Science.gov

Sample records for adult tissue repair

  1. Tissue repair

    PubMed Central

    2010-01-01

    As living beings that encounter every kind of traumatic event from paper cut to myocardial infarction, we must possess ways to heal damaged tissues. While some animals are able to regrow complete body parts following injury (such as the earthworm who grows a new head following bisection), humans are sadly incapable of such feats. Our means of recovery following tissue damage consists largely of repair rather than pure regeneration. Thousands of times in our lives, a meticulously scripted but unseen wound healing drama plays, with cells serving as actors, extracellular matrix as the setting and growth factors as the means of communication. This article briefly reviews the cells involved in tissue repair, their signaling and proliferation mechanisms and the function of the extracellular matrix, then presents the actors and script for the three acts of the tissue repair drama. PMID:21220961

  2. Progerin expression disrupts critical adult stem cell functions involved in tissue repair

    PubMed Central

    Pacheco, Laurin Marie; Gomez, Lourdes Adriana; Dias, Janice; Ziebarth, Noel M; Howard, Guy A; Schiller, Paul C

    2014-01-01

    Vascular disease is one of the leading causes of death worldwide. Vascular repair, essential for tissue maintenance, is critically reduced during vascular disease and aging. Efficient vascular repair requires functional adult stem cells unimpaired by aging or mutation. One protein candidate for reducing stem cell–mediated vascular repair is progerin, an alternative splice variant of lamin A. Progerin results from erroneous activation of cryptic splice sites within the LMNA gene, and significantly increases during aging. Mutations triggering progerin overexpression cause the premature aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS), in which patients die at approximately 13-years of age due to atherosclerosis-induced disease. Progerin expression affects tissues rich in cells that can be derived from marrow stromal cells (MSCs). Studies using various MSC subpopulations and models have led to discrepant results. Using a well-defined, immature subpopulation of MSCs, Marrow Isolated Adult Multilineage Inducible (MIAMI) cells, we find progerin significantly disrupts expression and localization of self-renewal markers, proliferation, migration, and membrane elasticity. One potential treatment, farnesyltransferase inhibitor, ameliorates some of these effects. Our results confirm proposed progerin-induced mechanisms and suggest novel ways in which progerin disturbs critical stem cell functions collectively required for proper tissue repair, offering promising treatment targets for future therapies. PMID:25567453

  3. Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs)

    PubMed Central

    Prockop, Darwin J; Kota, Daniel J; Bazhanov, Nikolay; Reger, Roxanne L

    2010-01-01

    Abstract In this review, we focus on the adult stem/progenitor cells that were initially isolated from bone marrow and first referred to as colony forming units-fibroblastic, then as marrow stromal cells and subsequently as either mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs). The current interest in MSCs and similar cells from other tissues is reflected in over 10,000 citations in PubMed at the time of this writing with 5 to 10 new publications per day. It is also reflected in over 100 registered clinical trials with MSCs or related cells (http//www.clinicaltrials.gov). As a guide to the vast literature, this review will attempt to summarize many of the publications in terms of three paradigms that have directed much of the work: an initial paradigm that the primary role of the cells was to form niches for haematopoietic stem cells (paradigm I); a second paradigm that the cells repaired tissues by engraftment and differentiation to replace injured cells (paradigm II); and the more recent paradigm that MSCs engage in cross-talk with injured tissues and thereby generate microenvironments or ‘quasi-niches’ that enhance the repair tissues (paradigm III). PMID:20716123

  4. Adult-derived stem cells and their potential for use in tissue repair and molecular medicine.

    PubMed

    Young, Henry E; Duplaa, Cecile; Katz, Ryan; Thompson, Tina; Hawkins, Kristina C; Boev, Angel N; Henson, Nicholas L; Heaton, Matthew; Sood, Rajiv; Ashley, Dennis; Stout, Christopher; Morgan, Joe H; Uchakin, Peter N; Rimando, Marylen; Long, Gypsy F; Thomas, Crystal; Yoon, Jee-In; Park, Ji Eun; Hunt, Darren J; Walsh, Nancy M; Davis, Josh C; Lightner, Joel E; Hutchings, Anna M; Murphy, Meredith L; Boswell, Elizabeth; McAbee, Jessica A; Gray, Brandon M; Piskurich, Janet; Blake, Lisa; Collins, Julie A; Moreau, Catherine; Hixson, Douglas; Bowyer, Frank P; Black, Asa C

    2005-01-01

    This report reviews three categories of precursor cells present within adults. The first category of precursor cell, the epiblast-like stem cell, has the potential of forming cells from all three embryonic germ layer lineages, e.g., ectoderm, mesoderm, and endoderm. The second category of precursor cell, the germ layer lineage stem cell, consists of three separate cells. Each of the three cells is committed to form cells limited to a specific embryonic germ layer lineage. Thus the second category consists of germ layer lineage ectodermal stem cells, germ layer lineage mesodermal stem cells, and germ layer lineage endodermal stem cells. The third category of precursor cells, progenitor cells, contains a multitude of cells. These cells are committed to form specific cell and tissue types and are the immediate precursors to the differentiated cells and tissues of the adult. The three categories of precursor cells can be readily isolated from adult tissues. They can be distinguished from each other based on their size, growth in cell culture, expressed genes, cell surface markers, and potential for differentiation. This report also discusses new findings. These findings include the karyotypic analysis of germ layer lineage stem cells; the appearance of dopaminergic neurons after implantation of naive adult pluripotent stem cells into a 6-hydroxydopamine-lesioned Parkinson's model; and the use of adult stem cells as transport mechanisms for exogenous genetic material. We conclude by discussing the potential roles of adult-derived precursor cells as building blocks for tissue repair and as delivery vehicles for molecular medicine.

  5. Lin28: time for tissue repair.

    PubMed

    Reddien, Peter W

    2013-11-07

    Embryos and juveniles in many organisms repair tissue injuries better than adults. In this issue, Shyh-Chang et al. find that postnatal activation of Lin28a, a gene typically active in embryonic development, promotes better than normal tissue repair in mice, including following ear and digit injuries. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Bone marrow stromal cell-mediated tissue sparing enhances functional repair after spinal cord contusion in adult rats.

    PubMed

    Ritfeld, Gaby J; Nandoe Tewarie, Rishi D S; Vajn, Katarina; Rahiem, Sahar T; Hurtado, Andres; Wendell, Dane F; Roos, Raymund A C; Oudega, Martin

    2012-01-01

    Bone marrow stromal cell (BMSC) transplantation has shown promise for repair of the spinal cord. We showed earlier that a BMSC transplant limits the loss of spinal nervous tissue after a contusive injury. Here, we addressed the premise that BMSC-mediated tissue sparing underlies functional recovery in adult rats after a contusion of the thoracic spinal cord. Our results reveal that after 2 months BMSCs had elicited a significant increase in spared tissue volumes and in blood vessel density in the contusion epicenter. A strong functional relationship existed between spared tissue volumes and blood vessel density. BMSC-transplanted rats exhibited significant improvements in motor, sensorimotor, and sensory functions, which were strongly correlated with spared tissue volumes. Retrograde tracing revealed that rats with BMSCs had twice as many descending brainstem neurons with an axon projecting beyond the contused spinal cord segment and these correlated strongly with the improved motor/sensorimotor functions but not sensory functions. Together, our data indicate that tissue sparing greatly contributes to BMSC-mediated functional repair after spinal cord contusion. The preservation/formation of blood vessels and sparing/regeneration of descending brainstem axons may be important mediators of the BMSC-mediated anatomical and functional improvements.

  7. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2014-04-01

    in order to minimize scarring and injected dissociated adult DRGs rostral to a dorsal column transection of the spinal cord. From the sensory... columns were dissected and post-fixed overnight in 4% paraformaldehyde, and then spinal cords were dissected from spinal columns and cryoprotected...AD______________ Award Number: W81XWH-10-1-0941 TITLE: Spinal Cord Repair with Engineered Nervous Tissue

  8. Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms.

    PubMed

    Prockop, Darwin J

    2009-06-01

    Research on stem cells has progressed at a rapid pace and, as might be anticipated, the results have generated several controversies, a few myths and a change in a major paradigm. Some of these issues will be reviewed in this study with special emphasis on how they can be applied to the adult stem/progenitor cells from bone marrow, referred to as MSCs.

  9. Nerves and Tissue Repair.

    DTIC Science & Technology

    1994-07-01

    axolotl limbs are transected the concentration of transferrin in the distal limb tissue declines rapidly and limb regeneration stops. These results...transferrin binding and expression of the transferrin gene in cells of axolotl peripheral nerve indicate that both uptake and synthesis of this factor occur

  10. The promise of perfect adult tissue repair and regeneration in mammals: Learning from regenerative amphibians and fish.

    PubMed

    Godwin, James

    2014-09-01

    Regenerative medicine promises to greatly impact on human health by improving repair outcomes in a range of tissues and injury contexts. Successful therapies will rely on identifying both intrinsic and extrinsic biological circuits that control wound healing, proliferation, cell survival, and developmental cell fate. Animals such as the zebrafish and the salamander display powerful examples of near-perfect regeneration and scar-free healing in a range of injury contexts not attained in mammals. By studying regeneration in a range of highly regenerative species that maintain regenerative potential throughout life, many instructive and permissive factors have been identified that could assist in the development of regenerative therapies. This review highlights some of the recent observations in immune regulation, epigenetic regulation, stem cell mobilization, and regenerative signatures that have improved our understanding of the regenerative process. Potential opportunities in harnessing this knowledge for future translation into the clinic are discussed.

  11. Neural repair in the adult brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury to the adult brain often results in substantial loss of neural tissue and subsequent permanent functional impairment. Over the last two decades, a number of approaches have been developed to harness the regenerative potential of neural stem cells and the existing fate plasticity of neural cells in the nervous system to prevent tissue loss or to enhance structural and functional regeneration upon injury. Here, we review recent advances of stem cell-associated neural repair in the adult brain, discuss current challenges and limitations, and suggest potential directions to foster the translation of experimental stem cell therapies into the clinic. PMID:26918167

  12. Lin28 enhances tissue repair by reprogramming cellular metabolism.

    PubMed

    Shyh-Chang, Ng; Zhu, Hao; Yvanka de Soysa, T; Shinoda, Gen; Seligson, Marc T; Tsanov, Kaloyan M; Nguyen, Liem; Asara, John M; Cantley, Lewis C; Daley, George Q

    2013-11-07

    Regeneration capacity declines with age, but why juvenile organisms show enhanced tissue repair remains unexplained. Lin28a, a highly conserved RNA-binding protein expressed during embryogenesis, plays roles in development, pluripotency, and metabolism. To determine whether Lin28a might influence tissue repair in adults, we engineered the reactivation of Lin28a expression in several models of tissue injury. Lin28a reactivation improved hair regrowth by promoting anagen in hair follicles and accelerated regrowth of cartilage, bone, and mesenchyme after ear and digit injuries. Lin28a inhibits let-7 microRNA biogenesis; however, let-7 repression was necessary but insufficient to enhance repair. Lin28a bound to and enhanced the translation of mRNAs for several metabolic enzymes, thereby increasing glycolysis and oxidative phosphorylation (OxPhos). Lin28a-mediated enhancement of tissue repair was negated by OxPhos inhibition, whereas a pharmacologically induced increase in OxPhos enhanced repair. Thus, Lin28a enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics. PAPERCLIP: Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Lin28 enhances tissue repair by reprogramming cellular metabolism

    PubMed Central

    Shyh-Chang, Ng; Zhu, Hao; de Soysa, T. Yvanka; Shinoda, Gen; Seligson, Marc T.; Tsanov, Kaloyan M.; Nguyen, Liem; Asara, John M.; Cantley, Lewis C.; Daley, George Q.

    2014-01-01

    SUMMARY Regeneration capacity declines with age, but why juvenile organisms show enhanced tissue repair remains unexplained. Lin28a, a highly-conserved RNA binding protein expressed during embryogenesis, plays roles in development, pluripotency and metabolism. To determine if Lin28a might influence tissue repair in adults, we engineered the reactivation of Lin28a expression in several models of tissue injury. Lin28a reactivation improved hair regrowth by promoting anagen in hair follicles, and accelerated regrowth of cartilage, bone and mesenchyme after ear and digit injuries. Lin28a inhibits let-7 microRNA biogenesis; however let-7 repression was necessary but insufficient to enhance repair. Lin28a bound to and enhanced the translation of mRNAs for several metabolic enzymes, thereby increasing glycolysis and oxidative phosphorylation (OxPhos). Lin28a-mediated enhancement of tissue repair was negated by OxPhos inhibition, whereas a pharmacologically-induced increase in OxPhos enhanced repair. Thus, Lin28a enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics. PMID:24209617

  14. Macrophages in tissue repair, regeneration, and fibrosis

    PubMed Central

    Wynn, Thomas A.; Vannella, Kevin M.

    2016-01-01

    Inflammatory monocytes and resident tissue macrophages are key regulators of tissue repair, regeneration, and fibrosis. Following tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, with uncontrolled inflammatory mediator and growth factor production, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contributing to a state of persistent injury, which may lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue regenerating phenotypes following injury, and highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically. PMID:26982353

  15. Engineered neural tissue for peripheral nerve repair.

    PubMed

    Georgiou, Melanie; Bunting, Stephen C J; Davies, Heather A; Loughlin, Alison J; Golding, Jonathan P; Phillips, James B

    2013-10-01

    A new combination of tissue engineering techniques provides a simple and effective method for building aligned cellular biomaterials. Self-alignment of Schwann cells within a tethered type-1 collagen matrix, followed by removal of interstitial fluid produces a stable tissue-like biomaterial that recreates the aligned cellular and extracellular matrix architecture associated with nerve grafts. Sheets of this engineered neural tissue supported and directed neuronal growth in a co-culture model, and initial in vivo tests showed that a device containing rods of rolled-up sheets could support neuronal growth during rat sciatic nerve repair (5 mm gap). Further testing of this device for repair of a critical-sized 15 mm gap showed that, at 8 weeks, engineered neural tissue had supported robust neuronal regeneration across the gap. This is, therefore, a useful new approach for generating anisotropic engineered tissues, and it can be used with Schwann cells to fabricate artificial neural tissue for peripheral nerve repair.

  16. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2012-10-01

    success of bridging a lateral hemisection in the rat spinal cord with engineered (“stretch-grown”) living nervous tissue constructs 2 . For the current...AD_________________ Award Number: W81XWH-10-1-0941 TITLE: Spinal Cord Repair with Engineered...SUBTITLE Spinal Cord Repair with Engineered Nervous Tissue 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-10-1-0941 5c. PROGRAM ELEMENT NUMBER 6

  17. Chitosan adhesive for laser tissue repair

    NASA Astrophysics Data System (ADS)

    Lauto, A.; Stoodley, M.; Avolio, A.; Foster, L. J. R.

    2006-02-01

    Background. Laser tissue repair usually relies on haemoderivate solders, based on serum albumin. These solders have intrinsic limitations that impair their widespread use, such as limited repair strength, high solubility, brittleness and viral transmission. Furthermore, the solder activation temperature (65-70 °C) can induce significant damage to tissue. In this study, a new laser-activated biomaterial for tissue repair was developed and tested in vitro and in vivo to overcome some of the shortcomings of traditional solders. Materials and Methods. Flexible and insoluble strips of chitosan adhesive (surface area ~34 mm2, thickness ~20 μm) were developed and bonded on sheep intestine with a laser fluence and irradiance of 52 +/- 2 J/cm2 and ~15 W/cm2 respectively. The temperature between tissue and adhesive was measured using small thermocouples. The strength of repaired tissue was tested by a calibrated tensiometer. The adhesive was also bonded in vivo to the sciatic nerve of rats to assess the thermal damage induced by the laser (fluence = 65 +/- 11 J/cm2, irradiance = 15 W/cm2) four days post-operatively. Results. Chitosan adhesives successfully repaired intestine tissue, achieving a repair strength of 0.50 +/- 0.15 N (shear stress = 14.7 +/- 4.7 KPa, n=30) at a temperature of 60-65 °C. The laser caused demyelination of axons at the operated site; nevertheless, the myelinated axons retained their normal morphology proximally and distally.

  18. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2011-10-01

    funded grant, we demonstrated proof-of-concept success of bridging a lateral hemisection of the rat spinal cord with engineered (“stretch-grown...AD_________________ Award Number: W81XWH-10-1-0941 TITLE: Spinal Cord Repair with Engineered...5a. CONTRACT NUMBER Spinal Cord Repair with Engineered Nervous Tissue 5b. GRANT NUMBER W81XWH-10-1-0941 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

  19. miRNA Control of Tissue Repair and Regeneration

    PubMed Central

    Sen, Chandan K.; Ghatak, Subhadip

    2016-01-01

    Tissue repair and regeneration rely on the function of miRNA, molecular silencers that enact post-transcriptional gene silencing of coding genes. Disruption of miRNA homeostasis is developmentally lethal, indicating that fetal tissue development is tightly controlled by miRNAs. Multiple critical facets of adult tissue repair are subject to control by miRNAs, as well. Sources of cell pool for tissue repair and regeneration are diverse and provided by processes including cellular dedifferentiation, transdifferentiation, and reprogramming. Each of these processes is regulated by miRNAs. Furthermore, induced pluripotency may be achieved by miRNA-based strategies independent of transcription factor manipulation. The observation that miRNA does not integrate into the genome makes miRNA-based therapeutic strategies translationally valuable. Tools to manipulate cellular and tissue miRNA levels include mimics and inhibitors that may be specifically targeted to cells of interest at the injury site. Here, we discuss the extraordinary importance of miRNAs in tissue repair and regeneration based on emergent reports and rapid advances in miRNA-based therapeutics. PMID:26056933

  20. Cell sheet transplantation for heart tissue repair.

    PubMed

    Matsuura, Katsuhisa; Haraguchi, Yuji; Shimizu, Tatsuya; Okano, Teruo

    2013-08-10

    Cell transplantation is attracting considerable attention as the next-generation therapy for treatment of cardiovascular diseases. We have developed cell sheet engineering as a type of scaffold-less tissue engineering for application in myocardial tissue engineering and the repair of injured heart tissue by cell transplantation. Various types of cell sheet transplantation have improved cardiac function in animal models and clinical settings. Furthermore, cell-based tissue engineering with human induced pluripotent stem cell technology is about to create thick vascularized cardiac tissue for cardiac grafts and heart tissue models. In this review, we summarize the current cardiac cell therapies for treating heart failure with cell sheet technology and cell sheet-based tissue engineering.

  1. Native Tissue Prolapse Repairs: Comparative Effectiveness Trials.

    PubMed

    Siff, Lauren N; Barber, Matthew D

    2016-03-01

    This report reviews the success rates and complications of native tissue (nonmesh) vaginal reconstruction of pelvic organ prolapse by compartment. For apical prolapse, both uterosacral ligament suspensions and sacrospinous ligament fixations are effective and provided similar outcomes in anatomy and function with few adverse events. In the anterior compartment, traditional colporrhaphy technique is no different than ultralateral suturing. In the posterior compartment, transvaginal rectocele repair is superior to transanal repair. For uterine preservation, sacrospinous hysteropexy is not inferior to vaginal hysterectomy with uterosacral ligament suspension for treatment of apical uterovaginal prolapse. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Interface tissue engineering: next phase in musculoskeletal tissue repair.

    PubMed

    Sahoo, Sambit; Teh, Thomas Kh; He, Pengfei; Toh, Siew Lok; Goh, James Ch

    2011-05-01

    Increasing incidence of musculoskeletal injuries coupled with limitations in the current treatment options have necessitated tissue engineering and regenerative medicine- based approaches. Moving forward from engineering isolated musculoskeletal tissues, research strategies are now being increasingly focused on repairing and regenerating the interfaces between dissimilar musculoskeletal tissues with the aim to achieve seamless integration of engineered musculoskeletal tissues. This article reviews the state-of-the-art in the tissue engineering of musculoskeletal tissue interfaces with a focus on Singapore's contribution in this emerging field. Various biomimetic scaffold and cellbased strategies, the use of growth factors, gene therapy and mechanical loading, as well as animal models for functional validation of the tissue engineering strategies are discussed.

  3. Roles for Hedgehog signaling in adult organ homeostasis and repair

    PubMed Central

    Petrova, Ralitsa; Joyner, Alexandra L.

    2014-01-01

    The hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner. PMID:25183867

  4. Cell-based and biomaterial approaches to connective tissue repair

    NASA Astrophysics Data System (ADS)

    Stalling, Simone Suzette

    Connective tissue injuries of skin, tendon and ligament, heal by a reparative process in adults, filling the wound site with fibrotic, disorganized scar tissue that poorly reflects normal tissue architecture or function. Conversely, fetal skin and tendon have been shown to heal scarlessly. Complete regeneration is not intrinsically ubiquitous to all fetal tissues; fetal diaphragmatic and gastrointestinal injuries form scars. In vivo studies suggest that the presence of fetal fibroblasts is essential for scarless healing. In the orthopaedic setting, adult anterior cruciate ligament (ACL) heals poorly; however, little is known about the regenerative capacity of fetal ACL or fetal ACL fibroblasts. We characterized in vitro wound healing properties of fetal and adult ACL fibroblasts demonstrating that fetal ACL fibroblasts migrate faster and elaborate greater quantities of type I collagen, suggesting the healing potential of the fetal ACL may not be intrinsically poor. Similar to fetal ACL fibroblasts, fetal dermal fibroblasts also exhibit robust cellular properties. We investigated the age-dependent effects of dermal fibroblasts on tendon-to-bone healing in rat supraspinatus tendon injuries, a reparative injury model. We hypothesized delivery of fetal dermal fibroblasts would increase tissue organization and mechanical properties in comparison to adult dermal fibroblasts. However, at 1 and 8 weeks, the presence of dermal fibroblasts, either adult or fetal, had no significant effect on tissue histology or mechanical properties. There was a decreasing trend in cross-sectional area of repaired tendons treated with fetal dermal fibroblasts in comparison to adult, but this finding was not significant in comparison to controls. Finally, we synthesized a novel polysaccharide, methacrylated methylcellulose (MA-MC), and fabricated hydrogels using a well-established photopolymerization technique. We characterized the physical and mechanical properties of MA-MC hydrogels in

  5. Laparoscopic repair of adult Bochdalek's hernia

    PubMed Central

    Husain, Musharraf; Hajini, Firdoos Farooq; Ganguly, Pavitra; Bukhari, Syed

    2013-01-01

    Bochdalek's hernia is a type of congenital diaphragmatic hernia occurring in approximately 1 in 2200–12 500 live births. It is considered to be extremely rare in adults and poses a diagnostic challenge. We present a case of a young man who was diagnosed as a case of congenital Bochdalek's hernia and underwent laparoscopic mesh repair. PMID:23761496

  6. Photochemical tissue bonding: a promising technique for peripheral nerve repair.

    PubMed

    Johnson, T Shane; O'Neill, Anne C; Motarjem, Pejman M; Amann, Christopher; Nguyen, Tuan; Randolph, Mark A; Winograd, Jonathan M; Kochevar, Irene E; Redmond, Robert W

    2007-12-01

    Photochemical tissue bonding (PTB) is a novel tissue repair technique that uses visible light and a photosensitizing dye to crosslink proteins on tissue surfaces. This technique has been successfully demonstrated in a number of tissue repair models. An ideal nerve repair technique would be atraumatic and avoid placement of foreign bodies at the repair site. The epineurium is suited to photochemical repair as it is thin, translucent and has a relatively high collagen content. This study was designed to determine if PTB could be successfully applied in a peripheral nerve repair model. Forty Sprague Dawley rats underwent transection of the sciatic nerve. Animals were then randomized to four treatment groups; epineurial suture repair, epineurial cuff with PTB, epineurial cuff alone, and no repair. Functional recovery was assessed at 10 day intervals using walking track analysis and sciatic function index calculations. At 90 days postoperatively animals were sacrificed and sciatic nerves harvested for histology and histomorphometry. Functional recovery in the suture repair and epineural cuff with PTB groups were not significantly different (-70.6 +/- 17.8 versus -76.9 +/- 10.3, P = 0.64) at 90 days postrepair. Histology showed good axonal regeneration with all repair techniques. Histomorphometric analysis found no significant difference between the repair groups. This study illustrates that peripheral nerves can be successfully repaired using a photochemical tissue bonding technique with results similar to those achieved with the current gold standard. With further development and refinement PTB may prove a useful tool in peripheral nerve repair.

  7. Bone tissue engineering and repair by gene therapy.

    PubMed

    Betz, Volker M; Betz, Oliver B; Harris, Mitchel B; Vrahas, Mark S; Evans, Christopher H

    2008-01-01

    Many clinical conditions require the stimulation of bone growth. The use of recombinant bone morphogenetic proteins does not provide a satisfying solution to these conditions due to delivery problems and high cost. Gene therapy has emerged as a very promising approach for bone repair that overcomes limitations of protein-based therapy. Several preclinical studies have shown that gene transfer technology has the ability to deliver osteogenic molecules to precise anatomical locations at therapeutic levels for sustained periods of time. Both in-vivo and ex-vivo transduction of cells can induce bone formation at ectopic and orthotopic sites. Genetic engineering of adult stem cells from various sources with osteogenic genes has led to enhanced fracture repair, spinal fusion and rapid healing of bone defects in animal models. This review describes current viral and non-viral gene therapy strategies for bone tissue engineering and repair including recent work from the author's laboratory. In addition, the article discusses the potential of gene-enhanced tissue engineering to enter widespread clinical use.

  8. Apparatus for enhancing tissue repair in mammals

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J. (Inventor); Parker, Clayton R. (Inventor)

    2007-01-01

    An apparatus is disclosed for enhancing tissue repair in mammals, with the apparatus comprising: a sleeve for encircling a portion of a mammalian body part, said sleeve comprising an electrically conductive coil capable of generating an electromagnetic field when an electrical current is applied thereto, means for supporting the sleeve on the mammalian body part; and means for supplying the electrically conductive coil with a square wave time varying electrical current sufficient to create a time varying electromagnetic force of from approximately 0.05 gauss to 0.05 gauss within the interior of the coil in order that when the sleeve is placed on a mammalian body part and the time varying electromagnetic force of from approximately 0.05 gauss to 0.05 gauss is generated on the mammalian body part for an extended period of time, tissue regeneration within the mammalian body part is increased to a rate in excess of the normal tissue regeneration rate that would occur without application of the time varying electromagnetic force.

  9. Aortic coarctation repair in the adult.

    PubMed

    Cardoso, Goncalo; Abecasis, Miguel; Anjos, Rui; Marques, Marta; Koukoulis, Giovanna; Aguiar, Carlos; Neves, José Pedro

    2014-07-01

    Aortic coarctation can be repaired surgically or percutaneously. The decision should be made according to the anatomy and location of the coarctation, age of the patient, presence of other cardiac lesions, and other anatomic determinants (extensive collaterals or aortic calcification). This article reviews the different therapeutic options available, explaining the differences between children and adults, describing different approaches to the same disease, exemplified by three cases of nonclassic surgical approach and one percutaneous treatment.

  10. Bioactive Polymeric Materials for Tissue Repair

    PubMed Central

    Bienek, Diane R.; Tutak, Wojtek; Skrtic, Drago

    2017-01-01

    Bioactive polymeric materials based on calcium phosphates have tremendous appeal for hard tissue repair because of their well-documented biocompatibility. Amorphous calcium phosphate (ACP)-based ones additionally protect against unwanted demineralization and actively support regeneration of hard tissue minerals. Our group has been investigating the structure/composition/property relationships of ACP polymeric composites for the last two decades. Here, we present ACP’s dispersion in a polymer matrix and the fine-tuning of the resin affects the physicochemical, mechanical, and biological properties of ACP polymeric composites. These studies illustrate how the filler/resin interface and monomer/polymer molecular structure affect the material’s critical properties, such as ion release and mechanical strength. We also present evidence of the remineralization efficacy of ACP composites when exposed to accelerated acidic challenges representative of oral environment conditions. The utility of ACP has recently been extended to include airbrushing as a platform technology for fabrication of nanofiber scaffolds. These studies, focused on assessing the feasibility of incorporating ACP into various polymer fibers, also included the release kinetics of bioactive calcium and phosphate ions from nanofibers and evaluate the biorelevance of the polymeric ACP fiber networks. We also discuss the potential for future integration of the existing ACP scaffolds into therapeutic delivery systems used in the precision medicine field. PMID:28134776

  11. Current options in inguinal hernia repair in adult patients

    PubMed Central

    Kulacoglu, H

    2011-01-01

    Inguinal hernia is a very common problem. Surgical repair is the current approach, whereas asymptomatic or minimally symptomatic hernias may be good candidate for watchful waiting. Prophylactic antibiotics can be used in centers with high rate of wound infection. Local anesthesia is a suitable and economic option for open repairs, and should be popularized in day-case setting. Numerous repair methods have been described to date. Mesh repairs are superior to "nonmesh" tissue-suture repairs. Lichtenstein repair and endoscopic/laparoscopic techniques have similar efficacy. Standard polypropylene mesh is still the choice, whereas use of partially absorbable lightweight meshes seems to have some advantages. PMID:22435019

  12. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2013-10-01

    transplanted nervous tissue constructs on...recovery of motor function. Specific Aim 2: Evaluation of the survival and integration of transplanted living nervous tissue constructs and host... Nervous Tissue PRINCIPAL INVESTIGATOR: Douglas H. Smith, M.D. CONTRACTING

  13. Neural tissue transplantation, repair, and rehabilitation.

    PubMed

    Dunnett, Stephen B

    2013-01-01

    Transplants of cells and tissues to the central nervous system of adult mammals can, under appropriate conditions, survive, integrate, and function. In particular, the grafted cells can sustain functional recovery in animal models of a range of neurodegenerative conditions including genetic and idiopathic neurodegenerative diseases of adulthood and aging, ischemic stroke, and brain and spinal cord trauma. In a restricted subset of such conditions, cell transplantation has progressed to application in humans in early-stage clinical trials. At the present stage of play, there is clear evidence of clinical efficacy of fetal cell transplants in Parkinson disease (notwithstanding a range of technical difficulties still to be fully resolved), and preliminary claims of promising outcomes in several other severe neurodegenerative conditions, including Huntington disease and stroke. Moreover, the experimental literature is increasingly suggesting that the experience and training of the graft recipient materially affects the functional outcome. For example, environmental enrichment, behavioral activity, and specific training can enhance the recovery process to maximize functional recovery. There are even circumstances where the grafted cells have been demonstrated to restore the neural substrate for new learning. Consequently, it is not sufficient to replace lost cells anatomically; rather, for the grafts to be effective, they need to be integrated functionally into the host circuitry, and the host animal requires training and rehabilitation to maximize function of the reconstructed graft-host circuitry. Such observations require reconsideration of the design of the next generation of clinical trials and subsequent service delivery, to include physiotherapists, cognitive therapists, and rehabilitation experts as core members of the transplant team, along with the neurologists and neurosurgeons that have conventionally led the field.

  14. Regulation of tissue repair and regeneration by electric fields.

    PubMed

    Wang, En-tong; Zhao, Min

    2010-02-01

    Endogenous electric fields (EFs) have been detected at wounds and damaged tissues. The potential roles of EFs in tissue repair and regeneration have been an intriguing topic for centuries. Recent researches have provided significant insights into how naturally occurring EFs may participate in the control of tissue repair and regeneration. Applied EFs equivalent to the size of fields measured in vivo direct cell migration, cell proliferation and nerve sprouting at wounds. More remarkably, physiological EFs are a guidance cue that directs cell migration which overrides other well accepted directional signals including initial injury stimulation, wound void, contact inhibition release, population pressure and chemotaxis. EFs activate many intracellular signaling pathways in a directional manner. Modulation of endogenous wound EFs affects epithelial cell migration, cell proliferation, and nerve growth at cornea wounds in vivo. Electric stimulation is being tested clinically for the treatments of bone fracture, wound healing and spinal cord injury. EFs thus may represent a novel type of signaling paradigm in tissue repair and regeneration. Combination of the electric stimulation and other well understood biochemical regulatory mechanisms may offer powerful and effective therapies for tissue repair and regeneration. This review introduces experimental evidence for the existence of endogenous EFs and discusses their roles in tissue repair and regeneration.

  15. Cell sheet engineering for heart tissue repair.

    PubMed

    Masuda, Shinako; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

    2008-01-14

    Recently, myocardial tissue engineering has emerged as one of the most promising therapies for patients suffering from severe heart failure. Nevertheless, conventional methods in tissue engineering involving the seeding of cells into biodegradable scaffolds have intrinsic shortcomings, such as inflammatory reactions and fibrous tissue formation caused by scaffold degradation. On the other hand, we have developed cell sheet engineering as scaffoldless tissue engineering, and applied it for myocardial tissue engineering. Using temperature-responsive culture surfaces, cells can be harvested as intact sheets and cell-dense thick tissues are constructed by layering these cell sheets. Myocardial cell sheets non-invasively harvested from temperature-responsive culture surfaces are successfully layered, resulting in electrically communicative 3-dimensional (3-D) cardiac constructs. Transplantation of cell sheets onto damaged hearts improved heart function in several animal models. In this review, we summarize the development of myocardial tissue engineering using cell sheets harvested from temperature-responsive culture surfaces and discuss about future views.

  16. Laparoscopic repair of inguinal hernia in adults

    PubMed Central

    Yang, Xue-Fei

    2016-01-01

    Laparoscopic repair of inguinal hernia is mini-invasive and has confirmed effects. The procedures include intraperitoneal onlay mesh (IPOM) repair, transabdominal preperitoneal (TAPP) repair and total extraperitoneal (TEP) repair. These procedures have totally different anatomic point of view, process and technical key points from open operations. The technical details of these operations are discussed in this article, also the strategies of treatment for some special conditions. PMID:27867954

  17. Native tissue repair for central compartment prolapse: a narrative review.

    PubMed

    Paz-Levy, Dorit; Yohay, David; Neymeyer, Joerg; Hizkiyahu, Ranit; Weintraub, Adi Y

    2017-02-01

    Central descent due to a level 1 defect is a main component in pelvic organ prolapse (POP) reconstructive surgery, whether for symptomatic apical prolapse or for the prolapse repair of other compartments. A recent growth in the rate of native tissue repair procedures for POP, following the US Food and Drug Administration (FDA) warnings regarding the safety and efficacy of synthetic meshes, requires a re-evaluation of these procedures. The safety, efficacy, and determination of the optimal surgical approach should be the center of attention. Functional outcome measures and patient-centered results have lately gained importance and received focus. A comprehensive literature review was performed to evaluate objective and subjective outcomes of apical prolapse native tissue repair, with a special focus on studies reporting impact on patients' functional outcomes, quality of life, and satisfaction. We performed a MEDLINE search for articles in the English language by using the following key words: apical prolapse, sacrospinous ligament fixation, uterosacral ligament suspension, sacral colpopexy, McCall culdoplasty, iliococcygeus vaginal fixation, and functional outcomes. We reviewed references as well. Despite a prominent shortage of studies reporting standardized prospective outcomes for native tissue repair interventions, we noted a high rate of safety and efficacy, with a low complication rate for most procedures and low recurrence or re-treatment rates. The objective and subjective results of different procedures are reviewed. Functional outcomes of native tissue repair procedures have not been studied sufficiently, though existing data present those procedures as favorable and not categorically inferior to sacrocolpopexy. Apical compartment prolapse repair using native tissue is not a compromise. Functional outcomes of native tissue repair procedures are favorable, have a high rate of success, improve women's quality of life (QoL), and result in high rates of

  18. Role of tissue repair in toxicologic interactions among hepatotoxic organics.

    PubMed Central

    Soni, M G; Mehendale, H M

    1998-01-01

    It is widely recognized that exposure to combinations or mixtures of chemicals may result in highly exaggerated toxicity even though individual chemicals might not be toxic at low doses. Chemical mixtures may also cause additive or less than additive toxicity. From the perspective of public health, highly exaggerated toxicity is of significant concern. Assessment of risk from exposure to chemical mixtures requires knowledge of the underlying mechanisms. Previous studies from this laboratory have shown that nontoxic doses of chlordecone (10 ppm, 15 days) and carbon tetrachloride (CCl4) (100 microliters/kg) interact at the biologic interface, resulting in potentiated liver injury and 67-fold amplification of CCl4 lethality. In contrast, although interaction between phenobarbital and CCl4 leads to even higher injury, animal survival is unaffected because of highly stimulated compensatory tissue repair. A wide variety of additional experimental evidence confirms the central role of stimulated tissue repair as a decisive determinant of the final outcome of liver injury inflicted by hepatotoxicants. These findings led us to propose a two-stage model of toxicity. In this model, tissue injury is inflicted in stage one by the well-described mechanisms of toxicity, whereas in stage two the ultimate toxic outcome is determined by whether timely and sufficient tissue repair response accompanies this injury. In an attempt to validate this model, dose-response relationships for injury and tissue repair as opposing responses have been developed for model hepatotoxicants. Results of these studies suggest that tissue repair increases in a dose-dependent manner, restraining injury up to a threshold dose, whereupon it is inhibited, allowing an unrestrained progression of injury. These findings indicate that tissue repair is a quantifiable response to toxic injury and that inclusion of this response in risk assessment may help in fine-tuning prediction of toxicity outcomes. Images

  19. Customized Fabrication of Osteochondral Tissue for Articular Joint Surface Repair

    DTIC Science & Technology

    2015-09-01

    it is a disease of the cartilage, bone and surrounding soft tissue that disables 9-10% of the US population. In the US military , combat and non...cartilage – it is a disease of the cartilage, bone and surrounding soft tissue that disables 9-10% of the US population. In the US military , combat and...1 AD______________ AWARD NUMBER: W81XWH-14-1-0217 TITLE: “Customized Fabrication of Osteochondral Tissue for Articular Joint Surface Repair

  20. Key Role of DAMP in Inflammation, Cancer, and Tissue Repair.

    PubMed

    Pandolfi, Franco; Altamura, Simona; Frosali, Simona; Conti, Pio

    2016-05-01

    This review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role of DAMP molecules in inflammation, cancer, and tissue repair. The high-mobility group box (HMGB)-1 and adenosine triphosphate proteins are well-known DAMP molecules and have been primarily associated with inflammation. However, as we shall see, recent data have linked these molecules to tissue repair. HMGB1 is associated with cancer-related inflammation. It activates nuclear factor kB, which is involved in cancer regulation via its receptor for advanced glycation end-products (RAGE), Toll-like receptors 2 and 4. Proinflammatory activity and tissue repair may lead to pharmacologic intervention, by blocking DAMP RAGE and Toll like receptor 2 and 4 role in inflammation and by increasing their concentration in tissue repair, respectively. We conducted a MEDLINE search for articles pertaining to the various issues related to DAMP, and we discuss the most relevant articles especially (ie, not only those published in journals with a higher impact factor). A cluster of remarkable articles on DAMP have appeared in the literature in recent years. Regarding inflammation, several strategies have been proposed to target HMGB1, from antibodies to recombinant box A, which interacts with RAGE, competing with the full molecule. In tissue repair, it was reported that the overexpression of HMGB1 or the administration of exogenous HMGB1 significantly increased the number of vessels and promoted recovery in skin-wound, ischemic injury. Due to the bivalent nature of DAMP, it is often difficult to explain the relative role of DAMP in inflammation versus its role in tissue repair. However, this point is crucial as DAMP-related treatments move into clinical practice. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  1. Tissue Engineering to Repair Diaphragmatic Defect in a Rat Model

    PubMed Central

    Liao, G. P.; Vojnits, K.; Xue, H.; Aroom, K.; Meng, F.; Pan, H. Y.; Hetz, R. A.; Corkins, C. J.; Hughes, T. G.; Triolo, F.; Johnson, A.; Moise, Kenneth J.; Lally, K. P.

    2017-01-01

    Tissue engineering is an emerging strategy for repairing damaged tissues or organs. The current study explored using decellularized rat diaphragm scaffolds combined with human amniotic fluid-derived multipotent stromal cells (hAFMSC) to provide a scaffold, stem cell construct that would allow structural barrier function during tissue ingrowth/regeneration. We created an innovative cell infusion system that allowed hAFMSC to embed into scaffolds and then implanted the composite tissues into rats with surgically created left-sided diaphragmatic defects. Control rats received decellularized diaphragm scaffolds alone. We found that the composite tissues that combined hAFMSCs demonstrated improved physiological function as well as the muscular-tendon structure, compared with the native contralateral hemidiaphragm of the same rat. Our results indicate that the decellularized diaphragm scaffolds are a potential support material for diaphragmatic hernia repair and the composite grafts with hAFMSC are able to accelerate the functional recovery of diaphragmatic hernia. PMID:28928772

  2. ECM-Chitosan Bandage for Tissue Repair

    NASA Astrophysics Data System (ADS)

    Lauto, Antonio; Longo, Leonardo

    2010-05-01

    Extracellular matrices (ECMs) are currently applied in reconstructive surgery to enhance wound healing and tissue remodelling. Sutures and staples are usually employed to stabilize ECM on tissue although they may damage the matrix structure. In this investigation, a novel biocompatible bandage was developed to implant ECM on tissue without sutures. An adhesive film, based on chitosan, was integrated with small intestine submucosa (SIS) in a single bandage strip. This bandage was bonded to sheep small intestine upon laser irradiation of the chitosan film (P = 0.12 W, Fluence = 46±1 J/cm2) to assess tissue adhesion strength. Thermocouples were used to estimate temperatures under SIS during laser irradiation. The bandage successfully bonded to intestine achieving a shear stress of 9.6±1.6 kPa(n = 15). During laser irradiation, the temperature increased modestly to 31±2 0C(n = 14) beneath the ECM portion of the bandage. The SIS-chitosan bandage bonded effectively to tissue without sutures and preserved the ECM structure avoiding irreversible thermal denaturation of imbedded bioactive proteins.

  3. Regenerating functional heart tissue for myocardial repair

    PubMed Central

    Alcon, Andre; Bozkulak, Esra Cagavi; Qyang, Yibing

    2012-01-01

    Heart disease is one of the leading causes of death worldwide and the number of patients with the disease is likely to grow with the continual decline in health for most of the developed world. Heart transplantation is one of the only treatment options for heart failure due to an acute myocardial infarction, but limited donor supply and organ rejection limit its widespread use. Cellular cardiomyoplasty, or cellular implantation, combined with various tissue-engineering methods aims to regenerate functional heart tissue. This review highlights the numerous cell sources that have been used to regenerate the heart as well as cover the wide range of tissue-engineering strategies that have been devised to optimize the delivery of these cells. It will probably be a long time before an effective regenerative therapy can make a serious impact at the bedside. PMID:22388688

  4. Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface.

    PubMed

    Qu, Feini; Pintauro, Michael P; Haughan, Joanne E; Henning, Elizabeth A; Esterhai, John L; Schaer, Thomas P; Mauck, Robert L; Fisher, Matthew B

    2015-01-01

    Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues.

  5. Repair of Dense Connective Tissues via Biomaterial-Mediated Matrix Reprogramming of the Wound Interface

    PubMed Central

    Qu, Feini; Pintauro, Michael P.; Haughan, Joanne; Henning, Elizabeth A.; Esterhai, John L.; Schaer, Thomas P.; Mauck, Robert L.; Fisher, Matthew B.

    2014-01-01

    Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues. PMID:25477175

  6. Extracellular Matrices (ECM) for Tissue Repair.

    PubMed

    Polanco, Thais O; Xylas, Joanna; Lantis, John C

    2016-04-01

    Persistence of skin wounds due to underlying disease, bacterial contamination, and/or repeated trauma, causes a chronic condition where a functional extracellular matrix (ECM) cannot be established and the normal wound-healing cascade is unable to progress. These open chronic wounds leave the body susceptible to infection and present a major healthcare problem. To this end, a broad range of biologic ECM scaffolds have been developed that can provide other therapeutic options aside from traditional wound care approaches. These tissue engineered ECM scaffolds aim to facilitate the restoration of functional skin-like tissue by altering the chronic wound environment and facilitating cellular attachment, proliferation, and differentiation. This discussion will center on reviewing current ECM scaffolds and highlighting their properties and mechanism of action with respect to the clinical application in chronic, non-healing wounds.

  7. Decellularization technology in CNS tissue repair.

    PubMed

    Wang, Hui; Lin, Xian-Feng; Wang, Li-Ren; Lin, Yi-Qian; Wang, Jiang-Tao; Liu, Wen-Yue; Zhu, Gui-Qi; Braddock, Martin; Zhong, Ming; Zheng, Ming-Hua

    2015-05-01

    Decellularization methodologies have been successfully used in a variety of tissue engineering and regenerative technologies and methods of decellularization have been developed for target tissues and organs of interest. The technology to promote regeneration and functional recovery in the CNS, including brain and spinal cord, has, however, made slow progress mainly because the intrinsic regenerative potential of the CNS is regarded as low. To date, currently available therapies have been unable to provide significant functional recovery and successful therapies, which could provide functional restoration to the injured brain and spinal cord are controversial. In this review, the authors provide a critical analysis, comparing the advantages and limitations of the major decellularization methods and considering the effects of these methods upon the biologic scaffold material. The authors also review studies that supplement decellularized grafts with exogenous factors, such as stem cells and growth factors, to both promote and enhance regeneration through decellularized allografts.

  8. The role of DNA damage repair in aging of adult stem cells.

    PubMed

    Kenyon, Jonathan; Gerson, Stanton L

    2007-01-01

    DNA repair maintains genomic stability and the loss of DNA repair capacity results in genetic instability that may lead to a decline of cellular function. Adult stem cells are extremely important in the long-term maintenance of tissues throughout life. They regenerate and renew tissues in response to damage and replace senescent terminally differentiated cells that no longer function. Oxidative stress, toxic byproducts, reduced mitochondrial function and external exposures all damage DNA through base modification or mis-incorporation and result in DNA damage. As in most cells, this damage may limit the survival of the stem cell population affecting tissue regeneration and even longevity. This review examines the hypothesis that an age-related loss of DNA damage repair pathways poses a significant threat to stem cell survival and longevity. Normal stem cells appear to have strict control of gene expression and DNA replication whereas stem cells with loss of DNA repair may have altered patterns of proliferation, quiescence and differentiation. Furthermore, stem cells with loss of DNA repair may be susceptible to malignant transformation either directly or through the emergence of cancer-prone stem cells. Human diseases and animal models of loss of DNA repair provide longitudinal analysis of DNA repair processes in stem cell populations and may provide links to the physiology of aging.

  9. Mechanical stimulation of tissue repair in the hydraulic bone chamber.

    PubMed

    Guldberg, R E; Caldwell, N J; Guo, X E; Goulet, R W; Hollister, S J; Goldstein, S A

    1997-08-01

    A hydraulically activated bone chamber model was utilized to investigate cellular and microstructural mechanisms of mechanical adaptation during bone repair. Woven trabecular bone and fibrotic granulation tissue filled the initially empty chambers by 8 weeks postimplantation into canine tibial and femoral metaphyses. Without mechanical stimulation, active bone remodeling to lamellar trabecular bone and reconstitution of marrow elements were observed between 8 and 24 weeks. In subsequent loading studies, the hydraulic mechanism was activated on one randomly chosen side of 10 dogs following 8 weeks of undisturbed bone repair. The loading treatment applied an intermittent compressive force (18 N, 1.0 Hz, 1800 cycles/day) for durations of a few days up to 12 weeks. Stereological analysis of three-dimensional microcomputed tomography images revealed an increase in trabecular plate thickness and connectivity associated with the loaded repair tissue microstructure relative to unloaded contralateral controls. These microstructural alterations corresponded to an over 600% increase in the apparent modulus of the loaded bone tissue. A significant increase in the percentage of trabecular surfaces lined by osteoblasts immunopositive for type I procollagen after a few days of loading provided further evidence for mechanical stimulation of bone matrix synthesis. The local principal tissue strains associated with these adaptive changes were estimated to range from approximately -2000 to +3000 mustrain using digital image-based finite element methods. This study demonstrates the sensitivity of bone tissue and cells to a controlled in vivo mechanical stimulus and identifies microstructural mechanisms of mechanical adaptation during bone repair. The hydraulic bone chamber is introduced as an efficient experimental model to study the effects of mechanical and biological factors on bone repair and regeneration.

  10. Host Responses in Tissue Repair and Fibrosis

    PubMed Central

    Duffield, Jeremy S.; Lupher, Mark; Thannickal, Victor J.

    2013-01-01

    Myofibroblasts accumulate in the spaces between organ structures and produce extracellular matrix (ECM) proteins, including collagen I. They are the primary “effector” cells in tissue remodeling and fibrosis. Previously, leukocyte progenitors termed fibrocytes and myofibroblasts generated from epithelial cells through epithelial-to-mesenchymal transition (EMT) were considered the primary sources of ECM-producing myofibroblasts in injured tissues. However, genetic fate mapping experiments suggest that mesenchyme-derived cells, known as resident fibroblasts, and pericytes are the primary precursors of scar-forming myofibroblasts, whereas epithelial cells, endothelial cells, and myeloid leukocytes contribute to fibrogenesis predominantly by producing key fibrogenic cytokines and by promoting cell-to-cell communication. Numerous cytokines derived from T cells, macrophages, and other myeloid cell populations are important drivers of myofibroblast differentiation. Monocyte-derived cell populations are key regulators of the fibrotic process: They act as a brake on the processes driving fibrogenesis, and they dismantle and degrade established fibrosis. We discuss the origins, modes of activation, and fate of myofibroblasts in various important fibrotic diseases and describe how manipulation of macrophage activation could help ameliorate fibrosis. PMID:23092186

  11. Micro- and Nanostructured Biomaterials for Sutureless Tissue Repair.

    PubMed

    Frost, Samuel J; Mawad, D; Hook, J; Lauto, Antonio

    2016-02-18

    Sutureless procedures for wound repair and closure have recently integrated nanostructured devices to improve their effectiveness and clinical outcome. This review highlights the major advances in gecko-inspired bioadhesives that relies mostly on van der Waals bonding forces. These are challenged by the moist environment of surgical settings that weaken adherence to tissue. The incorporation of nanoparticles in biomatrices and their role in tissue repair and drug delivery is also reviewed with an emphasis on procedures involving adhesives that are laser-activated. Nanostructured adhesive devices have the advantage of being minimally invasive to tissue, can seal wounds, and deliver drugs in situ. All these tasks are very difficult to accomplish by sutures or staples that are invasive to host organs and often cause scarring.

  12. Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction.

    PubMed

    Hasan, Anwarul; Khattab, Ahmad; Islam, Mohammad Ariful; Hweij, Khaled Abou; Zeitouny, Joya; Waters, Renae; Sayegh, Malek; Hossain, Md Monowar; Paul, Arghya

    2015-11-01

    Cardiac tissue damage due to myocardial infarction (MI) is one of the leading causes of mortality worldwide. The available treatments of MI include pharmaceutical therapy, medical device implants, and organ transplants, all of which have severe limitations including high invasiveness, scarcity of donor organs, thrombosis or stenosis of devices, immune rejection, and prolonged hospitalization time. Injectable hydrogels have emerged as a promising solution for in situ cardiac tissue repair in infarcted hearts after MI. In this review, an overview of various natural and synthetic hydrogels for potential application as injectable hydrogels in cardiac tissue repair and regeneration is presented. The review starts with brief discussions about the pathology of MI, its current clinical treatments and their limitations, and the emergence of injectable hydrogels as a potential solution for post MI cardiac regeneration. It then summarizes various hydrogels, their compositions, structures and properties for potential application in post MI cardiac repair, and recent advancements in the application of injectable hydrogels in treatment of MI. Finally, the current challenges associated with the clinical application of injectable hydrogels to MI and their potential solutions are discussed to help guide the future research on injectable hydrogels for translational therapeutic applications in regeneration of cardiac tissue after MI.

  13. Tissue Engineering a Biological Repair Strategy for Lumbar Disc Herniation

    PubMed Central

    O'Connell, Grace D.; Leach, J. Kent; Klineberg, Eric O.

    2015-01-01

    Abstract The intervertebral disc is a critical part of the intersegmental soft tissue of the spinal column, providing flexibility and mobility, while absorbing large complex loads. Spinal disease, including disc herniation and degeneration, may be a significant contributor to low back pain. Clinically, disc herniations are treated with both nonoperative and operative methods. Operative treatment for disc herniation includes removal of the herniated material when neural compression occurs. While this strategy may have short-term advantages over nonoperative methods, the remaining disc material is not addressed and surgery for mild degeneration may have limited long-term advantage over nonoperative methods. Furthermore, disc herniation and surgery significantly alter the mechanical function of the disc joint, which may contribute to progression of degeneration in surrounding tissues. We reviewed recent advances in tissue engineering and regenerative medicine strategies that may have a significant impact on disc herniation repair. Our review on tissue engineering strategies focuses on cell-based and inductive methods, each commonly combined with material-based approaches. An ideal clinically relevant biological repair strategy will significantly reduce pain and repair and restore flexibility and motion of the spine. PMID:26634189

  14. Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction

    PubMed Central

    Khattab, Ahmad; Islam, Mohammad Ariful; Hweij, Khaled Abou; Zeitouny, Joya; Waters, Renae; Sayegh, Malek; Hossain, Md Monowar; Paul, Arghya

    2015-01-01

    Cardiac tissue damage due to myocardial infarction (MI) is one of the leading causes of mortality worldwide. The available treatments of MI include pharmaceutical therapy, medical device implants, and organ transplants, all of which have severe limitations including high invasiveness, scarcity of donor organs, thrombosis or stenosis of devices, immune rejection, and prolonged hospitalization time. Injectable hydrogels have emerged as a promising solution for in situ cardiac tissue repair in infarcted hearts after MI. In this review, an overview of various natural and synthetic hydrogels for potential application as injectable hydrogels in cardiac tissue repair and regeneration is presented. The review starts with brief discussions about the pathology of MI, its current clinical treatments and their limitations, and the emergence of injectable hydrogels as a potential solution for post MI cardiac regeneration. It then summarizes various hydrogels, their compositions, structures and properties for potential application in post MI cardiac repair, and recent advancements in the application of injectable hydrogels in treatment of MI. Finally, the current challenges associated with the clinical application of injectable hydrogels to MI and their potential solutions are discussed to help guide the future research on injectable hydrogels for translational therapeutic applications in regeneration of cardiac tissue after MI. PMID:27668147

  15. A normal tissue dose response model of dynamic repair processes

    NASA Astrophysics Data System (ADS)

    Alber, Markus; Belka, Claus

    2006-01-01

    A model is presented for serial, critical element complication mechanisms for irradiated volumes from length scales of a few millimetres up to the entire organ. The central element of the model is the description of radiation complication as the failure of a dynamic repair process. The nature of the repair process is seen as reestablishing the structural organization of the tissue, rather than mere replenishment of lost cells. The interactions between the cells, such as migration, involved in the repair process are assumed to have finite ranges, which limits the repair capacity and is the defining property of a finite-sized reconstruction unit. Since the details of the repair processes are largely unknown, the development aims to make the most general assumptions about them. The model employs analogies and methods from thermodynamics and statistical physics. An explicit analytical form of the dose response of the reconstruction unit for total, partial and inhomogeneous irradiation is derived. The use of the model is demonstrated with data from animal spinal cord experiments and clinical data about heart, lung and rectum. The three-parameter model lends a new perspective to the equivalent uniform dose formalism and the established serial and parallel complication models. Its implications for dose optimization are discussed.

