been observed to be covered by some soft, cartilage-like tissue when arthroscopy has been indicated after such procedures. To evaluate the soft tissue covering of J-bone grafts by use of magnetic resonance imaging (MRI) and histological analysis. Case series; Level of evidence, 4. Patients underwent MRI at 1 year after the J-bone graft procedures. Radiological data were digitally processed and evaluated by segmentation of axial images. Independent from the MRI analysis, 2 biopsy specimens of J-bone grafts were harvested for descriptive histological analysis. Segmentation of the images revealed that all grafts were covered by soft tissue. This layer had an average thickness of 0.87 mm compared with 1.96 mm at the adjacent native glenoid. Of the 2 biopsy specimens, one exhibited evident hyaline-like cartilage and the other presented patches of chondrocytes embedded in a glycosaminoglycan-rich extracellular matrix. J-bone grafts are covered by soft tissue that can differentiate into fibrous and potentially hyaline cartilage. This feature may prove beneficial for delaying the onset of dislocation arthropathy of the shoulder.

Treatment of Gingival Recessions Associated to Cervical Abrasion Lesions with Subepithelial Connective Tissue Graft: A Case Report

PubMed Central

Deliberador, Tatiana M.; Bosco, Alvaro F.; Martins, Thiago M.; Nagata, Maria J. H.

2009-01-01

Extensive gingival recessions associated with cervical abrasions are common among the population. Several different surgical and/or restorative therapies have been proposed to correct these lesions. This manuscript reports the treatment of multiple gingival recessions associated to cervical abrasions. The procedure involved the utilization of subepithelial connective tissue graft (SCTG) combined with coronally advanced flap onto a previously restored root surface. At the postoperative follow-up visits, the success of the restorative/surgical approach was confirmed by the absence of bleeding to probing and periodontal pockets as well as presence of gingival tissue with normal color, texture and contouring. After 18 months of follow-up, the clinical conditions are stable with satisfactory root coverage and periodontal health. An excellent esthetical outcome was achieved and the patient is satisfied with case resolution. PMID:19826605

Repair of bone defects in vivo using tissue engineered hypertrophic cartilage grafts produced from nasal chondrocytes.

PubMed

Bardsley, Katie; Kwarciak, Agnieska; Freeman, Christine; Brook, Ian; Hatton, Paul; Crawford, Aileen

2017-01-01

The regeneration of large bone defects remains clinically challenging. The aim of our study was to use a rat model to use nasal chondrocytes to engineer a hypertrophic cartilage tissue which could be remodelled into bone in vivo by endochondral ossification. Primary adult rat nasal chondrocytes were isolated from the nasal septum, the cell numbers expanded in monolayer culture and the cells cultured in vitro on polyglycolic acid scaffolds in chondrogenic medium for culture periods of 5-10 weeks. Hypertrophic differentiation was assessed by determining the temporal expression of key marker genes and proteins involved in hypertrophic cartilage formation. The temporal changes in the genes measured reflected the temporal changes observed in the growth plate. Collagen II gene expression increased 6 fold by day 7 and was then significantly downregulated from day 14 onwards. Conversely, collagen X gene expression was detectable by day 14 and increased 100-fold by day 35. The temporal increase in collagen X expression was mirrored by increases in alkaline phosphatase gene expression which also was detectable by day 14 with a 30-fold increase in gene expression by day 35. Histological and immunohistochemical analysis of the engineered constructs showed increased chondrocyte cell volume (31-45 μm), deposition of collagen X in the extracellular matrix and expression of alkaline phosphatase activity. However, no cartilage mineralisation was observed in in vitro culture of up to 10 weeks. On subcutaneous implantation of the hypertrophic engineered constructs, the grafts became vascularised, cartilage mineralisation occurred and loss of the proteoglycan in the matrix was observed. Implantation of the hypertrophic engineered constructs into a rat cranial defect resulted in angiogenesis, mineralisation and remodelling of the cartilage tissue into bone. Micro-CT analysis indicated that defects which received the engineered hypertrophic constructs showed 38.48% in bone volume

The Architecture of Fat Grafting: What Lies beneath the Surface.