  16. Tissue-specific accelerated aging in nucleotide excision repair deficiency

    PubMed Central

    Niedernhofer, Laura J.

    2008-01-01

    Nucleotide excision repair (NER) is a multi-step DNA repair mechanism that removes helix-distorting modified nucleotides from the genome. NER is divided into two subpathways depending on the location of DNA damage in the genome and how it is first detected. Global genome NER identifies and repairs DNA lesions throughout the genome. This subpathway of NER primarily protects against the accumulation of mutations in the genome. Transcription-coupled (TC) NER rapidly repairs lesions in the transcribed strand of DNA that block transcription by RNA polymerase II. TC-NER prevents cell death in response to stalled transcription. Defects in NER cause three distinct human diseases: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Each of these syndromes is characterized by premature onset of pathologies that overlap with those associated with old age in humans. This reveals the contribution of DNA damage to multiple age-related diseases. Tissues affected include the skin, eye, bone marrow, nervous system and endocrine axis. This review emphasizes accelerated aging associated with xeroderma pigmentosum and discusses the cause of these pathologies, either mutation accumulation or cell death as a consequence of failure to repair DNA damage. PMID:18538374

  17. HYDROGEL-BASED NANOCOMPOSITES OF THERAPEUTIC PROTEINS FOR TISSUE REPAIR

    PubMed Central

    Zhu, Suwei; Segura, Tatiana

    2014-01-01

    The ability to design artificial extracellular matrices as cell instructive scaffolds has opened the door to technologies capable of studying cell fates in vitro and to guide tissue repair in vivo. One main component of the design of artificial extracellular matrices is the incorporation of protein-based biochemical cues to guide cell phenotypes and multicellular organizations. However, promoting the long-term bioactivity, controlling the bioavailability and understanding how the physical presentations of these proteins impacts cellular fates are among the challenges of the field. Nanotechnolgy has advanced to meet the challenges of protein therapeutics. For example, the approaches to incorporating proteins into tissue repairing scaffolds have ranged from bulk encapsulations to smart nanodepots that protect proteins from degradations and allow opportunities for controlled release. PMID:24778979

  18. HYDROGEL-BASED NANOCOMPOSITES OF THERAPEUTIC PROTEINS FOR TISSUE REPAIR.

    PubMed

    Zhu, Suwei; Segura, Tatiana

    2014-05-01

    The ability to design artificial extracellular matrices as cell instructive scaffolds has opened the door to technologies capable of studying cell fates in vitro and to guide tissue repair in vivo. One main component of the design of artificial extracellular matrices is the incorporation of protein-based biochemical cues to guide cell phenotypes and multicellular organizations. However, promoting the long-term bioactivity, controlling the bioavailability and understanding how the physical presentations of these proteins impacts cellular fates are among the challenges of the field. Nanotechnolgy has advanced to meet the challenges of protein therapeutics. For example, the approaches to incorporating proteins into tissue repairing scaffolds have ranged from bulk encapsulations to smart nanodepots that protect proteins from degradations and allow opportunities for controlled release.

  19. New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

    PubMed Central

    Musumeci, Giuseppe; Castrogiovanni, Paola; Leonardi, Rosalia; Trovato, Francesca Maria; Szychlinska, Marta Anna; Di Giunta, Angelo; Loreto, Carla; Castorina, Sergio

    2014-01-01

    In this paper review we describe benefits and disadvantages of the established methods of cartilage regeneration that seem to have a better long-term effectiveness. We illustrated the anatomical aspect of the knee joint cartilage, the current state of cartilage tissue engineering, through mesenchymal stem cells and biomaterials, and in conclusion we provide a short overview on the rehabilitation after articular cartilage repair procedures. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, and to date several researchers aim to implement clinical application of cell-based therapies for cartilage repair. A literature review was conducted on PubMed, Scopus and Google Scholar using appropriate keywords, examining the current literature on the well-known tissue engineering methods for the treatment of knee osteoarthritis. PMID:24829869

  20. Biodegradable Materials for Bone Repair and Tissue Engineering Applications

    PubMed Central

    Sheikh, Zeeshan; Najeeb, Shariq; Khurshid, Zohaib; Verma, Vivek; Rashid, Haroon; Glogauer, Michael

    2015-01-01

    This review discusses and summarizes the recent developments and advances in the use of biodegradable materials for bone repair purposes. The choice between using degradable and non-degradable devices for orthopedic and maxillofacial applications must be carefully weighed. Traditional biodegradable devices for osteosynthesis have been successful in low or mild load bearing applications. However, continuing research and recent developments in the field of material science has resulted in development of biomaterials with improved strength and mechanical properties. For this purpose, biodegradable materials, including polymers, ceramics and magnesium alloys have attracted much attention for osteologic repair and applications. The next generation of biodegradable materials would benefit from recent knowledge gained regarding cell material interactions, with better control of interfacing between the material and the surrounding bone tissue. The next generations of biodegradable materials for bone repair and regeneration applications require better control of interfacing between the material and the surrounding bone tissue. Also, the mechanical properties and degradation/resorption profiles of these materials require further improvement to broaden their use and achieve better clinical results. PMID:28793533

  1. Epithelial-mesenchymal transition in tissue repair and fibrosis.

    PubMed

    Stone, Rivka C; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I; Tomic-Canic, Marjana

    2016-09-01

    The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).

  2. Biodegradable Materials for Bone Repair and Tissue Engineering Applications.

    PubMed

    Sheikh, Zeeshan; Najeeb, Shariq; Khurshid, Zohaib; Verma, Vivek; Rashid, Haroon; Glogauer, Michael

    2015-08-31

    This review discusses and summarizes the recent developments and advances in the use of biodegradable materials for bone repair purposes. The choice between using degradable and non-degradable devices for orthopedic and maxillofacial applications must be carefully weighed. Traditional biodegradable devices for osteosynthesis have been successful in low or mild load bearing applications. However, continuing research and recent developments in the field of material science has resulted in development of biomaterials with improved strength and mechanical properties. For this purpose, biodegradable materials, including polymers, ceramics and magnesium alloys have attracted much attention for osteologic repair and applications. The next generation of biodegradable materials would benefit from recent knowledge gained regarding cell material interactions, with better control of interfacing between the material and the surrounding bone tissue. The next generations of biodegradable materials for bone repair and regeneration applications require better control of interfacing between the material and the surrounding bone tissue. Also, the mechanical properties and degradation/resorption profiles of these materials require further improvement to broaden their use and achieve better clinical results.

  3. Mechanotherapy: how physical therapists' prescription of exercise promotes tissue repair.

    PubMed

    Khan, K M; Scott, A

    2009-04-01

    Mechanotransduction is the physiological process where cells sense and respond to mechanical loads. This paper reclaims the term "mechanotherapy" and presents the current scientific knowledge underpinning how load may be used therapeutically to stimulate tissue repair and remodelling in tendon, muscle, cartilage and bone. The purpose of this short article is to answer a frequently asked question "How precisely does exercise promote tissue healing?" This is a fundamental question for clinicians who prescribe exercise for tendinopathies, muscle tears, non-inflammatory arthropathies and even controlled loading after fractures. High-quality randomised controlled trials and systematic reviews show that various forms of exercise or movement prescription benefit patients with a wide range of musculoskeletal problems.1(-)4 But what happens at the tissue level to promote repair and remodelling of tendon, muscle, articular cartilage and bone? The one-word answer is "mechanotransduction", but rather than finishing there and limiting this paper to 95 words, we provide a short illustrated introduction to this remarkable, ubiquitous, non-neural, physiological process. We also re-introduce the term "mechanotherapy" to distinguish therapeutics (exercise prescription specifically to treat injuries) from the homeostatic role of mechanotransduction. Strictly speaking, mechanotransduction maintains normal musculoskeletal structures in the absence of injury. After first outlining the process of mechanotransduction, we provide well-known clinical therapeutic examples of mechanotherapy-turning movement into tissue healing.

  4. Materials science and tissue engineering: repairing the heart.

    PubMed

    Radisic, Milica; Christman, Karen L

    2013-08-01

    Heart failure after a myocardial infarction continues to be a leading killer in the Western world. Currently, there are no therapies that effectively prevent or reverse the cardiac damage and negative left ventricular remodeling process that follows a myocardial infarction. Because the heart has limited regenerative capacity, there has been considerable effort to develop new therapies that could repair and regenerate the myocardium. Although cell transplantation alone was initially studied, more recently, tissue engineering strategies using biomaterial scaffolds have been explored. In this review, we cover the different approaches to engineering the myocardium, including cardiac patches, which are in vitro-engineered constructs of functional myocardium, and injectable scaffolds, which can either encourage endogenous repair and regeneration or act as vehicles to support the delivery of cells and other therapeutics. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  5. Materials Science and Tissue Engineering: Repairing the Heart

    PubMed Central

    Radisic, Milica; Christman, Karen L.

    2013-01-01

    Heart failure following a myocardial infarction continues to be a leading killer in the western world. Currently there are no therapies that effectively prevent or reverse the cardiac damage and negative left ventricular remodeling process that follows a myocardial infarction. Since the heart has limited regenerative capacity, there has been significant effort to develop new therapies that could repair and regenerate the myocardium. While cell transplantation alone was initially studied, more recently tissue engineering strategies using biomaterial scaffolds have been explored. In this review, we cover the different approaches to engineer the myocardium. These include cardiac patches, which are in vitro engineered constructs of functional myocardium, as well as injectable scaffolds that can either encourage endogenous repair and regeneration, or act as vehicles to support delivery of cells and other therapeutics. PMID:23910415

  6. Extralinguistic Features in Conversational Repairs of Adult Second Language Learners.

    ERIC Educational Resources Information Center

    Schwartz, Joan

    Conversations between adult students of English as a second language were recorded, transcribed, and analyzed in order to establish principles of extralinguistic conversational repair technique among second language learners. A variety of gestural and kinesic features were discovered; these are described in detail and their use is contextualized…

  7. Tissue engineering osteochondral implants for temporomandibular joint repair.

    PubMed

    Schek, R M; Taboas, J M; Hollister, S J; Krebsbach, P H

    2005-11-01

    Tissue engineering has provided an alternative to traditional strategies to repair and regenerate temporomandibular joints (TMJ). A successful strategy to engineer osteochondral tissue, such as that found in the TMJ, will produce tissue that is both biologically and mechanically functional. Image-based design (IBD) and solid free-form (SFF) fabrication can be used to generate scaffolds that are load bearing and match patient and defect site geometry. The objective of this study was to demonstrate how scaffold design, materials, and biological factors can be used in an integrated approach to regenerate a multi-tissue interface. IBD and SFF were first used to create biomimetic scaffolds with appropriate bulk geometry and microarchitecture. Biphasic composite scaffolds were then manufactured with the same techniques and used to simultaneously generate bone and cartilage in discrete regions and provide for the development of a stable interface between cartilage and subchondral bone. Poly-l-lactic acid/hydroxyapatite composite scaffolds were differentially seeded with fibroblasts transduced with an adenovirus expressing bone morphogenetic protein-7 in the ceramic phase and fully differentiated chondrocytes in the polymeric phase, and were subcutaneously implanted into mice. Following implantation in the ectopic site, the biphasic scaffolds promoted the simultaneous growth of bone, cartilage, and a mineralized interface tissue. Within the ceramic phase, the pockets of tissue generated included blood vessels, marrow stroma, and adipose tissue. This combination of IBD and SFF-fabricated biphasic scaffolds with gene and cell therapy is a promising approach to regenerate osteochondral defects and, ultimately, the TMJ.

  8. Apparatus and method for enhancing tissue repair in mammals

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J. (Inventor); Parker, Clayton R. (Inventor)

    2009-01-01

    An apparatus is introduced for the use of enhancing tissue repair in mammals. The apparatus includes a sleeve; an electrically conductive coil; a sleeve support; an electrical circuit configured to supply the coil with a square wave time varying electrical current sufficient to create approximately 0.05 gauss to 0.5 gauss. When in use, the sleeve of the apparatus is placed on a mammalian body part and the time varying electromagnetic force of from approximately 0.05 gauss to 0.5 gauss is generated on the mammalian body for an extended period of time so that the tissue is encouraged to be regenerated in the mammalian body part at a rate in excess of the normal tissue regeneration rate relative to regeneration without application of the time varying electromagnetic force.

  9. Use of NASA Bioreactor in Engineering Tissue for Bone Repair

    NASA Technical Reports Server (NTRS)

    Duke, Pauline

    1998-01-01

    This study was proposed in search for a new alternative for bone replacement or repair. Because the systems commonly used in repair of bony defects form bone by going through a cartilaginous phase, implantation of a piece of cartilage could enhance the healing process by having a more advanced starting point. However, cartilage has seldom been used to replace bone due, in part, to the limitations in conventional culture systems that did not allow production of enough tissue for implants. The NASA-developed bioreactors known as STLV (Slow Turning Lateral Vessel) provide homogeneous distribution of cells, nutrients, and waste products, with less damaging turbulence and shear forces than conventional systems. Cultures under these conditions have higher growth rates, viability, and longevity, allowing larger "tissue-like" aggregates to form, thus opening the possibilities of producing enough tissue for implantation, along with the inherent advantages of in vitro manipulations. To assure large numbers of cells and to eliminate the use of timed embryos, we proposed to use an immortalized mouse limb bud cell line as the source of cells.

  10. Cutaneous tissue repair following CO2 laser irradiation.

    PubMed

    Kamat, B R; Carney, J M; Arndt, K A; Stern, R S; Rosen, S

    1986-08-01

    We studied the mechanism of repair following exposure of normal skin to the CO2 laser in a focused mode. Exposed areas were biopsied at 0, 24, 48 h; 1, 2 weeks; 1, 2 1/2 months (pulse width varying from 0.1 to 1.0 s) after irradiation. The initial pattern was a V-shaped zone of cauterized collagen with a central crevice, the depth of which correlated with the total energy applied. The epidermal changes consisted of transepidermal cauterization and basal vacuolar changes lateral to the site of impact. Over a period of 1 week, the wound crevice decreased in depth and width and the central margins of the zone of cauterized collagen approximated. The cauterized collagen was extruded and was noted in the epidermal crust; minimal granulation tissue was present. Biopsies at later time periods showed formation of granulation tissue and retention of small amounts of necrotic collagen; the process of collagen extrusion was largely prevented by suturing. These observations show that dermal contraction and necrotic collagen extrusion are important components of initial tissue repair following limited dermal destruction produced by CO2 irradiation.

  11. Macrophages: supportive cells for tissue repair and regeneration.

    PubMed

    Chazaud, Bénédicte

    2014-03-01

    Macrophages, and more broadly inflammation, have been considered for a long time as bad markers of tissue homeostasis. However, if it is indisputable that macrophages are associated with many diseases in a deleterious way, new roles have emerged, showing beneficial properties of macrophages during tissue repair and regeneration. This discrepancy is likely due to the high plasticity of macrophages, which may exhibit a wide range of phenotypes and functions depending on their environment. Therefore, regardless of their role in immunity, macrophages play a myriad of roles in the maintenance and recovery of tissue homeostasis. They take a major part in the resolution of inflammation. They also exert various effects of parenchymal cells, including stem and progenitor cell, of which they regulate the fate. In the present review, few examples from various tissues are presented to illustrate that, beyond their specific properties in a given tissue, common features have been described that sustain a role of macrophages in the recovery and maintenance of tissue homeostasis.

  12. Experiment K-7-29: Connective Tissue Studies. Part 3; Rodent Tissue Repair: Skeletal Muscle

    NASA Technical Reports Server (NTRS)

    Stauber, W.; Fritz, V. K.; Burkovskaya, T. E.; Ilyina-Kakueva, E. I.

    1994-01-01

    Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

  13. Experiment K-7-29: Connective Tissue Studies. Part 3; Rodent Tissue Repair: Skeletal Muscle

    NASA Technical Reports Server (NTRS)

    Stauber, W.; Fritz, V. K.; Burkovskaya, T. E.; Ilyina-Kakueva, E. I.

    1994-01-01

    Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

  14. Asymptomatic right ventricular dysfunction in surgically repaired adult tetralogy of fallot patients

    PubMed Central

    Nair, Krishna Kumar Mohanan; Ganapathi, Sanjay; Sasidharan, Bijulal; Thajudeen, Anees; Pillai, Harikrishnan Sivadasan; Tharakan, Jaganmohan; Titus, Thomas; Kumaran, Ajitkumar Valaparambil; Sivasubramonian, Sivasankaran; Krishnamoorthy, Kavassery Mahadevan

    2013-01-01

    Background: Right ventricular (RV) dysfunction after surgical repair of Tetralogy of Fallot (TOF) is often asymptomatic and may be detected by tissue Doppler imaging (TDI). The severity of RV dysfunction is more after intracardiac repair with transannular patch (TAP). Methods: One hundred seventy-three adult patients who have undergone surgical repair for TOF were prospectively analyzed for RV function using 2D echocardiography and TDI. RV function was compared between patients who have undergone intracardiac repair with and without TAP. Results: In both the patient sub-groups, TDI derived myocardial performance index (MPI) and myocardial velocities were abnormal even when 2D echocardiography derived RV functional area change was normal. TDI derived MPI was significantly higher (0.5 ± 0.1 vs. 0.4 ± 0 P < 0.001) and Systolic tricuspid annular velocity (Sa) (9.2 ± 1.3 vs. 10.8 ± 1.6 P < 0.001) was significantly lower in the TAP group. Older age at surgery and severity of pulmonary regurgitation on follow-up were among the significant predictors of TDI derived MPI. Conclusions: Asymptomatic RV dysfunction in surgically repaired adult TOF atients can be detected by TDI. Extent of RV dysfunction was significantly greater with patients requiring TAP, in those operated at older age, and in patients with severe pulmonary regurgitation. PMID:23626431

  15. Method of tissue repair using a composite material

    DOEpatents

    Hutchens, Stacy A.; Woodward, Jonathan; Evans, Barbara R.; O'Neill, Hugh M.

    2016-03-01

    A composite biocompatible hydrogel material includes a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa. A calcium comprising salt is disposed in at least some of the pores. The porous polymer matrix can comprise cellulose, including bacterial cellulose. The composite can be used as a bone graft material. A method of tissue repair within the body of animals includes the steps of providing a composite biocompatible hydrogel material including a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa, and inserting the hydrogel material into cartilage or bone tissue of an animal, wherein the hydrogel material supports cell colonization in vitro for autologous cell seeding.

  16. Method of tissue repair using a composite material

    DOEpatents

    Hutchens, Stacy A; Woodward, Jonathan; Evans, Barbara R; O'Neill, Hugh M

    2014-03-18

    A composite biocompatible hydrogel material includes a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa. A calcium comprising salt is disposed in at least some of the pores. The porous polymer matrix can comprise cellulose, including bacterial cellulose. The composite can be used as a bone graft material. A method of tissue repair within the body of animals includes the steps of providing a composite biocompatible hydrogel material including a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa, and inserting the hydrogel material into cartilage or bone tissue of an animal, wherein the hydrogel material supports cell colonization in vitro for autologous cell seeding.

  17. Monocyte and macrophage plasticity in tissue repair and regeneration.

    PubMed

    Das, Amitava; Sinha, Mithun; Datta, Soma; Abas, Motaz; Chaffee, Scott; Sen, Chandan K; Roy, Sashwati

    2015-10-01

    Heterogeneity and high versatility are the characteristic features of the cells of monocyte-macrophage lineage. The mononuclear phagocyte system, derived from the bone marrow progenitor cells, is primarily composed of monocytes, macrophages, and dendritic cells. In regenerative tissues, a central role of monocyte-derived macrophages and paracrine factors secreted by these cells is indisputable. Macrophages are highly plastic cells. On the basis of environmental cues and molecular mediators, these cells differentiate to proinflammatory type I macrophage (M1) or anti-inflammatory or proreparative type II macrophage (M2) phenotypes and transdifferentiate into other cell types. Given a central role in tissue repair and regeneration, the review focuses on the heterogeneity of monocytes and macrophages with current known mechanisms of differentiation and plasticity, including microenvironmental cues and molecular mediators, such as noncoding RNAs. Copyright © 2015. Published by Elsevier Inc.

  18. Monocyte and Macrophage Plasticity in Tissue Repair and Regeneration

    PubMed Central

    Das, Amitava; Sinha, Mithun; Datta, Soma; Abas, Motaz; Chaffee, Scott; Sen, Chandan K.; Roy, Sashwati

    2016-01-01

    Heterogeneity and high versatility are the characteristic features of the cells of monocyte-macrophage lineage. The mononuclear phagocyte system, derived from the bone marrow progenitor cells, is primarily composed of monocytes, macrophages, and dendritic cells. In regenerative tissues, a central role of monocyte-derived macrophages and paracrine factors secreted by these cells is indisputable. Macrophages are highly plastic cells. On the basis of environmental cues and molecular mediators, these cells differentiate to proinflammatory type I macrophage (M1) or anti-inflammatory or proreparative type II macrophage (M2) phenotypes and transdifferentiate into other cell types. Given a central role in tissue repair and regeneration, the review focuses on the heterogeneity of monocytes and macrophages with current known mechanisms of differentiation and plasticity, including microenvironmental cues and molecular mediators, such as noncoding RNAs. PMID:26118749

  19. Cellular forces and matrix assembly coordinate fibrous tissue repair

    PubMed Central

    Sakar, Mahmut Selman; Eyckmans, Jeroen; Pieters, Roel; Eberli, Daniel; Nelson, Bradley J.; Chen, Christopher S.

    2016-01-01

    Planar in vitro models have been invaluable tools to identify the mechanical basis of wound closure. Although these models may recapitulate closure dynamics of epithelial cell sheets, they fail to capture how a wounded fibrous tissue rebuilds its 3D architecture. Here we develop a 3D biomimetic model for soft tissue repair and demonstrate that fibroblasts ensconced in a collagen matrix rapidly close microsurgically induced defects within 24 h. Traction force microscopy and time-lapse imaging reveal that closure of gaps begins with contractility-mediated whole-tissue deformations. Subsequently, tangentially migrating fibroblasts along the wound edge tow and assemble a progressively thickening fibronectin template inside the gap that provide the substrate for cells to complete closure. Unlike previously reported mechanisms based on lamellipodial protrusions and purse-string contraction, our data reveal a mode of stromal closure in which coordination of tissue-scale deformations, matrix assembly and cell migration act together to restore 3D tissue architecture. PMID:26980715

  20. Parthenogenetic stem cells for tissue-engineered heart repair

    PubMed Central

    Didié, Michael; Christalla, Peter; Rubart, Michael; Muppala, Vijayakumar; Döker, Stephan; Unsöld, Bernhard; El-Armouche, Ali; Rau, Thomas; Eschenhagen, Thomas; Schwoerer, Alexander P.; Ehmke, Heimo; Schumacher, Udo; Fuchs, Sigrid; Lange, Claudia; Becker, Alexander; Tao, Wen; Scherschel, John A.; Soonpaa, Mark H.; Yang, Tao; Lin, Qiong; Zenke, Martin; Han, Dong-Wook; Schöler, Hans R.; Rudolph, Cornelia; Steinemann, Doris; Schlegelberger, Brigitte; Kattman, Steve; Witty, Alec; Keller, Gordon; Field, Loren J.; Zimmermann, Wolfram-Hubertus

    2013-01-01

    Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair. PMID:23434590

  1. Fibroblast growth factors as tissue repair and regeneration therapeutics

    PubMed Central

    Kinnunen, Tarja K.

    2016-01-01

    Cell communication is central to the integration of cell function required for the development and homeostasis of multicellular animals. Proteins are an important currency of cell communication, acting locally (auto-, juxta-, or paracrine) or systemically (endocrine). The fibroblast growth factor (FGF) family contributes to the regulation of virtually all aspects of development and organogenesis, and after birth to tissue maintenance, as well as particular aspects of organism physiology. In the West, oncology has been the focus of translation of FGF research, whereas in China and to an extent Japan a major focus has been to use FGFs in repair and regeneration settings. These differences have their roots in research history and aims. The Chinese drive into biotechnology and the delivery of engineered clinical grade FGFs by a major Chinese research group were important enablers in this respect. The Chinese language clinical literature is not widely accessible. To put this into context, we provide the essential molecular and functional background to the FGF communication system covering FGF ligands, the heparan sulfate and Klotho co-receptors and FGF receptor (FGFR) tyrosine kinases. We then summarise a selection of clinical reports that demonstrate the efficacy of engineered recombinant FGF ligands in treating a wide range of conditions that require tissue repair/regeneration. Alongside, the functional reasons why application of exogenous FGF ligands does not lead to cancers are described. Together, this highlights that the FGF ligands represent a major opportunity for clinical translation that has been largely overlooked in the West. PMID:26793421

  2. Transplanted human embryonic stem cells as biological 'catalysts' for tissue repair and regeneration.

    PubMed

    Heng, Boon Chin; Liu, Hua; Cao, Tong

    2005-01-01

    Human embryonic stem cells have tremendous potential in the newly emerging field of regenerative medicine. Recently, it was demonstrated that the rescue of lethal cardiac defects in Id knockout mutant mouse embryos was not due to the transplanted cells giving rise to functional new tissues within the defective embryonic heart. Instead, there is indirect evidence that the observed therapeutic effect was due to various secreted factors emanating from the transplanted cells. This therefore, introduces the exciting prospect of utilizing human embryonic stem cells as biological 'catalysts' to promote tissue repair and regeneration in transplantation therapy. However, the immunological barrier against allogenic transplantation, as well as the teratogenic potential of human embryonic stem cells poses major technical challenges. A possible strategy to overcome the immunological barrier may be to impose a temporary regimen of immunosuppressive drugs followed by their gradual withdrawal, once adequate tissue regeneration has been achieved. Other more novel alternatives include the use of microencapsulation to block interaction with the transplant recipient's immune system, and co-transplantation with bone marrow-derived mesenchymal stem cells, which have been demonstrated to possess immuno-suppressive properties. The teratogenic potential of human embryonic stem cells could possibly be alleviated by directing the differentiation of these cells to specific lineages prior to transplantation, or through mitotic inactivation (gamma irradiation or mitomycin C exposure). Co-transplantation with autologous adult stem cells may represent a novel strategy to further enhance the 'catalytic' effects of human embryonic stem cells. The various factors secreted by human embryonic stem cells could then have a concentrated localized effect on relatively large numbers of co-transplanted autologous adult stem cells, which may in turn lead to enhanced repair and regeneration of the damaged

  3. [Azoospermia and a history of inguinal hernia repair in adult].

    PubMed

    Khodari, M; Ouzzane, A; Marcelli, F; Yakoubi, R; Mitchell, V; Zerbib, P; Rigot, J-M

    2015-10-01

    Inguinal hernia repair is one of the most performed surgeries in the world. It is recognized that any surgery of the pelvic floor may represent a risk factor of male infertility. Retrospective study of patients with azoospermia and a history of adult inguinal hernia repair surgery and referred to our center between January 1990 and January 2011 for infertility. Among 69 azoospermia patients with history of adult inguinal hernia repair surgery, 60 patients underwent surgical extraction of sperm that was successful in 75% (45/60). Positive extraction rate decreases in the subgroup of patients with risk factors for infertility (61.4%) as well as in the group with bilateral inguinal hernia (67.9%). There was no statistically significant difference in the positive rate of sperm retrieval according to surgical technique or according to the use of polypropylene mesh (P>0.05). The obstruction of the vas deferens due to an inguinal hernia repair was a potential iatrogenic cause of male infertility that was rare and underestimated. The influence of using a polypropylene mesh was not clearly demonstrated. The management of these patients is based on prevention in order to identify patients with risk factors of infertility in order to propose a presurgery cryopreservation of sperm. 5. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

    PubMed

    Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

    2014-10-01

    Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.]. Copyright 2014, SLACK Incorporated.

  5. [New challenge of tissue repair and regenerative medicine: to achieve a perfect repair and regeneration of multiple tissues in wound sites].

    PubMed

    Fu, X B

    2016-01-01

    Great achievements in the study of tissue repair and regeneration have been made, and many of these successes have been shown to be beneficial to the patients in recent years. However, perfect tissue repair and regeneration of damaged tissues and organs remain to be great challenges in the management of trauma and diseases. Based on the progress in developmental biology in animals and advances in stem cell biology, it is possible to attain the aim of perfect repair and regeneration by means of somatic cell reprogramming and different inducing techniques.

  6. Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke.

    PubMed

    Cook, Douglas J; Nguyen, Cynthia; Chun, Hyun N; L Llorente, Irene; Chiu, Abraham S; Machnicki, Michal; Zarembinski, Thomas I; Carmichael, S Thomas

    2017-03-01

    Stroke is the leading cause of adult disability. Systemic delivery of candidate neural repair therapies is limited by the blood-brain barrier and off-target effects. We tested a bioengineering approach for local depot release of BDNF from the infarct cavity for neural repair in chronic periods after stroke. The brain release levels of a hyaluronic acid hydrogel + BDNF were tested in several stroke models in mouse (strains C57Bl/6, DBA) and non-human primate ( Macaca fascicularis) and tracked with MRI. The behavioral recovery effects of hydrogel + BDNF and the effects on tissue repair outcomes were determined. Hydrogel-delivered BDNF diffuses from the stroke cavity into peri-infarct tissue over 3 weeks in two mouse stroke models, compared with 1 week for direct BDNF injection. Hydrogel delivery of BDNF promotes recovery of motor function. Mapping of motor system connections indicates that hydrogel-BDNF induces axonal sprouting within existing cortical and cortico-striatal systems. Pharmacogenetic studies show that hydrogel-BDNF induces the initial migration of immature neurons into the peri-infarct cortex and their long-term survival. In chronic stroke in the non-human primate, hydrogel-released BDNF can be detected up to 2 cm from the infarct, a distance relevant to human functional recovery in stroke. The hydrogel can be tracked by MRI in mouse and primate.

  7. Preclinical validation and imaging of Wnt-induced repair in human 3D lung tissue cultures.

    PubMed

    Uhl, Franziska E; Vierkotten, Sarah; Wagner, Darcy E; Burgstaller, Gerald; Costa, Rita; Koch, Ina; Lindner, Michael; Meiners, Silke; Eickelberg, Oliver; Königshoff, Melanie

    2015-10-01

    Chronic obstructive pulmonary disease (COPD) is characterised by a progressive loss of lung tissue. Inducing repair processes within the adult diseased lung is of major interest and Wnt/β-catenin signalling represents a promising target for lung repair. However, the translation of novel therapeutic targets from model systems into clinical use remains a major challenge.We generated murine and patient-derived three-dimensional (3D) ex vivo lung tissue cultures (LTCs), which closely mimic the 3D lung microenvironment in vivo. Using two well-known glycogen synthase kinase-3β inhibitors, lithium chloride (LiCl) and CHIR 99021 (CT), we determined Wnt/β-catenin-driven lung repair processes in high spatiotemporal resolution using quantitative PCR, Western blotting, ELISA, (immuno)histological assessment, and four-dimensional confocal live tissue imaging.Viable 3D-LTCs exhibited preserved lung structure and function for up to 5 days. We demonstrate successful Wnt/β-catenin signal activation in murine and patient-derived 3D-LTCs from COPD patients. Wnt/β-catenin signalling led to increased alveolar epithelial cell marker expression, decreased matrix metalloproteinase-12 expression, as well as altered macrophage activity and elastin remodelling. Importantly, induction of surfactant protein C significantly correlated with disease stage (per cent predicted forced expiratory volume in 1 s) in patient-derived 3D-LTCs.Patient-derived 3D-LTCs represent a valuable tool to analyse potential targets and drugs for lung repair. Enhanced Wnt/β-catenin signalling attenuated pathological features of patient-derived COPD 3D-LTCs.

  8. Tissue and cellular biomechanics during corneal wound injury and repair.

    PubMed

    Raghunathan, Vijay Krishna; Thomasy, Sara M; Strøm, Peter; Yañez-Soto, Bernardo; Garland, Shaun P; Sermeno, Jasmyne; Reilly, Christopher M; Murphy, Christopher J

    2017-08-01

    Corneal wound healing is an enormously complex process that requires the simultaneous cellular integration of multiple soluble biochemical cues, as well as cellular responses to the intrinsic chemistry and biophysical attributes associated with the matrix of the wound space. Here, we document how the biomechanics of the corneal stroma are altered through the course of wound repair following keratoablative procedures in rabbits. Further we documented the influence that substrate stiffness has on stromal cell mechanics. Following corneal epithelial debridement, New Zealand white rabbits underwent phototherapeutic keratectomy (PTK) on the right eye (OD). Wound healing was monitored using advanced imaging modalities. Rabbits were euthanized and corneas were harvested at various time points following PTK. Tissues were characterized for biomechanics with atomic force microscopy and with histology to assess inflammation and fibrosis. Factor analysis was performed to determine any discernable patterns in wound healing parameters. The matrix associated with the wound space was stiffest at 7days post PTK. The greatest number of inflammatory cells were observed 3days after wounding. The highest number of myofibroblasts and the greatest degree of fibrosis occurred 21days after wounding. While all clinical parameters returned to normal values 400days after wounding, the elastic modulus remained greater than pre-surgical values. Factor analysis demonstrated dynamic remodeling of stroma occurs between days 10 and 42 during corneal stromal wound repair. Elastic modulus of the anterior corneal stroma is dramatically altered following PTK and its changes coincide initially with the development of edema and inflammation, and later with formation of stromal haze and population of the wound space with myofibroblasts. Factor analysis demonstrates strongest correlation between elastic modulus, myofibroblasts, fibrosis and stromal haze thickness, and between edema and central corneal

  9. Is soft tissue repair a right choice to avoid early dislocation after THA in posterior approach?

    PubMed

    Zhou, Yiqin; Cao, Shiqi; Li, Lintao; Narava, Manoj; Fu, Qiwei; Qian, Qirong

    2017-05-19

    Dislocation is the second most common complication after total hip arthroplasty (THA). The effectiveness of soft tissue repair to reduce dislocation rate is still debated and thus a meta-analysis was conducted. A systematic search in PubMed, Embase, and Cochrane databases was conducted for this meta-analysis. clinical comparative trials on the use of soft tissue repair including rotators and capsule repair in primary THA. The main data outcome were the incidences of early hip dislocation after primary THA. HSS score, incidence of other complications was also included in the outcomes. A total of 4816 cases were included for the analysis from ten studies (3 RCTs/7 Retrospective trials). Overall, the soft tissue repair group showed a significant lower early dislocation rate and higher HSS score compared to the no repair group; but no significant difference was observed between the two groups in regards to the early dislocation rate in RCT studies only. The capsule repair group showed a significant lower early dislocation rate than no capsule repair group while no significant difference was observed between the rotators repair group and no rotators repair group. In all included studies, 4 greater trochanter fractures, 2 sciatic nerve palsies and 1 infection were reported in soft tissue repair group while no cases were observed in the no repair group. The efficacy of soft tissue repair is positive but still not conclusive to reduce the early dislocation rate after primary THA while soft tissue repair may bring more other complications. Capsule repair seems more effective than rotators repair only.

  10. Advances and Perspectives on Tissue Repair and Healing

    NASA Astrophysics Data System (ADS)

    Pinheiro, Antonio L. B.; Marques, Aparecida M. C.; de Sousa, Ana Paula C.; Aciole, Jouber M. S.; Soares, Luiz G. P.

    2011-08-01

    Wound healing involves local and systemic responses that reflect the etiology of the lesion, type of tissue, systemic condition and others. Despite being essentially the same for different wounds, the pattern of healing may change due to intrinsic and/or extrinsic factors. The type of tissue has also to be considered. Several therapeutic approaches have been used to improve healing including phototherapies such as Laser, LEDs and Lamps. Their effects on soft and mineralized tissues are well reported. The choice of appropriated parameters is essential for the results of the treatment and includes wavelength, power density, energy, duration and frequency of application and others. We studied the effects of different types of light on the healing of both soft and mineralized tissues using different models. We found that the use of Laser and polarized light are effective on improving the healing of diabetic and undernourished animals. We also found that Laser light is capable of improving the healing of drug-induced impairment and on increasing the survival rate of flaps on both diabetic and non-diabetic animals. We have also studied and shown the influence of the laser parameters on the healing of surgical and laser wounds. Lately we verified the positive effect of LEDs on healing. We used Laser/LED light for improving bone healing in conditions such as in dental implants, autologous grafts, biomaterials and fractures. From these reports and our own experience we have no doubt whatsoever that the use of phototherapies, carried out with appropriate parameters, promotes quicker tissue repair.

  11. Neuroinflammation in Parkinson's disease: role in neurodegeneration and tissue repair.

    PubMed

    Vivekanantham, Sayinthen; Shah, Savan; Dewji, Rizwan; Dewji, Abbas; Khatri, Chetan; Ologunde, Rele

    2015-01-01

    Neuroinflammation in Parkinson's disease [PD] is a process that occurs alongside the loss of dopaminergic neurons, and is associated with alterations to many cell types, most notably microglia. This review examines the key evidence contributing to our understanding of the role of inflammation-mediated degeneration of the dopaminergic (DA) nigrostriatal pathway in PD. It will consider the potential role inflammation plays in tissue repair within the brain, inflammation linked gene products that are associated with sporadic Parkinsonian phenotypes (alpha-synuclein, Parkin and Nurr 1), and developing anti-inflammatory drug treatments in PD. With growing evidence supporting the key role of neuroinflammation in PD pathogenesis, new molecular targets are being found that could potentially prevent or delay nigrostriatal DA neuron loss. Hence, this creates the opportunity for disease modifying treatment, to currently what is an incurable disease.

  12. Extracellular vesicles: small bricks for tissue repair/regeneration

    PubMed Central

    Taverna, Simona; Pucci, Marzia

    2017-01-01

    Extracellular vesicles (EVs) are nano-sized membrane vesicles involved in intercellular communication. EVs have pleiotropic actions in physiological and pathological conditions. The ability of EVs to transports proteins, drugs and nucleic acid, to target specific cells and to increase the stability of therapeutic cargo, make EVs interesting as new devices for the treatment of human disease. In a recently published issue of European journal of pharmaceutical sciences, Silva and colleagues reviewed the ability of EVs to modulate tissue repair and regeneration, focusing on their roles and therapeutic potential as immunomodulatory messengers. In this perspective, we discussed the open questions regarding the dual role of EVs in immune system, as well as the technical limitation of the procedure for EVs isolation and administration in clinical practices. EV-based therapies require further studies to consider EVs as promising candidate for a novel cell-free therapy in the context of regeneration medicine. PMID:28275628

  13. Therapeutic potential of HDL in cardioprotection and tissue repair.

    PubMed

    Van Linthout, Sophie; Frias, Miguel; Singh, Neha; De Geest, Bart

    2015-01-01

    Epidemiological studies support a strong association between high-density lipoprotein (HDL) cholesterol levels and heart failure incidence. Experimental evidence from different angles supports the view that low HDL is unlikely an innocent bystander in the development of heart failure. HDL exerts direct cardioprotective effects, which are mediated via its interactions with the myocardium and more specifically with cardiomyocytes. HDL may improve cardiac function in several ways. Firstly, HDL may protect the heart against ischaemia/reperfusion injury resulting in a reduction of infarct size and thus in myocardial salvage. Secondly, HDL can improve cardiac function in the absence of ischaemic heart disease as illustrated by beneficial effects conferred by these lipoproteins in diabetic cardiomyopathy. Thirdly, HDL may improve cardiac function by reducing infarct expansion and by attenuating ventricular remodelling post-myocardial infarction. These different mechanisms are substantiated by in vitro, ex vivo, and in vivo intervention studies that applied treatment with native HDL, treatment with reconstituted HDL, or human apo A-I gene transfer. The effect of human apo A-I gene transfer on infarct expansion and ventricular remodelling post-myocardial infarction illustrates the beneficial effects of HDL on tissue repair. The role of HDL in tissue repair is further underpinned by the potent effects of these lipoproteins on endothelial progenitor cell number, function, and incorporation, which may in particular be relevant under conditions of high endothelial cell turnover. Furthermore, topical HDL therapy enhances cutaneous wound healing in different models. In conclusion, the development of HDL-targeted interventions in these strategically chosen therapeutic areas is supported by a strong clinical rationale and significant preclinical data.

  14. Imaging stem cell differentiation for cell-based tissue repair.

    PubMed

    Lee, Zhenghong; Dennis, James; Alsberg, Eben; Krebs, Melissa D; Welter, Jean; Caplan, Arnold

    2012-01-01

    Mesenchymal stem cells (MSCs) can differentiate into a number of tissue lineages and possess great potential in tissue regeneration and cell-based therapy. For bone fracture or cartilage wear and tear, stem cells need to be delivered to the injury site for repair. Assessing engraftment of the delivered cells and their differentiation status is crucial for the optimization of novel cell-based therapy. A longitudinal and quantitative method is needed to track stem cells transplanted/implanted to advance our understanding of their therapeutic effects and facilitate improvements in cell-based therapy. Currently, there are very few effective noninvasive ways to track the differentiation of infused stem cells. A brief review of a few existing approaches, mostly using transgenic animals, is given first, followed by newly developed in vivo imaging strategies that are intended to track implanted MSCs using a reporter gene system. Specifically, marker genes are selected to track whether MSCs differentiate along the osteogenic lineage for bone regeneration or the chondrogenic lineage for cartilage repair. The general strategy is to use the promoter of a differentiation-specific marker gene to drive the expression of an established reporter gene for noninvasive and repeated imaging of stem cell differentiation. The reporter gene system is introduced into MSCs by way of a lenti-viral vector, which allows the use of human cells and thus offers more flexibility than the transgenic animal approach. Imaging osteogenic differentiation of implanted MSCs is used as a demonstration of the proof-of-principle of this differentiation-specific reporter gene approach. This framework can be easily extended to other cell types and for differentiation into any other cell lineage for which a specific marker gene (promoter) can be identified. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Satellite-like cells contribute to pax7-dependent skeletal muscle repair in adult zebrafish.

    PubMed

    Berberoglu, Michael A; Gallagher, Thomas L; Morrow, Zachary T; Talbot, Jared C; Hromowyk, Kimberly J; Tenente, Inês M; Langenau, David M; Amacher, Sharon L

    2017-04-15

    Satellite cells, also known as muscle stem cells, are responsible for skeletal muscle growth and repair in mammals. Pax7 and Pax3 transcription factors are established satellite cell markers required for muscle development and regeneration, and there is great interest in identifying additional factors that regulate satellite cell proliferation, differentiation, and/or skeletal muscle regeneration. Due to the powerful regenerative capacity of many zebrafish tissues, even in adults, we are exploring the regenerative potential of adult zebrafish skeletal muscle. Here, we show that adult zebrafish skeletal muscle contains cells similar to mammalian satellite cells. Adult zebrafish satellite-like cells have dense heterochromatin, express Pax7 and Pax3, proliferate in response to injury, and show peak myogenic responses 4-5 days post-injury (dpi). Furthermore, using a pax7a-driven GFP reporter, we present evidence implicating satellite-like cells as a possible source of new muscle. In lieu of central nucleation, which distinguishes regenerating myofibers in mammals, we describe several characteristics that robustly identify newly-forming myofibers from surrounding fibers in injured adult zebrafish muscle. These characteristics include partially overlapping expression in satellite-like cells and regenerating myofibers of two RNA-binding proteins Rbfox2 and Rbfoxl1, known to regulate embryonic muscle development and function. Finally, by analyzing pax7a; pax7b double mutant zebrafish, we show that Pax7 is required for adult skeletal muscle repair, as it is in the mouse.

  16. The neonate versus adult mammalian immune system in cardiac repair and regeneration.

    PubMed

    Sattler, Susanne; Rosenthal, Nadia

    2016-07-01

    The immune system is a crucial player in tissue homeostasis and wound healing. A sophisticated cascade of events triggered upon injury ensures protection from infection and initiates and orchestrates healing. While the neonatal mammal can readily regenerate damaged tissues, adult regenerative capacity is limited to specific tissue types, and in organs such as the heart, adult wound healing results in fibrotic repair and loss of function. Growing evidence suggests that the immune system greatly influences the balance between regeneration and fibrotic repair. The neonate mammalian immune system has impaired pro-inflammatory function, is prone to T-helper type 2 responses and has an immature adaptive immune system skewed towards regulatory T cells. While these characteristics make infants susceptible to infection and prone to allergies, it may also provide an immunological environment permissive of regeneration. In this review we will give a comprehensive overview of the immune cells involved in healing and regeneration of the heart and explore differences between the adult and neonate immune system that may explain differences in regenerative ability. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Basal ganglia function, stuttering, sequencing, and repair in adult songbirds.

    PubMed

    Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D

    2014-10-13

    A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations.

  18. Evaluation of skeletal tissue repair, part 2: enhancement of skeletal tissue repair through dual-growth-factor-releasing hydrogels within an ex vivo chick femur defect model.

    PubMed

    Smith, E L; Kanczler, J M; Gothard, D; Roberts, C A; Wells, J A; White, L J; Qutachi, O; Sawkins, M J; Peto, H; Rashidi, H; Rojo, L; Stevens, M M; El Haj, A J; Rose, F R A J; Shakesheff, K M; Oreffo, R O C

    2014-10-01

    There is an unmet need for improved, effective tissue engineering strategies to replace or repair bone damaged through disease or injury. Recent research has focused on developing biomaterial scaffolds capable of spatially and temporally releasing combinations of bioactive growth factors, rather than individual molecules, to recapitulate repair pathways present in vivo. We have developed an ex vivo embryonic chick femur critical size defect model and applied the model in the study of novel extracellular matrix (ECM) hydrogel scaffolds containing spatio-temporal combinatorial growth factor-releasing microparticles and skeletal stem cells for bone regeneration. Alginate/bovine bone ECM (bECM) hydrogels combined with poly(d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30% PDLLGA-PEG-PLDLGA) microparticles releasing dual combinations of vascular endothelial growth factor (VEGF), chondrogenic transforming growth factor beta 3 (TGF-β3) and the bone morphogenetic protein BMP2, with human adult Stro-1+bone marrow stromal cells (HBMSCs), were placed into 2mm central segmental defects in embryonic day 11 chick femurs and organotypically cultured. Hydrogels loaded with VEGF combinations induced host cell migration and type I collagen deposition. Combinations of TGF-β3/BMP2, particularly with Stro-1+HBMSCs, induced significant formation of structured bone matrix, evidenced by increased Sirius red-stained matrix together with collagen expression demonstrating birefringent alignment within hydrogels. This study demonstrates the successful use of the chick femur organotypic culture system as a high-throughput test model for scaffold/cell/growth factor therapies in regenerative medicine. Temporal release of dual growth factors, combined with enriched Stro-1+HBMSCs, improved the formation of a highly structured bone matrix compared to single release modalities. These studies highlight the potential of a unique alginate/bECM hydrogel dual growth factor release

  19. Bioactive Nanocomposites for Tissue Repair and Regeneration: A Review

    PubMed Central

    Bramhill, Jane; Ross, Sukunya; Ross, Gareth

    2017-01-01

    This review presents scientific findings concerning the use of bioactive nanocomposites in the field of tissue repair and regeneration. Bioactivity is the ability of a material to incite a specific biological reaction, usually at the boundary of the material. Nanocomposites have been shown to be ideal bioactive materials due the many biological interfaces and structures operating at the nanoscale. This has resulted in many researchers investigating nanocomposites for use in bioapplications. Nanocomposites encompass a number of different structures, incorporating organic-inorganic, inorganic-inorganic and bioinorganic nanomaterials and based upon ceramic, metallic or polymeric materials. This enables a wide range of properties to be incorporated into nanocomposite materials, such as magnetic properties, MR imaging contrast or drug delivery, and even a combination of these properties. Much of the classical research was focused on bone regeneration, however, recent advances have enabled further use in soft tissue body sites too. Despite recent technological advances, more research is needed to further understand the long-term biocompatibility impact of the use of nanoparticles within the human body. PMID:28085054

  20. Repair and tissue engineering techniques for articular cartilage

    PubMed Central

    Makris, Eleftherios A.; Gomoll, Andreas H.; Malizos, Konstantinos N.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2015-01-01

    Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of regenerative biological products that over the next decade could revolutionize joint care by functionally healing articular cartilage. These products include cell-based and cell-free materials such as autologous and allogeneic cell-based approaches and multipotent and pluripotent stem-cell-based techniques. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed. PMID:25247412

  1. The 22nd annual meeting of the European Tissue Repair Society (ETRS) in Athens, Greece

    PubMed Central

    2013-01-01

    The 22nd Annual Meeting of the European Tissue Repair Society, Athens, Greece, October 4 to 5, 2012 informed about pathophysiological mechanisms in tissue repair and on the development of clinical treatments of chronic wounds, fibrosis, and cancer, considering recent advances in molecular biology and biotechnology. PMID:23374673

  2. Laparoscopic Repair of Congenital Diaphragmatic Hernia in Adults

    PubMed Central

    Kumar, Satendra; Afaque, Yusuf; Bhartia, Abhishek Kumar; Bhartia, Vishnu Kumar

    2016-01-01

    Background, Aims, and Objectives. Congenital diaphragmatic hernia typically presents in childhood but in adults is extremely rare entity. Surgery is indicated for symptomatic and asymptomatic patients who are fit for surgery. It can be done by laparotomy, thoracotomy, thoracoscopy, or laparoscopy. With the advent of minimal access techniques, the open surgical repair for this hernia has decreased and results are comparable with early recovery and less hospital stay. The aim of this study is to establish that laparoscopic repair of congenital diaphragmatic hernia is a safe and effective modality of surgical treatment. Materials and Methods. A retrospective study of laparoscopic diaphragmatic hernia repair done during May 2011 to Oct 2014. Total n = 13 (M/F: 11/2) cases of confirmed diaphragmatic hernia on CT scan, 4 cases Bochdalek hernia (BH), 8 cases of left eventration of the diaphragm (ED), and one case of right-sided eventration of the diaphragm (ED) were included in the study. Largest defect found on the left side was 15 × 6 cm and on the right side it was 15 × 8 cm. Stomach, small intestine, transverse colon, and omentum were contents in the hernial sac. The contents were reduced with harmonic scalpel and thin sacs were usually excised. The eventration was plicated and hernial orifices were repaired with interrupted horizontal mattress sutures buttressed by Teflon pieces. A composite mesh was fixed with nonabsorbable tackers. All patients had good postoperative recovery and went home early with normal follow-up and were followed up for 2 years. Conclusion. The laparoscopic repair is a safe and effective modality of surgical treatment for congenital diaphragmatic hernia in experienced hands. PMID:28074156

  3. Repair of Craniomaxillofacial Traumatic Soft Tissue Defects With Tissue Expansion in the Early Stage.

    PubMed

    Han, Yan; Zhao, Jianhui; Tao, Ran; Guo, Lingli; Yang, Hongyan; Zeng, Wei; Song, Baoqiang; Xia, Wensen

    2017-09-01

    Craniomaxillofacial traumatic soft tissue defects severely affect the function and appearance of the patients. The traditional skin grafting or free flap transplantation can only close the defects in the early stage of operation but cannot ensure similar color, texture, and relative aesthetic contour. In the present study, the authors have explored a novel strategy to repair craniomaxillofacial traumatic soft tissue defects by tissue expansion in the early stage and have obtained satisfactory results. Eighteen patients suffering large craniomaxillofacial traumatic soft tissue defects were treated by thorough debridement leaving the wounds unclosed or simply closed with thin split-thickness scalp grafts, adjacent expander implantation in the first stage, and expanded flap transposition in the second stage. There were 11 male patients and 7 female patients ranging in age from 3.5 to 40 years (mean, 19.4 ± 12.2 years), with average 15 months follow-up (range, 3-67 months). The average expansion time was 74.3 days (range, 53-96 days). The 18 patients with a total of 22 expanders were treated with satisfactory results. All the flaps survived and the skin color, texture, and contour well matched those of the peripheral tissue. Only 1 complication of infection happened in the 18 cases (5.56%) and the 22 expanders (4.55%), which was similar to the rate reported in the literature. No other complications related to the expanders occurred. Debridement and tissue expansion in the early stage has been proved to be a more effective strategy to repair craniomaxillofacial traumatic soft tissue defects. This strategy can not only achieve satisfactory color, unbulky and well-matched texture similar to normal, but also avoid unnecessary donor site injuries.

  4. An in vitro model of adult mammalian nerve repair.

    PubMed

    Vyas, Alka; Li, Zhaobo; Aspalter, Manuela; Feiner, Jeffrey; Hoke, Ahmet; Zhou, Chunhua; O'Daly, Andres; Abdullah, Madeel; Rohde, Charles; Brushart, Thomas M

    2010-05-01

    The role of pathway-derived growth factors in the support of peripheral axon regeneration remains elusive. Few appropriate knock-out mice are available, and gene silencing techniques are rarely 100% effective. To overcome these difficulties, we have developed an in vitro organotypic co-culture system that accurately models peripheral nerve repair in the adult mammal. Spinal cord sections from P4 mice that express YFP in their neurons are used to innervate segments of P4 peripheral nerve. This reconstructed ventral root is then transected and joined to a nerve graft. Growth of axons across the nerve repair and into the graft can be imaged repeatedly with fluorescence microscopy to define regeneration speed, and parent neurons can be labeled in retrograde fashion to identify contributing neurons. Nerve graft harvested from adult mice remains viable in culture by both morphologic and functional criteria. Motoneurons are supported with GDNF for the first week in culture, after which they survive axotomy, and are thus functionally adult. This platform can be modified by using motoneurons from any genetically modified mouse that can be bred to express XFP, by harvesting nerve graft from any source, or by treating the culture systemically with antibodies, growth factors, or pathway inhibitors. The regeneration environment is controlled to a degree not possible in vivo, and the use of experimental animals is reduced substantially. The flexibility and control offered by this technique should thus make it a useful tool for the study of regeneration biology.

  5. A radiation damage repair model for normal tissues

    NASA Astrophysics Data System (ADS)

    Partridge, Mike

    2008-07-01

    A cellular Monte Carlo model describing radiation damage and repair in normal epithelial tissues is presented. The deliberately simplified model includes cell cycling, cell motility and radiation damage response (cell cycle arrest and cell death) only. Results demonstrate that the model produces a stable equilibrium system for mean cell cycle times in the range 24-96 h. Simulated irradiation of these stable equilibrium systems produced a range of responses that are shown to be consistent with experimental and clinical observation, including (i) re-epithelialization of radiation-induced lesions by a mixture of cell migration into the wound and repopulation at the periphery; (ii) observed radiosensitivity that is quantitatively consistent with both rate of induction of irreparable DNA lesions and, independently, with the observed acute oral and pharyngeal mucosal reactions to radiotherapy; (iii) an observed time between irradiation and maximum toxicity that is consistent with experimental data for skin; (iv) quantitatively accurate predictions of low-dose hyper-radiosensitivity; (v) Gomperzian repopulation for very small lesions (~2000 cells) and (vi) a linear rate of re-epithelialization of 5-10 µm h-1 for large lesions (>15 000 cells).

  6. The less-often-traveled surface of stem cells: caveolin-1 and caveolae in stem cells, tissue repair and regeneration

    PubMed Central

    2013-01-01

    Stem cells are an important resource for tissue repair and regeneration. While a great deal of attention has focused on derivation and molecular regulation of stem cells, relatively little research has focused on how the subcellular structure and composition of the cell membrane influences stem cell activities such as proliferation, differentiation and homing. Caveolae are specialized membrane lipid rafts coated with caveolin scaffolding proteins, which can regulate cholesterol transport and the activity of cell signaling receptors and their downstream effectors. Caveolin-1 is involved in the regulation of many cellular processes, including growth, control of mitochondrial antioxidant levels, migration and senescence. These activities are of relevance to stem cell biology, and in this review evidence for caveolin-1 involvement in stem cell biology is summarized. Altered stem and progenitor cell populations in caveolin-1 null mice suggest that caveolin-1 can regulate stem cell proliferation, and in vitro studies with isolated stem cells suggest that caveolin-1 regulates stem cell differentiation. The available evidence leads us to hypothesize that caveolin-1 expression may stabilize the differentiated and undifferentiated stem cell phenotype, and transient downregulation of caveolin-1 expression may be required for transition between the two. Such regulation would probably be critical in regenerative applications of adult stem cells and during tissue regeneration. We also review here the temporal changes in caveolin-1 expression reported during tissue repair. Delayed muscle regeneration in transgenic mice overexpressing caveolin-1 as well as compromised cardiac, brain and liver tissue repair and delayed wound healing in caveolin-1 null mice suggest that caveolin-1 plays an important role in tissue repair, but that this role may be negative or positive depending on the tissue type and the nature of the repair process. Finally, we also discuss how caveolin-1

  7. Informing future cartilage repair strategies: a comparative study of three different human cell types for cartilage tissue engineering.

    PubMed

    Saha, Sushmita; Kirkham, Jennifer; Wood, David; Curran, Stephen; Yang, Xuebin B

    2013-06-01

    A major clinical need exists for cartilage repair and regeneration. Despite many different strategies having been pursued, the identification of an optimised cell type and of pre-treatment conditions remains a challenge. This study compares the cartilage-like tissue generated by human bone marrow stromal cells (HBMSCs) and human neonatal and adult chondrocytes cultured on three-dimensional (3D) scaffolds under various conditions in vitro and in vivo with the aim of informing future cartilage repair strategies based upon tissue-engineering approaches. After 3 weeks in vitro culture, all three cell types showed cartilage-like tissue formation on 3D poly (lactide-co-glycolide) acid scaffolds only when cultured in chondrogenic medium. After 6 weeks of chondro-induction, neonatal chondrocyte constructs revealed the most cartilage-like tissue formation with a prominent superficial zone-like layer, a middle zone-like structure and the thinnest fibrous capsule. HBMSC constructs had the thickest fibrous capsule formation. Under basal culture conditions, neonatal articular chondrocytes failed to form any tissue, whereas HBMSCs and adult chondrocytes showed thick fibrous capsule formation at 6 weeks. After in vivo implantation, all groups generated more compact tissues compared with in vitro constructs. Pre-culturing in chondrogenic media for 1 week before implantation reduced fibrous tissue formation in all cell constructs at week 3. After 6 weeks, only the adult chondrocyte group pre-cultured in chondrogenic media was able to maintain a more chondrogenic/less fibrocartilaginous phenotype. Thus, pre-culture under chondrogenic conditions is required to maintain a long-term chondrogenic phenotype, with adult chondrocytes being a more promising cell source than HBMSCs for articular cartilage tissue engineering.

  8. Adult stem cells in neural repair: Current options, limitations and perspectives.

    PubMed

    Mariano, Eric Domingos; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi; Lepski, Guilherme

    2015-03-26

    Stem cells represent a promising step for the future of regenerative medicine. As they are able to differentiate into any cell type, tissue or organ, these cells are great candidates for treatments against the worst diseases that defy doctors and researchers around the world. Stem cells can be divided into three main groups: (1) embryonic stem cells; (2) fetal stem cells; and (3) adult stem cells. In terms of their capacity for proliferation, stem cells are also classified as totipotent, pluripotent or multipotent. Adult stem cells, also known as somatic cells, are found in various regions of the adult organism, such as bone marrow, skin, eyes, viscera and brain. They can differentiate into unipotent cells of the residing tissue, generally for the purpose of repair. These cells represent an excellent choice in regenerative medicine, every patient can be a donor of adult stem cells to provide a more customized and efficient therapy against various diseases, in other words, they allow the opportunity of autologous transplantation. But in order to start clinical trials and achieve great results, we need to understand how these cells interact with the host tissue, how they can manipulate or be manipulated by the microenvironment where they will be transplanted and for how long they can maintain their multipotent state to provide a full regeneration.

  9. The effects of transcutaneous electrical nerve stimulation on tissue repair: A literature review

    PubMed Central

    Machado, Aline Fernanda Perez; Santana, Eduardo Ferreira; Tacani, Pascale Mutti; Liebano, Richard Eloin

    2012-01-01

    BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) consists of a generic application of low-frequency, pulsed electrical currents transmitted by electrodes through the skin surface. It is a therapeutic modality that is nonpharmacological, noninvasive, inexpensive, easy to use and widely applied in clinical practice. OBJECTIVE: To narratively review the scientific evidence of the effects of TENS on tissue repair with respect to wound healing, skin flap viability and tendinous repair. METHODS: The study was conducted using the MEDLINE, Lilacs and Scielo databases, without limit to the period of publication, and was completed in November 2011. Inclusion criteria were randomized or nonrandomized, controlled or noncontrolled clinical trials, and experimental trials involving rats subjected to TENS for tissue repair. RESULTS: Thirty articles on tissue repair were found and, among these, 14 reported on wound healing, 14 reported on skin flaps and two analyzed tedinous repair. DISCUSSION: It was suggested that TENS stimulates skin wound healing and tendon repair, as well as the viability of random skin flaps. Such effects may be due to the release of substance P and calcitonin gene-related peptide, which would increase blood flow and, consequently, hasten the events leading to tissue repair. CONCLUSIONS: Based on the scientific evidence regarding the effects of TENS on tissue repair, the findings of the present literature review were inconclusive because data from the randomized controlled clinical trials were insufficient to confirm such effects. PMID:24294017

  10. Tissue-engineering strategies to repair joint tissue in osteoarthritis: nonviral gene-transfer approaches.

    PubMed

    Madry, Henning; Cucchiarini, Magali

    2014-10-01

    Loss of articular cartilage is a common clinical consequence of osteoarthritis (OA). In the past decade, substantial progress in tissue engineering, nonviral gene transfer, and cell transplantation have provided the scientific foundation for generating cartilaginous constructs from genetically modified cells. Combining tissue engineering with overexpression of therapeutic genes enables immediate filling of a cartilage defect with an engineered construct that actively supports chondrogenesis. Several pioneering studies have proved that spatially defined nonviral overexpression of growth-factor genes in constructs of solid biomaterials or hydrogels is advantageous compared with gene transfer or scaffold alone, both in vitro and in vivo. Notably, these investigations were performed in models of focal cartilage defects, because advanced cartilage-repair strategies based on the principles of tissue engineering have not advanced sufficiently to enable resurfacing of extensively degraded cartilage as therapy for OA. These studies serve as prototypes for future technological developments, because they raise the possibility that cartilage constructs engineered from genetically modified chondrocytes providing autocrine and paracrine stimuli could similarly compensate for the loss of articular cartilage in OA. Because cartilage-tissue-engineering strategies are already used in the clinic, combining tissue engineering and nonviral gene transfer could prove a powerful approach to treat OA.

  11. 2010 Nicolas Andry Award: Multipotent adult stem cells from adipose tissue for musculoskeletal tissue engineering.

    PubMed

    Guilak, Farshid; Estes, Bradley T; Diekman, Brian O; Moutos, Franklin T; Gimble, Jeffrey M

    2010-09-01

    Cell-based therapies such as tissue engineering provide promising therapeutic possibilities to enhance the repair or regeneration of damaged or diseased tissues but are dependent on the availability and controlled manipulation of appropriate cell sources. The goal of this study was to test the hypothesis that adult subcutaneous fat contains stem cells with multilineage potential and to determine the influence of specific soluble mediators and biomaterial scaffolds on their differentiation into musculoskeletal phenotypes. We reviewed recent studies showing the stem-like characteristics and multipotency of adipose-derived stem cells (ASCs), and their potential application in cell-based therapies in orthopaedics. Under controlled conditions, ASCs show phenotypic characteristics of various cell types, including chondrocytes, osteoblasts, adipocytes, neuronal cells, or muscle cells. In particular, the chondrogenic differentiation of ASCs can be induced by low oxygen tension, growth factors such as bone morphogenetic protein-6 (BMP-6), or biomaterial scaffolds consisting of native tissue matrices derived from cartilage. Finally, focus is given to the development of a functional biomaterial scaffold that can provide ASC-based constructs with mechanical properties similar to native cartilage. Adipose tissue contains an abundant source of multipotent progenitor cells. These cells show cell surface marker profiles and differentiation characteristics that are similar to but distinct from other adult stem cells, such as bone marrow mesenchymal stem cells (MSCs). The availability of an easily accessible and reproducible cell source may greatly facilitate the development of new cell-based therapies for regenerative medicine applications in the musculoskeletal system.

  12. Rational design of nanofiber scaffolds for orthopedic tissue repair and regeneration

    PubMed Central

    Ma, Bing; Xie, Jingwei; Jiang, Jiang; Shuler, Franklin D; Bartlett, David E

    2013-01-01

    This article reviews recent significant advances in the design of nanofiber scaffolds for orthopedic tissue repair and regeneration. It begins with a brief introduction on the limitations of current approaches for orthopedic tissue repair and regeneration. It then illustrates that rationally designed scaffolds made up of electrospun nanofibers could be a promising solution to overcome the problems that current approaches encounter. The article also discusses the intriguing properties of electrospun nanofibers, including control of composition, structures, orders, alignments and mechanical properties, use as carriers for topical drug and/or gene sustained delivery, and serving as substrates for the regulation of cell behaviors, which could benefit musculoskeletal tissue repair and regeneration. It further highlights a few of the many recent applications of electrospun nanofiber scaffolds in repairing and regenerating various orthopedic tissues. Finally, the article concludes with perspectives on the challenges and future directions for better design, fabrication and utilization of nanofiber scaffolds for orthopedic tissue engineering. PMID:23987110

  13. Immune modulation by MANF promotes tissue repair and regenerative success in the retina.

    PubMed

    Neves, Joana; Zhu, Jie; Sousa-Victor, Pedro; Konjikusic, Mia; Riley, Rebeccah; Chew, Shereen; Qi, Yanyan; Jasper, Heinrich; Lamba, Deepak A

    2016-07-01

    Regenerative therapies are limited by unfavorable environments in aging and diseased tissues. A promising strategy to improve success is to balance inflammatory and anti-inflammatory signals and enhance endogenous tissue repair mechanisms. Here, we identified a conserved immune modulatory mechanism that governs the interaction between damaged retinal cells and immune cells to promote tissue repair. In damaged retina of flies and mice, platelet-derived growth factor (PDGF)-like signaling induced mesencephalic astrocyte-derived neurotrophic factor (MANF) in innate immune cells. MANF promoted alternative activation of innate immune cells, enhanced neuroprotection and tissue repair, and improved the success of photoreceptor replacement therapies. Thus, immune modulation is required during tissue repair and regeneration. This approach may improve the efficacy of stem-cell-based regenerative therapies.

  14. Rational design of nanofiber scaffolds for orthopedic tissue repair and regeneration.

    PubMed

    Ma, Bing; Xie, Jingwei; Jiang, Jiang; Shuler, Franklin D; Bartlett, David E

    2013-09-01

    This article reviews recent significant advances in the design of nanofiber scaffolds for orthopedic tissue repair and regeneration. It begins with a brief introduction on the limitations of current approaches for orthopedic tissue repair and regeneration. It then illustrates that rationally designed scaffolds made up of electrospun nanofibers could be a promising solution to overcome the problems that current approaches encounter. The article also discusses the intriguing properties of electrospun nanofibers, including control of composition, structures, orders, alignments and mechanical properties, use as carriers for topical drug and/or gene sustained delivery, and serving as substrates for the regulation of cell behaviors, which could benefit musculoskeletal tissue repair and regeneration. It further highlights a few of the many recent applications of electrospun nanofiber scaffolds in repairing and regenerating various orthopedic tissues. Finally, the article concludes with perspectives on the challenges and future directions for better design, fabrication and utilization of nanofiber scaffolds for orthopedic tissue engineering.

  15. Hematopoietic tissue repair under chronic low daily dose irradiation

    NASA Astrophysics Data System (ADS)

    Seed, T. M.

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). In our laboratory we have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3-26.3 cGy d^-1). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific (three major responding subgroups identified) and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup 1), the failure to augment basic repair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments (particularly marked within erythroid compartments) that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccommodated and either prone- or not prone to ML, subgroup 2 & 3) appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high-tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity. The kinetics of these repair-mediated, regenerative hematopoietic

  16. Interspecies comparisons of tissue DNA damage, repair, fixation, and replication.

    PubMed Central

    Slaga, T J

    1988-01-01

    The many anatomical, physiological, and biochemical differences among various mammalian species make it difficult to extrapolate carcinogenic potency data from animals to humans. The process is further complicated by the multistep origin of most malignant tumors in animals and humans due to the interaction of target cells with both endogenous and exogenous factors. Species differences in these aspects of carcinogenesis must also be considered when attempting to evaluate the carcinogenic risks of chemicals to humans. Cancer development in animals involves at least three distinct stages: initiation, promotion, and progression. Intra- and interspecies differences in susceptibility to carcinogenesis may be related to any one or a combination of these stages. Variation in species susceptibility to tumor initiation may result from differences in the abilities of various species to metabolize a potential carcinogen to an ultimate carcinogenic form and/or to detoxify the carcinogen. Most comparative studies among species have only revealed subtle differences in metabolism. DNA adducts from several activated carcinogens have been found to be the same in a number of tissues from various species, including humans. Capacity for DNA repair is apparently a critical factor in the initiation of carcinogenesis in target cells of different species but is less critical among mice that differ in susceptibility to two-stage carcinogenesis of the skin and liver. Susceptibility variations among stocks and strains to such carcinogenesis appear to be related to alterations in tumor promotion. Additional comparative studies are critically needed on all aspects of carcinogenesis to permit effective extrapolation of carcinogenic potency data from animals to humans. PMID:3289910

  17. Interspecies comparisons of tissues DNA damage, repair, fixation, and replication

    SciTech Connect

    Slaga, T.J.

    1988-04-01

    The many anatomical, physiological, and biochemical differences among various mammalian species make it difficult to extrapolate carcinogenic potency data from animals to humans. The process is further complicated by the multistep origin of most malignant tumors in animals and humans due to the interaction of target cells with both endogenous and exogenous factors. Species differences in these aspects of carcinogenesis must also be considered when attempting to evaluate the carcinogenic risks of chemicals to humans. Cancer development in animals involves at least three distinct stages: initiation, promotion, and progression. Intra- and interspecies differences in susceptibility to carcinogenesis may be related to any one or a combination of these stages. Variation in species susceptibility to tumor initiation may result from differences in the abilities of various species to metabolize a potential carcinogen to an ultimate carcinogenic form and/or to detoxify the carcinogen. Most comparative studies among species have only revealed subtle differences in metabolism. DNA adducts from several activated carcinogens have been found to be the same in a number of tissues from various species, including humans. Capacity for DNA repair is apparently a critical factor in the initiation of carcinogenesis in target cells of different species but is less critical among mice that differ in susceptibility to two-stage carcinogenesis of the skin and liver. Susceptibility variations among stocks and strains to such carcinogenesis appear to be related to alterations in tumor promotion. Additional comparative studies are critically needed on all aspects of carcinogenesis to permit effective extrapolation of carcinogenic potency data from animals to humans.

  18. Laparoscopic repair of complicated umbilical hernia with Strattice Laparoscopic™ reconstructive tissue matrix.

    PubMed

    Tsuda, Shawn

    2014-01-01

    Complex hernias continue to present a challenge. Surgical techniques for repair are carefully considered to reduce risk for complications. Laparoscopic repairs improve postoperative infection rates, and placement of biologic mesh decreases mesh infection rates. However, laparoscopic repairs using biologic mesh is generally challenging due to difficulty with maneuverability. We present a case of a complex ventral hernia that was laparoscopically repaired using a new FDA cleared laparoscopic biologic graft. The patient had multiple comorbidities, including obesity, hepatitis C, endocarditis secondary to IV drug use, tobacco smoking, bilateral inguinal hernia, and recurrent umbilical hernia. The recurrent hernia was larger, irreducible, and discolored compared to original defect. The patient underwent laparoscopic repair with primary closure and reinforcement with Strattice™ Tissue Matrix Laparoscopic (LifeCell Corporation, Branchburg, NJ). At nine months postoperative, the patient had no evidence of recurrence, infection, or chronic pain, demonstrating early success from the surgical management. Presence of multiple comorbidities and incarcerated recurrent hernia increase risk for complications during and/or after hernia repair. Considering these factors, laparoscopic repair with Strattice Laparoscopic and defect closure was a reasonable technique for repair. Laparoscopic suture repair reinforced with biologic dermal tissue matrix was successfully performed during a complex hernia repair. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  19. Self assembling bioactive materials for cell adhesion in tissue repair

    NASA Astrophysics Data System (ADS)

    Hwang, Julia J.

    This work involved the study of biodegradable and biocompatible materials that have the potential to modify tissue engineering scaffolds through self assembly, generating multiple layers that deliver bioactivity. Diblock biomaterials containing cholesteryl moieties and oligomers of lactic acid units were found to form single crystals when precipitated from hot ethanol and smectic liquid crystalline phases when cast as a film. Cell culture experiments on these films with 3T3 and 3T6 fibroblasts indicated that these ordered materials form surfaces with specific chemistries that favored cell adhesion, spreading, and proliferation suggesting the potential of mediating human tissue repair. The author believes the cholesteryl moieties found on the surface play a key role in determining cell behavior. Cholesteryl-(L-lactic acid) diblock molecules were then functionalized with moieties including vitamin Bx, cholesterol, and the anti-inflammatory drug indomethacin. An unstable activated ester between indomethacin and the diblock molecule resulted in the release of indomethacin into the culture medium which inhibited the proliferation of 3T3 fibroblasts. Finally, a series of molecules were designed to incorporate dendrons based on amino acids at the termini of the diblock structures. It was determined that lysine, a basic amino acid, covalently coupled to cholesteryl-(L-lactic acid) can promote cell adhesion and spreading while negatively charged and zwitterionic 2nd generation dendrons based on aspartic acid do not. Incorporation of the well known arginine-glycine-aspartic acid (RGD) sequence, which is found in many adhesive proteins, to the dendrons imparted integrin-mediated cell adhesion as evidenced by the formation of stress fibers. We also explored the capacity of integrin receptors to bind to ligands that are not the linear form of RGD, but have R, G, and D spatially positioned to mimic the linear RGD environments. For this purpose, the arms of the 2 nd generation

  20. How Somatic Adult Tissues Develop Organizer Activity.

    PubMed

    Vogg, Matthias C; Wenger, Yvan; Galliot, Brigitte

    2016-01-01

    The growth and patterning of anatomical structures from specific cellular fields in developing organisms relies on organizing centers that instruct surrounding cells to modify their behavior, namely migration, proliferation, and differentiation. We discuss here how organizers can form in adult organisms, a process of utmost interest for regenerative medicine. Animals like Hydra and planarians, which maintain their shape and fitness thanks to a highly dynamic homeostasis, offer a useful paradigm to study adult organizers in steady-state conditions. Beside the homeostatic context, these model systems also offer the possibility to study how organizers form de novo from somatic adult tissues. Both extracellular matrix remodeling and caspase activation play a key role in this transition, acting as promoters of organizer formation in the vicinity of the wound. Their respective roles and the crosstalk between them just start to be deciphered.

  1. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    PubMed Central

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications. PMID:27338364

  2. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration.

    PubMed

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-06-21

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  3. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process

    PubMed Central

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix–only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications

  4. Outcomes of thoracic endovascular aortic repair in adult coarctation patients.

    PubMed

    Lala, Salim; Scali, Salvatore T; Feezor, Robert J; Chandrekashar, Satish; Giles, Kristina A; Fatima, Javairiah; Berceli, Scott A; Back, Martin R; Huber, Thomas S; Beaver, Thomas M; Beck, Adam W

    2017-09-22

    Aortic coarctation (AC) is most commonly identified in pediatric patients; however, adults can present with late sequelae of untreated coarctation or complications of prior open repair. To date, there are limited data about the role of thoracic endovascular aortic repair (TEVAR) in this group of patients. The purpose of this analysis was to describe our experience with management of adult coarctation patients using TEVAR. All TEVAR patients treated for primary coarctation or late sequelae of previous open repair (eg, pseudoaneurysm, recurrent coarctation or anastomotic stenosis related to index open coarctation repair) were reviewed. Demographics, comorbidities, procedure-related variables, postoperative outcomes, and reintervention were recorded. Computed tomography centerline assessments of endograft morphology were completed to delineate stent anatomy at the coarctation site. Survival and reintervention were estimated using life-table analysis. A total of 21 patients were identified (median age, 46 years [range, 33-71 years]; 67% male [n = 14]). Nine patients (43%) were treated for symptomatic primary (n = 6) or recurrent (n = 3) coarctation. Other indications included degenerative thoracic aneurysm (n = 6), pseudoaneurysm (n = 4), and dissection (n = 2). Technical success was 100% (95% confidence interval [CI], 84%-100%). No 30-day mortality or paraplegia events occurred; however, two patients (10%) experienced postoperative nondisabling stroke. In primary or recurrent coarctation patients with available computed tomography imaging (n = 8 of 9), nominal stent graft diameters were achieved proximal and distal to the coarctation (range, -0.4 to -1.2 mm of desired final stent diameter). Specific to the coarctation site, there was a significant increase in aortic diameter after TEVAR (before stenting, 11.5 [95% CI, 6.8-12.3] mm; after stenting, 15 [95% CI, 13.7-15.7] mm; P = .004). Concurrently, systolic arterial blood pressure at time of discharge was

  5. Hematopoietic tissue repair under chronic low daily dose irradiation

    SciTech Connect

    Seed, T.M.

    1994-12-01

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3{minus}26.3 cGy d{sup {minus}1}). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 & 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity.

  6. Factors influencing the long-term behavior of extracellular matrix-derived scaffolds for musculoskeletal soft tissue repair

    PubMed Central

    Rowland, Christopher R.; Little, Dianne; Guilak, Farshid

    2013-01-01

    Musculoskeletal connective tissues such as tendon, ligament, and cartilage possess a limited ability for self-repair. Tissue engineering seeks to use combinations of cells, bioactive molecules, and biomaterials to develop new treatment options for the repair or replacement of damaged tissues. The use of native extracellular matrix as scaffold material for tissue engineering has become increasingly attractive as such tissues can not only provide structural support, but also regulate cell behavior. While demineralized bone matrix has long been recognized for its osteoinductive abilities, recent studies have identified the ability of cartilage and tendon extracellular matrices to stimulate the differentiation of mesenchymal or adipose-derived adult stem cells toward chondrogenic or tenogenic lineages respectively. This review discusses the motivation for fabricating scaffolds from musculoskeletal tissues, the in vitro and in vivo efficacy of these tissue-derived scaffolds, and various processing techniques such as decellularization or crosslinking that can mitigate immunogenic responses, moderate degradation profile, and enhance the mechanical properties of these constructs following long-term implantation in vivo. PMID:23582110

  7. Laparoscopic Repair of Bochdalek Diaphragmatic Hernia in Adults.

    PubMed

    Machado, Norman Oneil

    2016-02-01

    Bochdalek hernia (BH) is an uncommon form of diaphragmatic hernia. The rarity of this hernia and its nonspecific presentation leads to delay in the diagnosis, with the potential risk of complications. This review summarizes the relevant aspects of its presentation and management, based on the present evidence in the literature. A literature search was performed on PubMed, Google Scholar, and EMBASE for articles in English on BH in adults. All case reports and series from the period after 1955 till January 2015 were included. A total of 180 articles comprising 368 cases were studied. The mean age of these patients was 51 years (range 15-90 years) with a male preponderance of 57% (211/368). Significantly, 6.5% of patients were above 70 years, with 3.5% of these being above 80 years. The majority of the hernias were on the left side (63%), with right-sided hernias and bilateral occurring in 27% and 10%, respectively. Precipitating factors were noted in 24%, with 5.3% of them being pregnant. Congenital anomalies were seen in 11%. The presenting symptoms included abdominal (62%), respiratory (40%), obstructive (vomiting/abdominal distension; 36%), strangulation (26%); 14% of them were asymptomatic (detected incidentally). In the 184 patients who underwent surgical intervention, the surgical approach involved laparotomy in 74 (40.27%), thoracotomy in 50 (27.7%), combined thoracoabdominal approach in 27 (14.6%), laparoscopy in 23 (12.5%), and thoracoscopic repair in 9 (4.89%). An overall recurrence rate of 1.6% was noted. Among these patients who underwent laparoscopic repair, 82% underwent elective procedure; 66% underwent primary repair, with 61% requiring interposition of mesh or reenforcement with or without primary repair. The overall mortality was 2.7%. Therefore, BH should form one of the differential diagnoses in patients who present with simultaneous abdominal and chest symptoms. Minimal access surgery offers a good alternative with short hospital stay and is

  8. Alternatively activated macrophages determine repair of the infarcted adult murine heart

    PubMed Central

    Shiraishi, Manabu; Shintani, Yasunori; Shintani, Yusuke; Ishida, Hidekazu; Saba, Rie; Yamaguchi, Atsushi; Adachi, Hideo; Yashiro, Kenta

    2016-01-01

    Alternatively activated (also known as M2) macrophages are involved in the repair of various types of organs. However, the contribution of M2 macrophages to cardiac repair after myocardial infarction (MI) remains to be fully characterized. Here, we identified CD206+F4/80+CD11b+ M2-like macrophages in the murine heart and demonstrated that this cell population predominantly increases in the infarct area and exhibits strengthened reparative abilities after MI. We evaluated mice lacking the kinase TRIB1 (Trib1–/–), which exhibit a selective depletion of M2 macrophages after MI. Compared with control animals, Trib1–/– mice had a catastrophic prognosis, with frequent cardiac rupture, as the result of markedly reduced collagen fibril formation in the infarct area due to impaired fibroblast activation. The decreased tissue repair observed in Trib1–/– mice was entirely rescued by an external supply of M2-like macrophages. Furthermore, IL-1α and osteopontin were suggested to be mediators of M2-like macrophage–induced fibroblast activation. In addition, IL-4 administration achieved a targeted increase in the number of M2-like macrophages and enhanced the post-MI prognosis of WT mice, corresponding with amplified fibroblast activation and formation of more supportive fibrous tissues in the infarcts. Together, these data demonstrate that M2-like macrophages critically determine the repair of infarcted adult murine heart by regulating fibroblast activation and suggest that IL-4 is a potential biological drug for treating MI. PMID:27140396

  9. Delivery of Mesenchymal Stem Cells in Chitosan/Collagen Microbeads for Orthopaedic Tissue Repair

    PubMed Central

    Wang, Limin; Rao, Rameshwar R.; Stegemann, Jan P.

    2013-01-01

    Microencapsulation and delivery of stem cells in biomaterials is a promising approach to repairing damaged tissue in a minimally invasive manner. An appropriate biomaterial niche can protect the embedded cells from the challenging environment in the host tissue, while also directing stem cell differentiation toward the desired lineage. In this study, adult human mesenchymal stem cells (MSC) were embedded in hydrogel microbeads consisting of chitosan and Type I collagen using an emulsification process. Glyoxal and β-glycerophosphate were used as physical and chemical crosslinkers to initiate co-polymerization of the matrix materials. The average size and size distribution of the microbeads could be varied by controlling the emulsification conditions. Spheroidal microbeads ranging in diameter from 82±19 to 290±78 μm were produced. Viability staining showed that MSC survived the encapsulation process (>90% viability), and spread inside the matrix over a period of 9 days in culture. Induced osteogenic differentiation using medium supplements showed that MSC increased gene expression of osterix and osteocalcin over time in culture, and also deposited calcium mineral. Bone sialoprotein and Type I collagen gene expression were not affected. Delivery of microbeads through standard needles at practically relevant flow rates did not adversely affect cell viability, and microbeads also could be easily molded into prescribed geometries for delivery. Such protein-based microbeads may have utility in orthopaedic tissue regeneration by allowing minimally invasive delivery of progenitor cells in microenvironments that are both protective and instructive. PMID:23571151

  10. Augmentation of Rotator Cuff Repair With Soft Tissue Scaffolds

    PubMed Central

    Thangarajah, Tanujan; Pendegrass, Catherine J.; Shahbazi, Shirin; Lambert, Simon; Alexander, Susan; Blunn, Gordon W.

    2015-01-01

    Background Tears of the rotator cuff are one of the most common tendon disorders. Treatment often includes surgical repair, but the rate of failure to gain or maintain healing has been reported to be as high as 94%. This has been substantially attributed to the inadequate capacity of tendon to heal once damaged, particularly to bone at the enthesis. A number of strategies have been developed to improve tendon-bone healing, tendon-tendon healing, and tendon regeneration. Scaffolds have received considerable attention for replacement, reconstruction, or reinforcement of tendon defects but may not possess situation-specific or durable mechanical and biological characteristics. Purpose To provide an overview of the biology of tendon-bone healing and the current scaffolds used to augment rotator cuff repairs. Study Design Systematic review; Level of evidence, 4. Methods A preliminary literature search of MEDLINE and Embase databases was performed using the terms rotator cuff scaffolds, rotator cuff augmentation, allografts for rotator cuff repair, xenografts for rotator cuff repair, and synthetic grafts for rotator cuff repair. Results The search identified 438 unique articles. Of these, 214 articles were irrelevant to the topic and were therefore excluded. This left a total of 224 studies that were suitable for analysis. Conclusion A number of novel biomaterials have been developed into biologically and mechanically favorable scaffolds. Few clinical trials have examined their effect on tendon-bone healing in well-designed, long-term follow-up studies with appropriate control groups. While there is still considerable work to be done before scaffolds are introduced into routine clinical practice, there does appear to be a clear indication for their use as an interpositional graft for large and massive retracted rotator cuff tears and when repairing a poor-quality degenerative tendon. PMID:26665095

  11. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode

    PubMed Central

    Doni, Andrea; Musso, Tiziana; Morone, Diego; Bastone, Antonio; Zambelli, Vanessa; Sironi, Marina; Castagnoli, Carlotta; Cambieri, Irene; Stravalaci, Matteo; Pasqualini, Fabio; Laface, Ilaria; Valentino, Sonia; Tartari, Silvia; Ponzetta, Andrea; Maina, Virginia; Barbieri, Silvia S.; Tremoli, Elena; Catapano, Alberico L.; Norata, Giuseppe D.; Bottazzi, Barbara; Garlanda, Cecilia

    2015-01-01

    Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity. PMID:25964372

  12. The Role of Tissue Engineering in Articular Cartilage Repair and Regeneration

    PubMed Central

    Zhang, Lijie; Hu, Jerry; Athanasiou, Kyriacos A.

    2011-01-01

    Articular cartilage repair and regeneration continue to be largely intractable due to the poor regenerative properties of this tissue. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased articular cartilage functionality, has evoked intense interest and holds great potential for improving articular cartilage therapy. This review provides an overall description of the current state and progress in articular cartilage repair and regeneration. Traditional therapies and related problems are introduced. More importantly, a variety of promising cell sources, biocompatible tissue engineered scaffolds, scaffoldless techniques, growth factors, and mechanical stimuli used in current articular cartilage tissue engineering are reviewed. Finally, the technical and regulatory challenges of articular cartilage tissue engineering and possible future directions are discussed. PMID:20201770

  13. Adult neurogenesis and repair of the adult CNS with neural progenitors, precursors, and stem cells.

    PubMed

    Emsley, Jason G; Mitchell, Bartley D; Kempermann, Gerd; Macklis, Jeffrey D

    2005-04-01

    Recent work in neuroscience has shown that the adult central nervous system contains neural progenitors, precursors, and stem cells that are capable of generating new neurons, astrocytes, and oligodendrocytes. While challenging previous dogma that no new neurons are born in the adult mammalian CNS, these findings bring with them future possibilities for the development of novel neural repair strategies. The purpose of this review is to present current knowledge about constitutively occurring adult mammalian neurogenesis, to highlight the critical differences between "neurogenic" and "non-neurogenic" regions in the adult brain, and to describe the cardinal features of two well-described neurogenic regions-the subventricular zone/olfactory bulb system, and the dentate gyrus of the hippocampus. We also provide an overview of currently used models for studying neural precursors in vitro, mention some precursor transplantation models, and emphasize that, in this rapidly growing field of neuroscience, one must take caution with respect to a variety of methodological considerations for studying neural precursor cells both in vitro and in vivo. The possibility of repairing neural circuitry by manipulating neurogenesis is an intriguing one, and, therefore, we also review recent efforts to understand the conditions under which neurogenesis can be induced in non-neurogenic regions of the adult CNS. This work aims toward molecular and cellular manipulation of endogenous neural precursors in situ, without transplantation. We conclude this review with a discussion of what the function might be of newly generated neurons in the adult brain and provide a summary of current thinking about the consequences of disturbed adult neurogenesis and the reaction of neurogenic regions to disease.

  14. Functional tissue engineering of tendon: Establishing biological success criteria for improving tendon repair.

    PubMed

    Breidenbach, Andrew P; Gilday, Steven D; Lalley, Andrea L; Dyment, Nathaniel A; Gooch, Cynthia; Shearn, Jason T; Butler, David L

    2014-06-27

    Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: (1) scleraxis-expressing cells; (2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and (3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs. © 2013 Published by Elsevier Ltd.

  15. Functional Tissue Engineering of Tendon: Establishing Biological Success Criteria for Improving Tendon Repair

    PubMed Central

    Breidenbach, Andrew P; Gilday, Steven D; Lalley, Andrea L; Dyment, Nathaniel A; Gooch, Cynthia; Shearn, Jason T; Butler, David L

    2013-01-01

    Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: 1) scleraxis-expressing cells; 2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and 3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs. PMID:24200342

  16. The Application of Tissue Engineering Procedures to Repair the Larynx

    ERIC Educational Resources Information Center

    Ringel, Robert L.; Kahane, Joel C.; Hillsamer, Peter J.; Lee, Annie S.; Badylak, Stephen F.

    2006-01-01

    The field of tissue engineering/regenerative medicine combines the quantitative principles of engineering with the principles of the life sciences toward the goal of reconstituting structurally and functionally normal tissues and organs. There has been relatively little application of tissue engineering efforts toward the organs of speech, voice,…

  17. The Application of Tissue Engineering Procedures to Repair the Larynx

    ERIC Educational Resources Information Center

    Ringel, Robert L.; Kahane, Joel C.; Hillsamer, Peter J.; Lee, Annie S.; Badylak, Stephen F.

    2006-01-01

    The field of tissue engineering/regenerative medicine combines the quantitative principles of engineering with the principles of the life sciences toward the goal of reconstituting structurally and functionally normal tissues and organs. There has been relatively little application of tissue engineering efforts toward the organs of speech, voice,…

  18. Macrophage activation-induced thymosin beta 4 production: a tissue repair mechanism

    USDA-ARS?s Scientific Manuscript database

    Macrophages play significant role in immunity which not only kill pathogens, produce cytokines but also clear dead tissues at the site of inflammation and stimulate wound healing. Much less is known how these cells contribute to tissue repair process. In course of our studies comparing the peptide...

  19. Tail regeneration in Xenopus laevis as a model for understanding tissue repair.

    PubMed

    Tseng, A-S; Levin, M

    2008-09-01

    Augmentation of regenerative ability is a powerful strategy being pursued for the biomedical management of traumatic injury, cancer, and degeneration. While considerable attention has been focused on embryonic stem cells, it is clear that much remains to be learned about how somatic cells may be controlled in the adult organism. The tadpole of the frog Xenopus laevis is a powerful model system within which fundamental mechanisms of regeneration are being addressed. The tadpole tail contains spinal cord, muscle, vasculature, and other terminally differentiated cell types and can fully regenerate itself through tissue renewal--a process that is most relevant to mammalian healing. Recent insight into this process has uncovered fascinating molecular details of how a complex appendage senses injury and rapidly repairs the necessary morphology. Here, we review what is known about the chemical and bioelectric signals underlying this process and draw analogies to evolutionarily conserved pathways in other patterning systems. The understanding of this process is not only of fundamental interest for the evolutionary and cell biology of morphogenesis, but will also generate information that is crucial to the development of regenerative therapies for human tissues and organs.

  20. Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

    PubMed Central

    Pereira, Marcelo G.; Silva, Meiricris T.; Carlassara, Eduardo O. C.; Gonçalves, Dawit A.; Abrahamsohn, Paulo A.; Kettelhut, Isis C.; Moriscot, Anselmo S.; Aoki, Marcelo S.; Miyabara, Elen H.

    2014-01-01

    This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases. PMID:25268835

  1. Leucine supplementation accelerates connective tissue repair of injured tibialis anterior muscle.

    PubMed

    Pereira, Marcelo G; Silva, Meiricris T; Carlassara, Eduardo O C; Gonçalves, Dawit A; Abrahamsohn, Paulo A; Kettelhut, Isis C; Moriscot, Anselmo S; Aoki, Marcelo S; Miyabara, Elen H

    2014-09-29

    This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.

  2. The macrophage and its role in inflammation and tissue repair: mathematical and systems biology approaches.

    PubMed

    Dunster, Joanne L

    2016-01-01

    Macrophages are central to the inflammatory response and its ability to resolve effectively. They are complex cells that adopt a range of subtypes depending on the tissue type and stimulus that they find themselves under. This flexibility allows them to play multiple, sometimes opposing, roles in inflammation and tissue repair. Their central role in the inflammatory process is reflected in macrophage dysfunction being implicated in chronic inflammation and poorly healing wounds. In this study, we discuss recent attempts to model mathematically and computationally the macrophage and how it partakes in the complex processes of inflammation and tissue repair. There are increasing data describing the variety of macrophage phenotypes and their underlying transcriptional programs. Dynamic mathematical and computational models are an ideal way to test biological hypotheses against experimental data and could aid in understanding this multi-functional cell and its potential role as an attractive therapeutic target for inflammatory conditions and tissue repair.

  3. Muscle regeneration by adipose tissue-derived adult stem cells attached to injectable PLGA spheres.

    PubMed

    Kim, MiJung; Choi, Yu Suk; Yang, Seung Hye; Hong, Hea-Nam; Cho, Sung-Woo; Cha, Sang Myun; Pak, Jhang Ho; Kim, Chan Wha; Kwon, Seog Woon; Park, Chan Jeoung

    2006-09-22

    The [corrected] use of adult stem cells for cell-based tissue engineering and regeneration strategies represents a promising approach for skeletal muscle repair. We have evaluated the combination of adipose tissue-derived adult stem cells (ADSCs) obtained from autologous liposuction and injectable poly(lactic-co-glycolic acid) (PLGA) spheres for muscle regeneration. ADSCs attached to PLGA spheres and PLGA spheres alone were cultured in myogenic medium for 21 days and injected subcutaneously into the necks of nude mice. After 30 and 60 days, the mice were sacrificed, and newly formed tissues were analyzed by immunostaining, H and E staining, and RT-PCR. We found that ADSCs attached to PLGA spheres, but not PLGA spheres alone, were able to generate muscle tissue. These findings suggest that ADSCs and PLGA spheres are useful materials for muscle tissue engineering and that their combination can be used in clinical settings for muscle regeneration.

  4. Collagen Type IV and Laminin Expressions during Cartilage Repair and in Late Clinically Failed Repair Tissues from Human Subjects

    PubMed Central

    Foldager, Casper Bindzus; Toh, Wei Seong; Christensen, Bjørn Borsøe; Lind, Martin; Gomoll, Andreas H.; Spector, Myron

    2016-01-01

    Objective To identify the collagen type IV (Col4) isoform in articular cartilage and to evaluate the expressions of Col4 and laminin in the pericellular matrix (PCM) in damaged cartilage and during cartilage repair. Design The Col4 isoform was determined in chondrocytes isolated from 6 patients cultured up to 6 days and in 21% O2 or 1% O2, and the gene expression of Col4 α-chains was investigated. The distribution of Col4 and laminin in traumatically damaged cartilage (n = 7) and clinically failed cartilage repair (microfracture, TruFit, autologous chondrocyte implantation; n = 11) were investigated using immunohistochemistry. Normal human cartilage was used as control (n = 8). The distribution during clinical cartilage repair procedures was investigated in a minipig model with 6-month follow-up (untreated chondral, untreated osteochondral, microfracture, autologous chondrocyte implantation; n = 10). Results The Col4 isoform in articular cartilage was characterized as α1α1α2, which is an isoform containing antiangiogenic domains in the NC1-terminals (arresten and canstatin). In normal cartilage, laminin and Col4 was exclusively found in the PCM. High amounts (>50%) of Col4 in the PCM significantly decreased in damaged cartilage (P = 0.004) and clinically failed repair tissue (P < 0.001). Laminin was only found with high expression (>50%) in 4/8 of the normal samples, which was not statistically significantly different from damaged cartilage (P = 0.15) or failed cartilage repair (P = 0.054). Conclusions Col4 in cartilage contain antiangiogenic domains and may play a role in the hypoxic environment in articular cartilage. Col4 and laminin was not found in the PCM of damaged and clinically failed repair. PMID:26958317

  5. Use of a tissue adhesive to repair fetal bodies after dissection.

    PubMed Central

    Gau, G S; Napier, K; Bhundia, J

    1991-01-01

    The repair of fetal bodies after dissection is extremely difficult because of the delicacy of the skin. A tissue adhesive, Histoacryl blue, was used to repair bodies that had been dissected either before or after immersion in formalin. The repairs were achieved rapidly and neatly. The technique was easy to learn and, providing the method of repair described was followed, there was no breakdown subsequently. The body cavities and reflected skin surfaces were lightly dried with absorbent paper towels and the body loosely packed with cotton wool. "Holding lines" of glue were made and a mid-line strip of glue was applied to the sternum, abdomen, and skull vault, allowing the skin edges to align neatly. Care must be taken to avoid using excess glue as this produces an exothermic reaction. It is recommended that if a fetus has to be repaired after dissection Histoacryl blue will give a good result. Images PMID:1918405

  6. Pain in adults post surgical repair of congenital heart defects.

    PubMed

    Jensen, Louise; Rebeyka, Darlene; Urquhart, Gayle; Roschkov, Sylvia

    2004-01-01

    The purpose of this study was to describe pain in adults post surgical repair for congenital heart defects. What is the intensity, sensory, and affective dimensions of pain experienced post-operatively? What is the trend in pain experienced post-operatively over time? What is the effectiveness of post-operative pain management strategies? What factors influence the dimensions of post-operative pain experienced? A descriptive prospective repeated measures design was used with 30 adult congenital heart (ACH) post-operative patients. Pain assessments using the McGill Short Form Questionnaire (MSFQ), a visual analogue pain scale (VAP), and recordings of other variables (analgesic, anxiety, activity level, non-pharmacologic intervention) were performed three times daily until hospital discharge. Mean pain intensity scores ranged from 2.44 +/- 1.31 following extubation to 1.30 +/- 0.66 on post-operative day (POD) five (scale, 0-5). Mean MSFQ scores ranged from 9.26 +/- 7.21 following extubation to 4.40 +/- 5.22 on POD five (scale, 0-45). Mean VAP scores ranged from 50.77 +/- 25.79 following extubation to 18.76 +/- 18.50 on POD five (scale, 0-100). Mean number of narcotic doses per day ranged from 4.61 +/- 2.01 to 1.88 +/- 1.98 on PODs one and five, respectively. Anxiety predicted VAP and MSFQ scores on PODs one and two; anxiety and analgesia doses predicted VAP and MSFQ scores on POD three; analgesia doses predicted MSFQ scores, analgesia and anxiety predicted VAP scores on POD four; analgesia doses and anxiety predicted VAP and MSFQ scores on POD five. No relationships were found among pain and other demographic, treatment, or clinical variables. Overall, pain was reported as mild to moderate intensity, variable in sensations, decreased over time, and adequately managed.

  7. Hepatic stellate cells and astrocytes: Stars of scar formation and tissue repair.

    PubMed

    Schachtrup, Christian; Le Moan, Natacha; Passino, Melissa A; Akassoglou, Katerina

    2011-06-01

    Scar formation inhibits tissue repair and regeneration in the liver and central nervous system. Activation of hepatic stellate cells (HSCs) after liver injury or of astrocytes after nervous system damage is considered to drive scar formation. HSCs are the fibrotic cells of the liver, as they undergo activation and acquire fibrogenic properties after liver injury. HSC activation has been compared to reactive gliosis of astrocytes, which acquire a reactive phenotype and contribute to scar formation after nervous system injury, much like HSCs after liver injury. It is intriguing that a wide range of neuroglia-related molecules are expressed by HSCs. We identified an unexpected role for the p75 neurotrophin receptor in regulating HSC activation and liver repair. Here we discuss the molecular mechanisms that regulate HSC activation and reactive gliosis and their contributions to scar formation and tissue repair. Juxtaposing key mechanistic and functional similarities in HSC and astrocyte activation might provide novel insight into liver regeneration and nervous system repair.

  8. Repair of articular cartilage defects with tissue-engineered osteochondral composites in pigs.

    PubMed

    Cui, Weiding; Wang, Qing; Chen, Gang; Zhou, Shixiang; Chang, Qing; Zuo, Qiang; Ren, Kewei; Fan, Weimin

    2011-04-01

    To compare the results of repair of knee cartilage defects with tissue-engineered osteochondral composites and tissue-engineered cartilage in pigs. Autologous chondrocytes and osteoblasts were seeded on scaffolds of polylactic-co-glycolic acid (PLGA) and tricalcium phosphate (TCP) to generate tissue-engineered cartilage and tissue-engineered bone, respectively. The tissue-engineered osteochondral composite was formed by a chondrocyte-PLGA construct sutured to an osteoblast-TCP construct with an absorbable suture. Cartilage defects were surgically created at the weightbearing surface of the bilateral femoral medial condyles of 12 mini-pigs. Thus, 24 defects in 12 pigs were randomly assigned to three treatment groups: tissue-engineered osteochondral composite group, tissue-engineered cartilage group, and blank control group. Six months after surgery, the regenerated cartilage was scored macroscopically and histologically. The compressive properties and glycosaminoglycan (GAG) content of the cartilage were also assessed. The gross grading scale indicated that the mean scores of the tissue-engineered osteochondral composite group were significantly higher than those of the tissue-engineered cartilage group. According to the International Cartilage Repair Society (ICRS) Visual Histological Assessment Scale, the scores of the osteochondral composite group were significantly better than those of the tissue-engineered cartilage group and blank control group. Assessment of compressive properties and GAG content showed better repair results in the osteochondral composite group than those of the tissue-engineered cartilage group. Using tissue-engineered osteochondral composites to repair cartilage defects was better than that of tissue-engineered cartilage.

  9. A hypothesis: factor VII governs clot formation, tissue repair and apoptosis.

    PubMed

    Coleman, Lewis S

    2007-01-01

    A hypothesis: thrombin is a "Universal Enzyme of Energy Transduction" that employs ATP energy in flowing blood to activate biochemical reactions and cell effects in both hemostasis and tissue repair. All cells possess PAR-1 (thrombin) receptors and are affected by thrombin elevations, and thrombin effects on individual cell types are determined by their unique complement of PAR-1 receptors. Disruption of the vascular endothelium (VE) activates a tissue repair mechanism (TRM) consisting of the VE, tissue factor (TF), and circulating Factors VII, IX and X that governs localized thrombin elevations to activate clot formation and cellular effects that repair tissue damage. The culmination of the repair process occurs with the restoration of the VE followed by declines in thrombin production that causes Apoptosis ("programmed cell death") in wound-healing fibroblasts, which functions as a mechanism to draw wound edges together. The location and magnitude of TRM activity governs the location and magnitude of Factor VIII activity and clot formation, but the large size of Factor VIII prevents it from penetrating the clot formed by its activity, so that its effects are self-limiting. Factors VII, IX and X function primarily as tissue repair enzymes, while Factor VIII and Factor XIII are the only serine protease enzymes in the "Coagulation Cascade" that are exclusively associated with hemostasis.

  10. Repairing nerve gaps by vein conduits filled with lipoaspirate-derived entire adipose tissue hinders nerve regeneration.

    PubMed

    Papalia, Igor; Raimondo, Stefania; Ronchi, Giulia; Magaudda, Ludovico; Giacobini-Robecchi, Maria G; Geuna, Stefano

    2013-05-01

    In spite of great recent advancements, the definition of the optimal strategy for bridging a nerve defect, especially across long gaps, still remains an open issue since the amount of autologous nerve graft material is limited while the outcome after alternative tubulization techniques is often unsatisfactory. The aim of this study was to investigate a new tubulization technique based on the employment of vein conduits filled with whole subcutaneous adipose tissue obtained by lipoaspiration. In adult rats, a 1cm-long defect of the left median nerve was repaired by adipose tissue-vein-combined conduits and compared with fresh skeletal muscle tissue-vein-combined conduits and autologous nerve grafts made by the excised nerve segment rotated by 180°. Throughout the postoperative period, functional recovery was assessed using the grasping test. Regenerated nerve samples were withdrawn at postoperative month-6 and processed for light and electron microscopy and stereology of regenerated nerve fibers. Results showed that functional recovery was significantly slower in the adipose tissue-enriched group in comparison to both control groups. Light and electron microscopy showed that a large amount of adipose tissue was still present inside the vein conduits at postoperative month-6. Stereology showed that all quantitative morphological predictors analyzed performed significantly worse in the adipose tissue-enriched group in comparison to the two control groups. On the basis of this experimental study in the rat, the use of whole adipose tissue for tissue engineering of peripheral nerves should be discouraged. Pre-treatment of adipose tissue aimed at isolating stromal vascular fraction and/or adipose derived stem/precursor cells should be considered a fundamental requisite for nerve repair. Copyright © 2012 Elsevier GmbH. All rights reserved.

  11. Quantitative assessment of optical properties in healthy cartilage and repair tissue by optical coherence tomography and histology (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jansen, Sanne M. A.; Cernohorsky, Paul; de Bruin, Daniel M.; van der Pol, Edwin; Savci-Heijink, Cemile D.; Strackee, Simon D.; Faber, Dirk J.; van Leeuwen, Ton G.

    2016-02-01

    Quantification of the OCT signal is an important step toward clinical implementation of a diagnostic tool in cartilage imaging. Discrimination of structural cartilage differences in patients with osteoarthritis is critical, yet challenging. This study assesses the variation in the optical attenuation coefficient (μOCT) between healthy cartilage, repair tissue, bone and layers within repair tissue in a controlled setting. OCT and histology was used to assess goat talus articular surfaces in which central osteochondral defects were created. Exact matches of OCT and histology were selected for research. μOCT measurements were taken from healthy cartilage, repair tissue and bone. Measured μOCT in healthy cartilage was higher compared to both repair tissue and bone tissue. Two possible mechanisms for the difference in attenuation were investigated. We studied morphological parameters in terms of nucleus count, nucleus size and inter-nucleus distance. Collagen content in healthy cartilage and repair tissue was assessed using polarization microscopy. Quantitative analysis of the nuclei did not demonstrate a difference in nucleus size and count between healthy cartilage and repair tissue. In healthy cartilage, cells were spaced farther apart and had a lower variation in local nuclear density compared to repair tissue. Polarization microscopy suggested higher collagen content in healthy cartilage compared to repair tissue. μOCT measurements can distinguish between healthy cartilage, repair tissue and bone. Results suggest that cartilage OCT attenuation measurements could be of great impact in clinical diagnostics of osteoarthritis.

  12. Tissue Engineering for Rotator Cuff Repair: An Evidence-Based Systematic Review

    PubMed Central

    Maffulli, Nicola; Longo, Umile Giuseppe; Loppini, Mattia; Berton, Alessandra; Spiezia, Filippo; Denaro, Vincenzo

    2012-01-01

    The purpose of this systematic review was to address the treatment of rotator cuff tears by applying tissue engineering approaches to improve tendon healing, specifically platelet rich plasma (PRP) augmentation, stem cells, and scaffolds. Our systematic search was performed using the combination of the following terms: “rotator cuff”, “shoulder”, “PRP”, “platelet rich plasma”, “stemcells”, “scaffold”, “growth factors”, and “tissue engineering”. No level I or II studies were found on the use of scaffolds and stem cells for rotator cuff repair. Three studies compared rotator cuff repair with or without PRP augmentation. All authors performed arthroscopic rotator cuff repair with different techniques of suture anchor fixation and different PRP augmentation. The three studies found no difference in clinical rating scales and functional outcomes between PRP and control groups. Only one study showed clinical statistically significant difference between the two groups at the 3-month follow up. Any statistically significant difference in the rates of tendon rerupture between the control group and the PRP group was found using the magnetic resonance imaging. The current literature on tissue engineering application for rotator cuff repair is scanty. Comparative studies included in this review suggest that PRP augmented repair of a rotator cuff does not yield improved functional and clinical outcome compared with non-augmented repair at a medium and long-term followup. PMID:25098365

  13. Composite tissue flap at perforating branches of saphenous artery: a new design for repairing composite tissue defects in anterior knee.