PubMed

Bourne, Debra A; James, Isaac B; Wang, Sheri S; Marra, Kacey G; Rubin, J Peter

2016-03-01

Fat grafting is a powerful procedure limited by unpredictable volume loss. Grafted tissue survives via plasmatic imbibition until neovascularization occurs; therefore, fat that is deposited more than 0.2 cm from capillaries will undergo central necrosis. This study aims to determine the architecture of fat deposits within the recipient bed following fat grafting. Fat was harvested by liposuction and stained with methylene blue. Stained fat was grafted into 4 × 4 × 2-cm sections of pannus tissue at graft-to-recipient volume ratios ranging from 1:10 to 1:1. Each tissue block was sectioned for stained graft visualization. The diameter of each deposit and the percentage with a radius greater than 0.2 cm were recorded. Average tunnel diameter was 0.20 ± 0.01 cm at a graft-to-recipient ratio of 1:10, 0.25 ± 0.01 cm at 1:8, 0.26 ± 0.01 cm at 1:6, 0.31 ± 0.01 cm at 1:4, 0.40 ± 0.01 cm at 1:2, and 0.57 ± 0.02 cm at 1:1. All comparisons reached statistical significance (p ≤ 0.05) except 1:8 versus 1:6 (p = 0.96). The percentage of fat parcels with a radius greater than 0.2 cm was 3.0 percent at 1:10, 5.3 percent at 1:8, 9.5 percent at 1:6, 20.9 percent at 1:4, 42.0 percent at 1:2, and 68.3 percent at 1:1. All percentage comparisons were significant except 1:10 versus 1:8 (p = 0.15). As the total volume transferred increases, grafted deposits coalesce to form larger globules, particularly at ratios beyond 1:4, likely contributing to central necrosis and subsequent volume loss. Therapeutic, V.

Two-step transplantation with adipose tissue-derived stem cells increases follicle survival by enhancing vascularization in xenografted frozen-thawed human ovarian tissue.

PubMed

Manavella, D D; Cacciottola, L; Pommé, S; Desmet, C M; Jordan, B F; Donnez, J; Amorim, C A; Dolmans, M M

2018-06-01

Do adipose tissue-derived stem cells (ASCs) enhance vascularization and follicle survival in xenografted ovarian tissue using a two-step transplantation approach? Higher rates of oxygenation and vascularization of ovarian tissue, as well as increased follicle survival rates, were detected in the early post-grafting period. ASCs have multilineage differentiation potential, proangiogenic properties and enhance vascularization in a peritoneal grafting site. Some studies suggest that using ASCs may improve ovarian tissue quality by enhancing graft angiogenesis. A total of 15 severe combined immunodeficient (SCID) mice were intraperitoneally grafted with frozen-thawed human ovarian tissue (OT) from five different patients. A peritoneal transplantation site had been previously prepared in a first step using either empty fibrin (Fi+OT group [n = 5]) or ASC-loaded fibrin (Fi/ASCs+OT group [n = 5]) for 14 days prior to grafting. Five mice underwent the standard one-step transplantation procedure and served as controls (OT group). Lithium phthalocyanine (LiPc) crystals were inserted into all grafted human ovarian tissue before transplantation. Levels of partial pressure of oxygen (pO2) in grafts were monitored in vivo by electron paramagnetic resonance (EPR) oximetry on Days 3 and 7. Samples for histology and immunohistochemistry (IHC) were collected after euthanizing the mice on Day 7 following EPR. One piece of ovarian tissue per patient was fixed for analysis to serve as non-grafted controls. Prospective experimental study conducted at the Gynecology Research Unit, Université Catholique de Louvain. All materials were used to perform pO2 measurements (EPR oximetry), histological (haematoxylin and eosin staining), immunohistochemistry (anti-mouse and human double CD34 and anti-human Ki-67) and TUNEL analyses. A significant increase in pO2 was observed in all groups between Days 3 and 7 (P < 0.001). A significantly higher pO2 level was observed in the Fi/ASCs+OT group

Volumetric and linear changes at dental implants following grafting with volume-stable three-dimensional collagen matrices or autogenous connective tissue grafts: 6-month data.