    PubMed

    Sun, Guangfeng; Nie, Kaiyu; Jin, Wenhu; Wei, Zairong; Qi, Jianping; Wang, Dali

    2015-01-01

    So far it has been difficult to repair and reconstruct the composite tissue defects in knee. Saphenous artery flap has been widely used to repair complex wounds, but the design and clinical application of composite tissue flap at perforating branches of saphenous artery were not reported. In this research, we design a new composite tissue flap by carrying fascial flap in the medial gastrocnemius muscle with perforators flap in saphenous artery to repair and reconstruct the composite tissue defects in knee. By anatomic observation and analysis, we find that there exists blood-supply in netty form among saphenous arteries, medial artery below the knee, intermuscular branch in high-order position of posterior tibial artery and perforating branch in medial artery of calf. We chose saphenous artery as blood-supplying artery; utilized the netty blood-supplying mode in middle-up and medial part of shank; cut the composite tissue flap at perforating branches of saphenous artery with fascial flap carried in the medial gastrocnemius muscle; reconstructed the ligamentum patellae using medial head of gastrocnemius muscle and Achilles's tendon; and covered the wounds at front side of knee with flap. Composite tissues were survived completely, free from infection at wounds and exosmosis of joint fluid. Motion function of knee-joint proved satisfactory, and ambulatory function was recovered. There was no complication in donor site. Composite tissue flap at perforating branches of saphenous artery with fascial flap carried in the medial gastrocnemius muscle is one of the most ideal solutions for repairing the composite tissue defects at front side of knee joint.

  14. Modulation of tissue repair by regeneration enhancer elements.

    PubMed

    Kang, Junsu; Hu, Jianxin; Karra, Ravi; Dickson, Amy L; Tornini, Valerie A; Nachtrab, Gregory; Gemberling, Matthew; Goldman, Joseph A; Black, Brian L; Poss, Kenneth D

    2016-04-14

    How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lepb) is highly induced in regenerating hearts and fins of zebrafish. Epigenetic profiling identified a short DNA sequence element upstream and distal to lepb that acquires open chromatin marks during regeneration and enables injury-dependent expression from minimal promoters. This element could activate expression in injured neonatal mouse tissues and was divisible into tissue-specific modules sufficient for expression in regenerating zebrafish fins or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences upstream of pro- or anti-regenerative factors controlled the efficacy of regeneration in zebrafish. Our findings provide evidence for 'tissue regeneration enhancer elements' (TREEs) that trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs.

  15. Hyaluronan and RHAMM in wound repair and the "cancerization" of stromal tissues.

    PubMed

    Tolg, Cornelia; McCarthy, James B; Yazdani, Arjang; Turley, Eva A

    2014-01-01

    Tumors and wounds share many similarities including loss of tissue architecture, cell polarity and cell differentiation, aberrant extracellular matrix (ECM) remodeling (Ballard et al., 2006) increased inflammation, angiogenesis, and elevated cell migration and proliferation. Whereas these changes are transient in repairing wounds, tumors do not regain tissue architecture but rather their continued progression is fueled in part by loss of normal tissue structure. As a result tumors are often described as wounds that do not heal. The ECM component hyaluronan (HA) and its receptor RHAMM have both been implicated in wound repair and tumor progression. This review highlights the similarities and differences in their roles during these processes and proposes that RHAMM-regulated wound repair functions may contribute to "cancerization" of the tumor microenvironment.

  16. Hyaluronan and RHAMM in Wound Repair and the “Cancerization” of Stromal Tissues

    PubMed Central

    Tolg, Cornelia; McCarthy, James B.; Yazdani, Arjang; Turley, Eva A.

    2014-01-01

    Tumors and wounds share many similarities including loss of tissue architecture, cell polarity and cell differentiation, aberrant extracellular matrix (ECM) remodeling (Ballard et al., 2006) increased inflammation, angiogenesis, and elevated cell migration and proliferation. Whereas these changes are transient in repairing wounds, tumors do not regain tissue architecture but rather their continued progression is fueled in part by loss of normal tissue structure. As a result tumors are often described as wounds that do not heal. The ECM component hyaluronan (HA) and its receptor RHAMM have both been implicated in wound repair and tumor progression. This review highlights the similarities and differences in their roles during these processes and proposes that RHAMM-regulated wound repair functions may contribute to “cancerization” of the tumor microenvironment. PMID:25157350

  17. Olfactory mucosa for transplant-mediated repair: a complex tissue for a complex injury?

    PubMed

    Lindsay, Susan L; Riddell, John S; Barnett, Susan C

    2010-01-15

    Damage to the brain and spinal cord leads to permanent functional disability because of the very limited capacity of the central nervous system (CNS) for repair. Transplantation of cells into regions of CNS damage represents one approach to enhancing this repair. At present, the ideal cell type for transplant-mediated repair has not been identified but autologous transplantation would be advantageous. Olfactory tissue, in part because of its capacity for regeneration, has emerged as a promising source of cells and several clinical centers are using olfactory cells or tissues in the treatment of CNS damage. Until now, the olfactory ensheathing cell, a specialized glial cell of the olfactory system has been the main focus of attention. Transplants of this cell have been shown to have a neuroprotective function, support axonal regeneration, and remyelinate demyelinated axons. However, the olfactory mucosa is a heterogeneous tissue, composed of a variety of cells supporting both its normal function and its regenerative capacity. It is therefore possible that it contains several cell types that could participate in CNS repair including putative stem cells as well as glia. Here we review the cellular composition of the olfactory tissue and the evidence that equivalent cell types exist in both rodent and human olfactory mucosa suggesting that it is potentially a rich source of autologous cells for transplant-mediated repair of the CNS.

  18. Long-term results with autogenous tissue repair of traumatic extremity vascular injuries.

    PubMed Central

    McCready, R A; Logan, N M; Daugherty, M E; Mattingly, S S; Crocker, C; Hyde, G L

    1987-01-01

    With extensive vascular injuries in which a vascular conduit is required, there is controversy as to whether an autogenous or prosthetic graft is preferable. The authors reviewed their experience with 91 extremity arterial injuries in which autogenous tissue was used to repair vascular injuries of the extremities. Twenty-two patients also had concomitant repair of associated venous injuries with autogenous vein grafts. Ten patients required amputations, despite patent grafts in five patients, because of severe muscle necrosis. Two patients had thrombosis of their vein grafts develop in the early postoperative period but did not require amputation. The authors identified only one late vein graft failure in a patient in whom an infected pseudoaneurysm developed. Three patients with extensive soft tissue injuries had infection develop in vein grafts, with subsequent massive bleeding that ultimately required arterial ligation. Among the 22 patients with repair of their venous injuries, occlusion of popliteal vein repairs was documented in two patients and suspected in three others. The remainder of patients had satisfactory results. The excellent results obtained in the vast majority of the authors' patients with extremity vascular injuries reinforces their preference for using autogenous tissue whenever a vascular conduit is required. Exceptions include patients with extensive soft tissue loss precluding adequate graft coverage, the repair of large vessels, and life-threatening emergencies when there is insufficient time to harvest and prepare a vein. PMID:3689017

  19. Roles of microglia in brain development, tissue maintenance and repair.

    PubMed

    Michell-Robinson, Mackenzie A; Touil, Hanane; Healy, Luke M; Owen, David R; Durafourt, Bryce A; Bar-Or, Amit; Antel, Jack P; Moore, Craig S

    2015-05-01

    The emerging roles of microglia are currently being investigated in the healthy and diseased brain with a growing interest in their diverse functions. In recent years, it has been demonstrated that microglia are not only immunocentric, but also neurobiological and can impact neural development and the maintenance of neuronal cell function in both healthy and pathological contexts. In the disease context, there is widespread consensus that microglia are dynamic cells with a potential to contribute to both central nervous system damage and repair. Indeed, a number of studies have found that microenvironmental conditions can selectively modify unique microglia phenotypes and functions. One novel mechanism that has garnered interest involves the regulation of microglial function by microRNAs, which has therapeutic implications such as enhancing microglia-mediated suppression of brain injury and promoting repair following inflammatory injury. Furthermore, recently published articles have identified molecular signatures of myeloid cells, suggesting that microglia are a distinct cell population compared to other cells of myeloid lineage that access the central nervous system under pathological conditions. Thus, new opportunities exist to help distinguish microglia in the brain and permit the study of their unique functions in health and disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Tissue-engineered tendon constructs for rotator cuff repair in sheep.

    PubMed

    Novakova, Stoyna S; Mahalingam, Vasudevan D; Florida, Shelby E; Mendias, Christopher L; Allen, Answorth; Arruda, Ellen M; Bedi, Asheesh; Larkin, Lisa M

    2017-06-28

    Current rotator cuff repair commonly involves the use of single or double row suture techniques, and despite successful outcomes, failure rates continue to range from 20 to 95%. Failure to regenerate native biomechanical properties at the enthesis is thought to contribute to failure rates. Thus, the need for technologies that improve structural healing of the enthesis after rotator cuff repair is imperative. To address this issue, our lab has previously demonstrated enthesis regeneration using a tissue-engineered graft approach in a sheep anterior cruciate ligament (ACL) repair model. We hypothesized that our tissue-engineered graft designed for ACL repair also will be effective in rotator cuff repair. The goal of this study was to test the efficacy of our Engineered Tissue Graft for Rotator Cuff (ETG-RC) in a rotator cuff tear model in sheep and compare this novel graft technology to the commonly used double row suture repair technique. Following a 6-month recovery, the grafted and contralateral shoulders were removed, imaged using X-ray, and tested biomechanically. Additionally, the infraspinatus muscle, myotendinous junction, enthesis, and humeral head were preserved for histological analysis of muscle, tendon, and enthesis structure. Our results showed that our ETC-RCs reached 31% of the native tendon tangent modulus, which was a modest, non-significant, 11% increase over that of the suture-only repairs. However, the histological analysis showed the regeneration of a native-like enthesis in the ETG-RC-repaired animals. This advanced structural healing may improve over longer times and may diminish recurrence rates of rotator cuff tears and lead to better clinical outcomes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  1. [Evaluation of biological safety of continuous carbon-fiber reinforced polyolefin as hard tissue repair].

    PubMed

    Hou, Chunlin; Feng, Xue; Cen, Qingquan; Zhang, Wei; Yang, Guisheng; Sun, Jiao

    2005-01-01

    To evaluate the biological safety of continuous carbon-fiber reinforced polyolefin as hard tissue repair material. Biocompatibility of the material was evaluated through hemolysis test, pyrogen test, skin irritation test, cytotoxicity test, ames test, in vitro chromosome aberration test, and bone marrow cells Micronuclei test. No obvious hemolysis, pyrogenic characteristics, sensitivity, cytotoxicity, and mutagenicity were observed. The continuous carbon-fiber reinforced polyolefin composite material is of good biological safety. It meets all the demand made by biological safety as hard tissue repair material.

  2. Tissue-Derived Extracellular Matrix Bioscaffolds: Emerging Applications in Cartilage and Meniscus Repair.

    PubMed

    Monibi, Farrah A; Cook, James L

    2017-03-07

    Musculoskeletal injuries are a common problem in orthopedic practice. Given the long-term consequences of unaddressed cartilage and meniscal pathology, a number of treatments have been attempted to stimulate repair or to replace the injured tissue. Despite advances in orthopedic surgery, effective treatments for cartilage and meniscus injuries remain a significant clinical challenge. Tissue engineering is a developing field that aims to regenerate injured tissues with a combination of cells, scaffolds, and signals. Many natural and synthetic scaffold materials have been developed and tested for the repair and restoration of a number of musculoskeletal tissues. Among these, biological scaffolds derived from cell and tissue-derived extracellular matrix (ECM) have shown great promise in tissue engineering given the critical role of the ECM for maintaining the biological and biomechanical properties, structure, and function of native tissues. This review article presents emerging applications for tissue-derived ECM scaffolds in cartilage and meniscus repair. We examine normal ECM composition and the current and future methods for potential treatment of articular cartilage and meniscal defects with decellularized scaffolds.

  3. Tissue engineering approaches for bone repair: concepts and evidence.

    PubMed

    Schroeder, Josh E; Mosheiff, Rami

    2011-06-01

    Over the last decades, the medical world has advanced dramatically in the understanding of fracture repair. The three components needed for fracture healing are osteoconduction, osteoinduction and osteogenesis. With newly designed scaffolds, ex vivo produced growth factors and isolated stem cells, most of the challenges of critical size bone defects have been resolved in vitro, and in some cases in animal models as well. However, there are still challenges needed to be overcome before these technologies can be fully converted from the bench to the bedside. These technological and biological advancements need to be converted to mass production of affordable products that can be used in every part of the world. Vascularity, full substation of scaffolds by native bone, and bio-safety are the three most critical steps to be challenged before reaching the clinical setting. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Involvement of PPAR nuclear receptors in tissue injury and wound repair

    PubMed Central

    Michalik, Liliane; Wahli, Walter

    2006-01-01

    Tissue damage resulting from chemical, mechanical, and biological injury, or from interrupted blood flow and reperfusion, is often life threatening. The subsequent tissue response involves an intricate series of events including inflammation, oxidative stress, immune cell recruitment, and cell survival, proliferation, migration, and differentiation. In addition, fibrotic repair characterized by myofibroblast transdifferentiation and the deposition of ECM proteins is activated. Failure to initiate, maintain, or stop this repair program has dramatic consequences, such as cell death and associated tissue necrosis or carcinogenesis. In this sense, inflammation and oxidative stress, which are beneficial defense processes, can become harmful if they do not resolve in time. This repair program is largely based on rapid and specific changes in gene expression controlled by transcription factors that sense injury. PPARs are such factors and are activated by lipid mediators produced after wounding. Here we highlight advances in our understanding of PPAR action during tissue repair and discuss the potential for these nuclear receptors as therapeutic targets for tissue injury. PMID:16511592

  5. Using tissue adhesive for wound repair: a practical guide to dermabond.

    PubMed

    Bruns, T B; Worthington, J M

    2000-03-01

    Dermabond is a cyanoacrylate tissue adhesive that forms a strong bond across apposed wound edges, allowing normal healing to occur below. It is marketed to replace sutures that are 5-0 or smaller in diameter for incisional or laceration repair. This adhesive has been shown to save time during wound repair, to provide a flexible water-resistant protective coating and to eliminate the need for suture removal. The long-term cosmetic outcome with Dermabond is comparable to that of traditional methods of repair. Best suited for small, superficial lacerations, it may also be used with confidence on larger wounds where subcutaneous sutures are needed. This adhesive is relatively easy to use following appropriate wound preparation. Patients, especially children, readily accept the idea of being "glued" over traditional methods of repair.

  6. Morphological MRI and T2 mapping of cartilage repair tissue after mosaicplasty with tissue-engineered cartilage in a pig model

    PubMed Central

    Chen, Qichun; Zuo, Qiang; Hu, Qianqian; Feng, Yang; Cui, Weiding; Fan, Weimin; Zou, Yuefen

    2014-01-01

    Abstract The aim of this study was to evaluate the efficacy of mosaicplasty with tissue-engineered cartilage for the treatment of osteochondral defects in a pig model with advanced MR technique. Eight adolescent miniature pigs were used. The right knee underwent mosaicplasty with tissue-engineered cartilage for treatment of focal osteochondral defects, while the left knee was repaired via single mosaicplasty as controls. At 6, 12, 18 and 26 weeks after surgery, repair tissue was evaluated by magnetic resonance imaging (MRI) with the cartilage repair tissue (MOCART) scoring system and T2 mapping. Then, the results of MRI for 26 weeks were compared with findings of macroscopic and histologic studies. The MOCART scores showed that the repaired tissue of the tissue-engineered cartilage group was statistically better than that of controls (P < 0.001). A significant correlation was found between macroscopic and MOCART scores (P < 0.001). Comparable mean T2 values were found between adjacent cartilage and repair tissue in the experimental group (P > 0.05). For zonal T2 value evaluation, there were no significant zonal T2 differences for repair tissue in controls (P > 0.05). For the experimental group, zonal T2 variation was found in repair tissue (P < 0.05). MRI, macroscopy and histology showed better repair results and bony incorporation in mosaicplasty with the tissue-engineered cartilage group than those of the single mosaicplasty group. Mosaicplasty with the tissue-engineered cartilage is a promising approach to repair osteochodndral defects. Morphological MRI and T2 mapping provide a non-invasive method for monitoring the maturation and integration of cartilage repair tissue in vivo. PMID:25050115

  7. Morphological MRI and T2 mapping of cartilage repair tissue after mosaicplasty with tissue-engineered cartilage in a pig model.

    PubMed

    Chen, Qichun; Zuo, Qiang; Hu, Qianqian; Feng, Yang; Cui, Weiding; Fan, Weimin; Zou, Yuefen

    2014-07-01

    The aim of this study was to evaluate the efficacy of mosaicplasty with tissue-engineered cartilage for the treatment of osteochondral defects in a pig model with advanced MR technique. Eight adolescent miniature pigs were used. The right knee underwent mosaicplasty with tissue-engineered cartilage for treatment of focal osteochondral defects, while the left knee was repaired via single mosaicplasty as controls. At 6, 12, 18 and 26 weeks after surgery, repair tissue was evaluated by magnetic resonance imaging (MRI) with the cartilage repair tissue (MOCART) scoring system and T2 mapping. Then, the results of MRI for 26 weeks were compared with findings of macroscopic and histologic studies. The MOCART scores showed that the repaired tissue of the tissue-engineered cartilage group was statistically better than that of controls (P < 0.001). A significant correlation was found between macroscopic and MOCART scores (P < 0.001). Comparable mean T2 values were found between adjacent cartilage and repair tissue in the experimental group (P > 0.05). For zonal T2 value evaluation, there were no significant zonal T2 differences for repair tissue in controls (P > 0.05). For the experimental group, zonal T2 variation was found in repair tissue (P < 0.05). MRI, macroscopy and histology showed better repair results and bony incorporation in mosaicplasty with the tissue-engineered cartilage group than those of the single mosaicplasty group. Mosaicplasty with the tissue-engineered cartilage is a promising approach to repair osteochodndral defects. Morphological MRI and T2 mapping provide a non-invasive method for monitoring the maturation and integration of cartilage repair tissue in vivo.

  8. Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration

    PubMed Central

    Xu, Hui; Sandor, Maryellen; Lombardi, Jared

    2013-01-01

    Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of

  9. Nucleotide excision repair is reduced in oral epithelial tissues compared with skin.

    PubMed

    Mitchell, David; Paniker, Lakshmi; Godar, Dianne

    2012-01-01

    Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. To address potential carcinogenic risks of these procedures, we analyzed the formation and repair of the DNA photoproducts associated with the signature mutations of UVR. Radioimmunoassay was used to quantify the induction and repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts in DNA purified from three reconstructed tissues, EpiDerm(TM) , EpiGingival(TM) and EpiOral(TM) . We observed comparable levels of DNA damage in all tissues immediately after UVR exposure. In contrast, repair was significantly reduced in both oral tissues compared with EpiDerm(TM) . Our data suggest that UVR exposure of oral tissues can result in accumulation of DNA damage and increase the risk for carcinoma and melanoma of the mouth. Because NER is a broad-spectrum defense against DNA damage caused by a variety of agents in addition to UVR, our data suggest that the relatively low NER efficiency observed in oral tissues may have wide-ranging consequences in this highly exposed environment.

  10. Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

    PubMed Central

    Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J.; Nevins, Myron; Spector, Myron; Hammond, Paula T.

    2014-01-01

    Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID:25136093

  11. Customized Fabrication of Osteochondral Tissue for Articular Joint Surface Repair

    DTIC Science & Technology

    2016-09-01

    Significant changes in use of biohazards and/or select agents 6. PRODUCTS:  Publications, conference papers , and presentations Report only the major...Scaffolds for Cartilage Tissue Engineering. Frontiers in Bioengineering and Biotechnology. Nothing to Report Other publications, conference papers ...prepped using chlorhexidine and betadiene scrubs, and the limb was draped using sterile towels . The initial incision was positioned on the medial

  12. Engineering the matrix microenvironment for cell delivery and engraftment for tissue repair

    PubMed Central

    Cheng, Amy Y.; García, Andrés J.

    2013-01-01

    Cell-based therapies represent promising strategies for tissue repair, particularly in cases in which host cells, due to disease, age, or excessive trauma, are unable to repair the defect or deficiency alone, even with additional delivered therapeutics. Current cell therapies fail to address long term engraftment or delivery timing and location and result in modest improvements with long term engraftment rates of less than 1%. In many cell therapy applications, an appropriate carrier must be used to deliver transplanted cells and promote cell engraftment and function for a successful outcome by providing the appropriate microenvironment for the interactions between transplanted and host cells. This review highlights important considerations for engineering the microenvironment for cell delivery and engraftment in tissue repair. PMID:23647972

  13. Embryonic Wound Healing: A Primer for Engineering Novel Therapies for Tissue Repair

    PubMed Central

    Degen, Katherine E.; Gourdie, Robert G.

    2014-01-01

    Scar is the default tissue repair used by the body in response to most injuries–a response that occurs in wounds ranging in seriousness from minor skin cuts to complete severance of the spinal cord. By contrast, before the third trimester of pregnancy embryonic mammals tend to heal without scarring due to a variety of mechanisms and factors that are uniquely in operation during development in utero. The goal of tissue engineering is to develop safe and clinically effective biological substitutes that restore, maintain, or improve tissue function in patients. This review provides a comparative overview of wound healing during development and maturation and seeks to provide a perspective on just how much the embryo may be able teach us in the engineering of new therapies for tissue repair. PMID:23109321

  14. Stages of Adult Soft Tissue Sarcoma

    MedlinePlus

    ... soft tissue sarcomas: Childhood Soft Tissue Sarcoma Treatment Ewing Sarcoma Family of Tumors Treatment Gastrointestinal Stromal Tumors Treatment ... Sarcoma Home Page Childhood Soft Tissue Sarcoma Treatment Ewing Sarcoma Family of Tumors Treatment Gastrointestinal Stromal Tumors Treatment ...

  15. Treatment Options for Adult Soft Tissue Sarcoma

    MedlinePlus

    ... soft tissue sarcomas: Childhood Soft Tissue Sarcoma Treatment Ewing Sarcoma Family of Tumors Treatment Gastrointestinal Stromal Tumors Treatment ... Sarcoma Home Page Childhood Soft Tissue Sarcoma Treatment Ewing Sarcoma Family of Tumors Treatment Gastrointestinal Stromal Tumors Treatment ...

  16. Treatment Option Overview (Adult Soft Tissue Sarcoma)

    MedlinePlus

    ... soft tissue sarcomas: Childhood Soft Tissue Sarcoma Treatment Ewing Sarcoma Family of Tumors Treatment Gastrointestinal Stromal Tumors Treatment ... Sarcoma Home Page Childhood Soft Tissue Sarcoma Treatment Ewing Sarcoma Family of Tumors Treatment Gastrointestinal Stromal Tumors Treatment ...

  17. Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design

    PubMed Central

    Segar, Claire E; Sridhar, Sraeyes; Botchwey, Edward A

    2016-01-01

    Monocytes and macrophages play a critical role in tissue development, homeostasis, and injury repair. These innate immune cells participate in guiding vascular remodeling, stimulation of local stem and progenitor cells, and structural repair of tissues such as muscle and bone. Therefore, there is a great interest in harnessing this powerful endogenous cell source for therapeutic regeneration through immunoregenerative biomaterial engineering. These materials seek to harness specific subpopulations of monocytes/macrophages to promote repair by influencing their recruitment, positioning, differentiation, and function within a damaged tissue. Monocyte and macrophage phenotypes span a continuum of inflammatory (M1) to anti-inflammatory or pro-regenerative cells (M2), and their heterogeneous functions are highly dependent on microenvironmental cues within the injury niche. Increasing evidence suggests that division of labor among subpopulations of monocytes and macrophages could allow for harnessing regenerative functions over inflammatory functions of myeloid cells; however, the complex balance between necessary functions of inflammatory versus regenerative myeloid cells remains to be fully elucidated. Historically, biomaterial-based therapies for promoting tissue regeneration were designed to minimize the host inflammatory response; although, recent appreciation for the roles that innate immune cells play in tissue repair and material integration has shifted this paradigm. A number of opportunities exist to exploit known signaling systems of specific populations of monocytes/macrophages to promote repair and to better understand the biological and pathological roles of myeloid cells. This review seeks to outline the characteristics of distinct populations of monocytes and macrophages, identify the role of these cells within diverse tissue injury niches, and offer design criteria for immunoregenerative biomaterials given the intrinsic inflammatory response to their

  18. Single-stage soft tissue reconstruction and orbital fracture repair for complex facial injuries.

    PubMed

    Wu, Peng Sen; Matoo, Reshvin; Sun, Hong; Song, Li Yuan; Kikkawa, Don O; Lu, Wei

    2017-02-01

    Orbital fractures with open periorbital wounds cause significant morbidity. Timing of debridement with fracture repair and soft tissue reconstruction is controversial. This study focuses on the efficacy of early single-stage repair in combined bony and soft tissue injuries. Retrospective review. Twenty-three patients with combined open soft tissue wounds and orbital fractures were studied for single-stage orbital reconstruction and periorbital soft tissue repair. Inclusion criteria were open soft tissue wounds with clinical and radiographic evidence of orbital fractures and repair performed within 48 h after injury. Surgical complications and reconstructive outcomes were assessed over 6 months. The main outcome measures were enophthalmos, pre- and post-CT imaging of orbits, scar evaluation, presence of diplopia, and eyelid position. Enophthalmos was corrected in 16/19 cases and improved in 3/19 cases. 3D reconstruction of CT images showed markedly improved orbital alignment with objective measurements of the optic foramen to cornea distance (mm) in reconstructed orbits relative to intact orbits of 0.66, 95% confidence interval [CI] (lower 0.33, upper 0.99) mm. The mean baseline of Stony Brook Scar Evaluation Scale was 0.6, 95%CI (0.30-0.92), and for 6 months, the mean score was 3.4, 95%CI (3.05-3.73). Residual diplopia in secondary gazes was present in two patients; one patient had ectropion. Complications included one case of local wound infection. An early single-stage repair of combined soft tissue and orbital fractures yields satisfactory functional and aesthetic outcomes. Complications are low and likely related to trauma severity. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  19. Do biomechanical properties of anterior vaginal wall prolapse tissue predict outcome of surgical repair?

    PubMed

    Gilchrist, Alienor S; Gupta, Amit; Eberhart, Robert C; Zimmern, Philippe E

    2010-03-01

    We determined the relevance of the biomechanical properties of freshly harvested vaginal tissue during large cystocele repair on clinical outcome at a minimum 1-year followup. With institutional review board approval we prospectively studied the biomechanical properties of full thickness vaginal wall tissue from postmenopausal women with symptomatic Baden-Walker prolapse undergoing anterior vaginal wall suspension with cystocele repair from 2002 to 2005. A standardized biomechanical protocol was applied with stress-strain curves for Young's modulus obtained by blinded investigators. Failed repair was defined as recurrence on examination or reoperation for recurrent anterior prolapse. A total of 32 patients (median age 72 years) had a median followup of 34 months (range 12 to 62). Median Young's modulus was statistically different in tissue samples transported in immersed vs moistened media (median 3.8 vs 7.6, p = 0.008). Associations between Young's modulus and clinical variables were described. On followup 7 patients experienced failure of the repair. After controlling for tissue transport protocol no association was seen between Young's modulus and failures (HR 1.1, p = 0.34). This study found no association between Young's modulus and clinical results at long-term followup. This finding suggests that retropubic scarring and pelvic floor muscle properties may be more important for a successful reparative outcome than the intrinsic properties of the vaginal wall. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    NASA Astrophysics Data System (ADS)

    Matteini, P.; Ratto, F.; Rossi, F.; Pini, R.

    2014-07-01

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds.

  1. Adult tissue sources for new β cells.

    PubMed

    Nichols, Robert J; New, Connie; Annes, Justin P

    2014-04-01

    The diabetes pandemic incurs extraordinary public health and financial costs that are projected to expand for the foreseeable future. Consequently, the development of definitive therapies for diabetes is a priority. Currently, a wide spectrum of therapeutic strategies-from implantable insulin delivery devices to transplantation-based cell replacement therapy, to β-cell regeneration-focus on replacing the lost insulin-producing capacity of individuals with diabetes. Among these, β-cell regeneration remains promising but heretofore unproved. Indeed, recent experimental work has uncovered surprising biology that underscores the potential therapeutic benefit of β-cell regeneration. These studies have elucidated a variety of sources for the endogenous production of new β cells from existing cells. First, β cells, long thought to be postmitotic, have demonstrated the potential for regenerative capacity. Second, the presence of pancreatic facultative endocrine progenitor cells has been established. Third, the malleability of cellular identity has availed the possibility of generating β cells from other differentiated cell types. Here, we review the exciting developments surrounding endogenous sources of β-cell production and consider the potential of realizing a regenerative therapy for diabetes from adult tissues. Copyright © 2014 Mosby, Inc. All rights reserved.

  2. Cytoprotection: Immune and Matrix Modulation of Tissue Repair

    DTIC Science & Technology

    2013-04-01

    autoimmune conditions, such rheumatoid arthritis and inflammatory bowel disease. However, given the broad range of inflammatory mediated diseases...patients with rheumatoid arthritis . Clin Sci (Lond) 2004; 107: 291–296. 25 Girard N, Maingonnat C, Bertrand P, Vasse M, Delpech B. Hyaluronectin... rheumatoid arthritis show the imprint of synovial tissue heterogeneity: evidence of a link between an increased myofibroblast-like phenotype and high

  3. Evaluation of native hyaline cartilage and repair tissue after two cartilage repair surgery techniques with 23Na MR imaging at 7 T: initial experience.

    PubMed

    Zbýň, S; Stelzeneder, D; Welsch, G H; Negrin, L L; Juras, V; Mayerhoefer, M E; Szomolanyi, P; Bogner, W; Domayer, S E; Weber, M; Trattnig, S

    2012-08-01

    To compare the sodium normalized mean signal intensity (NMSI) values between patients after bone marrow stimulation (BMS) and matrix-associated autologous chondrocyte transplantation (MACT) cartilage repair procedures. Nine BMS and nine MACT patients were included. Each BMS patient was matched with one MACT patient according to age [BMS 36.7 ± 10.7 (mean ± standard deviation) years; MACT 36.9 ± 10.0 years], postoperative interval (BMS 33.5 ± 25.3 months; MACT 33.2 ± 25.7 months), and defect location. All magnetic resonance imaging (MRI) measurements were performed on a 7 T system. Proton images served for morphological evaluation of repair tissue using the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system. Sodium NMSI values in the repair area and morphologically normal cartilage were calculated. Clinical outcome was assessed right after MRI. Analysis of covariance, t-tests, and Pearson correlation coefficients were evaluated. Sodium NMSI was significantly lower in BMS (P = 0.004) and MACT (P = 0.006) repair tissue, compared to reference cartilage. Sodium NMSI was not different between the reference cartilage in MACT and BMS patients (P = 0.664), however it was significantly higher in MACT than in BMS repair tissue (P = 0.028). Better clinical outcome was observed in BMS than in MACT patients. There was no difference between MOCART scores for MACT and BMS patients (P = 0.915). We did not observe any significant correlation between MOCART score and sodium repair tissue NMSI (r = -0.001; P = 0.996). Our results suggest higher glycosaminoglycan (GAG) content, and therefore, repair tissue of better quality in MACT than in BMS patients. Sodium imaging might be beneficial in non-invasive evaluation of cartilage repair surgery efficacy. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  4. The use of bioactive peptides to modify materials for bone tissue repair.

    PubMed

    Wang, Cunyang; Liu, Yan; Fan, Yubo; Li, Xiaoming

    2017-06-01

    It has been well recognized that the modification of biomaterials with appropriate bioactive peptides could further enhance their functions. Especially, it has been shown that peptide-modified bone repair materials could promote new bone formation more efficiently compared with conventional ones. The purpose of this article is to give a general review of recent studies on bioactive peptide-modified materials for bone tissue repair. Firstly, the main peptides for inducing bone regeneration and commonly used methods to prepare peptide-modified bone repair materials are introduced. Then, current in vitro and in vivo research progress of peptide-modified composites used as potential bone repair materials are reviewed and discussed. Generally speaking, the recent related studies have fully suggested that the modification of bone repair materials with osteogenic-related peptides provide promising strategies for the development of bioactive materials and substrates for enhanced bone regeneration and the therapy of bone tissue diseases. Furthermore, we have proposed some research trends in the conclusion and perspectives part.

  5. The use of bioactive peptides to modify materials for bone tissue repair

    PubMed Central

    Wang, Cunyang; Liu, Yan; Fan, Yubo

    2017-01-01

    Abstract It has been well recognized that the modification of biomaterials with appropriate bioactive peptides could further enhance their functions. Especially, it has been shown that peptide-modified bone repair materials could promote new bone formation more efficiently compared with conventional ones. The purpose of this article is to give a general review of recent studies on bioactive peptide-modified materials for bone tissue repair. Firstly, the main peptides for inducing bone regeneration and commonly used methods to prepare peptide-modified bone repair materials are introduced. Then, current in vitro and in vivo research progress of peptide-modified composites used as potential bone repair materials are reviewed and discussed. Generally speaking, the recent related studies have fully suggested that the modification of bone repair materials with osteogenic-related peptides provide promising strategies for the development of bioactive materials and substrates for enhanced bone regeneration and the therapy of bone tissue diseases. Furthermore, we have proposed some research trends in the conclusion and perspectives part. PMID:28596916

  6. Tissue repair response as a function of dose in thioacetamide hepatotoxicity.

    PubMed Central

    Mangipudy, R S; Chanda, S; Mehendale, H M

    1995-01-01

    The purpose of the present study was to establish a dose-response relationship for thioacetamide (TA), where tissue regeneration as well as liver injury were two simultaneous but opposing responses. Male Sprague-Dawley rats were injected intraperitioneally with a 12-fold dose range of TA, and both liver injury and tissue repair were measured. Liver injury was assessed by serum enzyme elevations. Serum alanine aminotransferase (ALT) elevation did not show any dose response over a 12-fold dose range up to 24 hr. A dramatic ALT elevation was evident after 24 hr and only for the highest dose (600 mg/kg). Tissue regeneration response was measured by 3H-thymidine (3H-T) incorporation into hepatocellular DNA and by proliferating cell nuclear antigen (PCNA) procedure during a time course (6, 12, 24, 36, 48, 72, and 96 hr). Tissue regeneration, as indicated by 3H-T incorporation, peaked at 36 hr after administration of a low dose of TA (50 mg/kg). With increasing doses, a greater but delayed stimulation of cell division was observed until a threshold was reached (300 mg/kg). Above the tissue repair threshold (600 mg/kg), because stimulated tissue repair as revealed by 3H-T incorporation in hepatonuclear DNA was significantly delayed and attenuated, injury assessed by serum enzyme elevations was remarkably accelerated, indicating unrestrained progression of injury leading to animal death. These findings suggest that, in addition to the magnitude of tissue repair response, the time at which this occurs is critical in restraining the progression of injury, thereby determining the ultimate outcome of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. Figure 2. Figure 3. A Figure 3. B Figure 3. C Figure 3. D Figure 3. E Figure 3. F Figure 4. Figure 5. Figure 6. A Figure 6. B Figure 6. C Figure 7. A Figure 7. B Figure 7. C Figure 7. D Figure 7. E Figure 7. F PMID:7768227

  7. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode.

    PubMed

    Doni, Andrea; Musso, Tiziana; Morone, Diego; Bastone, Antonio; Zambelli, Vanessa; Sironi, Marina; Castagnoli, Carlotta; Cambieri, Irene; Stravalaci, Matteo; Pasqualini, Fabio; Laface, Ilaria; Valentino, Sonia; Tartari, Silvia; Ponzetta, Andrea; Maina, Virginia; Barbieri, Silvia S; Tremoli, Elena; Catapano, Alberico L; Norata, Giuseppe D; Bottazzi, Barbara; Garlanda, Cecilia; Mantovani, Alberto

    2015-06-01

    Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity. © 2015 Doni et al.

  8. Achilles tendon repair with acellular tissue graft augmentation in neglected ruptures.

    PubMed

    Lee, Daniel K

    2007-01-01

    Neglected Achilles tendon rupture injuries present surgical challenges because of the quality and quantity of tendon tissue during repair combined with the magnitude of mechanical forces placed on this tendon. The purpose of this study was to evaluate the effects of an acellular human dermal tissue matrix, GRAFTJACKET, as an augmentation material in neglected Achilles tendon repair. Nine patients with neglected Achilles tendon ruptures were evaluated and followed up for a minimum of 20 months. Primary repair was followed by augmentation with the graft and suturing circumferentially around the tendon. Patients were placed in an early, functional rehabilitation program with postoperative evaluation at 3, 6, and 12 months. Outcome scores were calculated based on the American Orthopaedic Foot and Ankle Society ankle-hindfoot scoring system. At 20 to 30 months postoperative follow-up range, there has been no incidence of re-rupture or recurrent pain. The average return-to-activity time was 15.2 +/- 1.7 weeks. The results from this retrospective clinical series suggest that using an acellular human dermal tissue matrix to augment neglected Achilles tendon rupture primary repair offers desirable return-to-activity time points and viable surgical alternative over previously reported surgical options.

  9. The cellular and molecular mechanisms of tissue repair and regeneration as revealed by studies in Xenopus

    PubMed Central

    Li, Jingjing; Zhang, Siwei

    2016-01-01

    Abstract Survival of any living organism critically depends on its ability to repair and regenerate damaged tissues and/or organs during its lifetime following injury, disease, or aging. Various animal models from invertebrates to vertebrates have been used to investigate the molecular and cellular mechanisms of wound healing and tissue regeneration. It is hoped that such studies will form the framework for identifying novel clinical treatments that will improve the healing and regenerative capacity of humans. Amongst these models, Xenopus stands out as a particularly versatile and powerful system. This review summarizes recent findings using this model, which have provided fundamental knowledge of the mechanisms responsible for efficient and perfect tissue repair and regeneration. PMID:27800170

  10. Tissue repair strength using chitosan adhesives with different physical-chemical characteristics.

    PubMed

    Barton, Matthew J; Morley, John W; Mahns, David A; Mawad, Damia; Wuhrer, Richard; Fania, David; Frost, Samuel J; Loebbe, Christian; Lauto, Antonio

    2014-11-01

    A range of chitosan-based biomaterials have recently been used to perform sutureless, laser-activated tissue repair. Laser-activation has the advantage of bonding to tissue through a non-contact, aseptic mechanism. Chitosan adhesive films have also been shown to adhere to sheep intestine strongly without any chemical modification to chitosan. In this study, we continue to investigate chitosan adhesive films and explore the impact on the tissue repair strength and tensile strength characteristics of four types of adhesive film based on chitosan with different molecular weight and degree of deacetylation. Results showed that adhesives based on chitosan with medium molecular weight achieved the highest bonding strength, tensile strength and E-modulus when compared to the other adhesives.

  11. Urinary bladder matrix promotes site appropriate tissue formation following right ventricle outflow tract repair

    PubMed Central

    Remlinger, Nathaniel T; Gilbert, Thomas W; Yoshida, Masahiro; Guest, Brogan N; Hashizume, Ryotaro; Weaver, Michelle L; Wagner, William R; Brown, Bryan N; Tobita, Kimimasa; Wearden, Peter D

    2013-01-01

    The current prevalence and severity of heart defects requiring functional replacement of cardiac tissue pose a serious clinical challenge. Biologic scaffolds are an attractive tissue engineering approach to cardiac repair because they avoid sensitization associated with homograft materials and theoretically possess the potential for growth in similar patterns as surrounding native tissue. Both urinary bladder matrix (UBM) and cardiac ECM (C-ECM) have been previously investigated as scaffolds for cardiac repair with modest success, but have not been compared directly. In other tissue locations, bone marrow derived cells have been shown to play a role in the remodeling process, but this has not been investigated for UBM in the cardiac location, and has never been studied for C-ECM. The objectives of the present study were to compare the effectiveness of an organ-specific C-ECM patch with a commonly used ECM scaffold for myocardial tissue repair of the right ventricle outflow tract (RVOT), and to examine the role of bone marrow derived cells in the remodeling response. A chimeric rat model in which all bone marrow cells express green fluorescent protein (GFP) was generated and used to show the ability of ECM scaffolds derived from the heart and bladder to support cardiac function and cellular growth in the RVOT. The results from this study suggest that urinary bladder matrix may provide a more appropriate substrate for myocardial repair than cardiac derived matrices, as shown by differences in the remodeling responses following implantation, as well as the presence of site appropriate cells and the formation of immature, myocardial tissue. PMID:23974174

  12. [Application of narrow hypodermal pedicled retroauricular flap in repairing preauricular soft tissue defect].

    PubMed

    Yu, Daojiang; Zhao, Tianlan; Xu, Youjia; Xie, Xiaoming; Chen, Qi; Han, Wenya; Wu, Lijun; Chai, Jun

    2012-06-01

    To investigate the technique and effectiveness of using narrow hypodermal pedicled retroauricular flap for repairing preauricular soft tissue defect. Between June 2008 and July 2011, 11 cases of preauricular soft tissue defect were treated, which were caused by resection of preauricular tumors, including 5 cases of pigmented nevus, 2 cases of basal cell carcinoma, 2 cases of mixed hemangioma, and 2 cases of skin papilloma. There were 7 males and 4 females, aged from 26 to 75 years (mean, 50 years). The disease duration was 3-50 years (mean, 35 years). The size of the soft tissue defect ranged from 1.5 cm x 1.0 cm to 3.5 cm x 3.0 cm. The narrow hypodermal pedicled retroauricular flap was designed with its pedicle along the pathway of the superficial temporal artery and posterior auricular artery through tunnel to repair the defects. The size of the flaps ranged from 1.8 cm x 1.3 cm to 3.8 cm x 3.3 cm with the pedicle of 2-5 cm in length and 0.4-0.7 cm in width. The donor site was sutured directly or repaired with local flap. All flaps survived and incisions healed primarily after operation. Eight cases were followed up 6 months to 1 year. The flaps had good texture, flexibility, and color, and the auricle appearance was satisfactory. No recurrence of tumor was found. The narrow hypodermal pedicled retroauricular flap has long and narrow pedicle, big transferring angle, large repairing area, no major blood vessel, and easy operation, so it is a simple and ideal technique for repairing preauricular soft tissue defect.

  13. [Radiotherapy of adult soft tissue sarcoma].

    PubMed

    Le Péchoux, C; Moureau-Zabotto, L; Llacer, C; Ducassou, A; Sargos, P; Sunyach, M P; Thariat, J

    2016-09-01

    Incidence of soft tissue sarcoma is low and requires multidisciplinary treatment in specialized centers. The objective of this paper is to report the state of the art regarding indications and treatment techniques of main soft tissue sarcoma localisations.

  14. Acute ethanol exposure suppresses the repair of O6-methylguanine DNA lesions in castrated adult male rats.

    PubMed

    Wilson, D M; Tentler, J J; Carney, J P; Wilson, T M; Kelley, M R

    1994-10-01

    Alcohol has clearly been associated with an increase of cancers in numerous tissue, including the respiratory tract, colon, rectum, liver, but especially the esophagus, larynx, pharynx, and mouth. Alcohol alone has not been shown to be a mutagen until it is converted to acetaldehyde and, therefore, alcohol presumably acts as a cocarcinogen. Previous data has shown that alcohol concentrations of 2% or greater inhibits DNA repair, and in light of the widespread consumption of alcoholic beverages with alcohol contents ranging from 4 to 5% (beer and wine coolers) to 50% (whiskey), interest in determining the mechanism(s) responsible for alcohol-induced carcinogenesis has heightened. Although previous studies, in intact rats, have investigated the effects of chronic alcohol exposure on some aspects of DNA repair, we have begun to address the effects of acute or "binge" alcohol exposure on mammalian DNA repair. Toward this end, we report the inhibition of O6-methylguanine-DNA methyltransferase (MGMT) by a single intraperitoneal injection of 30% ethanol in adult male castrated rats. This inhibition lasted for at least 24 hr. We also observed a dose-response effect of ethanol on MGMT activity, again only in the castrated rats. The finding of ethanol's effect on MGMT activity in castrated and not intact rats implies a hormonal component of MGMT DNA repair response, which has only been alluded to in past research.

  15. H2S-releasing nanoemulsions: a new formulation to inhibit tumor cells proliferation and improve tissue repair

    PubMed Central

    Carotenuto, Felicia; Khashoggi, Haneen A.; Nanni, Francesca; Melino, Sonia

    2016-01-01

    The improvement of solubility and/or dissolution rate of poorly soluble natural compounds is an ideal strategy to make them optimal candidates as new potential drugs. Accordingly, the allyl sulfur compounds and omega-3 fatty acids are natural hydrophobic compounds that exhibit two important combined properties: cardiovascular protection and antitumor activity. Here, we have synthesized and characterized a novel formulation of diallyl disulfide (DADS) and α-linolenic acid (ALA) as protein-nanoemulsions (BAD-NEs), using ultrasounds. BAD-NEs are stable over time at room temperature and show antioxidant and radical scavenging property. These NEs are also optimal H2S slow-release donors and show a significant anti-proliferative effect on different human cancer cell lines: MCF-7 breast cancer and HuT 78 T-cell lymphoma cells. BAD-NEs are able to regulate the ERK1/2 pathway, inducing apoptosis and cell cycle arrest at the G0/G1 phase. We have also investigated their effect on cell proliferation of human adult stem/progenitor cells. Interestingly, BAD-NEs are able to improve the Lin– Sca1+ human cardiac progenitor cells (hCPC) proliferation. This stem cell growth stimulation is combined with the expression and activation of proteins involved in tissue-repair, such as P-AKT, α-sma and connexin 43. Altogether, our results suggest that these antioxidant nanoemulsions might have potential application in selective cancer therapy and for promoting the muscle tissue repair. PMID:27741519

  16. Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair

    PubMed Central

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

    2014-01-01

    The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the structural layers of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and embedded within the OPF hydrogel matrix in a spatially controlled manner. Three different scaffold formations were implanted in a medial femoral condyle osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral layer, and 3) IGF-1 and BMP-2 in their respective separate layers. The quantity and quality of osteochondral repair was evaluated at 6 and 12 weeks with histological scoring and micro-computed tomography (micro-CT). While histological scoring results at 6 weeks showed no differences between experimental groups, micro-CT analysis revealed that the delivery of BMP-2 alone increased the number of bony trabecular islets formed, an indication of early bone formation, over that of IGF-1 delivery alone. At 12 weeks post-implantation, minimal differences were detected between the three groups for cartilage repair. However, the dual delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone repair, greater bone growth at the defect margins, and lower bone specific surface than the single delivery of IGF-1. These results suggest that the delivery of BMP-2 enhances subchondral bone formation and that, while the dual delivery of IGF-1 and BMP-2 in separate layers does not improve cartilage repair under the conditions studied, they may synergistically enhance the degree of subchondral bone formation. Overall, bilayered OPF hydrogel composites demonstrate potential as spatially-guided, multiple growth factor release vehicles for osteochondral tissue repair. PMID:25047629

  17. Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair.

    PubMed

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

    2014-10-01

    The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the structural layers of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and embedded within the OPF hydrogel matrix in a spatially controlled manner. Three different scaffold formulations were implanted in a medial femoral condyle osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral layer, and 3) IGF-1 and BMP-2 in their respective separate layers. The quantity and quality of osteochondral repair was evaluated at 6 and 12 weeks with histological scoring and micro-computed tomography (micro-CT). While histological scoring results at 6 weeks showed no differences between experimental groups, micro-CT analysis revealed that the delivery of BMP-2 alone increased the number of bony trabecular islets formed, an indication of early bone formation, over that of IGF-1 delivery alone. At 12 weeks post-implantation, minimal differences were detected between the three groups for cartilage repair. However, the dual delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone repair, greater bone growth at the defect margins, and lower bone specific surface than the single delivery of IGF-1. These results suggest that the delivery of BMP-2 enhances subchondral bone formation and that, while the dual delivery of IGF-1 and BMP-2 in separate layers does not improve cartilage repair under the conditions studied, they may synergistically enhance the degree of subchondral bone formation. Overall, bilayered OPF hydrogel composites demonstrate potential as spatially-guided, multiple growth factor release vehicles for osteochondral tissue repair.

  18. Influence of surgical decompression on the expression of inflammatory and tissue repair biomarkers in periapical cysts.

    PubMed

    Rodrigues, Janderson Teixeira; Dos Santos Antunes, Henrique; Armada, Luciana; Pires, Fábio Ramôa

    2017-07-05

    The biologic effects of surgical decompression on the epithelium and connective tissues of periapical cysts are not fully understood. The aim of this study was to evaluate the expression of tissue repair and inflammatory biomarkers in periapical cysts before and after surgical decompression. Nine specimens of periapical cysts treated with decompression before undergoing complete enucleation were immunohistochemically analyzed to investigate the expression of interleukin-1β, tumor necrosis factor-α, transforming growth factor-β1, matrix metalloproteinase-9, Ki-67, and epidermal growth factor receptor. Expression of the biomarkers was classified as positive, focal, or negative. Ki-67 immunoexpression was calculated as a cell proliferation index. The expression of the biomarkers was compared in the specimens from decompression and from the final surgical procedure. Computed tomography demonstrated that volume was reduced in all cysts after decompression. There were no differences in the immunoexpression of the proinflammatory and tissue repair biomarkers when comparing the specimens obtained before and after the decompression. Surgical decompression was efficient in reducing the volume of periapical cysts before complete enucleation. When comparing the specimens obtained from surgical decompression and from complete surgical removal, the immunohistochemical analysis did not show a decrease in proinflammatory biomarkers; neither did it show an increase in tissue repair biomarkers. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Surgical anatomy and utility of pedicled vascularized tissue flaps for multilayered repair of skull base defects.

    PubMed

    Safavi-Abbasi, Sam; Komune, Noritaka; Archer, Jacob B; Sun, Hai; Theodore, Nicholas; James, Jeffrey; Little, Andrew S; Nakaji, Peter; Sughrue, Michael E; Rhoton, Albert L; Spetzler, Robert F

    2016-08-01

    OBJECT The objective of this study was to describe the surgical anatomy and technical nuances of various vascularized tissue flaps. METHODS The surgical anatomy of various tissue flaps and their vascular pedicles was studied in 5 colored silicone-injected anatomical specimens. Medical records were reviewed of 11 consecutive patients who underwent repair of extensive skull base defects with a combination of various vascularized flaps. RESULTS The supraorbital, supratrochlear, superficial temporal, greater auricular, and occipital arteries contribute to the vascular supply of the pericranium. The pericranial flap can be designed based on an axial blood supply. Laterally, various flaps are supplied by the deep or superficial temporal arteries. The nasoseptal flap is a vascular pedicled flap based on the nasoseptal artery. Patients with extensive skull base defects can undergo effective repair with dual flaps or triple flaps using these pedicled vascularized flaps. CONCLUSIONS Multiple pedicled flaps are available for reconstitution of the skull base. Knowledge of the surgical anatomy of these flaps is crucial for the skull base surgeon. These vascularized tissue flaps can be used effectively as single or combination flaps. Multilayered closure of cranial base defects with vascularized tissue can be used safely and may lead to excellent repair outcomes.

  20. Role of Macrophages in the Repair Process during the Tissue Migrating and Resident Helminth Infections

    PubMed Central

    Faz-López, Berenice

    2016-01-01

    The Th1/Th2/Th17 balance is a fundamental feature in the regulation of the inflammatory microenvironment during helminth infections, and an imbalance in this paradigm greatly contributes to inflammatory disorders. In some cases of helminthiasis, an initial Th1 response could occur during the early phases of infection (acute), followed by a Th2 response that prevails in chronic infections. During the late phase of infection, alternatively activated macrophages (AAMs) are important to counteract the inflammation caused by the Th1/Th17 response and larval migration, limiting damage and repairing the tissue affected. Macrophages are the archetype of phagocytic cells, with the primary role of pathogen destruction and antigen presentation. Nevertheless, other subtypes of macrophages have been described with important roles in tissue repair and immune regulation. These types of macrophages challenge the classical view of macrophages activated by an inflammatory response. The role of these subtypes of macrophages during helminthiasis is a controversial topic in immunoparasitology. Here, we analyze some of the studies regarding the role of AAMs in tissue repair during the tissue migration of helminths. PMID:27648452

  1. Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration.

    PubMed

    Fan, Fuqin; He, Zhixiang; Kong, Lu-Lu; Chen, Qinghua; Yuan, Quan; Zhang, Shihao; Ye, Jinjin; Liu, Hao; Sun, Xiufeng; Geng, Jing; Yuan, Lunzhi; Hong, Lixin; Xiao, Chen; Zhang, Weiji; Sun, Xihuan; Li, Yunzhan; Wang, Ping; Huang, Lihong; Wu, Xinrui; Ji, Zhiliang; Wu, Qiao; Xia, Ning-Shao; Gray, Nathanael S; Chen, Lanfen; Yun, Cai-Hong; Deng, Xianming; Zhou, Dawang

    2016-08-17

    Tissue repair and regenerative medicine address the important medical needs to replace damaged tissue with functional tissue. Most regenerative medicine strategies have focused on delivering biomaterials and cells, yet there is the untapped potential for drug-induced regeneration with good specificity and safety profiles. The Hippo pathway is a key regulator of organ size and regeneration by inhibiting cell proliferation and promoting apoptosis. Kinases MST1 and MST2 (MST1/2), the mammalian Hippo orthologs, are central components of this pathway and are, therefore, strong target candidates for pharmacologically induced tissue regeneration. We report the discovery of a reversible and selective MST1/2 inhibitor, 4-((5,10-dimethyl-6-oxo-6,10-dihydro-5H-pyrimido[5,4-b]thieno[3,2-e][1,4]diazepin-2-yl)amino)benzenesulfonamide (XMU-MP-1), using an enzyme-linked immunosorbent assay-based high-throughput biochemical assay. The cocrystal structure and the structure-activity relationship confirmed that XMU-MP-1 is on-target to MST1/2. XMU-MP-1 blocked MST1/2 kinase activities, thereby activating the downstream effector Yes-associated protein and promoting cell growth. XMU-MP-1 displayed excellent in vivo pharmacokinetics and was able to augment mouse intestinal repair, as well as liver repair and regeneration, in both acute and chronic liver injury mouse models at a dose of 1 to 3 mg/kg via intraperitoneal injection. XMU-MP-1 treatment exhibited substantially greater repopulation rate of human hepatocytes in the Fah-deficient mouse model than in the vehicle-treated control, indicating that XMU-MP-1 treatment might facilitate human liver regeneration. Thus, the pharmacological modulation of MST1/2 kinase activities provides a novel approach to potentiate tissue repair and regeneration, with XMU-MP-1 as the first lead for the development of targeted regenerative therapeutics.