PubMed

Naenni, Nadja; Bienz, Stefan P; Benic, Goran I; Jung, Ronald E; Hämmerle, Christoph H F; Thoma, Daniel S

2018-04-01

The objective of this study was to test whether or not soft tissue augmentation with a volume-stable collagen matrix (VCMX) leads to similar volume gain around dental implants compared to autogenous subepithelial connective tissue graft (SCTG). In 12 adult beagle dogs, immediate implants were placed with simultaneous guided bone regeneration. After 25-45 weeks, soft tissue augmentation was randomly performed using VCMX, SCTG, or a sham-operated control. Impressions were taken pre-op and post-op (tissue augmentation) and again at sacrifice after healing periods of 4, 8, and 24 weeks. They were then digitized to allow for superimposition. Values of linear and volumetric changes were calculated. The median increase (pre-op to post-op) in buccal volume measured 0.92 mm for VCMX, 1.47 mm for SCTG, and 0.24 mm for SH. The values (pre-op to sacrifice) were - 0.25 mm for VCMX, 0.52 mm for SCTG, and - 0.06 mm for group SH. The median ridge width 2 mm below the crest measured - 0.26 mm for VCMX, 0.53 mm for SCTG, and - 0.15 mm for SH (pre-op to sacrifice). Volume augmentation using VCMX and SCTG resulted in an increase in ridge dimension (pre- to post-op). During the follow-up, the volume decreased in all three groups to a level close to the situation prior to surgery. Soft tissue volume augmentation around dental implants is usually performed using the patient's own tissue. This therapy is associated with an increased morbidity due to a second surgical site. Soft tissue volume at implant sites can be augmented using VCMX and SCTG. The gain on top of the ridge appears not to be stable during the follow-up in both groups.

Dermofat graft in deep nasolabial fold and facial rhytidectomy.

PubMed

Hwang, Kun; Han, Jin Yi; Kim, Dae Joong

2003-01-01

Fat and dermis or the combined tissues are used commonly in augmentation of the nasolabial fold. Guyuron obtained the dermofat graft from either the suprapubic or the groin region. The thickness of the preauricular skin was measured in seven Korean cadavers, five male and two female. We used the dermofat graft out of the preauricular skin remnant after facial rhytidectomy to augment the deep nasolabial fold in a patient. The average thickness of the epidermis was 56 +/- 12 microm, the dermis was 1820 +/- 265 microm thick, and the subcutaneous tissue was 4783 +/- 137 microm. More dense connective tissues, such as SMAS, are seen in the preauricular skin. The dermofat graft was easily obtained and prepared from the leftover preauricular skin after dissection of the lax skin in face lifting. This technique could be employed effectively and successfully to alleviate a deep nasolabial fold and concomitant facial rhytidectomy in an Asian with a thick preauricular skin.

Hyaline cartilage surface study with an environmental scanning electron microscope. An experimental study.

PubMed

Sastre, S; Suso, S; Segur, J M; Bori, G; Carbonell, J A; Agustí, E; Nuñez, M

2009-11-01

To obtain images of the articular surface of fresh osteochondral grafts using an environmental scanning electron microscope (ESEM). To evaluate and compare the main morphological aspects of the chondral surface of the fresh grafts. To develop a validated classification system on the basis of the images obtained via the ESEM. The study was based on osteochondral fragments from the internal condyle of the knee joint of New Zealand rabbits, corresponding to fresh chondral surface. One hundred images were obtained via the ESEM and these were classified by two observers according to a category system. The Kappa index and the corresponding confidence interval (CI) were calculated. Of the samples analysed, 62-72% had an even surface. Among the samples with an uneven surface 17-22% had a hillocky appearance and 12-16% a knobbly appearance. As regards splits, these were not observed in 92-95% of the surfaces; 4-7% showed superficial splits and only 1% deep splits. In 78-82% of cases no lacunae in the surface were observed, while 17-20% showed filled lacunae and only 1-2% presented empty lacunae. The study demonstrates that the ESEM is useful for obtaining and classifying images of osteochondral grafts.