  2. Heterozygous Vangl2(Looptail) mice reveal novel roles for the planar cell polarity pathway in adult lung homeostasis and repair.

    PubMed

    Poobalasingam, Thanushiyan; Yates, Laura L; Walker, Simone A; Pereira, Miguel; Gross, Nina Y; Ali, Akmol; Kolatsi-Joannou, Maria; Jarvelin, Marjo-Riitta; Pekkanen, Juha; Papakrivopoulou, Eugenia; Long, David A; Griffiths, Mark; Wagner, Darcy; Königshoff, Melanie; Hind, Matthew; Minelli, Cosetta; Lloyd, Clare M; Dean, Charlotte H

    2017-02-24

    Lung diseases impose a huge economic and health burden worldwide. A key aspect of several adult lung diseases, such as Idiopathic pulmonary fibrosis (IPF) and Chronic Obstructive pulmonary Disease (COPD), including emphysema, is aberrant tissue repair, which leads to an accumulation of damage and impaired respiratory function. Currently, there are few effective treatments available for these diseases and their incidence is rising.The Planar Cell Polarity (PCP) pathway is critical for the embryonic development of many organs, including kidney and lung. We have previously shown that perturbation of the PCP pathway impairs tissue morphogenesis, which disrupts the number and shape of epithelial tubes formed within these organs during embryogenesis. However, very little is known about the role of the PCP pathway beyond birth, partly due to the perinatal lethality of many PCP mouse mutant lines.Here we have investigated heterozygous Looptail (Lp) mice, in which a single copy of the core PCP gene, Vangl2, is disrupted. We show that these mice are viable but display severe airspace enlargement and impaired adult lung function. Underlying these defects, we find that Vangl2(Lp/+) lungs exhibit altered distribution of actin microfilaments and abnormal regulation of the actin modifying protein cofilin. In addition, we show that Vangl2(Lp/+) lungs exhibit many of the hallmarks of tissue damage including an altered macrophage population, abnormal elastin deposition and elevated levels of the elastin-modifying enzyme, Mmp12, all of which are observed in the lung disease, emphysema.In vitro, VANGL2 disruption impairs directed cell migration and reduces the rate of repair following scratch wounding of human alveolar epithelial cells. Moreover, using population data from a birth cohort of young adults, all aged 31, we found evidence of an interactive effect between VANGL2 and smoking (a tissue damaging insult) on lung function. Finally, we show that that PCP genes VANGL2 and

  3. Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

    PubMed

    Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

    2014-06-18

    After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

  4. Experiment K-7-29: Connective Tissue Studies. Part 1; Rat Skin, Normal and Repair

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Grindeland, R.; Ashman, R.; Choy, V.; Durnova, G.; Graf, B.; Griffith, P.; Kaplansky, A. S.; Kolis, S.; Martinez, D.; hide

    1994-01-01

    The skin repair studies started to be problematic for the following reasons: (1) It was very difficult to locate the wound and many lesions were not of the same dimensions. A considerable amount of time was devoted to the identification of the wound using polarized light. We understand that this experiment was added on to the overall project. Marking of the wound site and standard dimensions should be recommended for the next flight experiment. (2) The tissue was frozen, therefore thawing and fixation caused problems with some of the immunocytochemical staining for obtaining better special resolution with light microscopy image processing. Despite these problems, we were unable to detect any significant qualitative differences for the following wound markers: (1) Collagen Type 3, (2) Hematotoxylin and Eosin, and (3) Macrophage Factor 13. All protein markers were isolated from rat sources and antibodies prepared and tested for cross reactivity with other molecules at the University of Wisconsin Hybridoma Facility. However, rat skin from the non lesioned site 'normal' showed interesting biochemical results. Skin was prepared for the following measurements: (1) DNA content, (2) Collagen content by hydroxyproline, and (3) uronic acid content and estimation of ground substance. The results indicated there was a non-significant increase (10%) in the DNA concentration of skin from flight animals. However, the data expressed as a ratio DNA/Collagen estimates the cell or nuclear density that supports a given quantity of collagen showed a dramatic increase in the flight group (33%). This means flight conditions may have slowed down collagen secretion and/or increased cell proliferation in adult rat skin. Further biochemical tests are being done to determine the crosslinking of elastin which will enhance the insight to assessing changes in skin turnover.

  5. Experiment K-7-29: Connective Tissue Studies. Part 1; Rat Skin, Normal and Repair

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Grindeland, R.; Ashman, R.; Choy, V.; Durnova, G.; Graf, B.; Griffith, P.; Kaplansky, A. S.; Kolis, S.; Martinez, D.; Rao, J. S.; Rayford, A. R.; Reddy, B. R.; Sears, J.; Thielke, R.; Ulm, M.; Vanderby, R.

    1994-01-01

    The skin repair studies started to be problematic for the following reasons: (1) It was very difficult to locate the wound and many lesions were not of the same dimensions. A considerable amount of time was devoted to the identification of the wound using polarized light. We understand that this experiment was added on to the overall project. Marking of the wound site and standard dimensions should be recommended for the next flight experiment. (2) The tissue was frozen, therefore thawing and fixation caused problems with some of the immunocytochemical staining for obtaining better special resolution with light microscopy image processing. Despite these problems, we were unable to detect any significant qualitative differences for the following wound markers: (1) Collagen Type 3, (2) Hematotoxylin and Eosin, and (3) Macrophage Factor 13. All protein markers were isolated from rat sources and antibodies prepared and tested for cross reactivity with other molecules at the University of Wisconsin Hybridoma Facility. However, rat skin from the non lesioned site 'normal' showed interesting biochemical results. Skin was prepared for the following measurements: (1) DNA content, (2) Collagen content by hydroxyproline, and (3) uronic acid content and estimation of ground substance. The results indicated there was a non-significant increase (10%) in the DNA concentration of skin from flight animals. However, the data expressed as a ratio DNA/Collagen estimates the cell or nuclear density that supports a given quantity of collagen showed a dramatic increase in the flight group (33%). This means flight conditions may have slowed down collagen secretion and/or increased cell proliferation in adult rat skin. Further biochemical tests are being done to determine the crosslinking of elastin which will enhance the insight to assessing changes in skin turnover.

  6. Characterization of the cells in repair tissue following autologous chondrocyte implantation in mankind: a novel report of two cases.

    PubMed

    Wright, Karina T; Mennan, Claire; Fox, Hannah; Richardson, James B; Banerjee, Robin; Roberts, Sally

    2013-11-01

    Autologous chondrocyte implantation (ACI) is used worldwide for the treatment of cartilage defects. This study has aimed to assess for the first time the cells that are contained within human ACI repair tissues several years post-treatment. We have compared the phenotypic properties of cells from within the ACI repair with adjacent chondrocytes and subchondral bone-derived mesenchymal stromal/stem cells (MSCs). Two patients undergoing arthroplasty of their ACI-treated joint were investigated. Tissue and cells were isolated from the repair site, adjacent macroscopically normal cartilage and MSCs from the subchondral bone were characterized for their growth kinetics, morphology, immunoprofile and differentiation capacity. ACI repair tissue appeared fibrocartilaginous, and ACI repair cells were heterogeneous in morphology and size when freshly isolated, becoming more homogeneous, resembling chondrocytes from adjacent cartilage, after culture expansion. The same weight of ACI repair tissue resulted in less cells than macroscopically normal cartilage. During expansion, ACI repair cells proliferated faster than MSCs but slower than chondrocytes. ACI repair cell immunoprofiles resembled chondrocytes, but their differentiation capacity matched MSCs. This novel report demonstrates that human ACI repair cell phenotypes resemble both chondrocytes and MSCs but at different stages of their isolation and expansion in vitro.

  7. DNA damage and repair in tumour and non-tumour tissues of mice induced by nicotinamide.

    PubMed Central

    Olsson, A. R.; Sheng, Y.; Pero, R. W.; Chaplin, D. J.; Horsman, M. R.

    1996-01-01

    In vivo DNA damage and repair was induced by nicotinamide (NAM) in adenotype 12 virus-induced mouse sarcoma A12B3 and sarcoma F inoculated into CBA mice. DNA damage, NAM and NAD concentrations were measured after in vivo exposure to NAM, in tumours and spleens by alkaline elution and by HPLC analysis. Our results indicate that NAM between 100-1000 mg kg-1 causes a high level of in vivo DNA strand breaks in tumours and normal tissues in mice bearing the immunogenic sarcoma A12B3 but not in the non-immunogenic sarcoma F. The repair process was also delayed by the NAM treatment probably owing to inhibition of the DNA repair enzyme, poly(ADP-ribose)polymerase, as evidenced by accumulation of NAM and NAD. These data are consistent with NAM having a mechanism of action as a radiosensitiser at least in part by DNA repair inhibition. In addition, it should also be considered that high doses of NAM might cause considerable complications to normal tissue in tumour-bearing individuals. PMID:8695350

  8. Altered DNA base excision repair profile in brain tissue and blood in Alzheimer's disease.

    PubMed

    Lillenes, Meryl S; Rabano, Alberto; Støen, Mari; Riaz, Tahira; Misaghian, Dorna; Møllersen, Linda; Esbensen, Ying; Günther, Clara-Cecilie; Selnes, Per; Stenset, Vidar T V; Fladby, Tormod; Tønjum, Tone

    2016-05-28

    Alzheimer's disease (AD) is a progressive, multifactorial neurodegenerative disorder that is the main cause of dementia globally. AD is associated with increased oxidative stress, resulting from imbalance in production and clearance of reactive oxygen species (ROS). ROS can damage DNA and other macromolecules, leading to genome instability and disrupted cellular functions. Base excision repair (BER) plays a major role in repairing oxidative DNA lesions. Here, we compared the expression of BER components APE1, OGG1, PARP1 and Polβ in blood and postmortem brain tissue from patients with AD, mild cognitive impairment (MCI) and healthy controls (HC). BER mRNA levels were correlated to clinical signs and cerebrospinal fluid biomarkers for AD. Notably, the expression of BER genes was higher in brain tissue than in blood samples. Polβ mRNA and protein levels were significantly higher in the cerebellum than in the other brain regions, more so in AD patients than in HC. Blood mRNA levels of OGG1 was low and PARP1 high in MCI and AD. These findings reflect the oxidative stress-generating energy-consumption in the brain and the importance of BER in repairing these damage events. The data suggest that alteration in BER gene expression is an event preceding AD. The results link DNA repair in brain and blood to the etiology of AD at the molecular level and can potentially serve in establishing novel biomarkers, particularly in the AD prodromal phase.

  9. Diaphragmatic repair through fetal tissue engineering: a comparison between mesenchymal amniocyte- and myoblast-based constructs.

    PubMed

    Kunisaki, Shaun M; Fuchs, Julie R; Kaviani, Amir; Oh, Jung-Tak; LaVan, David A; Vacanti, Joseph P; Wilson, Jay M; Fauza, Dario O

    2006-01-01

    We have previously shown that fetal tissue engineering is a preferred alternative to diaphragmatic repair in a large animal model. This study was aimed at comparing diaphragmatic constructs seeded with mesenchymal amniocytes and fetal myoblasts in this model. Neonatal lambs (n = 14) underwent repair of an experimental diaphragmatic defect with identical scaffolds, either seeded with labeled autologous cells (mesenchymal amniocytes in group 1 and fetal myoblasts in group 2) or as an acellular graft (group 3). At 1 to 12 months postoperatively, implants were harvested for multiple analyses. Repair failure (reherniation or eventration) was significantly higher in group 3 than in groups 1 and 2, with no difference between groups 1 and 2. Seeded fetal myoblasts quickly lost their myogenic phenotype in vivo. All grafts contained cells with a fibroblastic-myofibroblastic profile. Elastin concentrations and both modular and ultimate tensile strengths were significantly higher in group 1 than in groups 2 and 3. There were no differences in glycosaminoglycans and type I collagen levels among the groups. Diaphragmatic repair with a mesenchymal amniocyte-based engineered tendon leads to improved structural outcomes when compared with equivalent fetal myoblast-based and acellular grafts. The amniotic fluid is a preferred cell source for tissue-engineered diaphragmatic reconstruction.

  10. A New Absorbable Synthetic Substitute With Biomimetic Design for Dural Tissue Repair.

    PubMed

    Shi, Zhidong; Xu, Tao; Yuan, Yuyu; Deng, Kunxue; Liu, Man; Ke, Yiquan; Luo, Chengyi; Yuan, Tun; Ayyad, Ali

    2016-04-01

    Dural repair products are evolving from animal tissue-derived materials to synthetic materials as well as from inert to absorbable features; most of them lack functional and structural characteristics compared with the natural dura mater. In the present study, we evaluated the properties and tissue repair performance of a new dural repair product with biomimetic design. The biomimetic patch exhibits unique three-dimensional nonwoven microfiber structure with good mechanical strength and biocompatibility. The animal study showed that the biomimetic patch and commercially synthetic material group presented new subdural regeneration at 90 days, with low level inflammatory response and minimal to no adhesion formation detected at each stage. In the biological material group, no new subdural regeneration was observed and severe adhesion between the implant and the cortex occurred at each stage. In clinical case study, there was no cerebrospinal fluid leakage, and all the postoperation observations were normal. The biomimetic structure and proper rate of degradation of the new absorbable dura substitute can guide the meaningful reconstruction of the dura mater, which may provide a novel approach for dural defect repair. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  11. Adipose tissue derived mesenchymal stem cells for musculoskeletal repair in veterinary medicine

    PubMed Central

    Arnhold, Stefan; Wenisch, Sabine

    2015-01-01

    Adipose tissue derived stem cells (ASCs) are mesenchymal stem cells which can be obtained from different adipose tissue sources within the body. It is an abundant cell pool, which is easy accessible and the cells can be obtained in large numbers, cultivated and expanded in vitro and prepared for tissue engineering approaches, especially for skeletal tissue repair. In the recent years this cell population has attracted a great amount of attention among researchers in human as well as in veterinary medicine. In the meantime ASCs have been well characterized and their use in regenerative medicine is very well established. This review focuses on the characterization of ASCs for their use for tissue engineering approaches especially in veterinary medicine and also highlights a selection of clinical trials on the basis of ASCs as the relevant cell source. PMID:25973326

  12. Tissue repair through cell competition and compensatory cellular hypertrophy in postmitotic epithelia

    PubMed Central

    Tamori, Yoichiro; Deng, Wu-Min

    2013-01-01

    Summary In multicellular organisms, tissue integrity and organ size are maintained through removal of aberrant or damaged cells and compensatory proliferation. Little is known, however, about this homeostasis system in postmitotic tissues, where tissue-intrinsic genetic programs constrain cell division and new cells no longer arise from stem cells. Here we show that, in postmitotic Drosophila follicular epithelia, aberrant but viable cells are eliminated through cell competition, and the resulting loss of local tissue volume triggers sporadic cellular hypertrophy to repair the tissue. This “compensatory cellular hypertrophy” (CCH) is implemented by acceleration of the endocycle, a variant cell cycle composed of DNA synthesis and gap phases without mitosis, dependent on activation of the insulin/IGF-like signaling pathway. These results reveal a remarkable homeostatic mechanism in postmitotic epithelia that ensures not only elimination of aberrant cells through cell competition but also proper organ-size control that involves compensatory cellular hypertrophy induced by physical parameters. PMID:23685249

  13. [Results of the experimental repair of osteochondral lesions in a pig model using tissue engineering].

    PubMed

    Villalobos Córdoba, F Enrique; Velasquillo Martínez, Cristina; Martínez López, Valentín; Lecona Butrón, Hugo; Reyes Marín, Baltasar; Estrada Villaseñor, Eréndira; Villegas, Castrejón Hilda; Solís Arrieta, Lilia; Espinosa Morales, Rolando; Ponce de León, Clemente Ibarra

    2007-01-01

    To repair experimental osteochondral knee lesions in pigs using tissue engineering. Eight 40-kg pigs underwent surgery. Cartilage and periosteal biopsies of their control knee were taken. Cartilage and periosteal cells were independently isolated, cultured and seeded in biodegradable PGA and PLA polymers that were fixed on the bottom of an osteochondral defect in the pig's experimental knee, with bioabsorbable Mitek implants. Four months later the pigs were sacrificed and the knees were analyzed with nuclear magnetic resonance imaging (NMRI), macroscopic assessment, histology, electron microscopy (EM), scanning electron microscopy (SEM) and SEM element analysis. All the defects were filled with cartilage-like tissue according to the NMRI evaluation and the visual examination. Hyaline-like cartilage was obtained in 3 defects and fibrocartilage in 5. The EM showed chondrocytes in the repair tissue. The SEM showed appropriate integration to the bone and the surrounding tissue. SEM element analysis showed sulphurized matrix attached to the bone with calcium and phosphates as predominant elements. Tissue engineering enabled the production of tissues similar to normal ones. The polymer fixation system was effective.

  14. Innate Lymphoid Cells: Balancing Immunity, Inflammation, and Tissue Repair in the Intestine

    PubMed Central

    Wojno, Elia D. Tait; Artis, David

    2012-01-01

    Innate lymphoid cells (ILCs) are a recently described group of innate immune cells that can regulate immunity, inflammation, and tissue repair in multiple anatomical compartments, particularly the barrier surfaces of the skin, airways, and intestine. Broad categories of ILCs have been defined based on transcription factor expression and the ability to produce distinct patterns of effector molecules. Recent studies have revealed that ILC populations can regulate commensal bacterial communities, contribute to resistance to helminth and bacterial pathogens, promote inflammation, and orchestrate tissue repair and wound healing. This review will examine the phenotype and function of murine and human ILCs and discuss the critical roles these innate immune cells play in health and disease. PMID:23084914

  15. Tendon phenotype should dictate tissue engineering modality in tendon repair: a review.

    PubMed

    Gott, Michael; Ast, Michael; Lane, Lewis B; Schwartz, John A; Catanzano, Anthony; Razzano, Pasquale; Grande, Daniel A

    2011-07-01

    Advancements in the technical aspects of tendon repair have significantly improved the treatment of tendon injuries. Arthroscopic techniques, suture material, and improved rehabilitation have all been contributing factors. Biological augmentation and tissue engineering appear to have the potential to improve clinical outcomes as well. After review of the physiology of tendon repair, three critical components of tissue engineering can be discerned: the cellular component, the carrier vehicle (matrix or scaffold), and the bioactive component (growth factors, platelet rich plasma). These three components are discussed with regard to each of three tendon types: Intra-synovial (flexor tendon), extra-synovial (Achilles tendon), and extra-synovial tendon under compression (rotator cuff). Scaffolds, biologically enhanced scaffolds, growth factors, platelet rich plasma, gene therapy, mesenchymal stem cells, and local environment factors in combination or alone may contribute to tendon healing. In the future it may be beneficial to differentiate these modes of healing augmentation with regard to tendon subtype.

  16. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    SciTech Connect

    Matteini, P; Ratto, F; Rossi, F; Pini, R

    2014-07-31

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  17. The maturity of tissue-engineered cartilage in vitro affects the repairability for osteochondral defect.

    PubMed

    Jin, Cheng Zhe; Cho, Jae-Ho; Choi, Byung Hyune; Wang, Li Ming; Kim, Moon Suk; Park, So Ra; Yoon, Jeong Ho; Yun, Jung Ho; Oh, Hyun Ju; Min, Byoung-Hyun

    2011-12-01

    Cartilage tissue engineering using cells and biocompatible scaffolds has emerged as a promising approach to repair of cartilage damage. To date, however, no engineered cartilage has proven to be equivalent to native cartilage in terms of biochemical and compression properties, as well as histological features. An alternative strategy for cartilage engineering is to focus on the in vivo regeneration potential of immature engineered cartilage. Here, we used a rabbit model to evaluate the extent to which the maturity of engineered cartilage influenced the remodeling and integration of implanted extracellular matrix scaffolds containing allogenous chondrocytes. Full-thickness osteochondral defects were created in the trochlear groove of New Zealand white rabbits. Left knee defects were left untreated as a control (group 1), and right knee defects were implanted with tissue-engineered cartilage cultured in vitro for 2 days (group 2), 2 weeks (group 3), or 4 weeks (group 4). Histological, chemical, and compression assays of engineered cartilage in vitro showed that biochemical composition became more cartilagenous, and biomechanical property for compression gradually increased with culture time. In an in vivo study, gross imaging and histological observation at 1 and 3 months after implanting in vitro-cultured engineered cartilage showed that defects in groups 3 and 4 were repaired with hyaline cartilage-like tissue, whereas defects were only partially filled with fibrocartilage after 1 month in groups 1 and 2. At 3 months, group 4 showed striking features of hyaline cartilage tissue, with a mature matrix and a columnar arrangement of chondrocytes. Zonal distribution of type II collagen was most prominent, and the International Cartilage Repair Society score was also highest at this time. In addition, the subchondral bone was well ossified. In conclusion, in vivo engineered cartilage was remodeled when implanted; however, its extent to maturity varied with cultivation

  18. Repair of articular cartilage defects in rabbits through tissue-engineered cartilage constructed with chitosan hydrogel and chondrocytes.

    PubMed

    Zhao, Ming; Chen, Zhu; Liu, Kang; Wan, Yu-qing; Li, Xu-dong; Luo, Xu-wei; Bai, Yi-guang; Yang, Ze-long; Feng, Gang

    2015-11-01

    In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was used to repair the articular cartilage defects. Chitosan hydrogels were prepared with a crosslinker formed by combining 1,6-diisocyanatohexane and polyethylene glycol. Chitosan hydrogel scaffold was seeded with rabbit chondrocytes that had been cultured for one week in vitro to form the preliminary tissue-engineered cartilage. This preliminary tissue-engineered cartilage was then transplanted into the defective rabbit articular cartilage. There were three treatment groups: the experimental group received preliminary tissue-engineered cartilage; the blank group received pure chitosan hydrogels; and, the control group had received no implantation. The knee joints were harvested at predetermined time. The repaired cartilage was analyzed through gross morphology, histologically and immunohistochemically. The repairs were scored according to the international cartilage repair society (ICRS) standard. The gross morphology results suggested that the defects were repaired completely in the experimental group after twelve weeks. The regenerated tissue connected closely with subchondral bone and the boundary with normal tissue was fuzzy. The cartilage lacuna in the regenerated tissue was similar to normal cartilage lacuna. The results of ICRS gross and histological grading showed that there were significant differences among the three groups (P<0.05). Chondrocytes implanted in the scaffold can adhere, proliferate, and secrete extracellular matrix. The novel tissue-engineered cartilage constructed in our research can completely repair the structure of damaged articular cartilage.

  19. Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis

    PubMed Central

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Squadrito, Francesco; Squadrito, Giovanni; Pallio, Socrate; Anastasi, Giuseppe P.; Cutroneo, Giuseppina; Macrì, Antonio; Altavilla, Domenica

    2016-01-01

    Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases. PMID:27601997

  20. A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue

    PubMed Central

    Nyengaard, Jens Randel; Lind, Martin; Spector, Myron

    2015-01-01

    Objective To implement stereological principles to develop an easy applicable algorithm for unbiased and quantitative evaluation of cartilage repair. Design Design-unbiased sampling was performed by systematically sectioning the defect perpendicular to the joint surface in parallel planes providing 7 to 10 hematoxylin–eosin stained histological sections. Counting windows were systematically selected and converted into image files (40-50 per defect). The quantification was performed by two-step point counting: (1) calculation of defect volume and (2) quantitative analysis of tissue composition. Step 2 was performed by assigning each point to one of the following categories based on validated and easy distinguishable morphological characteristics: (1) hyaline cartilage (rounded cells in lacunae in hyaline matrix), (2) fibrocartilage (rounded cells in lacunae in fibrous matrix), (3) fibrous tissue (elongated cells in fibrous tissue), (4) bone, (5) scaffold material, and (6) others. The ability to discriminate between the tissue types was determined using conventional or polarized light microscopy, and the interobserver variability was evaluated. Results We describe the application of the stereological method. In the example, we assessed the defect repair tissue volume to be 4.4 mm3 (CE = 0.01). The tissue fractions were subsequently evaluated. Polarized light illumination of the slides improved discrimination between hyaline cartilage and fibrocartilage and increased the interobserver agreement compared with conventional transmitted light. Conclusion We have applied a design-unbiased method for quantitative evaluation of cartilage repair, and we propose this algorithm as a natural supplement to existing descriptive semiquantitative scoring systems. We also propose that polarized light is effective for discrimination between hyaline cartilage and fibrocartilage. PMID:26069715

  1. A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue.

    PubMed

    Foldager, Casper Bindzus; Nyengaard, Jens Randel; Lind, Martin; Spector, Myron

    2015-04-01

    To implement stereological principles to develop an easy applicable algorithm for unbiased and quantitative evaluation of cartilage repair. Design-unbiased sampling was performed by systematically sectioning the defect perpendicular to the joint surface in parallel planes providing 7 to 10 hematoxylin-eosin stained histological sections. Counting windows were systematically selected and converted into image files (40-50 per defect). The quantification was performed by two-step point counting: (1) calculation of defect volume and (2) quantitative analysis of tissue composition. Step 2 was performed by assigning each point to one of the following categories based on validated and easy distinguishable morphological characteristics: (1) hyaline cartilage (rounded cells in lacunae in hyaline matrix), (2) fibrocartilage (rounded cells in lacunae in fibrous matrix), (3) fibrous tissue (elongated cells in fibrous tissue), (4) bone, (5) scaffold material, and (6) others. The ability to discriminate between the tissue types was determined using conventional or polarized light microscopy, and the interobserver variability was evaluated. We describe the application of the stereological method. In the example, we assessed the defect repair tissue volume to be 4.4 mm(3) (CE = 0.01). The tissue fractions were subsequently evaluated. Polarized light illumination of the slides improved discrimination between hyaline cartilage and fibrocartilage and increased the interobserver agreement compared with conventional transmitted light. We have applied a design-unbiased method for quantitative evaluation of cartilage repair, and we propose this algorithm as a natural supplement to existing descriptive semiquantitative scoring systems. We also propose that polarized light is effective for discrimination between hyaline cartilage and fibrocartilage.

  2. [Repair of perforating skin and soft tissue defects of the palms with dorsalis pedis parallel flaps].

    PubMed

    Feng, Shiming; Wang, Aiguo; Gao, Shunhong

    2015-04-01

    To explore the effect of dorsalis pedis parallel flaps in repairing perforating skin and soft tissue defects of the palms. Eighteen patients with perforating skin and soft tissue defects of the palms were hospitalized from July 2008 to November 2010. The area of skin defect ranged from 2.0 cm x 1.5 cm to 5.0 cm x 2.5 cm. The dorsalis pedis parallel flaps were used to repair these defects, with the area ranging from 2.0 cm x 2.0 cm to 5.5 cm x 3.0 cm. The donor sites were covered with autologous full-thickness skin from inner thigh. All the 18 flaps and skin grafts of donor sites survived completely. Seventeen patients were followed up for 6 to 23 months, with mean time of 10 months, and one patient was lost to follow-up. The texture, elasticity, and appearance of all the 17 flaps were satisfactory, with no obvious pigmentation or cicatricial contracture. At the last follow-up, the distance of two-point discrimination of flaps ranged from 6 to 9 mm, with mean distance of 7.4 mm, and the sensation of flaps reached S3 in 13 patients who had nerve anastomosis. The dorsalis pedis parallel flap, with reliable blood supply and flexible design, is a good choice for repairing perforating skin and soft tissue defects of the palms.

  3. Heterozygous Vangl2Looptail mice reveal novel roles for the planar cell polarity pathway in adult lung homeostasis and repair

    PubMed Central

    Poobalasingam, Thanushiyan; Yates, Laura L.; Walker, Simone A.; Pereira, Miguel; Gross, Nina Y.; Ali, Akmol; Kolatsi-Joannou, Maria; Jarvelin, Marjo-Riitta; Pekkanen, Juha; Papakrivopoulou, Eugenia; Long, David A.; Griffiths, Mark; Wagner, Darcy; Königshoff, Melanie; Hind, Matthew; Minelli, Cosetta; Lloyd, Clare M.

    2017-01-01

    ABSTRACT Lung diseases impose a huge economic and health burden worldwide. A key aspect of several adult lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), including emphysema, is aberrant tissue repair, which leads to an accumulation of damage and impaired respiratory function. Currently, there are few effective treatments available for these diseases and their incidence is rising. The planar cell polarity (PCP) pathway is critical for the embryonic development of many organs, including kidney and lung. We have previously shown that perturbation of the PCP pathway impairs tissue morphogenesis, which disrupts the number and shape of epithelial tubes formed within these organs during embryogenesis. However, very little is known about the role of the PCP pathway beyond birth, partly because of the perinatal lethality of many PCP mouse mutant lines. Here, we investigate heterozygous Looptail (Lp) mice, in which a single copy of the core PCP gene, Vangl2, is disrupted. We show that these mice are viable but display severe airspace enlargement and impaired adult lung function. Underlying these defects, we find that Vangl2Lp/+ lungs exhibit altered distribution of actin microfilaments and abnormal regulation of the actin-modifying protein cofilin. In addition, we show that Vangl2Lp/+ lungs exhibit many of the hallmarks of tissue damage, including an altered macrophage population, abnormal elastin deposition and elevated levels of the elastin-modifying enzyme, Mmp12, all of which are observed in emphysema. In vitro, disruption of VANGL2 impairs directed cell migration and reduces the rate of repair following scratch wounding of human alveolar epithelial cells. Moreover, using population data from a birth cohort of young adults, all aged 31, we found evidence of an interactive effect between VANGL2 and smoking on lung function. Finally, we show that PCP genes VANGL2 and SCRIB are significantly downregulated in lung

  4. Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain

    NASA Astrophysics Data System (ADS)

    Wei, Y. T.; Tian, W. M.; Yu, X.; Cui, F. Z.; Hou, S. P.; Xu, Q. Y.; Lee, In-Seop

    2007-09-01

    A biocompatible hydrogel of hyaluronic acid with the neurite-promoting peptide sequence of IKVAV was synthesized. The characterization of the hydrogel shows an open porous structure and a large surface area available for cell interaction. Its ability to promote tissue repair and axonal regeneration in the lesioned rat cerebrum is also evaluated. After implantation, the polymer hydrogel repaired the tissue defect and formed a permissive interface with the host tissue. Axonal growth occurred within the microstructure of the network. Within 6 weeks the polymer implant was invaded by host-derived tissue, glial cells, blood vessels and axons. Such a hydrogel matrix showed the properties of neuron conduction. It has the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost tissue.

  5. The Role of Cell Plasticity in Tissue Repair: Adaptive Cellular Reprogramming.

    PubMed

    Jessen, Kristjan R; Mirsky, Rhona; Arthur-Farraj, Peter

    2015-09-28

    It is becoming clear that a radical change of cell identity of differentiated cells in vivo, triggered by injury or other adversity, provides an essential route to recovery for many different mammalian tissues. This process, which we term adaptive cellular reprogramming, promotes regeneration in one of two ways: by providing a transient class of repair cells or by directly replacing cells lost during tissue damage. Controlling adaptive changes in cell fate in vivo in order to promote the body's own cell therapy, particularly by pharmacology rather than genetics, is likely to become an increasingly active area of future work. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair.

    PubMed

    Xin, Mei; Olson, Eric N; Bassel-Duby, Rhonda

    2013-08-01

    As the adult mammalian heart has limited potential for regeneration and repair, the loss of cardiomyocytes during injury and disease can result in heart failure and death. The cellular processes and regulatory mechanisms involved in heart growth and development can be exploited to repair the injured adult heart through 'reawakening' pathways that are active during embryogenesis. Heart function has been restored in rodents by reprogramming non-myocytes into cardiomyocytes, by expressing transcription factors (GATA4, HAND2, myocyte-specific enhancer factor 2C (MEF2C) and T-box 5 (TBX5)) and microRNAs (miR-1, miR-133, miR-208 and miR-499) that control cardiomyocyte identity. Stimulating cardiomyocyte dedifferentiation and proliferation by activating mitotic signalling pathways involved in embryonic heart growth represents a complementary approach for heart regeneration and repair. Recent advances in understanding the mechanistic basis of heart development offer exciting opportunities for effective therapies for heart failure.

  7. In situ strategy for bone repair by facilitated endogenous tissue engineering.

    PubMed

    Chen, Jingdi; Zhang, Yujue; Pan, Panpan; Fan, Tiantang; Chen, Mingmao; Zhang, Qiqing

    2015-11-01

    Traditional tissue engineering procedures are expensive and time consuming. Facilitated endogenous tissue engineering (FETE) provides a solution that can avoid the ex vivo culture of autologous cells and initiate in situ reparative endogenous repair processes in vivo. This method involves fabricating a porous scaffold that mimics the environment present during the bone formation process, consisting of components that provide biomimetic interfacial interactions to cells. After the scaffold is implanted, progenitor cells provided by autologous bone marrow and surrounding tissues then differentiate to bone cells under the direction of the in situ scaffold. This paper reports a biomimetic method to prepare a hierarchically structured hybrid scaffold. Bone-like nano hydroxyapatite (HA) was crystallized from a collagen and chitosan (CC) matrix to form a porous scaffold. The in vivo study demonstrates that this nanohybrid scaffold supports excellent bone repair. This means that the FETE approach, in which the cell culture portion of traditional tissue engineering takes place in vivo, can promote the intrinsic regenerative potential of endogenous tissues.

  8. Drug delivery strategies to control macrophages for tissue repair and regeneration

    PubMed Central

    Garash, Reham; Bajpai, Anamika; Marcinkiewicz, Brandon M

    2016-01-01

    Tissue repair and regeneration is a complex process. Our bodies have an excellent capacity to regenerate damaged tissues in many situations. However, tissue healing is impaired in injuries that exceed a critical size or are exacerbated by chronic inflammatory diseases like diabetes. In these instances, biomaterials and drug delivery strategies are often required to facilitate tissue regeneration by providing physical and biochemical cues. Inflammation is the body’s response to injury. It is critical for wound healing and biomaterial integration and vascularization, as long as the timing is well controlled. For example, chronic inflammation is well known to impair healing in chronic wounds. In this review, we highlight the importance of a well-controlled inflammatory response, primarily mediated by macrophages in tissue repair and regeneration and discuss various strategies designed to promote regeneration by controlling macrophage behavior. These strategies include temporally controlled delivery of anti-inflammatory drugs, delivery of macrophages as cellular therapy, controlled release of cytokines that modulate macrophage phenotype, and the design of nanoparticles that exploit the inherent phagocytic behavior of macrophages. A clear outcome of this review is that a deeper understanding of the role and timing of complex macrophage phenotypes or activation states is required to fully harness their abilities with drug delivery strategies. PMID:27190256

  9. Silk microfiber-reinforced silk hydrogel composites for functional cartilage tissue repair.

    PubMed

    Yodmuang, Supansa; McNamara, Stephanie L; Nover, Adam B; Mandal, Biman B; Agarwal, Monica; Kelly, Terri-Ann N; Chao, Pen-hsiu Grace; Hung, Clark; Kaplan, David L; Vunjak-Novakovic, Gordana

    2015-01-01

    Cartilage tissue lacks an intrinsic capacity for self-regeneration due to slow matrix turnover, a limited supply of mature chondrocytes and insufficient vasculature. Although cartilage tissue engineering has achieved some success using agarose as a scaffolding material, major challenges of agarose-based cartilage repair, including non-degradability, poor tissue-scaffold integration and limited processing capability, have prompted the search for an alternative biomaterial. In this study, silk fiber-hydrogel composites (SF-silk hydrogels) made from silk microfibers and silk hydrogels were investigated for their potential use as a support material for engineered cartilage. We demonstrated the use of 100% silk-based fiber-hydrogel composite scaffolds for the development of cartilage constructs with properties comparable to those made with agarose. Cartilage constructs with an equilibrium modulus in the native tissue range were fabricated by mimicking the collagen fiber and proteoglycan composite architecture of native cartilage using biocompatible, biodegradable silk fibroin from Bombyx mori. Excellent chondrocyte response was observed on SF-silk hydrogels, and fiber reinforcement resulted in the development of more mechanically robust constructs after 42 days in culture compared to silk hydrogels alone. Thus, we demonstrate the versatility of silk fibroin as a composite scaffolding material for use in cartilage tissue repair to create functional cartilage constructs that overcome the limitations of agarose biomaterials, and provide a much-needed alternative to the agarose standard.

  10. Strategies to develop endogenous stem cell-recruiting bioactive materials for tissue repair and regeneration.

    PubMed

    Pacelli, Settimio; Basu, Sayantani; Whitlow, Jonathan; Chakravarti, Aparna; Acosta, Francisca; Varshney, Arushi; Modaresi, Saman; Berkland, Cory; Paul, Arghya

    2017-07-19

    A leading strategy in tissue engineering is the design of biomimetic scaffolds that stimulate the body's repair mechanisms through the recruitment of endogenous stem cells to sites of injury. Approaches that employ the use of chemoattractant gradients to guide tissue regeneration without external cell sources are favored over traditional cell-based therapies that have limited potential for clinical translation. Following this concept, bioactive scaffolds can be engineered to provide a temporally and spatially controlled release of biological cues, with the possibility to mimic the complex signaling patterns of endogenous tissue regeneration. Another effective way to regulate stem cell activity is to leverage the inherent chemotactic properties of extracellular matrix (ECM)-based materials to build versatile cell-instructive platforms. This review introduces the concept of endogenous stem cell recruitment, and provides a comprehensive overview of the strategies available to achieve effective cardiovascular and bone tissue regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Diet restriction enhances compensatory liver tissue repair and survival following administration of lethal dose of thioacetamide.

    PubMed

    Ramaiah, S K; Soni, M G; Bucci, T J; Mehendale, H M

    1998-05-01

    Diet restriction is known to prevent a plethora of age-associated diseases including cancer. However, the effects of diet restriction on noncancer end points are not known. The objective of this study was to investigate whether diet restriction protects against hepatotoxicity of thioacetamide (TA), and if so, to investigate the underlying mechanism. Male Sprague-Dawley rats (250-275 g) were maintained on 65% of their ad libitum (AL) food consumption for a period of 3 weeks and then treated with a single low dose of 50 mg TA/kg i.p.. Plasma enzymes (ALT and SDH), hepatic glycogen levels, and 3H-thymidine incorporation into hepatocellular nuclear DNA were measured during a time course (0-120 h) after TA administration. Liver sections were examined for histopathology, and cell-cycle progression was assessed by proliferating cell nuclear antigen (PCNA) immunohistochemistry. In AL rats hepatic necrosis was evident at 12 h, peaked at 36 h, persisted up to 72 h, and was resolved by 96 h. In the diet-restricted (DR) group hepatic necrosis was observed at 12 h, peaked at 24 h, persisted till 72 h, and was resolved by 96 h. Maximal injury indicated by enzyme elevation occurred in DR rats and was approximately sixfold greater than that observed in the AL group. Histopathological examination of the liver sections revealed liver injury concordant with plasma enzyme elevations. There was a higher and sustained S-phase synthesis in the DR rats compared to AL group. S-phase stimulation was evident at 36 h, peaked at 48 h, and persisted until 96 h in the DR rats, whereas in the AL rats peak S-phase stimulation occurred at 36 h and subsided by 72 h. PCNA studies revealed a corresponding stimulation of cell-cycle progression indicating highly stimulated compensatory tissue repair. The 14-day lethality experiments (600 mg TA/kg i.p.) indicated 70% survival in the DR rats compared to 10% survival in the AL group. Although diet restriction increases hepatotoxic injury of TA, it protects

  12. Epimorphic regeneration approach to tissue replacement in adult mammals

    USDA-ARS?s Scientific Manuscript database

    Urodeles and fetal mammals are capable of impressive epimorphic regeneration in a variety of tissues, whereas the typical default response to injury in adult mammals consists of inflammation and scar tissue formation. One component of epimorphic regeneration is the recruitment of resident progenitor...

  13. Expanding epigenomics to archived FFPE tissues: An evaluation of DNA repair methodologies

    PubMed Central

    Siegel, Erin M; Berglund, Anders E.; Riggs, Bridget M; Eschrich, Steven A.; Putney, Ryan M.; Ajidahun, Abidemi O.; Coppola, Domenico; Shibata, David

    2014-01-01

    Background Epigenome-wide association studies are emerging in the field of cancer epidemiology with the rapid development of large-scale methylation array platforms. Until recently, these methods were only valid for DNA from fresh frozen (FF) tissues. Novel techniques for repairing DNA from formalin-fixed paraffin-embedded (FFPE) have emerged; however, a direct comparison of FFPE DNA repair methods prior to analysis on genome-wide methylation array to matched FF tissues has not been conducted. Methods We conducted a systematic performance comparison of two DNA repair methods (REPLI-g Ligase vs. Infinium HD Restore Kit) on FFPE-DNA compared to matched FF tissues on the Infinium 450K array. A threshold of discordant methylation between FF-FFPE pairs was set at Δβ>0.3. The correlations of β-values from FF-FFPE pairs were compared across methods and experimental conditions. Results The Illumina Restore kit outperformed the REPLI-g ligation method with respect to reproducibility of replicates(R2>0.970), highly correlated β-values between FF-FFPE(R2>0.888), and fewest discordant loci between FF-FFPE(≤0.61%). The performance of the Restore kit was validated in an independent set of 121 FFPE tissues. Conclusions The Restore kit outperformed RELPI-g ligation in restoring FFPE-derived DNA prior to analysis on the Infinium 450K methylation array. Our findings provide critical guidance that may significantly enhance the breadth of diseases that can be studied by methylomic profiling. Impact Epigenomic studies using FFPE tissues should now be considered among cancers that have not been fully characterized from an epigenomic standpoint. These findings promote novel epigenome-wide studies focused on cancer etiology, identification of novel biomarkers, and developing targeted therapies. PMID:25472669

  14. A new osteonecrosis animal model of the femoral head induced by microwave heating and repaired with tissue engineered bone

    PubMed Central

    Han, Rui; Geng, Chengkui; Wang, Yongnian; Wei, Lei

    2008-01-01

    The objective of this research was to induce a new animal model of osteonecrosis of the femoral head (ONFH) by microwave heating and then repair with tissue engineered bone. The bilateral femoral heads of 84 rabbits were heated by microwave at various temperatures. Tissue engineered bone was used to repair the osteonecrosis of femoral heads induced by microwave heating. The roentgenographic and histological examinations were used to evaluate the results. The femoral heads heated at 55°C for ten minutes showed low density and cystic changes in X-ray photographs, osteonecrosis and repair occurred simultaneously in histology at four and eight weeks, and 69% femoral heads collapsed at 12 weeks. The ability of tissue engineered bone to repair the osteonecrosis was close to that of cancellous bone autograft. The new animal model of ONFH could be induced by microwave heating, and the tissue engineering technique will provide an effective treatment. PMID:18956184

  15. The landscape of genomic imprinting across diverse adult human tissues.

    PubMed

    Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K; Rivas, Manuel A; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S; Kukurba, Kim R; Zhang, Rui; Eng, Celeste; Torgerson, Dara G; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R; Burchard, Esteban G; Seibold, Max A; MacArthur, Daniel G; Montgomery, Stephen B; Zaitlen, Noah A; Lappalainen, Tuuli

    2015-07-01

    Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. © 2015 Baran et al.; Published by Cold Spring Harbor Laboratory Press.

  16. The landscape of genomic imprinting across diverse adult human tissues

    PubMed Central

    Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K.; Rivas, Manuel A.; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S.; Kukurba, Kim R.; Zhang, Rui; Eng, Celeste; Torgerson, Dara G.; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R.; Burchard, Esteban G.; Seibold, Max A.; MacArthur, Daniel G.; Montgomery, Stephen B.; Zaitlen, Noah A.; Lappalainen, Tuuli

    2015-01-01

    Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. PMID:25953952

  17. Silk microfiber-reinforced silk hydrogel composites for functional cartilage tissue repair

    PubMed Central

    Yodmuang, Supansa; McNamara, Stephanie L.; Nover, Adam B.; Mandal, Biman B.; Agarwal, Monica; Kelly, Terri-Ann N.; Chao, Pen-hsiu Grace; Hung, Clark; Kaplan, David L.; Vunjak-Novakovic, Gordana

    2014-01-01

    Cartilage tissue lacks an intrinsic capacity for self-regeneration due to slow matrix turnover, a limited supply of mature chondrocytes and insufficient vasculature. Although cartilage tissue engineering has achieved some success using agarose as a scaffolding material, major challenges of agarose-based cartilage repair, including non-degradability, poor tissue–scaffold integration and limited processing capability, have prompted the search for an alternative biomaterial. In this study, silk fiber–hydrogel composites (SF–silk hydrogels) made from silk microfibers and silk hydrogels were investigated for their potential use as a support material for engineered cartilage. We demonstrated the use of 100% silk-based fiber–hydrogel composite scaffolds for the development of cartilage constructs with properties comparable to those made with agarose. Cartilage constructs with an equilibrium modulus in the native tissue range were fabricated by mimicking the collagen fiber and proteoglycan composite architecture of native cartilage using biocompatible, biodegradable silk fibroin from Bombyx mori. Excellent chondrocyte response was observed on SF–silk hydrogels, and fiber reinforcement resulted in the development of more mechanically robust constructs after 42 days in culture compared to silk hydrogels alone. Thus, we demonstrate the versatility of silk fibroin as a composite scaffolding material for use in cartilage tissue repair to create functional cartilage constructs that overcome the limitations of agarose biomaterials, and provide a much-needed alternative to the agarose standard. PMID:25281788

  18. Elastin-like protein matrix reinforced with collagen microfibers for soft tissue repair

    PubMed Central

    Caves, Jeffrey M.; Cui, Wanxing; Wen, Jing; Kumar, Vivek A.; Haller, Carolyn A.; Chaikof, Elliot L.

    2011-01-01

    Artificial composites designed to mimic the structure and properties of native extracellular matrix may lead to acellular materials for soft tissue repair and replacement, which display mechanical strength, stiffness, and resilience resembling native tissue. We describe the fabrication of thin lamellae consisting of continuous collagen microfiber embedded at controlled orientations and densities in a recombinant elastin-like protein polymer matrix. Multilamellar stacking affords flexible, protein-based composite sheets whose properties are dependent upon both the elastomeric matrix and collagen content and organization. Sheets are produced with properties that range over 13-fold in elongation to break (23 – 314%), six-fold in Young’s modulus (5.3 to 33.1 MPa), and more than two-fold in tensile strength (1.85 to 4.08 MPa), exceeding that of a number of native human tissues, including urinary bladder, pulmonary artery, and aorta. A sheet approximating the mechanical response of human abdominal wall fascia is investigated as a fascial substitute for ventral hernia repair. Protein-based composite patches prevent hernia recurrence in Wistar rats over an 8-week period with new tissue formation and sustained structural integrity. PMID:21550111

  19. Nuss procedure for repair of pectus excavatum after failed Ravitch procedure in adults: indications and caveats

    PubMed Central

    Kocher, Gregor J.; Gstrein, Nathalie; Jaroszewski, Dawn E.; Ewais, Mennatallah M.

    2016-01-01

    Background Recurrence of pectus excavatum (PE) is not an uncommon problem after open repair using the Ravitch technique. The optimal approach for redo surgery is still under debate, especially in adults with less chest wall pliability. Aim of this study was to investigate the usefulness and efficacy of the minimally invasive Nuss technique for repair of recurrent PE after conventional open repair. Methods We performed a retrospective multicentre review of 20 adult patients from University Hospital Bern (n=6) and the US Mayo Clinic (n=14) who underwent minimally invasive repair of recurrent PE after unsuccessful prior Ravitch procedure. Results Mean patient age at primary open correction was 21 years, with recurrence being evident after a mean duration of 10.5 years (range, 0.25–47 years). Mean age at redo surgery using the Nuss technique was 31 years, with a mean Haller index of 4.7 before and 2.5 after final correction. Main reason for redo surgery was recurrent or persistent deformity (100%), followed by chest pain (75%) and exercise intolerance (75%). No major intraoperative or postoperative complications occurred and successful correction was possible in all patients. Conclusions Although the procedure itself is more challenging, the minimally invasive Nuss technique can be safely and successfully used for repair of recurrent PE after failed open surgery. In our series final results were good to excellent in the majority of patients without major complications or recurrence. PMID:27621850

  20. Differential expression of tissue repair genes in the pathogenesis of chronic obstructive pulmonary disease.

    PubMed

    Gosselink, John V; Hayashi, Shizu; Elliott, W Mark; Xing, Li; Chan, Becky; Yang, Luojia; Wright, Claire; Sin, Don; Paré, Peter D; Pierce, John A; Pierce, Richard A; Patterson, Alex; Cooper, Joel; Hogg, James C

    2010-06-15

    The airflow limitation that defines severity of chronic obstructive pulmonary disease (COPD) is caused by a combination of small airway obstruction and emphysematous lung destruction. To examine the hypothesis that small airway obstructive and emphysematous destructive lesions are produced by differential expression of genes associated with tissue repair. The expression of 54 genes associated with repair of repetitively damaged tissue was measured in 136 paired samples of small bronchioles and surrounding lung tissue separated by laser capture microdissection. These samples were collected from 63 patients at different levels of disease severity who required surgery for either lung cancer or lung transplantation for very severe COPD. Gene expression was measured by quantitative polymerase chain reaction in these paired samples and compared with the FEV(1) by linear regression analysis. After corrections for false discovery rates, only 2 of 10 genes (serpin peptidase inhibitor/plasminogen activator inhibitor member 2 and matrix metalloproteinase [MMP] 10) increased, whereas 8 (MMP2, integrin-alpha1, vascular endothelial growth factor, a disintegrin and metallopeptidase domain 33, scatter factor/hepatocyte growth factor, tissue inhibitor of matrix metalloproteinase-2, fibronectin, and collagen 3alpha1) decreased in small airways in association with FEV(1). In contrast, 8/12 genes (early growth response factor 1, MMP1, MMP9, MMP10, plasminogen activator urokinase, plasminogen activator urokinase receptor, tumor necrosis factor, and IL13) increased and 4/12 (MMP2, tissue inhibitor of matrix metalloproteinase-1, collagen 1alpha1, and transforming growth factor-beta3) decreased in the surrounding lung tissue in association with progression of COPD. The progression of COPD is associated with the differential expression of a cluster of genes that favor the degradation of the tissue surrounding the small conducting airways.

  1. Investigation on laser-assisted tissue repair with NIR millisecond-long light pulses and Indocyanine Green-biopolymeric patches

    NASA Astrophysics Data System (ADS)

    Matteini, Paolo; Banchelli, Martina; Cottat, Maximilien; Osticioli, Iacopo; de Angelis, Marella; Rossi, Francesca; Pini, Roberto

    2016-03-01

    In previous works a minimally invasive laser-assisted technique for vascular repair was presented. The technique rests on the photothermal adhesion of a biocompatible and bioresorbable patch containing Indocyanine Green that is brought into contact with the site to be repaired. Afterward the use of NIR millisecond-long light pulses generates a strong welding effect between the patch and the underlying tissue and in turn the repair of the wound. This technique was shown to be effective in animal model and provides several advantages over conventional suturing methods. Here we investigate and discuss the optical stability of the ICG-biopolymeric patches and the photothermal effects induced to the irradiated tissue.

  2. Thrombospondin1 in tissue repair and fibrosis: TGF-β-dependent and independent mechanisms

    PubMed Central

    Sweetwyne, Mariya T.; Murphy-Ullrich, Joanne E.

    2012-01-01

    Thrombospondin 1(TSP1) plays major roles in both physiologic and pathologic tissue repair. TSP1 through its type 1 repeats is a known regulator of latent TGF-β activation and plays a role in wound healing and fibrosis. Binding of the TSP N-terminal domain to cell surface calreticulin in complex with LDL-receptor related protein 1 stimulates intermediate cell adhesion, cell migration, anoikis resistance and collagen expression and matrix deposition in an in vivo model of the foreign body response. There is also emerging evidence that TSP EGF-like repeats alters endothelial cell-cell interactions and stimulate epithelial migration through transactivation of EGF receptors. The mechanisms underlying these functions of TSP1 and the implications for physiologic and pathologic wound repair and fibrosis will be discussed. PMID:22266026

  3. Current Concepts of Bone Tissue Engineering for Craniofacial Bone Defect Repair

    PubMed Central

    Fishero, Brian Alan; Kohli, Nikita; Das, Anusuya; Christophel, John Jared; Cui, Quanjun

    2014-01-01

    Craniofacial fractures and bony defects are common causes of morbidity and contribute to increasing health care costs. Successful regeneration of bone requires the concomitant processes of osteogenesis and neovascularization. Current methods of repair and reconstruction include rigid fixation, grafting, and free tissue transfer. However, these methods carry innate complications, including plate extrusion, nonunion, graft/flap failure, and donor site morbidity. Recent research efforts have focused on using stem cells and synthetic scaffolds to heal critical-sized bone defects similar to those sustained from traumatic injury or ablative oncologic surgery. Growth factors can be used to augment both osteogenesis and neovascularization across these defects. Many different growth factor delivery techniques and scaffold compositions have been explored yet none have emerged as the universally accepted standard. In this review, we will discuss the recent literature regarding the use of stem cells, growth factors, and synthetic scaffolds as alternative methods of craniofacial fracture repair. PMID:25709750

  4. The use of autologous adult, allogenic juvenile, and combined juvenile-adult cartilage fragments for the repair of chondral defects.

    PubMed

    Bonasia, Davide Edoardo; Martin, James A; Marmotti, Antonio; Kurriger, Gail L; Lehman, Abigail D; Rossi, Roberto; Amendola, Annunziato

    2016-12-01

    The goal of the study was to evaluate the repair of chondral lesions treated with combined autologous adult/allogenic juvenile cartilage fragments, compared with isolated adult and isolated juvenile cartilage fragments. Fifty-eight adult (>16 week old) and five juvenile (<6 week old) New Zealand White female rabbits were used. A large osteochondral defect was created in the center of the femoral trochlea of adult rabbits. The rabbits were divided in four groups: Group 1 = untreated defects (controls); Group 2 = adult cartilage fragments; Group 3 = juvenile cartilage fragments; and Group 4 = adult + juvenile cartilage fragments. Killings were performed at 3 and 6 months. The defects were evaluated with ICRS macroscopic score, modified O'Driscoll score, and Collagen type II immunostaining. At 3 months, Group 4 performed better than Group 1, in terms of modified O'Driscoll score (p = 0.001) and Collagen type II immunostaining (p = 0.015). At 6 months, Group 4 showed higher modified O'Driscoll score (p = 0.003) and Collagen type II immunostaining score (p < 0.001) than Group 1. Histologically, also Group 3 performed better than Group 1 (p = 0.03), and Group 4 performed better than Group 2 (p = 0.004). Mixing adult and juvenile cartilage fragments improved cartilage repair in a rabbit model. In the clinical setting, a new "one-stage" procedure combining the two cartilage sources can be hypothesized, with the advantages of improved chondral repair and large defect coverage, because of the use of an off-the-shelf juvenile allograft. Further studies on larger animals and clinical trials are required to confirm these results.