Comparison of endothelial function of coronary artery bypass grafts in diabetic and nondiabetic patients: Which graft offers the best?

PubMed Central

Gür, Demet Özkaramanlı; Gür, Özcan; Gürkan, Selami; Cömez, Selcem; Gönültaş, Aylin; Yılmaz, Murat

2016-01-01

Objective: Diabetes associated endothelial dysfunction, which determines both long and short term graft patency, is not uniform in all coronary artery bypass surgery (CABG) grafts. Herein this study, we aimed to investigate the degree of endothelial dysfunction in diabetic radial artery (RA), internal mammarian artery (IMA) and saphenous vein (SV) grafts in vitro tissue bath system. Methods: This is a prospective experimental study. Fifteen diabetic and 15 non-diabetic patients were included to the study. A total number of 96 graft samples were collected; 16 graft samples for each graft type from both diabetic and non-diabetic patients. Arterial grafts were harvested with pedicles and SV grafts were harvested by ‘no touch’ technique. Vasodilatation response of vascular rings to carbachol, which induces nitric oxide (NO) mediated vasodilatation, was designated as the measure of endothelial function. Results: The IMA grafts had the most prominent NO mediated vasodilatation in both diabetic and non-diabetic patients, concluding a better preserved endothelial function than SV and RA. The ‘no-touch’ SV and RA grafts had similar vasodilatation responses in non-diabetic patients. In diabetic patients, on the other hand, RA grafts exhibited the least vasodilatation response (ie. worst endothelial function), even less vasodilatation than ‘no touch’ SV grafts (p<0.0001). Conclusion: Deteriorated function of RA grafts in diabetic patients, even worse than SV grafts made evident by this study, encourages the use of ‘no touch’ technique as the method of SV harvesting and more meticulous imaging of RA before its use as a graft in diabetic patients. PMID:26301347

Effectiveness of Acellular Dermal Matrix on Autologous Split-Thickness Skin Graft in Treatment of Deep Tissue Defect: Esthetic Subjective and Objective Evaluation.

PubMed

Lee, Yoo Jung; Park, Myong Chul; Park, Dong Ha; Hahn, Hyung Min; Kim, Sue Min; Lee, Il Jae

2017-10-01

A split-thickness skin graft (STSG) is performed to cover a large full-thickness skin defect. Esthetic and functional deficits can result, and many studies have sought to overcome them. This study compared the effectiveness of the acellular dermal matrix (ADM) graft and STSG concerning esthetic and functional effectiveness of ADM on scar quality. Of the patients who underwent anterolateral thigh free flap from 2011 to 2015, patients who received skin graft only (n = 10) or skin graft with ADM (n = 20) for coverage of the donor site were enrolled. In all cases, autologous STSG was performed with 1:1.5 meshed 0.008-0.010-inch-thick skin. In the skin graft with ADM group, 0.008-0.013-inch-thick meshed ADM (CGderm ® ; CGBio, Inc., Seungnam, Korea) was co-grafted. Negative-pressure wound therapy (CuraVAC ® ; CGBio, Inc., Seungnam, Korea) was applied to both groups in continuous mode at -120 mmHg. We investigate early outcomes (skin loss rate, duration of negative-pressure wound therapy, days to removal of stitches, days to achieve complete healing, and complications) and late outcomes in terms of scar quality (vascularity, pigmentation, pliability and height) and graft-related symptoms (itching sensation and pain). Assessments used the Vancouver Scar Scale and the Patient and Observer Scar Assessment Scale. Skin fold was measured to evaluate the elasticity of scar tissue. In the Vancouver Scar Scale, vascularity subscore (p = 0.003) and total score (p = 0.016) were significantly lower in the skin graft with ADM group. In Patient and Observer Scar Assessment Scale, the pain (p = 0.037) and stiffness subscores (p = 0.002), and total score (p = 0.017) were significantly lower in the skin graft with ADM group. Skin graft with ADM results in better scar quality in objective and subjective aspects. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to

Smooth muscle cells differentiated from mesenchymal stem cells are regulated by microRNAs and suitable for vascular tissue grafts.