  5. Glial scar and immune cell involvement in tissue remodeling and repair following acute CNS injuries.

    PubMed

    Raposo, Catarina; Schwartz, Michal

    2014-11-01

    Inadequate axonal regeneration is a common phenomenon occurring following acute injury to the central nervous system (CNS), and is often associated with permanent neurological deficits. The injured axons attempting to regenerate face the inhospitable environment of the CNS scar, which can hinder axonal growth and sprouting. In addition, in response to the insult, intense activation and infiltration of immune cells take place. Both the scar tissue and immune response, which have received a bad reputation in the context of CNS repair are essential for the overall recovery from CNS injuries, but are not optimally controlled. The glial scar contributes to protection of the spared neural tissues by establishing a boundary between damaged and salvageable tissue, and by educating the immune cells to promote the healing of the CNS tissue. In turn, the immune cells, and in particular the infiltrating macrophages, exert several functions at the lesion site, including resolution of the microglial response, control of scar tissue degradation, and production of growth factors; thereby, promoting neuronal survival, axonal regeneration, and tissue remodeling. As axonal regeneration and tissue remodeling are viewed as critical steps for the overall functional recovery following CNS injury, a detailed understanding of the mechanisms underlying the timely formation and degradation of the CNS scar, and its crosstalk with the inflammatory response, are of great importance, both biologically and clinically. © 2014 Wiley Periodicals, Inc.

  6. Experimental therapies for repair of the central nervous system: stem cells and tissue engineering.

    PubMed

    Forraz, N; Wright, K E; Jurga, M; McGuckin, C P

    2013-07-01

    Several stem cell-based therapeutic tools are currently being investigated for the regeneration of central nervous system (CNS) injuries. This review focuses on innovative approaches for CNS tissue repair via the use of implantable cellular devices. These devices are supported by biopharmaceuticals and conventional physiotherapy for the restoration of lost neuronal circuits and CNS function. This paper further reviews new and promising tools currently in pre-clinical and clinical tests for the treatment of CNS diseases where substantial loss of cellular and extracellular components of neural tissue has occurred such as stroke, encephalopathy and traumatic neural injuries. We also discuss selected 3D bioscaffolds co-cultured with clinically applicable human mesenchymal stem cells. Recent advances in neural tissue engineering and stem cell differentiation methods have shown promise for their clinical application in treating yet incurable CNS deficits.

  7. Emerging functions of amphiregulin in orchestrating immunity, inflammation and tissue repair

    PubMed Central

    Zaiss, Dietmar M.W.; Gause, William C.; Osborne, Lisa C.; Artis, David

    2016-01-01

    Type 2 inflammatory responses can be elicited by diverse stimuli, including toxins, venoms, allergens and infectious agents and play critical roles in resistance and tolerance associated with infection, wound healing, tissue repair and tumor development. Emerging data suggest that in addition to characteristic type 2-associated cytokines, the Epidermal Growth Factor (EGF)-like molecule Amphiregulin (AREG) may be a critical component of type 2-mediated resistance and tolerance. Notably, numerous studies demonstrate that in addition to the established role of epithelial- and mesenchymal-derived AREG, multiple leukocyte populations including mast cells, basophils, group 2 innate lymphoid cells (ILC2) and a subset of tissue-resident regulatory CD4+ T cells can express AREG. In this review, we discuss recent advances in our understanding of the AREG-EGF receptor pathway and its involvement in infection and inflammation, and propose a model for the function of this pathway in the context of resistance and tissue tolerance. PMID:25692699

  8. Cardiopulmonary response following surgical repair of pectus excavatum in adult patients.

    PubMed

    Neviere, Remi; Montaigne, David; Benhamed, Lotfi; Catto, Michele; Edme, Jean Louis; Matran, Regis; Wurtz, Alain

    2011-08-01

    Severe pectus excavatum are common in adult patients, often causing psychological complaints and physiological impairments. Although lung function at rest may minimally deteriorate after surgical correction, it remains unclear if surgery improves exercise capacity. The objective of present study is to assess whether the surgical repair of pectus excavatum in adults would improve exercise tolerance. A prospective study was performed to compare pulmonary and cardiovascular function at rest and at maximal exercise, before, and at 1 year after pectus excavatum repair. From December 2005 to May 2009, 120 adult patients underwent pectus excavatum repair. Of these patients, 70 (nine women, 61 men) underwent thorough preoperative, 6-, and 12-month postoperative assessments, and were included in the present study. Age ranged from 18 to 62 years (mean 27 years). The pectus index (Haller index) was 4.5 ± 1.1. Lung function tests at rest were within the normal range, whereas maximal oxygen uptake (peak VO₂) was only 77 ± 2% of the predicted value. At 1-year follow-up, the pectus excavatum repair was associated with minor changes in lung function tests and significant increase (p=0.0005) in VO₂ (87 ± 2% of the predicted value). Postoperative O₂ pulse increase at maximal exercise suggested that aerobic capacity improvement was the result of better cardiovascular adaptation at maximal workload. These results demonstrate sustained improvement in exercise cardiopulmonary function at 1-year follow-up of pectus excavatum surgical repair in adult patients. Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

  9. Matrix immobilization enhances the tissue repair activity of growth factor gene therapy vectors.

    PubMed

    Doukas, J; Chandler, L A; Gonzalez, A M; Gu, D; Hoganson, D K; Ma, C; Nguyen, T; Printz, M A; Nesbit, M; Herlyn, M; Crombleholme, T M; Aukerman, S L; Sosnowski, B A; Pierce, G F

    2001-05-01

    Although growth factor proteins display potent tissue repair activities, difficulty in sustaining localized therapeutic concentrations limits their therapeutic activity. We reasoned that enhanced histogenesis might be achieved by combining growth factor genes with biocompatible matrices capable of immobilizing vectors at delivery sites. When delivered to subcutaneously implanted sponges, a platelet-derived growth factor B-encoding adenovirus (AdPDGF-B) formulated in a collagen matrix enhanced granulation tissue deposition 3- to 4-fold (p < or = 0.0002), whereas vectors encoding fibroblast growth factor 2 or vascular endothelial growth factor promoted primarily angiogenic responses. By day 8 posttreatment of ischemic excisional wounds, collagen-formulated AdPDGF-B enhanced granulation tissue and epithelial areas up to 13- and 6-fold (p < 0.009), respectively, and wound closure up to 2-fold (p < 0.05). At longer times, complete healing without excessive scar formation was achieved. Collagen matrices were shown to retain both vector and transgene products within delivery sites, enabling the transduction and stimulation of infiltrating repair cells. Quantitative PCR and RT-PCR demonstrated both vector DNA and transgene mRNA within wound beds as late as 28 days posttreatment. By contrast, aqueous formulations allowed vector seepage from application sites, leading to PDGF-induced hyperplasia in surrounding tissues but not wound beds. Finally, repeated applications of PDGF-BB protein were required for neotissue induction approaching equivalence to a single application of collagen-immobilized AdPDGF-B, confirming the utility of this gene transfer approach. Overall, these studies demonstrate that immobilizing matrices enable the controlled delivery and activity of tissue promoting genes for the effective regeneration of injured tissues.

  10. Application of adipose tissue-derived stem cells in a rat rotator cuff repair model.

    PubMed

    Valencia Mora, Maria; Antuña Antuña, Samuel; García Arranz, Mariano; Carrascal, Maria Teresa; Barco, Raúl

    2014-10-01

    Healing tissue of the rotator cuff does not regenerate the native enthesis; fibrovascular scar tissue is formed instead and this has less favourable biomechanical properties. The purpose of this study was to determine if the application of adipose tissue-derived stem cells (ASCs) could improve biomechanical and histological properties of the repair. Fifty Sprague-Dawley rats underwent detachment and repair of the supraspinatus tendon, 32 for the biomechanical study and 18 for the histological examination. Animals were randomised in two groups to receive either a collagen carrier alone (untreated group) or the carrier plus 2×10(6) ASCs (ASCs group). A control group (suture only) was also included for the histological examination. The animals were sacrificed at 2 and 4 weeks for the biomechanical study and at 24 hours, and 1 and 4 weeks for the histological study. Maximum load failure energy, elastic energy, mechanical deformation, stiffness and absorbed energy were measured. Immunofluorescence testing was conducted to show the presence of ASCs in the repair area. There were no differences between the untreated group and the ASCs group in any of the biomechanical variables at the 2- and 4-week time points. The mechanical deformation before failure was higher for the ASCs group compared with the untreated group at 2 weeks and 4 weeks (p=0.09), as was the absorbed energy (p=0.06). Differences in maximum load to failure between 2 and 4 weeks were significant for the untreated group (p=0.04) but not for the ASCs group (p=0.17). Histological examination showed less acute inflammation with diminished presence of oedema and neutrophils in the ASCs group. There were no differences in the orientation of collagen fibres between groups at either time point. In the ASCs group, collagen was present only at the last time point. The application of ASCs in a rat rotator cuff repair model did not improve the biomechanical properties of the tendon-to-bone healing. However, the ASCs

  11. Type I collagen degradation during tissue repair: comparison of mechanisms following fracture and acute coronary syndromes.

    PubMed

    Stansfield, Rachel; Gossiel, Fatma; Morton, Allison; Newman, Christopher; Eastell, Richard

    2014-12-01

    There is turnover of type I collagen during tissue repair. The degradation of type I collagen by matrix metalloproteinases (MMPs) is reflected by serum ICTP and that by cathepsins by CTX-I. There is evidence for increases in ICTP after acute coronary syndromes (ACS) and in CTX-I during fracture repair. The involvement of the MMP pathway in fracture repair and cathepsins after myocardial infarction is unclear. We studied 74 men; 22 were admitted to the hospital on the day of their ACS (ST or non-ST elevation myocardial infarction) (mean age 56 years, range 39 to 82) and 9 attended hospital on the day of their tibial shaft fracture (mean age 33 years, range 21 to 79); we had 43 age-matched controls (mean age 54 years, range 20 to 82). Subjects with ACS and tibial shaft fracture were followed up for up to one year; control subjects were used to establish a reference interval. We measured serum ICTP by ELISA (reference interval 1.1 to 17.6 ng/mL) and CTX-I by chemiluminescence (reference interval 0.094 to 0.991 ng/mL). After ACS, the mean ICTP increased from 5.41 to 6.60 ng/mL within one day of admission (p<0.05); the mean CTX-I increased from 0.263 to 0.414 ng/mL (p<0.05). In two cases, the CTX increased to above the reference interval. After tibial shaft fracture, the mean ICTP increased from 5.51 to maximum of 8.71 ng/mL within 28 days of admission (p<0.01); the mean CTX increased from 0.200 to 0.374 ng/mL (p<0.001). In four cases, the CTX increased to above the reference interval. We conclude that the MMP and cathepsin pathways are both implicated in tissue repair in the bone and heart. This may have clinical implications; drugs that block either pathway (TIMPs, cathepsin K inhibitors) may affect the repair of both tissues. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Robust homology-directed repair within mouse mammary tissue is not specifically affected by Brca2 mutation

    PubMed Central

    Kass, Elizabeth M.; Lim, Pei Xin; Helgadottir, Hildur R.; Moynahan, Mary Ellen; Jasin, Maria

    2016-01-01

    The mammary gland undergoes significant proliferative stages after birth, but little is known about how the developmental changes impact DNA double-strand break (DSB) repair. Mutations in multiple genes involved in homology-directed repair (HDR), considered a particularly accurate pathway for repairing DSBs, are linked to breast cancer susceptibility, including BRCA2. Using reporter mice that express an inducible endonuclease, we find that HDR is particularly robust in mammary tissue during puberty and pregnancy, accounting for 34–40% of detected repair events, more than in other tissues examined. Brca2 hypomorphic mutation leads to HDR defects in mammary epithelium during puberty and pregnancy, including in different epithelial lineages. Notably, a similar dependence on Brca2 is observed in other proliferative tissues, including small intestine epithelium. Our results suggest that the greater reliance on HDR in the proliferating mammary gland, rather than a specific dependence on BRCA2, may increase its susceptibility to tumorigenesis incurred by BRCA2 mutation. PMID:27779185

  13. Evaluation of the effects of electrical stimulation on cartilage repair in adult male rats.

    PubMed

    Zuzzi, Denise Cristina; Ciccone, Carla de Campos; Neves, Lia Mara Grosso; Mendonça, Josué Sampaio; Joazeiro, Paulo Pinto; Esquisatto, Marcelo Augusto Marretto

    2013-08-01

    This study describes the organization of mature hyaline xiphoid cartilage during repair in animals submitted to electrical current stimulation. Twenty male Wistar rats, 90 days old, were divided into a control group (CG) and a treated group (TG). A cylindrical full-thickness cartilage defects were created with a 3-mm punch in anesthetized animals. After 24h, TG received daily applications of a continuous electrical current (1Hz/20μA) for 5min. The animals were sacrificed after 7, 21 and 35 days for structural analysis. In CG, the repair tissue presented fibrous characteristics, with fibroblastic cells being infiltrated and permeated by blood vessels. Basophilic foci of cartilage tissue were observed on day 35. In TG, the repair tissue also presented fibrous characteristics, but a larger number of thick collagen fibers were seen on day 21. A large number of cartilaginous nests were observed on day 35. Cell numbers were significantly higher in TG. Calcification points were detected in TG on day 35. There was no difference in elastic fibers between groups. Ultrastructural analysis revealed the presence of chondrocyte-like cells in CG at all time points, but only on days 21 and 35 in TG. The amount of cuprolinic blue-stained proteoglycans was higher in TG on day 35. Microcurrent stimulation accelerates the repair process in non-articular hyaline cartilage.

  14. SDF-1α peptide tethered polyester facilitates tissue repair by endogenous cell mobilization and recruitment.

    PubMed

    Shafiq, Muhammad; Kong, Deling; Kim, Soo Hyun

    2017-10-01

    The design of bioactive scaffolds that can invoke host's own regenerative capabilities and facilitate endogenous tissue repair hold great promise. This study aims to evaluate the potential of stromal cell-derived factor 1 alpha (SDF-1α)-derived peptide and heparin tethered poly(L-lactide-co-ε-caprolactone) (PLCL) copolymers for blood vessel regeneration applications. Amino acid analysis and toluidine blue assays confirm successful conjugation of SDF-1α peptide and heparin with the PLCL copolymers. Assessment of biocompatibility after subcutaneous implantation in rats discloses higher cell infiltration in SDF-1α peptide (SDF-1 group) or SDF-1 peptide and heparin (SDF-1/heparin group) than the control group. SDF-1 and SDF-1/heparin grafts also show more numbers of laminin(+) blood vessels, CD90(+) stem cells, and alpha smooth muscle actin(+) cells than the control group. However, SDF-1 and SDF-1/heparin groups did not significantly differ in terms of blood vessel regeneration and stem cell recruitment. Evaluation of the inflammatory response reveal less numbers of CD68(+) macrophages in SDF-1 and SDF-1/heparin groups compared with the control group; whereas three groups show similar numbers of CD206(+) macrophages. These results indicate that completely synthetic, cell-free grafts can attract endogenous cells and enhance tissue repair. Bioactive polyesters can be fabricated into different shapes and structures for various tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomater Res Part A: 105A: 2670-2684, 2017. © 2017 Wiley Periodicals, Inc.

  15. Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair.

    PubMed

    Tarish, Firas L; Schultz, Niklas; Tanoglidi, Anna; Hamberg, Hans; Letocha, Henry; Karaszi, Katalin; Hamdy, Freddie C; Granfors, Torvald; Helleday, Thomas

    2015-11-04

    Chemical castration improves responses to radiotherapy in prostate cancer, but the mechanism is unknown. We hypothesized that this radiosensitization is caused by castration-mediated down-regulation of nonhomologous end joining (NHEJ) repair of DNA double-strand breaks (DSBs). To test this, we enrolled 48 patients with localized prostate cancer in two arms of the study: either radiotherapy first or radiotherapy after neoadjuvant castration treatment. We biopsied patients at diagnosis and before and after castration and radiotherapy treatments to monitor androgen receptor, NHEJ, and DSB repair in verified cancer tissue. We show that patients receiving neoadjuvant castration treatment before radiotherapy had reduced amounts of the NHEJ protein Ku70, impaired radiotherapy-induced NHEJ activity, and higher amounts of unrepaired DSBs, measured by γ-H2AX foci in cancer tissues. This study demonstrates that chemical castration impairs NHEJ activity in prostate cancer tissue, explaining the improved response of patients with prostate cancer to radiotherapy after chemical castration. Copyright © 2015, American Association for the Advancement of Science.

  16. Acceleration of rat salivary gland tissue repair by basic fibroblast growth factor.

    PubMed

    Okazaki, Y; Kagami, H; Hattori, T; Hishida, S; Shigetomi, T; Ueda, M

    2000-10-01

    A model of atrophic rat submandibular gland was used to examine the ability of basic fibroblast growth factor (bFGF) to accelerate tissue repair. The gland duct was separated carefully from associated blood vessels and nerve, and ligated with a 8-0 suture under a surgical microscope. Two weeks after ligation, the glandular tissue showed severe atrophy and weight loss (to 26% of that in a sham-operated group). Thereafter, the ligature was removed and various amounts of bFGF, isoproterenol or saline were instilled retrogradely through the duct. Both isoproterenol and bFGF increased cell proliferation significantly. bFGF accelerated the proliferation of various cell types, including both acinar and ductal. The proliferative effects of bFGF peaked at a dose of 1 ng/gland. When bFGF (1 ng/gland) was administered to the atrophic gland, its weight increased to 125% of the glands in saline-treated control animals after 2 weeks. The effects of bFGF were also examined in normal submandibular glands: bFGF stimulated cell proliferation, but the effective concentration was at least 50 times higher than that required in the atrophic gland. The results from immunohistochemical tests against anti-FGF receptor-type 1 antibody demonstrated increased immunoreactivity in the damaged gland, which might be involved in the difference in the response to bFGF between damaged and normal glands. Overall, the results indicate that bFGF can accelerate tissue repair in salivary gland.

  17. Effect of porosities of bilayered porous scaffolds on spontaneous osteochondral repair in cartilage tissue engineering

    PubMed Central

    Dong, Jian; Ding, Jiandong

    2015-01-01

    Poly(lactide-co-glycolide)-bilayered scaffolds with the same porosity or different ones on the two layers were fabricated, and the porosity effect on in vivo repairing of the osteochondral defect was examined in a comparative way for the first time. The constructs of scaffolds and bone marrow-derived mesenchymal stem cells were implanted into pre-created osteochondral defects in the femoral condyle of New Zealand white rabbits. After 12 weeks, all experimental groups exhibited good cartilage repairing according to macroscopic appearance, cross-section view, haematoxylin and eosin staining, toluidine blue staining, immunohistochemical staining and real-time polymerase chain reaction of characteristic genes. The group of 92% porosity in the cartilage layer and 77% porosity in the bone layer resulted in the best efficacy, which was understood by more biomechanical mimicking of the natural cartilage and subchondral bone. This study illustrates unambiguously that cartilage tissue engineering allows for a wide range of scaffold porosity, yet some porosity group is optimal. It is also revealed that the biomechanical matching with the natural composite tissue should be taken into consideration in the design of practical biomaterials, which is especially important for porosities of a multi-compartment scaffold concerning connected tissues. PMID:26813511

  18. Present status and applications of bacterial cellulose-based materials for skin tissue repair.

    PubMed

    Fu, Lina; Zhang, Jin; Yang, Guang

    2013-02-15

    Bacterial cellulose (BC, also known as microbial cellulose, MC) is a promising natural polymer which is biosynthesized by certain bacteria. This review focused on BC-based materials which can be utilized for skin tissue repair. Firstly, it is illustrated that BC has unique structural and mechanical properties as compared with higher plant cellulose, and is thus expected to become a commodity material. Secondly, we summarized the basic properties and different types of BC, including self-assembled, oriented BC, and multiform BC. Thirdly, composites prepared by using BC in conjunction with other polymers are explored, and the research on BC for application in skin tissue engineering is addressed. Finally, experimental results and clinical treatments assessing the performance of wound healing materials based on BC were examined. With its superior mechanical properties, as well as its excellent biocompatibility, BC was shown to have great potential for biomedical application and very high clinical value for skin tissue repair. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Hydrogel coated mesh decreases tissue reaction resulting from polypropylene mesh implant: implication in hernia repair.

    PubMed

    Poppas, D P; Sung, J J; Magro, C M; Chen, J; Toyohara, J P; Ramshaw, B J; Felsen, D

    2016-08-01

    Use of polypropylene mesh (PPM) in hernia repair is associated with tissue reactivity. We examined, in a rat model, a novel non-biodegradable hydrogel coated PPM which may allow for decreased inflammation and a decreased foreign body reaction. Through a dorsal midline incision, a 2 cm × 2 cm section of PPM (either coated or uncoated) was placed on the fascial surface 1.5 cm from the incision on the dorsal wall of Sprague-Dawley rats. At 2 and 12 weeks after placement, the PPM and surrounding tissue were harvested. A board-certified dermatopathologist examined H&E stained slides for fibrosis and foreign body reaction. In addition, tissues were stained for apoptotic cells, oxidative damage, macrophages, fibroblasts, neovascularization and metalloproteases. At 2 and 12 weeks, there was a greater than 95 % decrease in foreign body giant cells in coated PPM samples compared to uncoated; fibrosis was decreased by 50 %. At 2 and 12 weeks, oxidative damage, fibroblast accumulation, apoptosis and macrophages were significantly decreased in coated PPM samples compared to uncoated PPM. These results demonstrate that a non-biodegradable hydrogel coating of PPM led to significant reduction in foreign body reaction, oxidative stress and apoptosis compared to uncoated PPM in vivo, and suggest that this coating could be clinically useful in hernia repair.

  20. Nanoscale Surface Modifications of Medical Implants for Cartilage Tissue Repair and Regeneration

    PubMed Central

    Griffin, MF; Szarko, M; Seifailan, A; Butler, PE

    2016-01-01

    Background: Natural cartilage regeneration is limited after trauma or degenerative processes. Due to the clinical challenge of reconstruction of articular cartilage, research into developing biomaterials to support cartilage regeneration have evolved. The structural architecture of composition of the cartilage extracellular matrix (ECM) is vital in guiding cell adhesion, migration and formation of cartilage. Current technologies have tried to mimic the cell’s nanoscale microenvironment to improve implants to improve cartilage tissue repair. Methods: This review evaluates nanoscale techniques used to modify the implant surface for cartilage regeneration. Results: The surface of biomaterial is a vital parameter to guide cell adhesion and consequently allow for the formation of ECM and allow for tissue repair. By providing nanosized cues on the surface in the form of a nanotopography or nanosized molecules, allows for better control of cell behaviour and regeneration of cartilage. Chemical, physical and lithography techniques have all been explored for modifying the nanoscale surface of implants to promote chondrocyte adhesion and ECM formation. Conclusion: Future studies are needed to further establish the optimal nanoscale modification of implants for cartilage tissue regeneration. PMID:28217208

  1. Current advances in tissue repair and regeneration: the future is bright

    PubMed Central

    2015-01-01

    Abstract The fifth EMBO conference on ‘The Molecular and Cellular Basis of Regeneration and Repair’ took place in the peaceful coastal town of Sant Feliu de Guixols (Spain) on September 2014. The meeting was organised by Emili Saló (U. Barcelona, Spain), Kimberly Mace (U. Manchester, UK), Patrizia Ferretti (University College London, UK) and Michael Brand (Centre for Regenerative Therapies Dresden, Germany) and received the generous support of Society for Developmental Biology, The Company of Biologists, Centre for Regenerative Therapies Dresden, Garland Science and the journals Regeneration and Cell Signalling. The natural surroundings provided an inspiring setting for 185 researchers from all over the world to share their latest findings and views on the field. The conference showcased the great diversity of model organisms used for studying regeneration and tissue repair, including invertebrate and vertebrate species (Fig. 1). Importantly, this diversity in animal models allowed for a global overview of the mechanisms that promote regeneration. In addition, it highlighted some of the unique aspects that confer differences in regenerative capacities among different species. These differences might lie in each of the different steps involved in performing regeneration, including triggering the regenerative response, controlling cellular plasticity, re‐stablishing the correct tissue patterns, as well as determining the roles of extrinsic factors, such as the role of inflammation in regeneration. A deeper understanding of these processes in the naturally regenerating species is a prerequisite for advancing the field of regenerative medicine and tissue repair in humans. PMID:27499870

  2. Pseudomonas aeruginosa lectin LecB inhibits tissue repair processes by triggering β-catenin degradation.

    PubMed

    Cott, Catherine; Thuenauer, Roland; Landi, Alessia; Kühn, Katja; Juillot, Samuel; Imberty, Anne; Madl, Josef; Eierhoff, Thorsten; Römer, Winfried

    2016-06-01

    Pseudomonas aeruginosa is an opportunistic pathogen that induces severe lung infections such as ventilator-associated pneumonia and acute lung injury. Under these conditions, the bacterium diminishes epithelial integrity and inhibits tissue repair mechanisms, leading to persistent infections. Understanding the involved bacterial virulence factors and their mode of action is essential for the development of new therapeutic approaches. In our study we discovered a so far unknown effect of the P. aeruginosa lectin LecB on host cell physiology. LecB alone was sufficient to attenuate migration and proliferation of human lung epithelial cells and to induce transcriptional activity of NF-κB. These effects are characteristic of impaired tissue repair. Moreover, we found a strong degradation of β-catenin, which was partially recovered by the proteasome inhibitor lactacystin. In addition, LecB induced loss of cell-cell contacts and reduced expression of the β-catenin targets c-myc and cyclin D1. Blocking of LecB binding to host cell plasma membrane receptors by soluble l-fucose prevented these changes in host cell behavior and signaling, and thereby provides a powerful strategy to suppress LecB function. Our findings suggest that P. aeruginosa employs LecB as a virulence factor to induce β-catenin degradation, which then represses processes that are directly linked to tissue recovery. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Pseudomonas aeruginosa lectin LecB inhibits tissue repair processes by triggering β-catenin degradation

    PubMed Central

    Cott, Catherine; Thuenauer, Roland; Landi, Alessia; Kühn, Katja; Juillot, Samuel; Imberty, Anne; Madl, Josef; Eierhoff, Thorsten; Römer, Winfried

    2016-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that induces severe lung infections such as ventilator-associated pneumonia and acute lung injury. Under these conditions, the bacterium diminishes epithelial integrity and inhibits tissue repair mechanisms, leading to persistent infections. Understanding the involved bacterial virulence factors and their mode of action is essential for the development of new therapeutic approaches. In our study we discovered a so far unknown effect of the P. aeruginosa lectin LecB on host cell physiology. LecB alone was sufficient to attenuate migration and proliferation of human lung epithelial cells and to induce transcriptional activity of NF-κB. These effects are characteristic of impaired tissue repair. Moreover, we found a strong degradation of β-catenin, which was partially recovered by the proteasome inhibitor lactacystin. In addition, LecB induced loss of cell–cell contacts and reduced expression of the β-catenin targets c-myc and cyclin D1. Blocking of LecB binding to host cell plasma membrane receptors by soluble l-fucose prevented these changes in host cell behavior and signaling, and thereby provides a powerful strategy to suppress LecB function. Our findings suggest that P. aeruginosa employs LecB as a virulence factor to induce β-catenin degradation, which then represses processes that are directly linked to tissue recovery. PMID:26862060

  4. Influence of Sterilization Technologies on Electrospun Poly(ester urea)s for Soft Tissue Repair.

    PubMed

    Wade, Mary Beth; Rodenberg, Eric; Patel, Umesh; Shah, Bhavin; Becker, Matthew L

    2016-10-10

    Degradable poly(ester urea)s (PEU)s were electrospun into nanofiber sheets and assessed for their potential to be used in soft tissue repair. The level of residual solvent was measured and the effects of ethylene oxide and electron beam sterilization techniques on molecular mass, mass distribution, and morphology were quantified. Two PEU compositions that formed stable nanofiber sheets were advanced into a pilot study in vitro and in vivo as candidate materials for hernia repair. Cell viability, spreading, proliferation, and migration were examined in vitro. Nanofiber sheets were implanted subcutaneously into mice and analyzed via microangiography and histology for tissue incorporation. Nanofiber sheets performed similarly to decellularized extracellular matrix (ECM) in vitro, but the lack of sufficient pore structure inhibited cellular infiltration after 14 days of culture. The lack of microporous features in nanofiber sheets also contributed to low levels of cellular infiltration, angiogenesis, and matrix deposition in vivo. A preliminary study to increase pore size in nanofibers was performed using coaxial electrospinning resulting in significant improvement in tissue infiltration in vivo.

  5. Reserve stem cells: Differentiated cells reprogram to fuel repair, metaplasia, and neoplasia in the adult gastrointestinal tract.

    PubMed

    Mills, Jason C; Sansom, Owen J

    2015-07-14

    It has long been known that differentiated cells can switch fates, especially in vitro, but only recently has there been a critical mass of publications describing the mechanisms adult, postmitotic cells use in vivo to reverse their differentiation state. We propose that this sort of cellular reprogramming is a fundamental cellular process akin to apoptosis or mitosis. Because reprogramming can invoke regenerative cells from mature cells, it is critical to the long-term maintenance of tissues like the pancreas, which encounter large insults during adulthood but lack constitutively active adult stem cells to repair the damage. However, even in tissues with adult stem cells, like the stomach and intestine, reprogramming may allow mature cells to serve as reserve ("quiescent") stem cells when normal stem cells are compromised. We propose that the potential downside to reprogramming is that it increases risk for cancers that occur late in adulthood. Mature, long-lived cells may have years of exposure to mutagens. Mutations that affect the physiological function of differentiated, postmitotic cells may lead to apoptosis, but mutations in genes that govern proliferation might not be selected against. Hence, reprogramming with reentry into the cell cycle might unmask those mutations, causing an irreversible progenitor-like, proliferative state. We review recent evidence showing that reprogramming fuels irreversible metaplastic and precancerous proliferation in the stomach and pancreas. Finally, we illustrate how we think reprogrammed differentiated cells are likely candidates as cells of origin for cancers of the intestine.

  6. Reserve stem cells: Reprogramming of differentiated cells fuels repair, metaplasia, and neoplasia in the adult gastrointestinal tract

    PubMed Central

    Mills, Jason C.; Sansom, Owen J.

    2016-01-01

    It has long been known that differentiated cells can switch fates, especially in vitro, but only recently has there been a critical mass of publications describing the mechanisms adult, post-mitotic cells use in vivo to reverse their differentiation state. We propose that this sort of cellular reprogramming is a fundamental cellular process akin to apoptosis or mitosis. Because reprogramming can invoke regenerative cells from mature cells, it is critical to the longterm maintenance of tissues like the pancreas, which encounter large insults during adulthood but lack constitutively active adult stem cells to repair the damage. However, even in tissues with adult stem cells, like stomach and intestine, reprogramming may allow mature cells to serve as reserve (“quiescent”) stem cells when normal stem cells are compromised. We propose that the potential downside to reprogramming is that it increases risk for cancers that occur late in adulthood. Mature, long-lived cells may have years of exposure to mutagens. Mutations that affect the physiological function of differentiated, post-mitotic cells may lead to apoptosis, but mutations in genes that govern proliferation might not be selected against. Hence, reprogramming with reentry into the cell cycle might unmask those mutations, causing an irreversible progenitor-like, proliferative state. We review recent evidence showing that reprogramming fuels irreversible metaplastic and precancerous proliferations in stomach and pancreas. Finally, we illustrate how we think reprogrammed differentiated cells are likely candidates as cells of origin for cancers of the intestine. PMID:26175494

  7. Aberrant repair of etheno-DNA adducts in leukocytes and colon tissue of colon cancer patients.

    PubMed

    Obtułowicz, Tomasz; Winczura, Alicja; Speina, Elzbieta; Swoboda, Maja; Janik, Justyna; Janowska, Beata; Cieśla, Jarosław M; Kowalczyk, Paweł; Jawien, Arkadiusz; Gackowski, Daniel; Banaszkiewicz, Zbigniew; Krasnodebski, Ireneusz; Chaber, Andrzej; Olinski, Ryszard; Nair, Jagadesaan; Bartsch, Helmut; Douki, Thierry; Cadet, Jean; Tudek, Barbara

    2010-09-15

    To assess the role of lipid peroxidation-induced DNA damage and repair in colon carcinogenesis, the excision rates and levels of 1,N(6)-etheno-2'-deoxyadenosine (epsilondA), 3,N(4)-etheno-2'-deoxycytidine (epsilondC), and 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-epsilondG) were analyzed in polymorphic blood leukocytes (PBL) and resected colon tissues of 54 colorectal carcinoma (CRC) patients and PBL of 56 healthy individuals. In PBL the excision rates of 1,N(6)-ethenoadenine (epsilonAde) and 3,N(4)-ethenocytosine (epsilonCyt), measured by the nicking of oligodeoxynucleotide duplexes with single lesions, and unexpectedly also the levels of epsilondA and 1,N(2)-epsilondG, measured by LC/MS/MS, were lower in CRC patients than in controls. In contrast the mRNA levels of repair enzymes, alkylpurine- and thymine-DNA glycosylases and abasic site endonuclease (APE1), were higher in PBL of CRC patients than in those of controls, as measured by QPCR. In the target colon tissues epsilonAde and epsilonCyt excision rates were higher, whereas the epsilondA and epsilondC levels in DNA, measured by (32)P-postlabeling, were lower in tumor than in adjacent colon tissue, although a higher mRNA level was observed only for APE1. This suggests that during the onset of carcinogenesis, etheno adduct repair in the colon seems to be under a complex transcriptional and posttranscriptional control, whereby deregulation may act as a driving force for malignancy.

  8. Role of endogenous Schwann cells in tissue repair after spinal cord injury.

    PubMed

    Zhang, Shu-Xin; Huang, Fengfa; Gates, Mary; Holmberg, Eric G

    2013-01-15

    Schwann cells are glial cells of peripheral nervous system, responsible for axonal myelination and ensheathing, as well as tissue repair following a peripheral nervous system injury. They are one of several cell types that are widely studied and most commonly used for cell transplantation to treat spinal cord injury, due to their intrinsic characteristics including the ability to secrete a variety of neurotrophic factors. This mini review summarizes the recent findings of endogenous Schwann cells after spinal cord injury and discusses their role in tissue repair and axonal regeneration. After spinal cord injury, numerous endogenous Schwann cells migrate into the lesion site from the nerve roots, involving in the construction of newly formed repaired tissue and axonal myelination. These invading Schwann cells also can move a long distance away from the injury site both rostrally and caudally. In addition, Schwann cells can be induced to migrate by minimal insults (such as scar ablation) within the spinal cord and integrate with astrocytes under certain circumstances. More importantly, the host Schwann cells can be induced to migrate into spinal cord by transplantation of different cell types, such as exogenous Schwann cells, olfactory ensheathing cells, and bone marrow-derived stromal stem cells. Migration of endogenous Schwann cells following spinal cord injury is a common natural phenomenon found both in animal and human, and the myelination by Schwann cells has been examined effective in signal conduction electrophysiologically. Therefore, if the inherent properties of endogenous Schwann cells could be developed and utilized, it would offer a new avenue for the restoration of injured spinal cord.

  9. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage.

    PubMed

    Huang, Brian J; Hu, Jerry C; Athanasiou, Kyriacos A

    2016-08-01

    One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of current research in the field, it is known that 90% of new drugs that advance past animal studies fail clinical trials. The objective of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

    PubMed Central

    Huang, Brian J.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2016-01-01

    One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of review articles on the paradigm of biomaterials, signals, and cells, it is reported that 90% of new drugs that advance past animal studies fail clinical trials (1). The intent of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by fully understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products. PMID:27177218

  11. Linking the Primary Cilium to Cell Migration in Tissue Repair and Brain Development

    PubMed Central

    Veland, Iben Rønn; Lindbæk, Louise; Christensen, Søren Tvorup

    2014-01-01

    Primary cilia are unique sensory organelles that coordinate cellular signaling networks in vertebrates. Inevitably, defects in the formation or function of primary cilia lead to imbalanced regulation of cellular processes that causes multisystemic disorders and diseases, commonly known as ciliopathies. Mounting evidence has demonstrated that primary cilia coordinate multiple activities that are required for cell migration, which, when they are aberrantly regulated, lead to defects in organogenesis and tissue repair, as well as metastasis of tumors. Here, we present an overview on how primary cilia may contribute to the regulation of the cellular signaling pathways that control cyclic processes in directional cell migration. PMID:26955067

  12. Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors

    PubMed Central

    Butler, Jason M.; Kobayashi, Hideki; Rafii, Shahin

    2010-01-01

    The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an ‘angiocrine’ mechanism by producing stem and progenitor cell-active trophogens. Identification of endothelial-derived instructive angiocrine factors will allow direct tumour targeting, while diminishing the unwanted side effects associated with the use of anti-angiogenic agents. PMID:20094048

  13. Use of tissue engineering strategies to repair joint tissues in osteoarthritis: viral gene transfer approaches.

    PubMed

    Cucchiarini, Magali; Madry, Henning

    2014-10-01

    Osteoarthritis (OA) is a major chronic disease of the joints, affecting mostly the articular cartilage but also all the surrounding tissues including the subchondral bone, synovium, meniscus, tendons, and ligaments. Despite the availability in the clinic of a variety of therapeutic approaches, there is crucial need for improved treatment to protect and regenerate the cartilage with full integrity and function. In this regard, combining gene, cell, and tissue engineering-based procedures is an attractive concept for novel, effective therapy against AO, a slow, progressive, and irreversible disease. Here, we provide an overview of the treatment available for management of the progression of the OA phenotype and discuss current progress and remaining challenges for potential future treatment of patients.

  14. Transforming growth factor beta signaling in adult cardiovascular diseases and repair

    PubMed Central

    Doetschman, Thomas; Barnett, Joey V.; Runyan, Raymond B.; Camenisch, Todd D.; Heimark, Ronald L.; Granzier, Henk L.; Conway, Simon J.; Azhar, Mohamad

    2011-01-01

    The majority of children with congenital heart disease now live into adulthood due to the remarkable surgical and medical advances that have taken place over the past half century. Because of this, the adults now represent the largest age group with adult cardiovascular diseases. They include patients with heart diseases that were not detected or not treated during childhood, those whose defects were surgically corrected but now need revision due to maladaptive responses to the procedure, those with exercise problems, and those with age-related degenerative diseases. Because adult cardiovascular diseases in this population are relatively new, they are not well understood. It is therefore necessary to understand the molecular and physiological pathways involved if we are to improve treatments. Since there is a developmental basis to adult cardiovascular disease, transforming growth factor beta (TGFβ) signaling pathways that are essential for proper cardiovascular development may also play critical roles in the homeostatic, repair and stress response processes involved in adult cardiovascular diseases. Consequently, we have chosen to summarize the current information on a subset of TGFβ ligand and receptor genes and related effector genes that when dysregulated are known to lead to cardiovascular diseases and adult cardiovascular deficiencies and/or pathologies. A better understanding of the TGFβ signaling network in cardiovascular disease and repair will impact genetic and physiologic investigations of cardiovascular diseases in elderly patients and lead to an improvement in clinical interventions. PMID:21953136

  15. Prion diseases and adult neurogenesis: How do prions counteract the brain's endogenous repair machinery?

    PubMed Central

    Relaño-Ginés, Aroa; Lehmann, Sylvain; Crozet, Carole

    2014-01-01

    Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process; however, it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies. PMID:24831876

  16. Prion diseases and adult neurogenesis: how do prions counteract the brain's endogenous repair machinery?

    PubMed

    Relaño-Ginés, Aroa; Lehmann, Sylvain; Crozet, Carole

    2014-01-01

    Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process, however it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies.

  17. Electric fish: new insights into conserved processes of adult tissue regeneration

    PubMed Central

    Unguez, Graciela A.

    2013-01-01

    Summary Biology is replete with examples of regeneration, the process that allows animals to replace or repair cells, tissues and organs. As on land, vertebrates in aquatic environments experience the occurrence of injury with varying frequency and to different degrees. Studies demonstrate that ray-finned fishes possess a very high capacity to regenerate different tissues and organs when they are adults. Among fishes that exhibit robust regenerative capacities are the neotropical electric fishes of South America (Teleostei: Gymnotiformes). Specifically, adult gymnotiform electric fishes can regenerate injured brain and spinal cord tissues and restore amputated body parts repeatedly. We have begun to identify some aspects of the cellular and molecular mechanisms of tail regeneration in the weakly electric fish Sternopygus macrurus (long-tailed knifefish) with a focus on regeneration of skeletal muscle and the muscle-derived electric organ. Application of in vivo microinjection techniques and generation of myogenic stem cell markers are beginning to overcome some of the challenges owing to the limitations of working with non-genetic animal models with extensive regenerative capacity. This review highlights some aspects of tail regeneration in S. macrurus and discusses the advantages of using gymnotiform electric fishes to investigate the cellular and molecular mechanisms that produce new cells during regeneration in adult vertebrates. PMID:23761473

  18. Electric fish: new insights into conserved processes of adult tissue regeneration.

    PubMed

    Unguez, Graciela A

    2013-07-01

    Biology is replete with examples of regeneration, the process that allows animals to replace or repair cells, tissues and organs. As on land, vertebrates in aquatic environments experience the occurrence of injury with varying frequency and to different degrees. Studies demonstrate that ray-finned fishes possess a very high capacity to regenerate different tissues and organs when they are adults. Among fishes that exhibit robust regenerative capacities are the neotropical electric fishes of South America (Teleostei: Gymnotiformes). Specifically, adult gymnotiform electric fishes can regenerate injured brain and spinal cord tissues and restore amputated body parts repeatedly. We have begun to identify some aspects of the cellular and molecular mechanisms of tail regeneration in the weakly electric fish Sternopygus macrurus (long-tailed knifefish) with a focus on regeneration of skeletal muscle and the muscle-derived electric organ. Application of in vivo microinjection techniques and generation of myogenic stem cell markers are beginning to overcome some of the challenges owing to the limitations of working with non-genetic animal models with extensive regenerative capacity. This review highlights some aspects of tail regeneration in S. macrurus and discusses the advantages of using gymnotiform electric fishes to investigate the cellular and molecular mechanisms that produce new cells during regeneration in adult vertebrates.

  19. Gene expression analysis distinguishes tissue specific and gender related functions among adult Ascaris suum tissues

    PubMed Central

    Wang, Zhengyuan; Gao, Xin; Martin, John; Yin, Yong; Abubucker, Sahar; Rash, Amy C.; Li, Ben-Wen; Nash, Bill; Hallsworth-Pepin, Kym; Jasmer, Douglas P.; Mitreva, Makedonka

    2013-01-01

    Over a billion people are infected by Ascaris spp. intestinal parasites. To clarify functional differences among tissues of adult A. suum, we compared gene expression by various tissues of these worms by expression microarray methods.. The A. suum genome was sequenced and assembled to allow generation of microarray elements. Expression of over 40,000 60-mer elements was investigated in a variety of tissues from both male and female adult worms. Nearly 50 percent of the elements for which signal was detected exhibited differential expression among different tissues. The unique profile of transcripts identified for each tissue clarified functional distinctions among tissues, such as chitin binding in the ovary and peptidase activity in the intestines. Interestingly, hundreds of gender-specific elements were characterized in multiple non-reproductive tissues of female or male worms, with most prominence of gender differences in intestinal tissue. A. suum genes from the same family were frequently expressed differently among tissues. Transcript abundance for genes specific to A. suum, by comparison to Caenorhabditis elegans, varied to a greater extent among tissues than for genes conserved between A. suum and C. elegans. Analysis using C. elegans protein interaction data identified functional modules conserved between these two nematodes, resulting in identification of functional predictions of essential subnetworks of protein interactions and how these networks may vary among nematode tissues. A notable finding was very high module similarity between adult reproductive tissues and intestine. Our results provide the most comprehensive assessment of gene expression among tissues of a parasitic nematode to date. PMID:23572074

  20. Harnessing the immunomodulatory and tissue repair properties of mesenchymal stem cells to restore β cell function

    PubMed Central

    Davis, Nicolynn E; Hamilton, Diana; Fontaine, Magali J

    2013-01-01

    Islet cell transplantation has therapeutic potential to cure type 1 diabetes (T1D), which is characterized by autoimmune-mediated destruction of insulin-producing β cells. However, current success rates are limited by long-term decline in islet graft function resulting partially from poor revascularization and immune destruction. MSCs have the potential to enhance islet transplantation and prevent disease progression by a multifaceted approach. MSCs have been shown to be effective at inhibiting inflammatory-mediated immune responses and at promoting tissue regeneration. The immunomodulatory and tissue repairing properties of MSCs may benefit β cell regeneration in the context of T1D. This review will elucidate how MSCs can minimize β cell damage by providing survival signals and simultaneously modulate the immune response by inhibiting activation and proliferation of several immune cell types. In addition, MSCs can enhance islet graft revascularization, maintaining long-term β cell viability and function. PMID:22869154

  1. Mesenchymal stem cell therapy in osteoarthritis: advanced tissue repair or intervention with smouldering synovial activation?

    PubMed

    van Lent, Peter L E M; van den Berg, Wim B

    2013-03-20

    Although it is generally accepted that osteoarthritis is a degenerative condition of the cartilage, other tissues such as synovium in which immunological and inflammatory reactions occur contribute to the development of joint pathology. This sheds new light on the potential mechanism of action of mesenchymal stem cell therapy in osteoarthritis. Rather than tissue repair due to local transformation of injected mesenchymal stem cells to chondrocytes and filling defects in cartilage, such treatment might suppress synovial activation and indirectly ameliorate cartilage damage. Desando and co-workers report in Arthritis Research & Therapy that intra-articular delivery of adipose-derived stem cells attenuates progression of synovial activation and joint destruction in osteoarthritis in an experimental rabbit model. Clinical studies are warranted to see whether this approach might be a novel way to combat development of joint destruction in inflammatory subtypes of osteoarthritis.

  2. Mesenchymal stem cell therapy in osteoarthritis: advanced tissue repair or intervention with smouldering synovial activation?

    PubMed Central

    2013-01-01

    Although it is generally accepted that osteoarthritis is a degenerative condition of the cartilage, other tissues such as synovium in which immunological and inflammatory reactions occur contribute to the development of joint pathology. This sheds new light on the potential mechanism of action of mesenchymal stem cell therapy in osteoarthritis. Rather than tissue repair due to local transformation of injected mesenchymal stem cells to chondrocytes and filling defects in cartilage, such treatment might suppress synovial activation and indirectly ameliorate cartilage damage. Desando and co-workers report in Arthritis Research & Therapy that intra-articular delivery of adipose-derived stem cells attenuates progression of synovial activation and joint destruction in osteoarthritis in an experimental rabbit model. Clinical studies are warranted to see whether this approach might be a novel way to combat development of joint destruction in inflammatory subtypes of osteoarthritis. PMID:23521980

  3. Cell and biomolecule delivery for tissue repair and regeneration in the central nervous system.

    PubMed

    Elliott Donaghue, Irja; Tam, Roger; Sefton, Michael V; Shoichet, Molly S

    2014-09-28

    Tissue engineering frequently involves cells and scaffolds to replace damaged or diseased tissue. It originated, in part, as a means of effecting the delivery of biomolecules such as insulin or neurotrophic factors, given that cells are constitutive producers of such therapeutic agents. Thus cell delivery is intrinsic to tissue engineering. Controlled release of biomolecules is also an important tool for enabling cell delivery since the biomolecules can enable cell engraftment, modulate inflammatory response or otherwise benefit the behavior of the delivered cells. We describe advances in cell and biomolecule delivery for tissue regeneration, with emphasis on the central nervous system (CNS). In the first section, the focus is on encapsulated cell therapy. In the second section, the focus is on biomolecule delivery in polymeric nano/microspheres and hydrogels for the nerve regeneration and endogenous cell stimulation. In the third section, the focus is on combination strategies of neural stem/progenitor cell or mesenchymal stem cell and biomolecule delivery for tissue regeneration and repair. In each section, the challenges and potential solutions associated with delivery to the CNS are highlighted.

  4. Stem cell delivery in tissue-specific hydrogel enabled meniscal repair in an orthotopic rat model.

    PubMed

    Yuan, Xiaoning; Wei, Yiyong; Villasante, Aránzazu; Ng, Johnathan J D; Arkonac, Derya E; Chao, Pen-Hsiu Grace; Vunjak-Novakovic, Gordana

    2017-04-04

    Interest in non-invasive injectable therapies has rapidly risen due to their excellent safety profile and ease of use in clinical settings. Injectable hydrogels can be derived from the extracellular matrix (ECM) of specific tissues to provide a biomimetic environment for cell delivery and enable seamless regeneration of tissue defects. We investigated the in situ delivery of human mesenchymal stem cells (hMSCs) in decellularized meniscus ECM hydrogel to a meniscal defect in a nude rat model. First, decellularized meniscus ECM hydrogel retained tissue-specific proteoglycans and collagens, and significantly upregulated expression of fibrochondrogenic markers by hMSCs versus collagen hydrogel alone in vitro. The meniscus ECM hydrogel in turn supported delivery of hMSCs for integrative repair of a full-thickness defect model in meniscal explants after in vitro culture and in vivo subcutaneous implantation. When applied to an orthotopic model of meniscal injury in nude rat, hMSCs in meniscus ECM hydrogel were retained out to eight weeks post-injection, contributing to tissue regeneration and protection from joint space narrowing, pathologic mineralization, and osteoarthritis development, as evidenced by macroscopic and microscopic image analysis. Based on these findings, we propose the use of tissue-specific meniscus ECM-derived hydrogel for the delivery of therapeutic hMSCs to treat meniscal injury.

  5. Direct Repair of Chronic Achilles Tendon Ruptures Using Scar Tissue Located Between the Tendon Stumps.

    PubMed

    Yasuda, Toshito; Shima, Hiroaki; Mori, Katsunori; Kizawa, Momoko; Neo, Masashi

    2016-07-20

    Several surgical procedures for chronically ruptured Achilles tendons have been reported. Resection of the interposed scar tissue located between the tendon stumps and reconstruction using normal autologous tissue have been well described. We developed a direct repair procedure that uses scar tissue, which obviates the need to use normal autologous tissue. Thirty consecutive patients with Achilles tendon ruptures with a delay in diagnosis of >4 weeks underwent removal of a section of scar and healing tissue with direct primary suture of the ends of the tendon without the use of allograft or autograft. Patients were followed for a mean time of 33 months. Preoperative and postoperative clinical outcomes were measured with the Achilles Tendon Total Rupture Score (ATRS) and the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score. In addition, the patients underwent preoperative and postoperative functional measurements and magnetic resonance imaging. Lastly, we evaluated the histology of the interposed healing tissue. The mean AOFAS scores were 82.8 points preoperatively and 98.1 points postoperatively. The mean postoperative ATRS was 92.0 points. At the time of the latest follow-up, none of the patients had experienced tendon reruptures or difficulties in walking or climbing stairs, and all except 2 patients could perform a single-limb heel rise. All athletes had returned to their pre-injury level of sports participation. Preoperative T2-weighted magnetic resonance imaging showed that 22 Achilles tendons were thickened with diffuse intratendinous high-signal alterations, and 8 Achilles tendons were thinned. Postoperative T2-weighted magnetic resonance imaging findings included fusiform-shaped tendon thickening and homogeneous low-signal alterations of the tendons in all patients. Histologically, the interposed scar tissue consisted of dense collagen fibers. Shortening of the tissue between the 2 tendon ends that included healing scar and direct

  6. A method to screen and evaluate tissue adhesives for joint repair applications.

    PubMed

    Dehne, Tilo; Zehbe, Rolf; Krüger, Jan Philipp; Petrova, Aneliya; Valbuena, Rafael; Sittinger, Michael; Schubert, Helmut; Ringe, Jochen

    2012-09-17

    Tissue adhesives are useful means for various medical procedures. Since varying requirements cause that a single adhesive cannot meet all needs, bond strength testing remains one of the key applications used to screen for new products and study the influence of experimental variables. This study was conducted to develop an easy to use method to screen and evaluate tissue adhesives for tissue engineering applications. Tissue grips were designed to facilitate the reproducible production of substrate tissue and adhesive strength measurements in universal testing machines. Porcine femoral condyles were used to generate osteochondral test tissue cylinders (substrates) of different shapes. Viability of substrates was tested using PI/FDA staining. Self-bonding properties were determined to examine reusability of substrates (n = 3). Serial measurements (n = 5) in different operation modes (OM) were performed to analyze the bonding strength of tissue adhesives in bone (OM-1) and cartilage tissue either in isolation (OM-2) or under specific requirements in joint repair such as filling cartilage defects with clinical applied fibrin/PLGA-cell-transplants (OM-3) or tissues (OM-4). The efficiency of the method was determined on the basis of adhesive properties of fibrin glue for different assembly times (30 s, 60 s). Seven randomly generated collagen formulations were analyzed to examine the potential of method to identify new tissue adhesives. Viability analysis of test tissue cylinders revealed vital cells (>80%) in cartilage components even 48 h post preparation. Reuse (n = 10) of test substrate did not significantly change adhesive characteristics. Adhesive strength of fibrin varied in different test settings (OM-1: 7.1 kPa, OM-2: 2.6 kPa, OM-3: 32.7 kPa, OM-4: 30.1 kPa) and was increasing with assembly time on average (2.4-fold). The screening of the different collagen formulations revealed a substance with significant higher adhesive strength on cartilage (14.8 kPa) and

  7. A method to screen and evaluate tissue adhesives for joint repair applications

    PubMed Central

    2012-01-01

    Background Tissue adhesives are useful means for various medical procedures. Since varying requirements cause that a single adhesive cannot meet all needs, bond strength testing remains one of the key applications used to screen for new products and study the influence of experimental variables. This study was conducted to develop an easy to use method to screen and evaluate tissue adhesives for tissue engineering applications. Method Tissue grips were designed to facilitate the reproducible production of substrate tissue and adhesive strength measurements in universal testing machines. Porcine femoral condyles were used to generate osteochondral test tissue cylinders (substrates) of different shapes. Viability of substrates was tested using PI/FDA staining. Self-bonding properties were determined to examine reusability of substrates (n = 3). Serial measurements (n = 5) in different operation modes (OM) were performed to analyze the bonding strength of tissue adhesives in bone (OM-1) and cartilage tissue either in isolation (OM-2) or under specific requirements in joint repair such as filling cartilage defects with clinical applied fibrin/PLGA-cell-transplants (OM-3) or tissues (OM-4). The efficiency of the method was determined on the basis of adhesive properties of fibrin glue for different assembly times (30 s, 60 s). Seven randomly generated collagen formulations were analyzed to examine the potential of method to identify new tissue adhesives. Results Viability analysis of test tissue cylinders revealed vital cells (>80%) in cartilage components even 48 h post preparation. Reuse (n = 10) of test substrate did not significantly change adhesive characteristics. Adhesive strength of fibrin varied in different test settings (OM-1: 7.1 kPa, OM-2: 2.6 kPa, OM-3: 32.7 kPa, OM-4: 30.1 kPa) and was increasing with assembly time on average (2.4-fold). The screening of the different collagen formulations revealed a substance with significant higher adhesive

  8. Resident adult neural stem cells in Parkinson's disease--the brain's own repair system?

    PubMed

    van den Berge, Simone A; van Strien, Miriam E; Hol, Elly M

    2013-11-05

    One important pathological process in the brain of Parkinson disease (PD) patients is the degeneration of the dopaminergic neurons in the substantia nigra, which leads to a decline in striatal dopamine levels and motor dysfunction. A major clinical problem is that this degenerative process currently cannot be stopped or reversed. Expectations from the restorative capacity of neural stem cells (NSCs) are high, as these cells can potentially replace the degenerating neurons. The discovery of the presence of NSCs in the adult human brain has instigated research into the potential of these cells as a resource to promote brain repair in neurodegenerative diseases. Neural stem and progenitor cells reside in the subventricular zone (SVZ), which is closely situated to the striatum, which is affected in PD. Therefore, restoring the dopamine levels in the striatum of PD patients through stimulating endogenous NSCs in the nearby SVZ to migrate into the striatum and differentiate into dopaminergic neurons might thus be an attractive future therapeutic approach. We will review the reported changes in NSCs in the SVZ of PD animal models and PD patients, which are due to a lack of striatal dopamine. Furthermore, we will summarise the reports that describe efforts to stimulate NSCs to replace dopaminergic cells in the SN and restore striatal dopamine levels. In our opinion, mobilizing the endogenous SVZ NSCs to replenish striatal dopamine is an attractive approach to alleviate the motor symptoms in PD patients, without the ethical and immunological challenges of transplantation of NSCs and foetal brain tissue. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Cartilage Repair in the Inflamed Joint: Considerations for Biological Augmentation Toward Tissue Regeneration.