PubMed

Gu, Wenduo; Hong, Xuechong; Le Bras, Alexandra; Nowak, Witold N; Issa Bhaloo, Shirin; Deng, Jiacheng; Xie, Yao; Hu, Yanhua; Ruan, Xiong Z; Xu, Qingbo

2018-05-25

Tissue-engineered vascular grafts with long-term patency are greatly needed in the clinical settings, and smooth muscle cells (SMCs) are a critical graft component. Human mesenchymal stem cells (MSCs) are used for generating SMCs, and understanding the underlying regulatory mechanisms of the MSC-to-SMC differentiation process could improve SMC generation in the clinic. Here, we found that in response to stimulation of transforming growth factor-β1 (TGFβ1), human umbilical cord-derived MSCs abundantly express the SMC markers α-smooth muscle actin (αSMA), smooth muscle protein 22 (SM22), calponin, and smooth muscle myosin heavy chain (SMMHC) at both gene and protein levels. Functionally, MSC-derived SMCs displayed contracting capacity in vitro and supported vascular structure formation in the Matrigel plug assay in vivo More importantly, SMCs differentiated from human MSCs could migrate into decellularized mouse aorta and give rise to the smooth muscle layer of vascular grafts, indicating the potential of utilizing human MSC-derived SMCs to generate vascular grafts. Of note, microRNA (miR) array analysis and TaqMan microRNA assays identified miR-503 and miR-222-5p as potential regulators of MSC differentiation into SMCs at early time points. Mechanistically, miR-503 promoted SMC differentiation by directly targeting SMAD7, a suppressor of SMAD-related, TGFβ1-mediated signaling pathways. Moreover, miR-503 expression was SMAD4-dependent. SMAD4 was enriched at the miR-503 promoter. Furthermore, miR-222-5p inhibited SMC differentiation by targeting and down-regulating ROCK2 and αSMA. In conclusion, MSC differentiation into SMCs is regulated by miR-503 and miR-222-5p and yields functional SMCs for use in vascular grafts. © 2018 Gu et al.

The effect of autologous adipose derived mesenchymal stem cell therapy in the treatment of a large osteochondral defect of the knee following unsuccessful surgical intervention of osteochondritis dissecans - a case study.

PubMed

Freitag, Julien; Shah, Kiran; Wickham, James; Boyd, Richard; Tenen, Abi

2017-07-14

A prospective analysis of the effect of autologous adipose derived mesenchymal stem cell (MSC) therapy in the treatment of an osteochondral defect of the knee with early progressive osteoarthritis following unsuccessful surgical intervention of osteochondritis dissecans (OCD). After failed conventional management of OCD a patient undergoes intra-articular MSC therapy. Patient outcome measures included the Numeric Pain Rating Scale (NPRS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Structural outcome was assessed using MRI with the novel technique of T2 mapping used to indicate cartilage quality. Following MSC therapy the patient reported improvement in pain and function as measured by NPRS, WOMAC and KOOS. Repeat MRI analysis showed regeneration of cartilage. MRI T2 mapping indicated hyaline like cartilage regrowth. In this report, the use of MSCs, after unsuccessful conventional OCD management, resulted in structural, functional and pain improvement. These results highlight the need to further study the regenerative potential of MSC therapy. Australian and New Zealand Clinical Trial Registry Number - ACTRN12615000258550 (Date registered 19/03/2015 - retrospectively registered).

Preparation and features of polycaprolactone vascular grafts with the incorporated vascular endothelial growth factor

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

Sevostyanova, V. V., E-mail: sevostyanova.victoria@gmail.com; Khodyrevskaya, Y. I.; Glushkova, T. V.

The development of tissue-engineered small-diameter vascular grafts is an urgent issue in cardiovascular surgery. In this study, we assessed how the incorporation of the vascular endothelial growth factor (VEGF) affects morphological and mechanical properties of polycaprolactone (PCL) vascular grafts along with its release kinetics. Vascular grafts were prepared using two-phase electrospinning. In pursuing our aims, we performed scanning electron microscopy, mechanical testing, and enzyme-linked immunosorbent assay. Our results demonstrated the preservation of a highly porous structure and improvement of PCL/VEGF scaffold mechanical properties as compared to PCL grafts. A prolonged VEGF release testifies the use of this construct as amore » scaffold for tissue-engineered vascular grafts.« less

Incidence of Osteochondritis Dissecans in Adults.

PubMed

Weiss, Jennifer M; Shea, Kevin G; Jacobs, John C; Cannamela, Peter C; Becker, Ian; Portman, Mark; Kessler, Jeffrey I

2018-04-01

Osteochondritis dissecans (OCD) has frequently been described in children and adolescents, but cases of OCD in adults are certainly encountered. Little has been published on the epidemiology of OCD in adult patients. To assess the frequency of OCD lesions in adults and assess the risk by age, sex, and ethnicity. Descriptive epidemiology study. The authors assessed all patients aged 20 to 45 years from the entire database of patients enrolled as members of Kaiser Permanente Southern California from January 2011 until December 2013. Kaiser Southern California is an integrated health care system serving a racially, ethnically, and socioeconomically diverse population of >3.5 million patients. A retrospective chart review was done on OCD during this period. Inclusion criteria included OCD of any joint. Exclusion criteria included traumatic osteochondral fractures and coexistence of intra-articular lesions other than OCD. Joint involvement/location, laterality, and all patient demographics were recorded. Among 122 patients, a total of 124 OCD lesions were found. The majority of lesions were in the ankle (n = 76) and knee (n = 43), with 3 foot lesions and 2 elbow lesions identified. OCD lesions were identified in 75 men (62%) and 47 women (38%). Overall incidence rates per 100,000 person-years were 3.42 for all OCD, 2.08 for ankle OCD, and 1.21 for knee OCD. The relative risk of adult OCD for men was twice that of women. The relative risk of adult OCD for white patients was 2.3 that of Asians and 1.7 that of Hispanics. Risk of knee OCD was 3.6 times higher for men than women. As compared with women, men had a higher risk for lateral femoral condyle OCD lesions versus the medial femoral condyle ( P = .05; odds ratio [OR], 5.19). This large cohort study of Southern California adults with OCD demonstrated an increased OR for men (vs women) of OCD in all joints. The majority of symptomatic lesions were present in the ankle rather than the knee, as previously found in

A bioreactor test system to mimic the biological and mechanical environment of oral soft tissues and to evaluate substitutes for connective tissue grafts.

PubMed

Mathes, Stephanie H; Wohlwend, Lorenz; Uebersax, Lorenz; von Mentlen, Roger; Thoma, Daniel S; Jung, Ronald E; Görlach, Christoph; Graf-Hausner, Ursula