    PubMed

    Scotti, Celeste; Gobbi, Alberto; Karnatzikos, Georgios; Martin, Ivan; Shimomura, Kazunori; Lane, John G; Peretti, Giuseppe Michele; Nakamura, Norimasa

    2016-04-01

    Cartilage repair/regeneration procedures (e.g., microfracture, autologous chondrocyte implantation [ACI]) typically result in a satisfactory outcome in selected patients. However, the vast majority of patients with chronic symptoms and, in general, a more diseased joint, do not benefit from these surgical techniques. The aims of this work were to (1) review factors negatively influencing the joint environment; (2) review current adjuvant therapies that can be used to improve results of cartilage repair/regeneration procedures in patients with more diseased joints, (3) outline future lines of research and promising experimental approaches. Chronicity of symptoms and advancing patient age appear to be the most relevant factors negatively affecting clinical outcome of cartilage repair/regeneration. Preliminary experience with hyaluronic acid, platelet-rich plasma, and mesenchymal stem cell has been positive but there is no strong evidence supporting the use of these products and this requires further assessment with high-quality, prospective clinical trials. The use of a Tissue Therapy strategy, based on more mature engineered tissues, holds promise to tackle limitations of standard ACI procedures. Current research has highlighted the need for more targeted therapies, and (1) induction of tolerance with granulocyte colony-stimulating factor (G-CSF) or by preventing IL-6 downregulation; (2) combined IL-4 and IL-10 local release; and (3) selective activation of the prostaglandin E2 (PGE2) signaling appear to be the most promising innovative strategies. For older patients and for those with chronic symptoms, adjuvant therapies are needed in combination with microfracture and ACI.

  10. Construction of tissue-engineered osteochondral composites and repair of large joint defects in rabbit.

    PubMed

    Deng, Tianzheng; Lv, Jing; Pang, Jianliang; Liu, Bing; Ke, Jie

    2014-07-01

    In this study, a novel three-dimensional (3D) heterogeneous/bilayered scaffold was constructed to repair large defects in rabbit joints. The scaffold includes two distinct but integrated layers corresponding to the cartilage and bone components. The upper layer consists of gelatin, chondroitin sulphate and sodium hyaluronate (GCH), and the lower layer consists of gelatin and ceramic bovine bone (GCBB). The two form a 3D bilayered scaffold (GCH-GCBB), which mimics the natural osteochondral matrix for use as a scaffold for osteochondral tissue engineering. The purpose of this study was to evaluate the efficacy of this novel scaffold, combined with chondrocytes and bone marrow stem cells (BMSCs) to repair large defects in rabbit joints. Thirty-six large defects in rabbit femoral condyles were created; 12 defects were treated with the same scaffold combined with cells (group A); another 12 defects were treated with cell-free scaffolds (group B); the others were untreated (group C). At 6 and 12 weeks, in group A hyaline-like cartilage formation could be observed by histological examination; the newly formed cartilage, which stained for type II collagen, was detected by RT-PCR at high-level expression. Most of the GCBB was replaced by bone, while little remained in the underlying cartilage. At 36 weeks, GCBB was completely resorbed and a tidemark was observed in some areas. In contrast, groups B and C showed no cartilage formation but a great amount of fibrous tissue, with only a little bone formation. In summary, this study demonstrated that a novel scaffold, comprising a top layer of GCH, having mechanical properties comparable to native cartilage, and a bottom layer composed of GCBB, could be used to repair large osteochondral defects in joints.

  11. The Treatment Efficacy of Bone Tissue Engineering Strategy for Repairing Segmental Bone Defects Under Osteoporotic Conditions.

    PubMed

    Wang, Zhen Xing; Chen, Cheng; Zhou, Quan; Wang, Xian Song; Zhou, Guangdong; Liu, Wei; Zhang, Zhi-Yong; Cao, Yilin; Zhang, Wen Jie

    2015-09-01

    The potential of increasing bone mass and preventing fractures in osteoporosis using stem cell therapy is currently an area of intense focus. However, there are very little data available regarding the postfracture bony defect healing efficacy under osteoporotic conditions. This study aims to investigate whether critical-sized segmental bone defects in a rabbit model of osteoporosis could be repaired using an allogenic stem cell-based tissue engineering (TE) approach and to investigate the potential influence of osteoporosis on the treatment efficacy. Rabbit fetal bone marrow mesenchymal stem cells (BMSCs) were harvested and expanded in vitro. Decalcified bone matrix (DBM) scaffolds were then seeded with allogenic fetal BMSCs and cultivated in osteogenic media to engineer BMSC/DBM constructs. Critical-sized radial defects were created in ovariectomized (OVX) rabbits and the defects were repaired either by insertion of BMSC/DBM constructs or by DBM scaffolds alone. Also, nonovariectomized age-matched (non-OVX) rabbits were served as control. At 3 months post-treatment under the osteoporotic condition (OVX rabbits), the BMSC/DBM constructs inserted within the defect generated significantly more bone tissue when compared to the DBM scaffold as demonstrated by the X-ray, microcomputed tomography, and histological analyses. In addition, when compared to a normal nonosteoporotic condition (age-matched non-OVX rabbits), the defect treatment efficacy was adversely affected by the osteoporotic condition with significantly less bone regeneration. This study demonstrated the potential of allogenic fetal BMSC-based TE strategy for repairing bone defects in an osteoporotic condition. However, the treatment efficacy could be considerably compromised in the OVX animals. Therefore, a more sophisticated strategy that addresses the complicated pathogenic conditions associated with osteoporosis is needed.

  12. Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study

    PubMed Central

    2011-01-01

    Background Various cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA. Methods Polymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-α treatment as a marker of RA severity was assessed. Results The IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity. Conclusions We here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA. PMID:21385363

  13. Muscle satellite (stem) cell activation during local tissue injury and repair

    PubMed Central

    Hill, Maria; Wernig, A; Goldspink, G

    2003-01-01

    In post-mitotic tissues, damaged cells are not replaced by new cells and hence effective local tissue repair mechanisms are required. In skeletal muscle, which is a syncytium, additional nuclei are obtained from muscle satellite (stem) cells that multiply and then fuse with the damaged fibres. Although insulin-like growth factor-I (IGF-I) had been previously implicated, it is now clear that muscle expresses at least two splice variants of the IGF-I gene: a mechanosensitive, autocrine, growth factor (MGF) and one that is similar to the liver type (IGF-IEa). To investigate this activation mechanism, local damage was induced by stretch combined with electrical stimulation or injection of bupivacaine in the rat anterior tibialis muscle and the time course of regeneration followed morphologically. Satellite cell activation was studied by the distribution and levels of expression of M-cadherin (M-cad) and related to the expression of the two forms of IGF-I. It was found that the following local damage MGF expression preceded that of M-cad whereas IGF-IEa peaked later than M-cad. The evidence suggests therefore that an initial pulse of MGF expression following damage is what activates the satellite cells and that this is followed by the later expression of IGF-IEa to maintain protein synthesis to complete the repair. PMID:12892408

  14. A novel basalt fiber-reinforced polylactic acid composite for hard tissue repair.

    PubMed

    Chen, Xi; Li, Yan; Gu, Ning

    2010-08-01

    A basalt fiber (BF) was, for the first time, introduced into a poly(l-lactic acid) (PLLA) matrix as innovative reinforcement to fabricate composite materials for hard tissue repair. Firstly, BF/PLLA composites and pure PLLA were produced by the methods of solution blending and freeze drying. The results showed that basalt fibers can be uniformly dispersed in the PLLA matrix and significantly improve the mechanical properties and hydrophilicity of the PLLA matrix. The presence of basalt fibers may retard the polymer degradation rate and neutralize the acid degradation from PLLA. Osteoblasts were cultured in vitro to evaluate the cytocompatibility of the composite. An MTT assay revealed that osteoblasts proliferated well for 7 days and there was little difference found in their viability on both PLLA and BF/PLLA films, which was consistent with the alkaline phosphatase (ALP) activity results. A fluorescent staining observation showed that osteoblasts grew well on the composites. SEM images displayed that osteoblasts tended to grow along the fiber axis. The formation of mineralized nodules was observed on the films by Alizarin red S staining. These results suggest that the presence of basalt fibers does not noticeably affect osteoblastic behavior and the designed composites are osteoblast compatible. It is concluded that basalt fibers, as reinforcing fibers, may have promising applications in hard tissue repair.

  15. Functional MMP-10 is required for efficient tissue repair after experimental hind limb ischemia.

    PubMed

    Gomez-Rodriguez, Violeta; Orbe, Josune; Martinez-Aguilar, Esther; Rodriguez, Jose A; Fernandez-Alonso, Leopoldo; Serneels, Jens; Bobadilla, Miriam; Perez-Ruiz, Ana; Collantes, Maria; Mazzone, Massimiliano; Paramo, Jose A; Roncal, Carmen

    2015-03-01

    We studied the role of matrix metalloproteinase-10 (MMP-10) during skeletal muscle repair after ischemia using a model of femoral artery excision in wild-type (WT) and MMP-10 deficient (Mmp10(-/-)) mice. Functional changes were analyzed by small animal positron emission tomography and tissue morphology by immunohistochemistry. Gene expression and protein analysis were used to study the molecular mechanisms governed by MMP-10 in hypoxia. Early after ischemia, MMP-10 deficiency resulted in delayed tissue reperfusion (10%, P < 0.01) and in increased necrosis (2-fold, P < 0.01), neutrophil (4-fold, P < 0.01), and macrophage (1.5-fold, P < 0.01) infiltration. These differences at early time points resulted in delayed myotube regeneration in Mmp10(-/-) soleus at later stages (regenerating myofibers: 30 ± 9% WT vs. 68 ± 10% Mmp10(-/-), P < 0.01). The injection of MMP-10 into Mmp10(-/-) mice rescued the observed phenotype. A molecular analysis revealed higher levels of Cxcl1 mRNA (10-fold, P < 0.05) and protein (30%) in the ischemic Mmp10(-/-) muscle resulting from a lack of transcriptional inhibition by MMP-10. This was further confirmed using siRNA against MMP-10 in vivo. Our results demonstrate an important role of MMP-10 for proper muscle repair after ischemia, and suggest that chemokine regulation such as Cxcl1 by MMP-10 is involved in muscle regeneration. © FASEB.

  16. Wound dressings based on silver sulfadiazine solid lipid nanoparticles for tissue repairing.

    PubMed

    Sandri, Giuseppina; Bonferoni, Maria Cristina; D'Autilia, Francesca; Rossi, Silvia; Ferrari, Franca; Grisoli, Pietro; Sorrenti, Milena; Catenacci, Laura; Del Fante, Claudia; Perotti, Cesare; Caramella, Carla

    2013-05-01

    The management of difficult to heal wounds can considerably reduce the time required for tissue repairing and promote the healing process, minimizing the risk of infection. Silver compounds, especially silver sulfadiazine (AgSD), are often used to prevent or to treat wound colonization, also in presence of antibiotic-resistant bacteria. However, AgSD has been shown to be cytotoxic in vitro toward fibroblasts and keratinocytes and consequently to retard wound healing in vivo. Recently, platelet lysate (PL) has been proposed in clinical practice for the healing of persistent lesions. The aim of the present work was the development of wound dressings based on AgSD loaded in solid lipid nanoparticles (SLNs), to be used in association with PL for the treatment for skin lesions. SLN were based on chondroitin sulfate and sodium hyaluronate, bioactive polymers characterized by well-known tissue repairing properties. The encapsulation of AgSD in SLN aimed at preventing the cytotoxic effect of the drug on normal human dermal fibroblasts (NHDFs) and at enabling the association of the drug with PL. SLN were loaded in wound dressings based on hydroxypropylmethyl cellulose (HPMC) or chitosan glutamate (CS glu). These polymers were chosen to obtain a sponge matrix with suitable elasticity and softness and, moreover, with good bioadhesive behavior on skin lesions. Dressings based on chitosan glutamate showed antimicrobial activity with and without PL. Even though further in vivo evaluation could be envisaged, chitosan based dressings demonstrated to be a suitable prototype for the treatment for skin lesions.

  17. Role of the immune system in cardiac tissue damage and repair following myocardial infarction.

    PubMed

    Saparov, Arman; Ogay, Vyacheslav; Nurgozhin, Talgat; Chen, William C W; Mansurov, Nurlan; Issabekova, Assel; Zhakupova, Jamilya

    2017-09-01

    The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

  18. Hiatal Hernia Repair with Gore Bio-A Tissue Reinforcement: Our Experience

    PubMed Central

    Antonino, Agrusa; Giorgio, Romano; Giuseppe, Frazzetta; Giovanni, De Vita; Silvia, Di Giovanni; Daniela, Chianetta; Giuseppe, Di Buono; Vincenzo, Sorce; Gaspare, Gulotta

    2014-01-01

    Type I hiatal hernia is associated with gastroesophageal reflux disease (GERD) in 50–90% of cases. Several trials strongly support surgery as an effective alternative to medical therapy. Today, laparoscopic fundoplication is considered as the procedure of choice. However, primary laparoscopic hiatal hernia repair is associated with upto 42% recurrence rate. Mesh reinforcement of the crural closure decreases the recurrence but can lead to complications, above all nonabsorbable ones. We experiment a new totally absorbable mesh by Gore. Case. We present a case of a 65-year-old female patient with a 6-year classic history of GERD. Endoscopy revealed a large hiatal hernia and esophagitis. pH study was positive for acid reflux; esophageal manometry revealed LES intrathoracic dislocation. With laparoscopic approach, the hiatal hernia defect was identified and primarily repaired, by crural closure. Gore Bio-A Tissue Reinforcement was trimmed to fit the defect accommodating the esophagus. Nissen fundoplication was performed. Result. Bio-A mesh was easily placed laparoscopically. It has good handling and could be cut and tailored intraoperatively for optimal adaptation. There were no short-term complications. Conclusion. Crural closure reinforcement can be done readily with this new totally absorbable mesh replaced by soft tissue over six months. However, further data and studies are needed to evaluate long-term outcomes. PMID:24864221

  19. Mesenchymal stromal cells; role in tissue repair, drug discovery and immune modulation.

    PubMed

    English, Karen; Mahon, Bernard P; Wood, Kathryn J

    2014-01-01

    Mesenchymal stromal cells (MSCs) participate in repair of damaged tissues, possess the potential to serve as a useful tool in the drug discovery field and exert immunosuppressive effects as demonstrated by their ability to modulate the immune response. Herein, the roles played by MSC differentiation and/or production of trophic factors involved in tissue repair are discussed. MSCs offer the opportunity to probe targets that conventional or differentiated cell lines do not express; thus providing a more refined system that allows identification of novel therapeutics. However, there are difficulties associated with drug discovery assays to which MSCs are not exempt. The immunosuppressive potential of MSCs has already been utilised in clinical trials where MSCs have been used to treat patients with graft- versus- host disease (GvHD) and autoimmune diseases. Another possible therapeutic application of MSCs lies in the field of transplantation tolerance. Although the capacity of MSCs to modulate immune responses has received much attention, the role of MSCs in transplantation tolerance is as yet unclear. In this review, we discuss the evidence for MSC induction of a state of tolerance in the transplantation setting.

  20. Tissue adaptations to gravitational stress - Newborn versus adult giraffes

    NASA Technical Reports Server (NTRS)

    Hargens, Alan R; Gershuni, David H.; Danzig, Larry A.; Millard, Ronald W.; Pettersson, Knut

    1988-01-01

    Preliminary results on developmental alterations in load-bearing tissues of newborn and adult giraffes are presented. Attention is focused on vascular wall thickness in relation to local blood pressure, and on meniscal adaptations to increased load bearing in the developing giraffe. It is believed that the developing giraffe provides an excellent model for investigations of adaptive mechanisms of increased weight bearing.

  1. Adult neurogenesis and its role in neuropsychiatric disease, brain repair and normal brain function.

    PubMed

    Braun, S M G; Jessberger, S

    2014-02-01

    Neural stem/progenitor cells (NSPCs) in the mammalian brain retain the ability to generate new neurones throughout life in discrete brain regions, through a process called adult neurogenesis. Adult neurogenesis, a dramatic form of adult brain circuitry plasticity, has been implicated in physiological brain function and appears to be of pivotal importance for certain forms of learning and memory. In addition, failing or altered neurogenesis has been associated with a variety of brain diseases such as major depression, epilepsy and age-related cognitive decline. Here we review recent advances in our understanding of the basic biology underlying the neurogenic process in the adult brain, focusing on mechanisms that regulate quiescence, proliferation and differentiation of NSPCs. In addition, we discuss how neurogenesis influences normal brain function, and in particular its role in memory formation, as well as its contribution to neuropsychiatric diseases. Finally, we evaluate the potential of targeting endogenous NSPCs for brain repair.

  2. Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications.

    PubMed

    Mouthuy, Pierre-Alexis; Somogyi Škoc, Maja; Čipak Gašparović, Ana; Milković, Lidija; Carr, Andrew J; Žarković, Neven

    2017-01-01

    Electrospun filaments represent a new generation of medical textiles with promising applications in soft tissue repair. A potential strategy to improve their design is to combine them with bioactive molecules. Curcumin, a natural compound found in turmeric, is particularly attractive for its antioxidant, anti-inflammatory, and antimicrobial properties. However, investigating the range of relevant doses of curcumin in materials designed for tissue regeneration has remained limited. In this paper, a wide range of curcumin concentrations was explored and the potential of the resulting materials for soft tissue repair applications was assessed. Polydioxanone (PDO) filaments were prepared with various amounts of curcumin: 0%, 0.001%, 0.01%, 0.1%, 1%, and 10% (weight to weight ratio). The results from the present study showed that, at low doses (≤0.1%), the addition of curcumin has no influence on the spinning process or on the physicochemical properties of the filaments, whereas higher doses lead to smaller fiber diameters and improved mechanical properties. Moreover, filaments with 0.001% and 0.01% curcumin stimulate the metabolic activity and proliferation of normal human dermal fibroblasts (NHDFs) compared with the no-filament control. However, this stimulation is not significant when compared to the control filaments (0%). Highly dosed filaments induce either the inhibition of proliferation (with 1%) or cell apoptosis (with 10%) as a result of the concentrations of curcumin found in the medium (9 and 32 μM, respectively), which are near or above the known toxicity threshold of curcumin (~10 μM). Moreover, filaments with 10% curcumin increase the catalase activity and glutathione content in NHDFs, indicating an increased production of reactive oxygen species resulting from the large concentration of curcumin. Overall, this study suggested that PDO electrospun filaments loaded with low amounts of curcumin are more promising compared with higher concentrations for

  3. Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications

    PubMed Central

    Mouthuy, Pierre-Alexis; Somogyi Škoc, Maja; Čipak Gašparović, Ana; Milković, Lidija; Carr, Andrew J; Žarković, Neven

    2017-01-01

    Electrospun filaments represent a new generation of medical textiles with promising applications in soft tissue repair. A potential strategy to improve their design is to combine them with bioactive molecules. Curcumin, a natural compound found in turmeric, is particularly attractive for its antioxidant, anti-inflammatory, and antimicrobial properties. However, investigating the range of relevant doses of curcumin in materials designed for tissue regeneration has remained limited. In this paper, a wide range of curcumin concentrations was explored and the potential of the resulting materials for soft tissue repair applications was assessed. Polydioxanone (PDO) filaments were prepared with various amounts of curcumin: 0%, 0.001%, 0.01%, 0.1%, 1%, and 10% (weight to weight ratio). The results from the present study showed that, at low doses (≤0.1%), the addition of curcumin has no influence on the spinning process or on the physicochemical properties of the filaments, whereas higher doses lead to smaller fiber diameters and improved mechanical properties. Moreover, filaments with 0.001% and 0.01% curcumin stimulate the metabolic activity and proliferation of normal human dermal fibroblasts (NHDFs) compared with the no-filament control. However, this stimulation is not significant when compared to the control filaments (0%). Highly dosed filaments induce either the inhibition of proliferation (with 1%) or cell apoptosis (with 10%) as a result of the concentrations of curcumin found in the medium (9 and 32 μM, respectively), which are near or above the known toxicity threshold of curcumin (~10 μM). Moreover, filaments with 10% curcumin increase the catalase activity and glutathione content in NHDFs, indicating an increased production of reactive oxygen species resulting from the large concentration of curcumin. Overall, this study suggested that PDO electrospun filaments loaded with low amounts of curcumin are more promising compared with higher concentrations for

  4. Exercise Performance in Children and Young Adults After Complete and Incomplete Repair of Congenital Heart Disease.

    PubMed

    Rosenblum, Omer; Katz, Uriel; Reuveny, Ronen; Williams, Craig A; Dubnov-Raz, Gal

    2015-12-01

    Few previous studies have addressed exercise capacity in patients with corrected congenital heart disease (CHD) and significant anatomical residua. The aim of this study was to determine the aerobic fitness and peak cardiac function of patients with corrected CHD with complete or incomplete repairs, as determined by resting echocardiography. Children, adolescents and young adults (<40 years) with CHD from both sexes, who had previously undergone biventricular corrective therapeutic interventions (n = 73), and non-CHD control participants (n = 76) underwent cardiopulmonary exercise testing. The CHD group was further divided according to the absence/presence of significant anatomical residua on a resting echocardiogram ("complete"/"incomplete" repair groups). Aerobic fitness and cardiac function were compared between groups using linear regression and analysis of covariance. Peak oxygen consumption, O2 pulse and ventilatory threshold were significantly lower in CHD patients compared with controls (all p < 0.01). Compared with the complete repair group, the incomplete repair group had a significantly lower mean peak work rate, age-adjusted O2 pulse (expressed as % predicted) and a higher VE/VCO2 ratio (all p ≤ 0.05). Peak oxygen consumption was comparable between the subgroups. Patients after corrected CHD have lower peak and submaximal exercise parameters. Patients with incomplete repair of their heart defect had decreased aerobic fitness, with evidence of impaired peak cardiac function and lower pulmonary perfusion. Patients that had undergone a complete repair had decreased aerobic fitness attributed only to deconditioning. These newly identified differences explain why in previous studies, the lowest fitness was seen in patients with the most hemodynamically significant heart malformations.

  5. Clinical application of adult olfactory bulb ensheathing glia for nervous system repair.

    PubMed

    Ramón-Cueto, Almudena; Muñoz-Quiles, Cintia

    2011-05-01

    The ability of adult olfactory bulb ensheathing glia (OB-OEG) to promote histological and functional neural repair has been broadly documented. Pre-clinical studies show that beneficial effects of adult OB-OEG are repeatable in the same type of spinal cord injury initially tested, in other spinal cord and CNS injury models, in different species and after the administration of these cells in different forms (either alone or in combination with other cells, drugs, products or devices). These studies demonstrate the reproducibility, robustness, fundamental nature and relevance of the findings. Therefore, the use of adult OB-OEG for spinal cord injury repair meets the scientific criteria established by the International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) for the translation to human application. Because there is so much heterogeneity in the way adult OEG is administered, each of these different OEG-based therapies must be individually categorized to determine whether they fulfill the requisites dictated by the consolidated regulatory body to be considered or not as a medicine. In the case they do, in Europe, they shall be subjected to the Regulatory European Framework for Advanced Therapy Medicinal Products and the European Clinical Trials Directive (Directives 2001/20/EC and 2009/120/EC). After a deep analysis of the European Regulation we have concluded that grafts consisting of suspensions of purified adult OEG, to be used for the promotion of axonal regeneration in the CNS, do not comply with the definition of Medicinal Product provided by the European Medicines Agency. In contrast, experimental therapies using OEG in combination with other cell types, drugs, products or devices, or genetically-modified OEG fall under the definitions of Medicinal Product. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Soft tissue sarcomas in adolescents and young adults: a comparison with their paediatric and adult counterparts.

    PubMed

    van der Graaf, Winette T A; Orbach, Daniel; Judson, Ian R; Ferrari, Andrea

    2017-03-01

    Survival outcomes for adolescent and young adult patients with soft tissue sarcomas lag behind those of children diagnosed with histologically similar tumours. To help understand these differences in outcomes, we discuss the following issues with regard to the management of these patients with soft tissue sarcomas: delays in diagnosis, trial availability and participation, aspects of the organisation of care (with an emphasis on age-specific needs), national centralisation of sarcoma care, international consortia, and factors related to tumour biology. Improved understanding of the causes of the survival gap between adolescents and young adults with sarcomas will help drive new initiatives to improve final health outcomes in these populations. In this Review, we specifically focus on embryonal and alveolar rhabdomyosarcoma, synovial sarcoma, and adult soft tissue sarcomas diagnosed in adolescents and young adults, and discuss the age-specific needs of these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Periorbital Soft Tissue Anthropometric Analysis of Young Adults.

    PubMed

    Ozdemir, Turan; Can, Fatma Ezgi; Isiklar, Sefa; Ercan, Ilker; Cankur, Nedim Simsek

    2017-06-01

    The authors aim to determine the periorbital soft tissue anthropometric norms for Turkish young adults for right and left eyes using a noninvasive two-dimensional photogrammetric analysis. Anthropometric measurements of the periorbital soft tissue were taken from 172 female and 56 male Turkish adults aged between 18 and 24 years. The periorbital soft tissue profiles (ocular and palpebral) for males and females were digitally analyzed using linear measurements made with standardized photographic records, taken in a natural head position. Statistically significant differences were found for ocular soft tissue measurements according to gender except inner intercanthal distance (P = 0.125) and right horizontal palpebral aperture (P = 0.240). Statistically significant differences were found for palpebral soft tissue measurements according to gender except right pretarsal skin height (P = 0.112) and left pretarsal skin height (P = 0.056). Results were compared with other ethnic groups. Normal periorbital soft tissue measurements are fundamental anatomical parameters utilized in ophthalmology, optometry, ophthalmic industry, oculoplastic surgery, clinical genetics, dermatocosmetology. Further, normal anthropometric measurements generate reference data for studies in craniofacial dysmorphology, oculoplastic surgery, dermatocosmetology, and comparative physical anthropology.

  8. Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: Implications for cartilage tissue repair

    NASA Astrophysics Data System (ADS)

    Kisiday, J.; Jin, M.; Kurz, B.; Hung, H.; Semino, C.; Zhang, S.; Grodzinsky, A. J.

    2002-07-01

    Emerging medical technologies for effective and lasting repair of articular cartilage include delivery of cells or cell-seeded scaffolds to a defect site to initiate de novo tissue regeneration. Biocompatible scaffolds assist in providing a template for cell distribution and extracellular matrix (ECM) accumulation in a three-dimensional geometry. A major challenge in choosing an appropriate scaffold for cartilage repair is the identification of a material that can simultaneously stimulate high rates of cell division and high rates of cell synthesis of phenotypically specific ECM macromolecules until repair evolves into steady-state tissue maintenance. We have devised a self-assembling peptide hydrogel scaffold for cartilage repair and developed a method to encapsulate chondrocytes within the peptide hydrogel. During 4 weeks of culture in vitro, chondrocytes seeded within the peptide hydrogel retained their morphology and developed a cartilage-like ECM rich in proteoglycans and type II collagen, indicative of a stable chondrocyte phenotype. Time-dependent accumulation of this ECM was paralleled by increases in material stiffness, indicative of deposition of mechanically functional neo-tissue. Taken together, these results demonstrate the potential of a self-assembling peptide hydrogel as a scaffold for the synthesis and accumulation of a true cartilage-like ECM within a three-dimensional cell culture for cartilage tissue repair.

  9. Concise review: The plasticity of stem cell niches: a general property behind tissue homeostasis and repair.

    PubMed

    Rojas-Ríos, Patricia; González-Reyes, Acaimo

    2014-04-01

    Stem cell activity is tightly regulated during development and in adult tissues through the combined action of local and systemic effectors. While stem cells and their microenvironments are capable of sustaining homeostasis in normal physiological circumstances, they also provide host tissues with a remarkable plasticity to respond to perturbations. Here, we review recent discoveries that shed light on the adaptive response of niches to systemic signals and aging, and on the ability of niches to modulate signaling upon local perturbations. These characteristics of stem cells and their niches give organs an essential advantage to deal with aging, injury or pathological conditions.

  10. Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells.

    PubMed

    Sohur, U Shivraj; Emsley, Jason G; Mitchell, Bartley D; Macklis, Jeffrey D

    2006-09-29

    Recent work in neuroscience has shown that the adult central nervous system (CNS) contains neural progenitors, precursors and stem cells that are capable of generating new neurons, astrocytes and oligodendrocytes. While challenging the previous dogma that no new neurons are born in the adult mammalian CNS, these findings bring with them the future possibilities for development of novel neural repair strategies. The purpose of this review is to present the current knowledge about constitutively occurring adult mammalian neurogenesis, highlight the critical differences between 'neurogenic' and 'non-neurogenic' regions in the adult brain, and describe the cardinal features of two well-described neurogenic regions-the subventricular zone/olfactory bulb system and the dentate gyrus of the hippocampus. We also provide an overview of presently used models for studying neural precursors in vitro, mention some precursor transplantation models and emphasize that, in this rapidly growing field of neuroscience, one must be cautious with respect to a variety of methodological considerations for studying neural precursor cells both in vitro and in vivo. The possibility of repairing neural circuitry by manipulating neurogenesis is an intriguing one, and, therefore, we also review recent efforts to understand the conditions under which neurogenesis can be induced in non-neurogenic regions of the adult CNS. This work aims towards molecular and cellular manipulation of endogenous neural precursors in situ, without transplantation. We conclude this review with a discussion of what might be the function of newly generated neurons in the adult brain, and provide a summary of present thinking about the consequences of disturbed adult neurogenesis and the reaction of neurogenic regions to disease.

  11. Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells

    PubMed Central

    Shivraj Sohur, U; Emsley, Jason G; Mitchell, Bartley D; Macklis, Jeffrey D

    2006-01-01

    Recent work in neuroscience has shown that the adult central nervous system (CNS) contains neural progenitors, precursors and stem cells that are capable of generating new neurons, astrocytes and oligodendrocytes. While challenging the previous dogma that no new neurons are born in the adult mammalian CNS, these findings bring with them the future possibilities for development of novel neural repair strategies. The purpose of this review is to present the current knowledge about constitutively occurring adult mammalian neurogenesis, highlight the critical differences between ‘neurogenic’ and ‘non-neurogenic’ regions in the adult brain, and describe the cardinal features of two well-described neurogenic regions—the subventricular zone/olfactory bulb system and the dentate gyrus of the hippocampus. We also provide an overview of presently used models for studying neural precursors in vitro, mention some precursor transplantation models and emphasize that, in this rapidly growing field of neuroscience, one must be cautious with respect to a variety of methodological considerations for studying neural precursor cells both in vitro and in vivo. The possibility of repairing neural circuitry by manipulating neurogenesis is an intriguing one, and, therefore, we also review recent efforts to understand the conditions under which neurogenesis can be induced in non-neurogenic regions of the adult CNS. This work aims towards molecular and cellular manipulation of endogenous neural precursors in situ, without transplantation. We conclude this review with a discussion of what might be the function of newly generated neurons in the adult brain, and provide a summary of present thinking about the consequences of disturbed adult neurogenesis and the reaction of neurogenic regions to disease. PMID:16939970

  12. Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair

    PubMed Central

    Xin, Mei; Olson, Eric N.; Bassel-Duby, Rhonda

    2013-01-01

    As the adult mammalian heart has limited potential for regeneration and repair, the loss of cardiomyocytes during injury and disease can result in heart failure and death. The cellular processes and regulatory mechanisms involved in heart growth and development can be exploited to repair the injured adult heart through ‘reawakening’ pathways that are active during embryogenesis. Heart function has been restored in rodents by reprogramming non-myocytes into cardiomyocytes, by expressing transcription factors (GATA4, HAND2, myocyte-specific enhancer factor 2C (MEF2C) and T-box 5 (TBX5)) and microRNAs (miR-1, miR-133, miR-208 and miR-499) that control cardiomyocyte identity. Stimulating cardiomyocyte dedifferentiation and proliferation by activating mitotic signalling pathways involved in embryonic heart growth represents a complementary approach for heart regeneration and repair. Recent advances in understanding the mechanistic basis of heart development offer exciting opportunities for effective therapies for heart failure. PMID:23839576

  13. Comparative long-term results of mitral valve repair in adults with chronic rheumatic disease and degenerative disease: is repair for "burnt-out" rheumatic disease still inferior to repair for degenerative disease in the current era?

    PubMed

    Dillon, Jeswant; Yakub, Mohd Azhari; Kong, Pau Kiew; Ramli, Mohd Faizal; Jaffar, Norfazlina; Gaffar, Intan Fariza

    2015-03-01

    Mitral valve repair is perceived to be of limited durability for advanced rheumatic disease in adults. We aim to examine the long-term outcomes of repair for rheumatic disease, identify predictors of durability, and compare with repair for degenerative disease. Rheumatic and degenerative mitral valve repairs in patients aged 40 years or more were prospectively analyzed. The primary outcomes investigated were mortality, freedom from reoperation, and valve failure. Logistic regression analysis was performed to define predictors of poor outcome. Between 1997 and 2011, 253 rheumatic and 148 degenerative mitral valves were repaired. The age of patients in both groups was similar, with a mean of 54.1 ± 8.4 years versus 55.6 ± 7.3 years (P = .49). Freedom from reoperation for rheumatic valves at 5 and 10 years was 98.4%, comparable to 95.3% (P = .12) for degenerative valves. Freedom from valve failure at 5 and 10 years was 91.4% and 81.5% for rheumatic repairs and 82.5% and 75.4% for degenerative repairs, respectively (P = .15). The presence of residual mitral regurgitation greater than 2+ before discharge was the only significant independent predictor of reoperation, whereas residual mitral regurgitation greater than 2+ and leaflet procedures were significant risk factors for valve failure. The durability of rheumatic mitral valve repair in the current era has improved and is comparable to the outstanding durability of repairs for degenerative disease, even in the adult rheumatic population. Modifications of standard repair techniques, adherence to the importance of good leaflet coaptation, and strict quality control with stringent use of intraoperative transesophageal echocardiography have all contributed to the improved long-term results. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  14. How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

    PubMed Central

    Perán, Macarena; García, María Angel; Lopez-Ruiz, Elena; Jiménez, Gema; Marchal, Juan Antonio

    2013-01-01

    Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i) skin; (ii) cartilage; (iii) bone; (iv) nerve; and (v) cardiac. PMID:28809213

  15. Bone marrow-derived cells homing for self-repair of periodontal tissues: a histological characterization and expression analysis.

    PubMed

    Wang, Yan; Zhou, Lili; Li, Chen; Xie, Han; Lu, Yuwang; Wu, Ying; Liu, Hongwei

    2015-01-01

    Periodontitis, a disease leads to the formation of periodontal defect, can result in tooth loss if left untreated. The therapies to repair/regenerate periodontal tissues have attracted lots of attention these years. Bone marrow-derived cells (BMDCs), a group of cells containing heterogeneous stem/progenitor cells, are capable of homing to injured tissues and participating in tissue repair/regeneration. The amplification of autologous BMDCs' potential in homing for self-repair/regeneration, therefore, might be considered as an alternative therapy except for traditional cell transplantation. However, the knowledge of the BMDCs' homing and participation in periodontal repair/regeneration is still known little. For the purpose of directly observing BMDCs' involvement in periodontal repair, chimeric mouse models were established to make their bone marrow cells reconstituted with cells expressing green enhanced fluorescence protein (EGFP) in this study. One month after bone marrow transplantation, periodontal defects were made on the mesial side of bilateral maxillary first molars in chimeric mice. The green fluorescence protein-positive (GFP+) BMDCS in periodontal defect regions were examined by bioluminescent imaging and immunofluorescence staining. GFP+ BMDCs were found to aggregate in the periodontal defect regions and emerge in newly-formed bones or fibers. Some of them also co-expressed markers of fibroblasts, osteoblasts or vascular endothelial cells. These results indicated that BMDCs might contribute to the formation of new fibers, bones and blood vessels during periodontal repair. In conclusion, we speculated that autologous BMDCs were capable of negotiating into the surgical sites created by periodontal operation and participating in tissue repair.

  16. Bone marrow-derived cells homing for self-repair of periodontal tissues: a histological characterization and expression analysis

    PubMed Central

    Wang, Yan; Zhou, Lili; Li, Chen; Xie, Han; Lu, Yuwang; Wu, Ying; Liu, Hongwei

    2015-01-01

    Periodontitis, a disease leads to the formation of periodontal defect, can result in tooth loss if left untreated. The therapies to repair/regenerate periodontal tissues have attracted lots of attention these years. Bone marrow-derived cells (BMDCs), a group of cells containing heterogeneous stem/progenitor cells, are capable of homing to injured tissues and participating in tissue repair/regeneration. The amplification of autologous BMDCs’ potential in homing for self-repair/regeneration, therefore, might be considered as an alternative therapy except for traditional cell transplantation. However, the knowledge of the BMDCs’ homing and participation in periodontal repair/regeneration is still known little. For the purpose of directly observing BMDCs’ involvement in periodontal repair, chimeric mouse models were established to make their bone marrow cells reconstituted with cells expressing green enhanced fluorescence protein (EGFP) in this study. One month after bone marrow transplantation, periodontal defects were made on the mesial side of bilateral maxillary first molars in chimeric mice. The green fluorescence protein-positive (GFP+) BMDCS in periodontal defect regions were examined by bioluminescent imaging and immunofluorescence staining. GFP+ BMDCs were found to aggregate in the periodontal defect regions and emerge in newly-formed bones or fibers. Some of them also co-expressed markers of fibroblasts, osteoblasts or vascular endothelial cells. These results indicated that BMDCs might contribute to the formation of new fibers, bones and blood vessels during periodontal repair. In conclusion, we speculated that autologous BMDCs were capable of negotiating into the surgical sites created by periodontal operation and participating in tissue repair. PMID:26722424

  17. In Vitro Spermatogenesis in Explanted Adult Mouse Testis Tissues.

    PubMed

    Sato, Takuya; Katagiri, Kumiko; Kojima, Kazuaki; Komeya, Mitsuru; Yao, Masahiro; Ogawa, Takehiko

    2015-01-01

    Research on in vitro spermatogenesis is important for elucidating the spermatogenic mechanism. We previously developed an organ culture method which can support spermatogenesis from spermatogonial stem cells up to sperm formation using immature mouse testis tissues. In this study, we examined whether it is also applicable to mature testis tissues of adult mice. We used two lines of transgenic mice, Acrosin-GFP and Gsg2-GFP, which carry the marker GFP gene specific for meiotic and haploid cells, respectively. Testis tissue fragments of adult GFP mice, aged from 4 to 29 weeks old, which express GFP at full extension, were cultured in medium supplemented with 10% KSR or AlbuMAX. GFP expression decreased rapidly and became the lowest at 7 to 14 days of culture, but then slightly increased during the following culture period. This increase reflected de novo spermatogenesis, confirmed by BrdU labeling in spermatocytes and spermatids. We also used vitamin A-deficient mice, whose testes contain only spermatogonia. The testes of those mice at 13-21 weeks old, showing no GFP expression at explantation, gained GFP expression during culturing, and spermatogenesis was confirmed histologically. In addition, the adult testis tissues of Sl/Sld mutant mice, which lack spermatogenesis due to Kit ligand mutation, were cultured with recombinant Kit ligand to induce spermatogenesis up to haploid formation. Although the efficiency of spermatogenesis was lower than that of pup, present results showed that the organ culture method is effective for the culturing of mature adult mouse testis tissue, demonstrated by the induction of spermatogenesis from spermatogonia to haploid cells.

  18. Asymptomatic and isolated accessory mitral valve tissue in an adult.

    PubMed

    Hisatomi, Kazuki; Hashizume, Koji; Tanigawa, Kazuyoshi; Miura, Takashi; Matsukuma, Seiji; Yokose, Shogo; Sumi, Mizuki; Eishi, Kiyoyuki

    2016-02-01

    Accessory mitral valve (AMV) tissue is a congenital anomaly that occurs in association with other congenital anomalies, and is an uncommon cause of left ventricular outflow tract obstruction. It is usually detected in early childhood when accompanied by symptoms of obstruction of the left ventricular outflow tract, and is rarely diagnosed in adults. We present a case of a 53-year-old man who was referred to our institution for evaluation of a systolic heart murmur. Echocardiography disclosed a diagnosis of AMV tissue. This case was uncommon because of the lack of severe obstruction of left ventricular outflow, cardiac symptoms, or other cardiac anomalies. We were able to carry out surgical resection of AMV tissue to avert possible progression of aortic insufficiency and the risk of a cerebrovascular embolization. The patient's postoperative course was uneventful, and postoperative echocardiography showed no residual accessory mitral tissue.

  19. Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration

    PubMed Central

    Mardones, Rodrigo; Jofré, Claudio M.; Minguell, José J.

    2015-01-01

    Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes. Latterly, an improved alternative for the above reparative strategy involved the infusion of mesenchymal stem cells (MSC), which in addition to a self-renewal capacity exhibit a differentiation potential to chondrocytes, as well as a capability to produce a vast array of growth factors, cytokines and extracellular matrix compounds involved in cartilage development. In addition to the above and foremost reparative options up till now in use, other therapeutic options have been developed, comprising the design of biomaterial substrates (scaffolds) capable of sustaining MSC attachment, proliferation and differentiation. The implantation of these engineered platforms, closely to the site of cartilage damage, may well facilitate the initiation of an ‘in situ’ cartilage reparation process. In this mini-review, we examined the timely and conceptual development of several cell-based methods, designed to repair/regenerate a damaged cartilage. In addition to the above described cartilage reparative options, other therapeutic alternatives still in progress are portrayed. PMID:26019754

  20. A Combination Tissue Engineering Strategy for Schwann Cell-Induced Spinal Cord Repair

    DTIC Science & Technology

    2016-10-01

    Cytocompatibility studies of the piezoelectric scaffold formulation for controlled release. Rat SCs, isolated from adult sciatic nerve and transfected...using purified DRG explants. Lumbar DRG explants isolated from E17 rat embryos were seeded on collagen coated petri dishes in purification media for...with neural tissues in the central nerve system when used at the concentration of 15%-20% (w/w) and prolonged drug release has been achieved with

  1. Detection of abnormalities in the superficial zone of cartilage repaired using a tissue engineered construct derived from synovial stem cells.

    PubMed

    Ando, Wataru; Fujie, Hiromichi; Moriguchi, Yu; Nansai, Ryosuke; Shimomura, Kazunori; Hart, David A; Yoshikawa, Hideki; Nakamura, Norimasa

    2012-09-28

    The present study investigated the surface structure and mechanical properties of repair cartilage generated from a tissue engineered construct (TEC) derived from synovial mesenchymal stem cells at six months post-implantation compared to those of uninjured cartilage. TEC-mediated repair tissue was cartilaginous with Safranin O staining, and had comparable macro-scale compressive properties with uninjured cartilage. However, morphological assessments revealed that the superficial zone of TEC-mediated tissue was more fibrocartilage-like, in contrast to the middle or deep zones that were more hyaline cartilage-like with Safranin O staining. Histological scoring of the TEC-mediated tissue was significantly lower in the superficial zone than in the middle and deep zones. Scanning electron microscopy showed a thick tangential bundle of collagen fibres at the most superficial layer of uninjured cartilage, while no corresponding structure was detected at the surface of TEC-mediated tissue. Immunohistochemical analysis revealed that PRG4 was localised in the superficial area of uninjured cartilage, as well as the TEC-mediated tissue. Friction testing showed that the lubrication properties of the two tissues was similar, however, micro-indentation analysis revealed that the surface stiffness of the TEC-repair tissue was significantly lower than that of uninjured cartilage. Permeability testing indicated that the TEC-mediated tissue exhibited lower water retaining capacity than did uninjured cartilage, specifically at the superficial zone. Thus, TEC-mediated tissue exhibited compromised mechanical properties at the superficial zone, properties which need improvement in the future for maintenance of long term repair cartilage integrity.

  2. [Repair of soft tissue defect in hand or foot with lobulated medial sural artery perforator flap].

    PubMed

    Fengjing, Zhao; Jianmin, Yao; Xingqun, Zhang; Liang, Ma; Longchun, Zhang; Yibo, Xu; Peng, Wang; Zhen, Zhu

    2015-11-01

    To explore the clinical effect of the lobulated medial sural artery perforator flap in repairing soft tissue defect in hand or foot. Since March 2012 to September 2014, 6 cases with soft tissue defects in hands or feet were treated by lobulated medial sural artery flaps pedicled with 1st musculo-cutaneous perforator and 2st musculo-cutaneous perforator of the medial sural artery. The size of the flaps ranged from 4.5 cm x 10.0 cm to 6.0 cm x 17.0 cm. 5 cases of lobulated flap survived smoothly, only 1 lobulated flap had venous articulo, but this flap also survived after the articulo was removed by vascular exploration. All flaps had desirable appearance and sensation and the two-point discrimination was 6 mm in mean with 4 to 12 months follow-up (average, 7 months). Linear scar was left in donor sites in 3 cases and skin scar in 3 cases. There was no malfunction in donor sites. Lobulated medial sural artery perforator flap is feasible and ideal method for the treatment of soft tissue defect in hand or foot with satisfactory effect.

  3. Functional tissue engineering in articular cartilage repair: is there a role for electromagnetic biophysical stimulation?

    PubMed

    Fini, Milena; Pagani, Stefania; Giavaresi, Gianluca; De Mattei, Monica; Ongaro, Alessia; Varani, Katia; Vincenzi, Fabrizio; Massari, Leo; Cadossi, Matteo

    2013-08-01

    Hyaline cartilage lesions represent an important global health problem. Several approaches have been developed in the last decades to resolve this disability cause, including tissue engineering, but to date, there is not a definitive procedure that is able to promote a repair tissue with the same mechanical and functional characteristics of native cartilage, and to obtain its integration in the subchondral bone. The need of resolutive technologies to obtain a "more effective" tissue substitutes has led Butler to propose the "Functional Tissue Engineering" (FTE) paradigm, whose principles are outlined in a so-called FTE road map. It consists of a two-phase strategy: in vitro tissue engineering and clinically surgery evaluation. The first phase, based on construct development, should take into account not only the chondrocyte biology, as their sensitivity to biochemical and physical stimuli, the risk of dedifferentiation in culture, and the ability to produce extracellular matrix, but also the features of suitable scaffolds. The in vivo phase analyzes the inflammatory microenvironment where the construct will be placed, because the cytokines released by synoviocytes and chondrocytes could affect the construct integrity, and, in particular, cause matrix degradation. The use of pulsed electromagnetic fields (PEMFs) represents an innovative therapeutic approach, because it is demonstrated that this physical stimulus increases the anabolic activity of chondrocytes and cartilage explants with consequent increase of matrix synthesis, but, at the same time, PEMFs limit the catabolic effects of inflammatory cytokines, reducing the construct degradation inside the surgical microenvironment. PEMFs mediate an up-regulation of A2A adenosine receptors and a potentiation of their anti-inflammatory effects.

  4. Topical retinoic acid enhances the repair of ultraviolet damaged dermal connective tissue.

    PubMed

    Kligman, L H; Duo, C H; Kligman, A M

    1984-01-01

    Ultraviolet (UV) irradiation induces excessive accumulations of elastic fibers in animal and human skin. Collagen is damaged and glycosaminoglycans are vastly increased. Formerly considered an irreversible change, we recently showed, post-irradiation, that a band of normal connective tissue was laid down subepidermally . Because of its ability to stimulate fibroblasts and enhance healing of wounds, we thought it likely that retinoic acid (RA) would promote the formation of this subepidermal zone of reconstruction. Hairless mice were irradiated for 10 weeks with Westinghouse FS20 sunlamps for a total UV dose of 7 J/cm2. Then, 0.05% RA was applied for 5 and 10 weeks. Observations were made by light and electron microscopy. In contrast to controls treated with vehicle, the reconstruction zone was significantly wider in RA-treated mice. The enhanced repair was dose related. Histochemically and ultrastructurally, collagen was normal, fibroblasts were numerous and in a configuration of high metabolic activity.

  5. Femoral fracture repair using a locking plate technique in an adult captive polar bear (Ursus maritimus).

    PubMed

    Zimmerman, Dawn M; Dew, Terry; Douglass, Michael; Perez, Edward

    2010-02-01

    To report successful femoral fracture repair in a polar bear. Case report. Female polar bear (Ursus maritimus) 5 years and approximately 250 kg. A closed, complete, comminuted fracture of the distal midshaft femur was successfully reduced and stabilized using a compression plating technique with 2 specialized human femur plates offering axial, rotational, and bending support, and allowing the bone to share loads with the implant. Postoperative radiographs were obtained at 11.5 weeks, 11 months, and 24 months. Bone healing characterized by marked periosteal reaction was evident at 11 months with extensive remodeling evident at 24 months. No complications were noted. Distal mid shaft femoral fracture was reduced, stabilized, and healed in an adult polar bear with a locking plate technique using 2 plates. Previously, femoral fractures in polar bears were considered irreparable. Use of 2 plates applied with a locking plate technique can result in successful fracture repair despite large body weight and inability to restrict postoperative activity.

  6. External longitudinal titanium support for the repair of complex pectus excavatum in adults.

    PubMed

    Puma, Francesco; Vannucci, Jacopo; Santoprete, Stefano

    2012-12-01

    Several techniques exist for the repair of complex pectus excavatum. The placement of retrosternal metal bars improves the results by reducing the recurrence rate, but entails several possible risks, complications and disadvantages. A new method, specifically conceived for the repair of severe, asymmetric forms in adult patients, is reported. The corrected bone is fixed in the proper position by two, patient-customized, titanium struts, externally screwed to the manubrium and sternal body. Any retrosternal bar is thus avoided, reducing possible complications, without hampering the chest wall dynamic. In this particularly difficult issue, this technique provides long-term good functional, mechanical and cosmetic results and does not entail a second surgery for struts removal.

  7. Tissue repair genes: the TiRe database and its implication for skin wound healing

    PubMed Central

    Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E.

    2016-01-01

    Wound healing is an inherent feature of any multicellular organism and recent years have brought about a huge amount of data regarding regular and abnormal tissue repair. Despite the accumulated knowledge, modulation of wound healing is still a major biomedical challenge, especially in advanced ages. In order to collect and systematically organize what we know about the key players in wound healing, we created the TiRe (Tissue Repair) database, an online collection of genes and proteins that were shown to directly affect skin wound healing. To date, TiRe contains 397 entries for four organisms: Mus musculus, Rattus norvegicus, Sus domesticus, and Homo sapiens. Analysis of the TiRe dataset of skin wound healing-associated genes showed that skin wound healing genes are (i) over-conserved among vertebrates, but are under-conserved in invertebrates; (ii) enriched in extracellular and immuno-inflammatory genes; and display (iii) high interconnectivity and connectivity to other proteins. The latter may provide potential therapeutic targets. In addition, a slower or faster skin wound healing is indicative of an aging or longevity phenotype only when assessed in advanced ages, but not in the young. In the long run, we aim for TiRe to be a one-station resource that provides researchers and clinicians with the essential data needed for a better understanding of the mechanisms of wound healing, designing new experiments, and the development of new therapeutic strategies. TiRe is freely available online at http://www.tiredb.org. PMID:27049721

  8. A biocompatible hybrid material with simultaneous calcium and strontium release capability for bone tissue repair.

    PubMed

    Almeida, J Carlos; Wacha, András; Gomes, Pedro S; Alves, Luís C; Fernandes, M Helena Vaz; Salvado, Isabel M Miranda; Fernandes, M Helena R

    2016-05-01

    The increasing interest in the effect of strontium in bone tissue repair has promoted the development of bioactive materials with strontium release capability. According to literature, hybrid materials based on the system PDMS-SiO2 have been considered a plausible alternative as they present a mechanical behavior similar to the one of the human bone. The main purpose of this study was to obtain a biocompatible hybrid material with simultaneous calcium and strontium release capability. A hybrid material, in the system PDMS-SiO2-CaO-SrO, was prepared with the incorporation of 0.05 mol of titanium per mol of SiO2. Calcium and strontium were added using the respective acetates as sources, following a sol-gel technique previously developed by the present authors. The obtained samples were characterized by FT-IR, solid-state NMR, and SAXS, and surface roughness was analyzed by 3D optical profilometry. In vitro studies were performed by immersion of the samples in Kokubo's SBF for different periods of time, in order to determine the bioactive potential of these hybrids. Surfaces of the immersed samples were observed by SEM, EDS and PIXE, showing the formation of calcium phosphate precipitates. Supernatants were analyzed by ICP, revealing the capability of the material to simultaneously fix phosphorus ions and to release calcium and strontium, in a concentration range within the values reported as suitable for the induction of the bone tissue repair. The material demonstrated to be cytocompatible when tested with MG63 osteoblastic cells, exhibiting an inductive effect on cell proliferation and alkaline phosphatase activity.