2010-12-15

Gingival cells of the oral connective tissue are exposed to complex mechanical forces during mastication, speech, tooth movement and orthodontic treatments. Especially during wound healing following surgical procedures, internal and external forces may occur, creating pressure upon the newly formed tissue. This clinical situation has to be considered when developing biomaterials to augment soft tissue in the oral cavity. In order to pre-evaluate a collagen sponge intended to serve as a substitute for autogenous connective tissue grafts (CTGs), a dynamic bioreactor system was developed. Pressure and shear forces can be applied in this bioreactor in addition to a constant medium perfusion to cell-material constructs. Three-dimensional volume changes and stiffness of the matrices were analyzed. In addition, cell responses such as cell vitality and extracellular matrix (ECM) production were investigated. The number of metabolic active cells constantly increased under fully dynamic culture conditions. The sponges remained elastic even after mechanical forces were applied for 14 days. Analysis of collagen type I and fibronectin revealed a statistically significant accumulation of these ECM molecules (P < 0.05-0.001) when compared to static cultures. An increased expression of tenascin-c, indicating tissue remodeling processes, was observed under dynamic conditions only. The results indicate that the tested in vitro cell culture system was able to mimic both the biological and mechanical environments of the clinical situation in a healing wound. © 2010 Wiley Periodicals, Inc.

Quickening: Translational design of resorbable synthetic vascular grafts.

PubMed

Stowell, Chelsea E T; Wang, Yadong

2018-08-01

Traditional tissue-engineered vascular grafts have yet to gain wide clinical use. The difficulty of scaling production of these cell- or biologic-based products has hindered commercialization. In situ tissue engineering bypasses such logistical challenges by using acellular resorbable scaffolds. Upon implant, the scaffolds become remodeled by host cells. This review describes the scientific and translational advantages of acellular, synthetic vascular grafts. It surveys in vivo results obtained with acellular synthetics over their fifty years of technological development. Finally, it discusses emerging principles, highlights strategic considerations for designers, and identifies questions needing additional research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Return to running following knee osteochondral repair using an anti-gravity treadmill: A case report.

PubMed

Hambly, Karen; Poomsalood, Somruthai; Mundy, Emma

2017-07-01

The purpose of this study was to assess the impact of an anti-gravity treadmill return to running programme on self-efficacy and subjective knee function following knee osteochondral surgery. A 39-year-old otherwise healthy female endurance runner with a left knee femoral cartilage grade 3-4 defect 3 cm 2 . The patient underwent single step arthroscopic microfracture with Bone Marrow Aspirate Concentrate. An AlterG ® anti-gravity treadmill was used to manipulate loading during a graduated phased return to running over 8 weeks. Self-efficacy was evaluated using the Self-Efficacy for Rehabilitation outcomes scale (SER) and the Knee Self-Efficacy Scale (K-SES). Subjective knee function was evaluated using the Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee Subjective Knee Form (IKDC). The programme resulted in improvements in SER (57%), K-SES present (89%) and K-SES future (65%) self-efficacy domains. The IKDC score demonstrated a clinically important improvement with an increase from 62.1 in week 1-86.2 in week 8 (39%). Only the KOOS Sport/Rec subscale showed a clinically important improvement from week 1 to week 8. The programme resulted in improved knee and rehabilitation self-efficacy and subjective knee function following osteochondral repair of the knee. This case report illustrates the importance of considering self-efficacy in rehabilitation after knee osteochondral surgery and highlights the potential role for anti-gravity treadmills in enhancing self-efficacy and subjective knee function in preparation for a return to sport. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Modified approach for keratinized tissue augmentation in multiple teeth

PubMed Central

Terenzi, Mayara; Pigossi, Suzane Cristina; Pires, Luana Carla; Cirelli, Joni Augusto; Sampaio, José Eduardo

2017-01-01

This case report demonstrated a modified technique of free gingival graft (FGG) aiming to increase keratinized attached tissue in large recipient areas. A FGG to increase the amount of attached gingival tissue, facilitate oral hygiene, and prevent further clinical attachment loss was realized in two patients. Because the extensive recipient area, a modified technique was performed to obtain a smaller graft of the donor area. A template of the graft was made about 25%–30% smaller than the total recipient area. After graft removal, interspersed incisions were made in the upper and lower edges of it. After 9–24 months of follow-up, the final width of the keratinized tissue was 4.0–4.4 times larger in comparison to initial clinical condition. In conclusion, this FGG technique can be considered an alternative to gain sufficient amount of keratinized gingival tissue using a smaller graft. PMID:29551874