  9. Immunohistochemical study of collagen types I and II and procollagen IIA in human cartilage repair tissue following autologous chondrocyte implantation.

    PubMed

    Roberts, S; Menage, J; Sandell, L J; Evans, E H; Richardson, J B

    2009-10-01

    This study has assessed the relative proportions of type I and II collagens and IIA procollagen in full depth biopsies of repair tissue in a large sample of patients treated with autologous chondrocyte implantation (ACI). Sixty five full depth biopsies were obtained from knees of 58 patients 8-60 months after treatment by ACI alone (n=55) or in combination with mosaicplasty (n=10). In addition articular cartilage was examined from eight individuals (aged 10-50) as controls. Morphology and semi-quantitative immunohistochemistry for collagen types I and II and procollagen IIA in the repair tissue were studied. Repair cartilage thickness was 2.89+/-1.5 mm and there was good basal integration between the repair cartilage, calcified cartilage and subchondral bone. Sixty five percent of the biopsies were predominantly fibrocartilage (mostly type I collagen and IIA procollagen), 15% were hyaline cartilage (mostly type II collagen), 17% were of mixed morphology and 3% were fibrous tissue (mostly type I collagen). Type II collagen and IIA procollagen were usually found in the lower regions near the bone and most type II collagen was present 30-60 months after treatment. The presence of type IIA procollagen in the repair tissue supports our hypothesis that this is indicative of a developing cartilage, with the ratio of type II collagen:procollagen IIA increasing from <2% in the first two years post-treatment to 30% three to five years after treatment. This suggests that cartilage repair tissue produced following ACI treatment, is likely to take some years to mature.

  10. Evaluation of a new range of light-activated surgical adhesives for tissue repair in a porcine model

    NASA Astrophysics Data System (ADS)

    Riley, Jill N.; Hodges, Diane E.; March, Keith L.; McNally-Heintzelman, Karen M.

    2001-05-01

    An in vitro study was conducted to determine the feasibility of using a new range of light-activated surgical adhesives for incision repair in a wide range of tissue types. Biodegradable polymer membranes of controlled porosity were fabricated with poly(L-lactic-co-glycolic acid) (PLGA) and salt particles using a solvent-casting and particulate- leaching technique. The porous membranes were doped with protein solder composed of 50%(w/v) bovine serum albumin solder and 0.5 mg/ml indocyanine green (ICG) dye mixed in deionized water. Tissue incisions were repaired using the surgical adhesive in conjunction with an 805-nm diode laser. Nine organs were tested ranging from skin to liver to the small intestine, as well as the coronary, pulmonary, carotid, femoral and splenetic arteries. Acute breaking strengths were measured and the data were analyzed by Student's T-test. Repairs formed on the small intestine were most successful followed by spleen, atrium, kidney, muscle and skin. The strongest vascular repairs were achieved in the carotid artery and femoral artery. The new surgical adhesive could possibly be used as a simple and effective method to stop bleeding and repair tissue quickly in an emergency situation, or as a substitute to mechanical staples or sutures in many clinical applications.

  11. Ectopic bone formation during tissue-engineered cartilage repair using autologous chondrocytes and novel plasma-derived albumin scaffolds.

    PubMed

    Robla Costales, David; Junquera, Luis; García Pérez, Eva; Gómez Llames, Sara; Álvarez-Viejo, María; Meana-Infiesta, Álvaro

    2016-10-01

    The aims of this study were twofold: first, to evaluate the production of cartilaginous tissue in vitro and in vivo using a novel plasma-derived scaffold, and second, to test the repair of experimental defects made on ears of New Zealand rabbits (NZr) using this approach. Scaffolds were seeded with chondrocytes and cultured in vitro for 3 months to check in vitro cartilage production. To evaluate in vivo cartilage production, a chondrocyte-seeded scaffold was transplanted subcutaneously to a nude mouse. To check in vivo repair, experimental defects made in the ears of five New Zealand rabbits (NZr) were filled with chondrocyte-seeded scaffolds. In vitro culture produced mature chondrocytes with no extracellular matrix (ECM). Histological examination of redifferentiated in vitro cultures showed differentiated chondrocytes adhered to scaffold pores. Subcutaneous transplantation of these constructs to a nude mouse produced cartilage, confirmed by histological study. Experimental cartilage repair in five NZr showed cartilaginous tissue repairing the defects, mixed with calcified areas of bone formation. It is possible to produce cartilaginous tissue in vivo and to repair experimental auricular defects by means of chondrocyte cultures and the novel plasma-derived scaffold. Further studies are needed to determine the significance of bone formation in the samples. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  12. Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows

    PubMed Central

    2012-01-01

    Background All cows experience bacterial contamination and tissue injury in the uterus postpartum, instigating a local inflammatory immune response. However mechanisms that control inflammation and achieve a physiologically functioning endometrium, while avoiding disease in the postpartum cow are not succinctly defined. This study aimed to identify novel candidate genes indicative of inflammation resolution during involution in healthy beef cows. Previous histological analysis of the endometrium revealed elevated inflammation 15 days postpartum (DPP) which was significantly decreased by 30 DPP. The current study generated a genome-wide transcriptomic profile of endometrial biopsies from these cows at both time points using mRNA-Seq. The pathway analysis tool GoSeq identified KEGG pathways enriched by significantly differentially expressed genes at both time points. Novel candidate genes associated with inflammatory resolution were subsequently validated in additional postpartum animals using quantitative real-time PCR (qRT-PCR). Results mRNA-Seq revealed 1,107 significantly differentially expressed genes, 73 of which were increased 15 DPP and 1,034 were increased 30 DPP. Early postpartum, enriched immune pathways (adjusted P < 0.1) included the T cell receptor signalling pathway, graft-versus-host disease and cytokine-cytokine receptor interaction pathways. However 30 DPP, where the majority of genes were differentially expressed, the enrichment (adjusted P < 0.1) of tissue repair and proliferative activity pathways was observed. Nineteen candidate genes selected from mRNA-Seq results, were independently assessed by qRT-PCR in additional postpartum cows (5 animals) at both time points. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes were significantly elevated 30 DPP and are functionally associated with tissue repair and the restoration of uterine homeostasis postpartum. Conclusions The results of this study reveal an early activation of the immune

  13. Shouldice inguinal hernia repair in the male adult: the gold standard? A multicenter controlled trial in 1578 patients.

    PubMed Central

    Hay, J M; Boudet, M J; Fingerhut, A; Poucher, J; Hennet, H; Habib, E; Veyrières, M; Flamant, Y

    1995-01-01

    BACKGROUND: Hernia repair is the second most frequently performed operation in France and in the United States, the prevalence being 36 for every 1000 males. Lowering the recurrence rate by 1% would mean 1000 fewer operations for hernia repair per year in France. METHODS: Between 1983 and 1989, 1578 adult males with a total of 1706 nonrecurrent inguinal hernias were prospectively and randomly allotted to undergo either a Bassini's repair, Cooper's ligament, or Shouldice repair with polypropylene or a Shouldice repair with stainless steel for determination of which technique was associated with the lowest recurrence rate. Fifty-nine hernia repairs were withdrawn after inclusion. Of the 1647 remaining hernias, 52.2% were indirect, 25.6% were direct, and 23.2% were combined. Patients were seen every 6 months for 3 years and then every year. Median follow-up was 5 years 8 months (range, 3 months-8.5 years). RESULTS: At 8.5 years, 5.6% of hernias were lost to follow-up. Ninety-seven hernia repairs failed, 50% during the first 2 years. The actuarial recurrence rate was 7.94% at 8.5 years. The Shouldice repair (stainless steel or polypropylene) was associated with fewer recurrences (6.1%) than either the Bassini's (8.6%) or Cooper's ligament repair (11.2%) technique (p < 0.001). This difference remained significant even when the maximal bias test was used. Fewer recurrences (5.9%) were observed with the stainless steel wire Shouldice repair than with polypropylene version (6.5%), but the difference was not significant. CONCLUSIONS: Shouldice hernia repair provides the patient with the best chances of nonrecurrence regardless of the anatomical type of hernia. The Shouldice hernia repair should be the gold standard for inguinal hernia repair in men and serves as the basis for comparison with all other techniques, be they prosthetic or laparoscopic. PMID:8526578

  14. Grade 3C open femur fractures with vascular repair in adults.

    PubMed

    Balci, Halil I; Saglam, Yavuz; Tunali, Onur; Akgul, Turgut; Aksoy, Murat; Dikici, Fatih

    2015-06-01

    Grade 3C open femur fractures are challenging injuries with higher rates of complications. This is a retrospective review of grade 3C open femur fractures with vascular repair between 2002 and 2012. Outcomes included initial MESS score, additional injuries, duration of operation, complications, secondary operations or amputations, and social life implications. Thirty-one of 39 total patients were selected for revascularization and fracture fixation based on soft tissue injury and MESS score. The intra-operative approach included temporary arterial shunt replacement, orthopedic fixation, arterial reconstruction venous and/or nerve repair and routine fasciotomies. An external fixation and reverse saphenous vein graft was used in a majority of the patients (respectively; 93.5%, 90.3%). The mean follow up was 5.4 years (range 2.2-10). The decision to amputate versus salvage should be left up to patients and their care teams after discussing options and future possibilities rather than using a scoring system.

  15. The Role of CCL5 in the Ability of Adipose Tissue-Derived Mesenchymal Stem Cells to Support Repair of Ischemic Regions

    PubMed Central

    Kimura, Kenichi; Nagano, Masumi; Salazar, Georgina; Yamashita, Toshiharu; Tsuboi, Ikki; Mishima, Hajime; Matsushita, Shonosuke; Sato, Fujio; Yamagata, Kenji

    2014-01-01

    Mesenchymal stem cells (MSC) are multipotent and possess high proliferative activity, and thus are thought to be a reliable cell source for cell therapies. Here, we isolated MSC from adult tissues—bone marrow (BM-MSC), dental tissue (DT-MSC), and adipose tissue (AT-MSC)—to compare how autotransplantation of these MSC effectively supports the repair of bone fracture and ischemic tissue. An analysis by in vitro differentiation assays showed no significant difference among these MSC. The degree of calcification at the joint region of bone fracture was higher in mice transplanted with AT-MSC than in mice transplanted with BM-MSC or DT-MSC. To compare the abilities of MSC, characterize how those MSC affect the repair of ischemic tissue, vascular occlusion was performed by ligation of the femoral artery and vein. Of note, the blood flow in the ischemic region rapidly increased in mice injected with AT-MSC, as contrasted with mice injected with BM- or DT-MSC. The number of CD45- and F4/80-positive cells at the femoral region was higher in AT-MSC recipients than in recipients of BM-MSC or DT-MSC. We evaluated the mRNA expression of angiogenic and migration factors in MSC and found the expression of CCL5 mRNA was higher in AT-MSC than in BM-MSC or DT-MSC. Transplantation of AT-MSC with impaired expression of CCL5 clearly showed a significant delay in the recovery of blood flow compared with the control. These findings have fundamental implications for the modulation of AT-MSC in the repair of vasculature and bone fracture. PMID:24171667

  16. Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition

    PubMed Central

    2013-01-01

    Background In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls. Methods Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with Tissue Factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received Tissue Factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair. Results All 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue. Conclusions Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair. PMID:23324433

  17. Double-Strand Break Repair by Interchromosomal Recombination: An In Vivo Repair Mechanism Utilized by Multiple Somatic Tissues in Mammals

    PubMed Central

    White, Ryan R.; Sung, Patricia; Vestal, C. Greer; Benedetto, Gregory; Cornelio, Noelle; Richardson, Christine

    2013-01-01

    Homologous recombination (HR) is essential for accurate genome duplication and maintenance of genome stability. In eukaryotes, chromosomal double strand breaks (DSBs) are central to HR during specialized developmental programs of meiosis and antigen receptor gene rearrangements, and form at unusual DNA structures and stalled replication forks. DSBs also result from exposure to ionizing radiation, reactive oxygen species, some anti-cancer agents, or inhibitors of topoisomerase II. Literature predicts that repair of such breaks normally will occur by non-homologous end-joining (in G1), intrachromosomal HR (all phases), or sister chromatid HR (in S/G2). However, no in vivo model is in place to directly determine the potential for DSB repair in somatic cells of mammals to occur by HR between repeated sequences on heterologs (i.e., interchromosomal HR). To test this, we developed a mouse model with three transgenes—two nonfunctional green fluorescent protein (GFP) transgenes each containing a recognition site for the I-SceI endonuclease, and a tetracycline-inducible I-SceI endonuclease transgene. If interchromosomal HR can be utilized for DSB repair in somatic cells, then I-SceI expression and induction of DSBs within the GFP reporters may result in a functional GFP+ gene. Strikingly, GFP+ recombinant cells were observed in multiple organs with highest numbers in thymus, kidney, and lung. Additionally, bone marrow cultures demonstrated interchromosomal HR within multiple hematopoietic subpopulations including multi-lineage colony forming unit–granulocyte-erythrocyte-monocyte-megakaryocte (CFU-GEMM) colonies. This is a direct demonstration that somatic cells in vivo search genome-wide for homologous sequences suitable for DSB repair, and this type of repair can occur within early developmental populations capable of multi-lineage differentiation. PMID:24349572

  18. Tissue migration capability of larval and adult Brugia pahangi.

    PubMed

    Chirgwin, Sharon R; Coleman, Sharon U; Porthouse, Kristina H; Klei, Thomas R

    2006-02-01

    Infection with mosquito-born filarial nematodes occurs when hosts are bitten by a vector carrying the infective third stage larvae (L3) of the parasites. These larvae, deposited on the skin by the feeding mosquito, are presumed to enter the skin via the vector-induced puncture wound. Larvae of Brugia spp. must then migrate from the entry site, penetrate various skin layers, and locate a lymphatic vessel that leads to their lymphatic predilection site. We have recently established an intradermal (ID) infection model using B. pahangi and the Mongolian gerbil, allowing us to investigate the migratory capability ofB. pahangi. Larval and adult parasites recovered from the peritoneal cavities of gerbils were capable of establishing an infection following ID (larvae) or subcutaneous (adult) injection. Third and fourth stage larvae both migrated away from the injection site within hours, although data suggest they localize to different lymphatic tissues at 3 days postinfection (DPI). Immature adult (28 day) B. pahangi also migrated away from their SC inoculation site within 7 DPI. Mature (45 day) adult B. pahangi displayed little migration away from the SC infection site, suggesting tissue migration may be limited to developing stages of the parasite.

  19. The dual roles of neutrophils and macrophages in inflammation: a critical balance between tissue damage and repair.

    PubMed

    Butterfield, Timothy A; Best, Thomas M; Merrick, Mark A

    2006-01-01

    To discuss the acute phase of inflammatory response with a focus on the neutrophilic response and its role in inflammation. We discuss the relative balance between the need for inflammation to stimulate repair and the need to limit inflammation because of the additional damage it causes. We conducted a MEDLINE search from 1966 to 2005 for literature related to acute inflammation, muscle injury, and repair using combinations of the key words inflammation, neutrophil, macrophage, and cytokines. Additional literature was acquired through cross-referencing of bibliographies of articles obtained through the MEDLINE searches. We reviewed more than 200 relevant articles. Although neutrophils are an important cell population in acute inflammation, few athletic trainers are familiar with the neutrophil's actions or its dichotomous role as both perpetrator of tissue damage and initiator of repair. Neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage by macrophages. These actions are orchestrated by numerous cytokines and the expression of their receptors, which represent a potential means for inhibiting selective aspects of inflammation. Neutrophils infiltrate injured tissues but can also be present after noninjurious exercise. These cells have both specific and nonspecific defensive immune system functions that can cause tissue damage in isolation or as sequelae to other tissue injury. It might seem that limiting the action of neutrophils would be clinically beneficial, but these cells are also responsible for initiating the reparative process that is later managed by macrophages. Although achieving a therapeutic balance between limiting inflammation and stimulating repair is important, the duplicitous roles of neutrophils and macrophages in both the inflammation and healing processes create a physiologic paradox for clinicians whose goals are to limit inflammation and to stimulate healing after acute soft tissue injury.

  20. Takotsubo Cardiomyopathy in an Adult Woman With Repaired Tetralogy of Fallot.

    PubMed

    Nguyen, Lan T; Schelbert, Erik B; Cook, Stephen C

    2016-05-01

    Takotsubo cardiomyopathy is a reversible form of cardiomyopathy rarely reported in the adult congenital patient. We describe a case of a 49-year-old woman with repaired tetralogy of Fallot who presented with acute dyspnea. A 12-lead electrocardiogram revealed diffuse anterolateral T-wave inversion suggestive of myocardial ischemia. Cardiac catheterization was performed, demonstrating angiographically normal coronary arteries. A cardiovascular magnetic resonance examination showed apical akinesis with associated myocardial edema, but no myocardial damage on late gadolinium enhancement imaging, which is a characteristic of Takotsubo cardiomyopathy. The patient was treated medically. A follow-up echocardiogram demonstrated normalization of left ventricular systolic function and apical wall motion abnormalities.

  1. Surgical repair of chronic complete hamstring tendon rupture in the adult patient.

    PubMed

    Cross, M J; Vandersluis, R; Wood, D; Banff, M

    1998-01-01

    Complete rupture of the hamstring tendons in the adult is a rare injury. This report discusses complete rupture of the hamstring tendons in nine patients treated by late operative repair. All patients were referred from outside centers for a second opinion after failed nonoperative treatment. The diagnosis was made quite easily on clinical grounds and was confirmed at surgery. Surgical treatment in all cases consisted of reattachment of the hamstring tendons to the origin on the ischium, and in all cases it was necessary to perform neurolysis of the sciatic nerve. Good results were achieved in all cases, at follow-up all patients were satisfied with the surgery.

  2. The Tissue Fibrinolytic System Contributes to the Induction of Macrophage Function and CCL3 during Bone Repair in Mice

    PubMed Central

    Kawao, Naoyuki; Tamura, Yukinori; Horiuchi, Yoshitaka; Okumoto, Katsumi; Yano, Masato; Okada, Kiyotaka; Matsuo, Osamu; Kaji, Hiroshi

    2015-01-01

    Macrophages play crucial roles in repair process of various tissues. However, the details in the role of macrophages during bone repair still remains unknown. Herein, we examined the contribution of the tissue fibrinolytic system to the macrophage functions in bone repair after femoral bone defect by using male mice deficient in plasminogen (Plg–/–), urokinase-type plasminogen activator (uPA–/–) or tissue-type plasminogen activator (tPA–/–) genes and their wild-type littermates. Bone repair of the femur was delayed in uPA–/– mice until day 6, compared with wild-type (uPA+/+) mice. Number of Osterix-positive cells and vessel formation were decreased in uPA–/– mice at the bone injury site on day 4, compared with those in uPA+/+ mice. Number of macrophages and their phagocytosis at the bone injury site were reduced in uPA–/– and Plg–/–, but not in tPA–/– mice on day 4. Although uPA or plasminogen deficiency did not affect the levels of cytokines, including TNF-α, IL-1β, IL-6, IL-4 and IFN-γ mRNA in the damaged femur, the elevation in CCL3 mRNA levels was suppressed in uPA–/– and Plg–/–, but not in tPA–/– mice. Neutralization of CCL3 antagonized macrophage recruitment to the site of bone injury and delayed bone repair in uPA+/+, but not in uPA–/– mice. Our results provide novel evidence that the tissue fibrinolytic system contributes to the induction of macrophage recruitment and CCL3 at the bone injury site, thereby, leading to the enhancement of the repair process. PMID:25893677

  3. Ultrasonic assessment of facial soft tissue thicknesses in adult Egyptians.

    PubMed

    El-Mehallawi, I H; Soliman, E M

    2001-03-01

    The production of a three-dimensional plastic face on an unknown human skull has been practiced sporadically since the latter part of the last century. In recent years, the technique has been revived and applied to forensic science cases. The morphometric method of forensic facial reconstruction rests heavily on the use of facial soft tissue depth measurements. Moreover, it has been established that measurements made on the living are of more value than those made on the dead. In view of the well-known genetic complexities of the Egyptians, and the lack of knowledge of average facial soft tissue depths of the Egyptians that makes facial reconstruction questionable, it was decided to set up a table of norms for facial tissue thicknesses in 204 adult Egyptians aged 20-35 years. Tissue depths at 17 established landmarks (according to Aulsebrook et al. [Forensic Sci. Int. 79 (1996) 83]) were obtained using ultrasonic probing. The study revealed a unique spectrum of measurements for the Egyptians that might be useful for facial reconstruction purposes with obvious sexual dimorphism in facial soft tissue thickness. Additionally, the study provided evidence for the presence of interpopulation differences in average facial soft tissue thicknesses as evidenced from the comparison of the present data of Egyptians with those previously reported for some other populations.

  4. Biocompatibility Evaluation of EndoSequence Root Repair Paste in the Connective Tissue of Rats.

    PubMed

    Taha, Nessrin A; Safadi, Rima A; Alwedaie, Manal S

    2016-10-01

    The aim of this study was to evaluate the subcutaneous connective tissue response to EndoSequence root repair paste (Brasseler, Savannah, GA) compared with mineral trioxide aggregate (MTA). Thirty-six Wistar rats each received 3 sterile tubes, containing 1 of the tested materials and control. The animals were killed 1, 3 and 6 weeks after implantation. The specimens were evaluated histologically for type of inflammation, intensity and extent of inflammatory cells, foreign body reaction, fibrous capsule thickness, perivascular fragments, calcific deposits and vascular congestion. EndoSequence provoked severe inflammation after 1 week, which was significantly different from MTA and control (P ˂ .05), with fragmented particles and foreign body reaction. MTA showed tissue-tolerance features almost comparable to control. EndoSequence was significantly more irritating than MTA and control at 1 and 3 weeks in terms of severity and extent of inflammation. After 6 weeks it displayed more biocompatible characteristics. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Macrophages and fibroblasts during inflammation and tissue repair in models of organ regeneration

    PubMed Central

    2017-01-01

    Abstract This review provides a concise summary of the changing phenotypes of macrophages and fibroblastic cells during the local inflammatory response, the onset of tissue repair, and the resolution of inflammation which follow injury to an organ. Both cell populations respond directly to damage and present coordinated sequences of activation states which determine the reparative outcome, ranging from true regeneration of the organ to fibrosis and variable functional deficits. Recent work with mammalian models of organ regeneration, including regeneration of full‐thickness skin, hair follicles, ear punch tissues, and digit tips, is summarized and the roles of local immune cells in these systems are discussed. New investigations of the early phase of amphibian limb and tail regeneration, including the effects of pro‐inflammatory and anti‐inflammatory agents, are then briefly discussed, focusing on the transition from the normally covert inflammatory response to the initiation of the regeneration blastema by migrating fibroblasts and the expression of genes for limb patterning. PMID:28616244

  6. Porcine Bone Scaffolds Adsorb Growth Factors Secreted by MSCs and Improve Bone Tissue Repair.

    PubMed

    Mijiritsky, Eitan; Ferroni, Letizia; Gardin, Chiara; Bressan, Eriberto; Zanette, Gastone; Piattelli, Adriano; Zavan, Barbara

    2017-09-08

    An ideal tissue-engineered bone graft should have both excellent pro-osteogenesis and pro-angiogenesis properties to rapidly realize the bone regeneration in vivo. To meet this goal, in this work a porcine bone scaffold was successfully used as a Trojan horse to store growth factors produced by mesenchymal stem cells (MSCs). This new scaffold showed a time-dependent release of bioactive growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), in vitro. The biological effect of the growth factors-adsorbed scaffold on the in vitro commitment of MSCs into osteogenic and endothelial cell phenotypes has been evaluated. In addition, we have investigated the activity of growth factor-impregnated granules in the repair of critical-size defects in rat calvaria by means of histological, immunohistochemical, and molecular biology analyses. Based on the results of our work bone tissue formation and markers for bone and vascularization were significantly increased by the growth factor-enriched bone granules after implantation. This suggests that the controlled release of active growth factors from porcine bone granules can enhance and promote bone regeneration.

  7. Visible Light Crosslinking of Methacrylated Hyaluronan Hydrogels for Injectable Tissue Repair

    PubMed Central

    Fenn, Spencer L.; Oldinski, Rachael A.

    2015-01-01

    Tissue engineering hydrogels are primarily cured in situ using ultraviolet (UV) radiation which limits the use of hydrogels as drug or cell carriers. Visible green light activated crosslinking systems are presented as a safe alternative to UV photocrosslinked hydrogels, without compromising material properties such as viscosity and stiffness. The objective of this study was to fabricate and characterize photocrosslinked hydrogels with well-regulated gelation kinetics and mechanical properties for the repair or replacement of soft tissue. An anhydrous methacrylation of hyaluronan (HA) was performed to control the degree of modification (DOM) of HA, verified by 1H-NMR spectroscopy. UV activated crosslinking was compared to visible green light activated crosslinking. While the different photocrosslinking techniques resulted in varied crosslinking times, comparable mechanical properties of UV and green light activated crosslinked hydrogels were achieved using each photocrosslinking method by adjusting time of light exposure. Methacrylated HA (HA-MA) hydrogels of varying molecular weight, DOM and concentration exhibited compressive moduli ranging from 1 kPa to 116 kPa, for UV crosslinking, and 3 kPa to 146 kPa, for green light crosslinking. HA-MA molecular weight and concentration were found to significantly influence moduli values. HA-MA hydrogels did not exhibit any significant cytotoxic affects towards human mesenchymal stem cells. Green light activated crosslinking systems are presented as a viable method to form natural-based hydrogels in situ. PMID:26097172

  8. Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells.

    PubMed

    Regnell, Christine Elisabeth; Hildrestrand, Gunn Annette; Sejersted, Yngve; Medin, Tirill; Moldestad, Olve; Rolseth, Veslemøy; Krokeide, Silje Zandstra; Suganthan, Rajikala; Luna, Luisa; Bjørås, Magnar; Bergersen, Linda H

    2012-09-27

    Accumulation of oxidative DNA damage has been proposed as a potential cause of age-related cognitive decline. The major pathway for removal of oxidative DNA base lesions is base excision repair, which is initiated by DNA glycosylases. In mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single-stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult neurogenesis is crucial for maintenance of hippocampus-dependent functions involved in behavior. Herein, behavioral studies reveal learning and memory deficits and reduced anxiety-like behavior in Neil3(-/-) mice. Neural stem/progenitor cells from aged Neil3(-/-) mice show impaired proliferative capacity and reduced DNA repair activity. Furthermore, hippocampal neurons in Neil3(-/-) mice display synaptic irregularities. It appears that Neil3-dependent repair of oxidative DNA damage in neural stem/progenitor cells is required for maintenance of adult neurogenesis to counteract the age-associated deterioration of cognitive performance.

  9. The small leucine-rich repeat proteoglycans in tissue repair and atherosclerosis

    PubMed Central

    Hultgårdh-Nilsson, Anna; Borén, Jan; Chakravarti, Shukti

    2015-01-01

    Proteoglycans consist of a protein core with one or more covalently attached glycosaminoglycan (GAG) side chains, and have multiple roles in the initiation and progression of atherosclerosis. Here we discuss the potential and known functions of a group of small leucine-rich repeat proteoglycans (SLRPs) in atherosclerosis. We focus on five SLRPs, decorin, biglycan lumican, fibromodulin, and PRELP, because these have been detected in atherosclerotic plaques or demonstrated to have a role in animal models of atherosclerosis. Decorin and biglycan are modified post translationally by substitution with chondroitin/dermatan sulfate GAGs, whereas lumican, fibromodulin, and PRELP have keratan sulfate side chains, and the core proteins have leucine-rich repeat (LRR) motifs that are characteristic of the LRR superfamily. The chondroitin/dermatan sulfate GAG side chains have been implicated in lipid retention in atherosclerosis. The core proteins are discussed here in the context of: (i) interactions with collagens and their implications in tissue integrity, fibrosis, and wound repair; and (ii) interactions with growth factors, cytokines, pathogen-associated molecular patterns, and cell surface receptors that impact normal physiology and disease processes such as inflammation, innate immune responses, and wound healing (i.e processes that are all important in plaque development and progression). Thus, studies of these SLRPs in the context of wound healing are providing clues about their functions that may be important in early stages of atherosclerosis to plaque vulnerability and cardiovascular disease at later stages. Understanding of signal transduction pathways regulated by the core protein interactions is leading to novel roles and therapeutic potential for these proteins in wound repair and atherosclerosis. PMID:26477596

  10. When repair is not feasible: prosthesis selection in children and adults with congenital heart disease.

    PubMed

    Said, Sameh M; Burkhart, Harold M

    2014-01-01

    Congenital heart surgeons face many challenges when dealing with valvular pathology in the pediatric population. Because of the concerns related to growth, repair should be the main goal. However, this is not always feasible and valve replacement becomes the only other alternative. Valve replacement also represents one of the most common procedures performed for adults with congenital heart disease, with several valve options existing including homografts, xenografts, autografts, and other artificial prostheses. The choice sometimes may be difficult because there are advantages and disadvantages to each valve substitute. In this article, we will address the different options of valve replacement in children and adults with congenital heart disease, and review the current literature that supports current practice. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. A new concept of endometriosis and adenomyosis: tissue injury and repair (TIAR).

    PubMed

    Leyendecker, Gerhard; Wildt, Ludwig

    2011-03-01

    Pelvic endometriosis, deeply infiltrating endometriosis and uterine adenomyosis share a common pathophysiology and may be integrated into the physiological mechanism and new nosological concept of 'tissue injury and repair' (TIAR) and may, in this context, just represent the extreme of a basically physiological, estrogen-related mechanism that is pathologically exaggerated in an extremely estrogen-sensitive reproductive organ. The acronym TIAR describes a fundamental and apparently ubiquitous biological system that becomes operative in mesenchymal tissues following tissue injury and, upon activation, results in the local production of estradiol. Endometriosis and adenomyosis are caused by trauma. In the spontaneously developing disease, chronic uterine peristaltic activity or phases of hyperperistalsis induce, at the endometrial-myometrial interface near the fundo-cornual raphe, microtraumatisations, with activation of the TIAR mechanism. With ongoing traumatisations, such sites of inflammation might accumulate and the increasingly produced estrogens interfere in a paracrine fashion with ovarian control over uterine peristaltic activity, resulting in permanent hyperperistalsis and a self-perpetuation of the disease process. Overt autotraumatisation of the uterus with dislocation of fragments of basal endometrium into the peritoneal cavity and infiltration of basal endometrium into the depth of the myometrial wall ensues. In most cases of endometriosis/adenomyosis a causal event early in the reproductive period of life must be postulated, rapidly leading to archimetral hyperestrogenism and uterine hyperperistalsis. In late premenopausal adenomyosis such an event might not have occurred. However, as indicated by the high prevalence of the disease, it appears to be unavoidable that, with time, chronic normoperistalsis throughout the reproductive period of life accumulates to the same extent of microtraumatisation. With activation of the TIAR mechanism followed by

  12. Neural crest stem cell population in craniomaxillofacial development and tissue repair.

    PubMed

    La Noce, M; Mele, L; Tirino, V; Paino, F; De Rosa, A; Naddeo, P; Papagerakis, P; Papaccio, G; Desiderio, V

    2014-10-28

    Neural crest cells, delaminating from the neural tube during migration, undergo an epithelial-mesenchymal transition and differentiate into several cell types strongly reinforcing the mesoderm of the craniofacial body area - giving rise to bone, cartilage and other tissues and cells of this human body area. Recent studies on craniomaxillofacial neural crest-derived cells have provided evidence for the tremendous plasticity of these cells. Actually, neural crest cells can respond and adapt to the environment in which they migrate and the cranial mesoderm plays an important role toward patterning the identity of the migrating neural crest cells. In our experience, neural crest-derived stem cells, such as dental pulp stem cells, can actively proliferate, repair bone and give rise to other tissues and cytotypes, including blood vessels, smooth muscle, adipocytes and melanocytes, highlighting that their use in tissue engineering is successful. In this review, we provide an overview of the main pathways involved in neural crest formation, delamination, migration and differentiation; and, in particular, we concentrate our attention on the translatability of the latest scientific progress. Here we try to suggest new ideas and strategies that are needed to fully develop the clinical use of these cells. This effort should involve both researchers/clinicians and improvements in good manufacturing practice procedures. It is important to address studies towards clinical application or take into consideration that studies must have an effective therapeutic prospect for humans. New approaches and ideas must be concentrated also toward stem cell recruitment and activation within the human body, overcoming the classical grafting.

  13. Tissue-engineered rhesus monkey nerve grafts for the repair of long ulnar nerve defects: similar outcomes to autologous nerve grafts

    PubMed Central

    Jiang, Chang-qing; Hu, Jun; Xiang, Jian-ping; Zhu, Jia-kai; Liu, Xiao-lin; Luo, Peng

    2016-01-01

    Acellular nerve allografts can help preserve normal nerve structure and extracellular matrix composition. These allografts have low immunogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autograft. The graft was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomorphology, electromyogram and immunohistochemistry findings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no significant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neurofilaments between the experimental and control groups. However, outcome was significantly better in the experimental group than in the blank group. These findings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. The outcomes are similar to those obtained with autologous nerve graft. PMID:28123431

  14. Echocardiographic assessment of the aortic root dilatation in adult patients after tetralogy of Fallot repair.

    PubMed

    Cruz, Cristina; Pinho, Teresa; Lebreiro, Ana; Silva Cardoso, José; Maciel, Maria Júlia

    2013-06-01

    Transthoracic echocardiography is an important tool after tetralogy of Fallot repair, of which aortic root dilatation is a recognized complication. In this study we aimed to assess its prevalence and potential predictors. We consecutively assessed adult patients by transthoracic echocardiography after tetralogy of Fallot repair, and divided them into two groups based on the maximum internal aortic diameter at the sinuses of Valsalva in parasternal long-axis view: group 1 with aortic root dilatation (≥38 mm) and group 2 without dilatation (<38 mm). A total of 53 patients were included, mean age 32±10 years, with a mean time since surgery of 23±7 years. An aortopulmonary shunt had been performed prior to complete repair in 25 patients, and a transannular patch was used in 19 patients. Aortic root measurement was possible in all patients. Aortic root dilatation was identified in eight patients (15%), all male. Male gender (p=0.001), body surface area (1.93±0.10 vs. 1.70±0.20 m(2), p=0.03) and increased left ventricular end-diastolic diameter (p=0.005) were predictors of aortic root dilatation. None of the surgical variables studied were predictors of aortic root dilatation. The prevalence of aortic root dilatation in this cohort was low and male gender was a predictor of its occurrence. The type of repair and time to surgery did not influence its occurrence. Quantification of aortic root diameter is possible by transthoracic echocardiography; we suggest indexing it to body surface area in clinical practice. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  15. Epimorphic regeneration approach to tissue replacement in adult mammals.

    PubMed

    Agrawal, Vineet; Johnson, Scott A; Reing, Janet; Zhang, Li; Tottey, Stephen; Wang, Gang; Hirschi, Karen K; Braunhut, Susan; Gudas, Lorraine J; Badylak, Stephen F

    2010-02-23

    Urodeles and fetal mammals are capable of impressive epimorphic regeneration in a variety of tissues, whereas the typical default response to injury in adult mammals consists of inflammation and scar tissue formation. One component of epimorphic regeneration is the recruitment of resident progenitor and stem cells to a site of injury. Bioactive molecules resulting from degradation of extracellular matrix (ECM) have been shown to recruit a variety of progenitor and stem cells in vitro in adult mammals. The ability to recruit multipotential cells to the site of injury by in vivo administration of chemotactic ECM degradation products in a mammalian model of digit amputation was investigated in the present study. Adult, 6- to 8-week-old C57/BL6 mice were subjected to midsecond phalanx amputation of the third digit of the right hind foot and either treated with chemotactic ECM degradation products or left untreated. At 14 days after amputation, mice treated with ECM degradation products showed an accumulation of heterogeneous cells that expressed markers of multipotency, including Sox2, Sca1, and Rex1 (Zfp42). Cells isolated from the site of amputation were capable of differentiation along neuroectodermal and mesodermal lineages, whereas cells isolated from control mice were capable of differentiation along only mesodermal lineages. The present findings demonstrate the recruitment of endogenous stem cells to a site of injury, and/or their generation/proliferation therein, in response to ECM degradation products.

  16. Fetal and adult fibroblasts display intrinsic differences in tendon tissue engineering and regeneration.

    PubMed

    Tang, Qiao-Mei; Chen, Jia Lin; Shen, Wei Liang; Yin, Zi; Liu, Huan Huan; Fang, Zhi; Heng, Boon Chin; Ouyang, Hong Wei; Chen, Xiao

    2014-07-03

    Injured adult tendons do not exhibit optimal healing through a regenerative process, whereas fetal tendons can heal in a regenerative fashion without scar formation. Hence, we compared FFs (mouse fetal fibroblasts) and AFs (mouse adult fibroblasts) as seed cells for the fabrication of scaffold-free engineered tendons. Our results demonstrated that FFs had more potential for tendon tissue engineering, as shown by higher levels of tendon-related gene expression. In the in situ AT injury model, the FFs group also demonstrated much better structural and functional properties after healing, with higher levels of collagen deposition and better microstructure repair. Moreover, fetal fibroblasts could increase the recruitment of fibroblast-like cells and reduce the infiltration of inflammatory cells to the injury site during the regeneration process. Our results suggest that the underlying mechanisms of better regeneration with FFs should be elucidated and be used to enhance adult tendon healing. This may assist in the development of future strategies to treat tendon injuries.

  17. Fetal and adult fibroblasts display intrinsic differences in tendon tissue engineering and regeneration

    PubMed Central

    Tang, Qiao-Mei; Chen, Jia Lin; Shen, Wei Liang; Yin, Zi; Liu, Huan Huan; Fang, Zhi; Heng, Boon Chin; Ouyang, Hong Wei; Chen, Xiao

    2014-01-01

    Injured adult tendons do not exhibit optimal healing through a regenerative process, whereas fetal tendons can heal in a regenerative fashion without scar formation. Hence, we compared FFs (mouse fetal fibroblasts) and AFs (mouse adult fibroblasts) as seed cells for the fabrication of scaffold-free engineered tendons. Our results demonstrated that FFs had more potential for tendon tissue engineering, as shown by higher levels of tendon-related gene expression. In the in situ AT injury model, the FFs group also demonstrated much better structural and functional properties after healing, with higher levels of collagen deposition and better microstructure repair. Moreover, fetal fibroblasts could increase the recruitment of fibroblast-like cells and reduce the infiltration of inflammatory cells to the injury site during the regeneration process. Our results suggest that the underlying mechanisms of better regeneration with FFs should be elucidated and be used to enhance adult tendon healing. This may assist in the development of future strategies to treat tendon injuries. PMID:24992450

  18. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    SciTech Connect

    Oorschot, Bregje van; Hovingh, Suzanne E.; Moerland, Perry D.; Medema, Jan Paul; Stalpers, Lukas J.A.; Vrieling, Harry; Franken, Nicolaas A.P.

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

  19. Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medical devices for tissue repair and regeneration.

    PubMed

    Williams, Simon F; Rizk, Said; Martin, David P

    2013-10-01

    Poly-4-hydroxybutyrate (P4HB) is a thermoplastic, linear polyester, produced by recombinant fermentation, that can be converted into a wide range of resorbable medical devices. P4HB fibers are exceptionally strong, and can be designed to provide prolonged strength retention in vivo. In 2007, the FDA cleared a monofilament suture made from P4HB for general soft tissue approximation and/or ligation. Subsequently, surgical mesh devices for hernia repair, tendon and ligament repair, and plastic and reconstructive surgery have been introduced for clinical use. This review describes the unique properties of P4HB, its clinical applications, and potential uses that are under development.

  20. High-resolution ultrasound and magnetic resonance imaging to document tissue repair after prolotherapy: a report of 3 cases.

    PubMed

    Fullerton, Bradley D

    2008-02-01

    High-resolution ultrasound imaging of musculoskeletal tissue is increasing in popularity because of patient tolerability, low cost, ability to visualize tissue in real-time motion, and superior resolution of highly organized tissue such as a tendon. Prolotherapy, defined as the injection of growth factors or growth factor production stimulants to grow normal cells or tissue, has been a controversial procedure for decades; it is currently gaining in popularity among physiatrists and other musculoskeletal physicians. This report describes imaging of tendons, ligaments, and medial meniscus disease (from trauma or degeneration). Although these tissues have been poorly responsive to nonsurgical treatment, it is proposed that tissue growth and repair after prolotherapy in these structures can be documented with ultrasound and confirmed with magnetic resonance imaging. Directions for future research application are discussed.

  1. A 10-year experience of totally extraperitoneal endoscopic repair for adult inguinal hernia.

    PubMed

    Toma, Hiroki; Eguchi, Toru; Toyoda, Shuichi; Okabe, Yasuhiro; Kobarai, Tomonari; Naritomi, Gen; Ogawa, Takahiro; Hirota, Ichio

    2015-11-01

    Laparoscopic surgery is fast becoming the treatment of choice for inguinal hernia. By reviewing our 10-year experience of performing totally extraperitoneal repair (TEP), we sought to establish its clinical significance in the treatment of adult inguinal hernia. We reviewed retrospectively the clinical records of patients who underwent TEP for adult inguinal hernia between January 2003 and December 2012. None of the 303 patients with adult primary or recurrent inguinal hernia in our study needed TEP converted to other procedures or suffered serious complications during the procedure. A significant difference was noted in the operation time between direct (n = 32) vs indirect (n = 128) hernias in the primary unilateral inguinal hernia group (91 ± 27 vs 80 ± 32 min, p = 0.033) and between direct/direct (n = 31) vs indirect/indirect (n = 24) hernias (136 ± 58 vs 89 ± 24 min, p = 0.01) in the primary bilateral inguinal hernia group. The only postoperative complications recorded were four cases of hernia recurrence (1.3 %) and one case of chronic pain (0.3 %). The results obtained for TEP over 10 years support this as a promising procedure for the treatment of adult inguinal hernia.

  2. Designer Dual Therapy Nanolayered Implant Coatings Eradicate Biofilms and Accelerate Bone Tissue Repair.

    PubMed

    Min, Jouha; Choi, Ki Young; Dreaden, Erik C; Padera, Robert F; Braatz, Richard D; Spector, Myron; Hammond, Paula T

    2016-04-26

    Infections associated with orthopedic implants cause increased morbidity and significant healthcare cost. A prolonged and expensive two-stage procedure requiring two surgical steps and a 6-8 week period of joint immobilization exists as today's gold standard for the revision arthroplasty of an infected prosthesis. Because infection is much more common in implant replacement surgeries, these issues greatly impact long-term patient care for a continually growing part of the population. Here, we demonstrate that a single-stage revision using prostheses coated with self-assembled, hydrolytically degradable multilayers that sequentially deliver the antibiotic (gentamicin) and the osteoinductive growth factor (BMP-2) in a time-staggered manner enables both eradication of established biofilms and complete and rapid bone tissue repair around the implant in rats with induced osteomyelitis. The nanolayered construct allows precise independent control of release kinetics and loading for each therapeutic agent in an infected implant environment. Antibiotics contained in top layers can be tuned to provide a rapid release at early times sufficient to eliminate infection, followed by sustained release for several weeks, and the underlying BMP-2 component enables a long-term sustained release of BMP-2, which induced more significant and mechanically competent bone formation than a short-term burst release. The successful growth factor-mediated osteointegration of the multilayered implants with the host tissue improved bone-implant interfacial strength 15-fold when compared with the uncoated one. These findings demonstrate the potential of this layered release strategy to introduce a durable next-generation implant solution, ultimately an important step forward to future large animal models toward the clinic.

  3. Immune modulation to improve tissue engineering outcomes for cartilage repair in the osteoarthritic joint.

    PubMed

    Fahy, Niamh; Farrell, Eric; Ritter, Thomas; Ryan, Aideen E; Murphy, J Mary

    2015-02-01

    Osteoarthritis (OA), the most common form of arthritis, is a disabling degenerative joint disease affecting synovial joints and is associated with cartilage destruction, inflammation of the synovial membrane, and subchondral bone remodeling. Inflammation of the synovial membrane may arise secondary to degenerative processes in articular cartilage (AC), or may be a primary occurrence in OA pathogenesis. However, synovial inflammation plays a key role in the pathogenesis and disease progression of OA through the production of pro-inflammatory mediators, and is associated with cartilage destruction and pain. The triggers that initiate activation of the immune response in OA are unknown, but crosstalk between osteoarthritic chondrocytes, cartilage degradation products, and the synovium may act to perpetuate this response. Increasing evidence has emerged highlighting an important role for pro-inflammatory mediators and infiltrating inflammatory cell populations in the progression of the disease. Tissue engineering strategies hold great potential for the repair of damaged AC in an osteoarthritic joint. However, an in-depth understanding of how OA-associated inflammation impacts chondrocyte and progenitor cell behavior is required to achieve efficient cartilage regeneration in a catabolic osteoarthritic environment. In this review, we will discuss the role of inflammation in OA, and investigate novel immune modulation strategies that may prevent disease progression and facilitate successful cartilage regeneration for the treatment of OA.

  4. Immune Modulation to Improve Tissue Engineering Outcomes for Cartilage Repair in the Osteoarthritic Joint

    PubMed Central

    Fahy, Niamh; Farrell, Eric; Ritter, Thomas; Ryan, Aideen E.

    2015-01-01

    Osteoarthritis (OA), the most common form of arthritis, is a disabling degenerative joint disease affecting synovial joints and is associated with cartilage destruction, inflammation of the synovial membrane, and subchondral bone remodeling. Inflammation of the synovial membrane may arise secondary to degenerative processes in articular cartilage (AC), or may be a primary occurrence in OA pathogenesis. However, synovial inflammation plays a key role in the pathogenesis and disease progression of OA through the production of pro-inflammatory mediators, and is associated with cartilage destruction and pain. The triggers that initiate activation of the immune response in OA are unknown, but crosstalk between osteoarthritic chondrocytes, cartilage degradation products, and the synovium may act to perpetuate this response. Increasing evidence has emerged highlighting an important role for pro-inflammatory mediators and infiltrating inflammatory cell populations in the progression of the disease. Tissue engineering strategies hold great potential for the repair of damaged AC in an osteoarthritic joint. However, an in-depth understanding of how OA-associated inflammation impacts chondrocyte and progenitor cell behavior is required to achieve efficient cartilage regeneration in a catabolic osteoarthritic environment. In this review, we will discuss the role of inflammation in OA, and investigate novel immune modulation strategies that may prevent disease progression and facilitate successful cartilage regeneration for the treatment of OA. PMID:24950588

  5. Ultrafine fibrous gelatin scaffolds with deep cell infiltration mimicking 3D ECMs for soft tissue repair.

    PubMed

    Jiang, Qiuran; Xu, Helan; Cai, Shaobo; Yang, Yiqi

    2014-07-01

    In this research, ultrafine fibrous scaffolds with deep cell infiltration and sufficient water stability have been developed from gelatin, aiming to mimic the extracellular matrices (ECMs) as three dimensional (3D) stromas for soft tissue repair. The ultrafine fibrous scaffolds produced from the current technologies of electrospinning and phase separation are either lack of 3D oriented fibrous structure or too compact to be penetrated by cells. Whilst electrospun scaffolds are able to emulate two dimensional (2D) ECMs, they cannot mimic the 3D ECM stroma. In this work, ultralow concentration phase separation (ULCPS) has been developed to fabricate gelatin scaffolds with 3D randomly oriented ultrafine fibers and loose structures. Besides, a non-toxic citric acid crosslinking system has been established for the ULCPS method. This system could endow the scaffolds with sufficient water stability, while maintain the fibrous structures of scaffolds. Comparing with electrospun scaffolds, the ULCPS scaffolds showed improved cytocompatibility and more importantly, cell infiltration. This research has proved the possibility of using gelatin ULCPS scaffolds as the substitutes of 3D ECMs.

  6. Egr-1: new conductor for the tissue repair orchestra directs harmony (regeneration) or cacophony (fibrosis)

    PubMed Central

    Bhattacharyya, Swati; Fang, Feng; Tourtellotte, Warren; Varga, John

    2014-01-01

    Fibroblasts and myofibroblasts are the key effector cells executing physiologic tissue repair leading to regeneration on one hand, and pathological fibrogenesis leading to chronic fibrosing conditions on the other. Recent studies identify the multifunctional transcription factor Early Growth Response-1(Egr-1) as an important mediator of fibroblast activation triggered by diverse stimuli. Egr-1 has potent stimulatory effects on fibrotic gene expression, and aberrant Egr-1 expression or function is associated with animal models of fibrosis and human fibrotic disorders including emphysema, pulmonary fibrosis, pulmonary hypertension and systemic sclerosis. Pharmacological suppression or genetic targeting of Egr-1 blocks fibrotic responses in vitro and ameliorates experimental fibrosis in the skin and lung. In contrast, Egr-1 appear to acts as a negative regulator of hepatic fibrosis in mouse models, suggesting a context-dependent role in fibrosis. The Egr-1-binding protein Nab2 is an endogenous inhibitor of Egr-1-mediated signaling, and abrogates the stimulation of fibrotic responses induced by transforming growth factor-ß (TGF-ß). Moreover, mice deficient in Nab2 show excessive collagen accumulation in the skin. These observations highlight a previously unsuspected fundamental physiologic function for the Egr-1/Nab2 signaling axis in regulating fibrogenesis, and suggest that Egr-1 may be a potential novel therapeutic target in human diseases complicated by fibrosis. This review summarizes recent advances in understanding the regulation and complex functional role of Egr-1 and its related proteins and inhibitors in pathological fibrosis. PMID:23132749

  7. The role of biologically active peptides in tissue repair using umbilical cord mesenchymal stem cells.

    PubMed

    Cabrera, Carlos; Carriquiry, Gabriela; Pierinelli, Chiara; Reinoso, Nancy; Arias-Stella, Javier; Paino, Javier

    2012-10-01

    The role of bioactive compounds in wound repair is critical. The preliminary work described herein includes the study of the effects of second degree burns in a Rex rabbit model and the action of human umbilical cord cells on the regulation and secretion of bioactive compounds. When applied on blood scaffolds as heterograft matrices, fibroblasts proliferate from these primary cultures and release biologically active peptides under tight control. Our work in progress indicates that mesenchymal stem cell (MSC)-mediated therapy provides better quality and more efficient burn reepithelialization of injured tissues by controlling the release of these peptides. Improvement of wound aesthetics is achieved in less time than without MSC-mediated therapy. Well-organized epidermal regeneration and overall better quality of reepithelialization, with no rejection, can be demonstrated consistently with periodic biopsies. Our studies indicate that MSCs have the capacity to produce, regulate, and deliver biologically active peptides that result in superior regeneration, compared with conventional treatments. © 2012 New York Academy of Sciences.

  8. A tissue-specific role for Nlrp3 in tubular epithelial repair after renal ischemia/reperfusion.

    PubMed

    Bakker, Pieter J; Butter, Loes M; Claessen, Nike; Teske, Gwendoline J D; Sutterwala, Fayyaz S; Florquin, Sandrine; Leemans, Jaklien C

    2014-07-01

    Ischemia/reperfusion injury is a major cause of acute kidney injury. Improving renal repair would represent a therapeutic strategy to prevent renal dysfunction. The innate immune receptor Nlrp3 is involved in tissue injury, inflammation, and fibrosis; however, its role in repair after ischemia/reperfusion is unknown. We address the role of Nlrp3 in the repair phase of renal ischemia/reperfusion and investigate the relative contribution of leukocyte- versus renal-associated Nlrp3 by studying bone marrow chimeric mice. We found that Nlrp3 expression was most profound during the repair phase. Although Nlrp3 expression was primarily expressed by leukocytes, both leukocyte- and renal-associated Nlrp3 was detrimental to renal function after ischemia/reperfusion. The Nlrp3-dependent cytokine IL-1β remained unchanged in kidneys of all mice. Leukocyte-associated Nlrp3 negatively affected tubular apoptosis in mice that lacked Nlrp3 expression on leukocytes, which correlated with reduced macrophage influx. Nlrp3-deficient (Nlrp3KO) mice with wild-type bone marrow showed an improved repair response, as seen by a profound increase in proliferating tubular epithelium, which coincided with increased hepatocyte growth factor expression. In addition, Nlrp3KO tubular epithelial cells had an increased repair response in vitro, as seen by an increased ability of an epithelial monolayer to restore its structural integrity. In conclusion, Nlrp3 shows a tissue-specific role in which leukocyte-associated Nlrp3 is associated with tubular apoptosis, whereas renal-associated Nlrp3 impaired wound healing. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Mesh complications and failure rates after transvaginal mesh repair compared with abdominal or laparoscopic sacrocolpopexy and to native tissue repair in treating apical prolapse.

    PubMed

    Dandolu, Vani; Akiyama, Megumi; Allenback, Gayle; Pathak, Prathamesh

    2017-02-01

    Our objective was to quantitate the extent of complications and failure rate for apical prolapse repair with transvaginal mesh (TVM) use versus sacrocolpopexy over a minimum of 2 years of follow-up. Truven CCAE and Medicare Supplemental databases 2008-2013 were used for analysis. Patients with apical prolapse repair via transvaginal mesh (TVMR), abdominal sacrocolpopexy (ASCP), laparoscopic sacrocolpopexy (LSCP), or native tissue repair (NTR) and continuously enrolled for years were in the study cohort. Surgical failures were identified by reoperation for any prolapse or subsequent use of pessary. SAS® 9.3 was used for analysis. Mesh removal/revision was reported highest in TVMR (5.1 %), followed by LSCP (1.7 %) and ASCP (1.2 %). In those with concomitant sling, combined rates for mesh/sling revision were high, at 9.0 % in TVMR + sling, 5.6 % in ASCP + sling, and 4.5 % LSCP + sling. Sling-alone cases reported a 3.5 % revision rate. Pelvic pain (16.4-22.7 %) and dyspareunia (5.6-7.5 %) were high in all three approaches for apical prolapse repairs. Reoperation for apical prolapse was more common for TVMR (2.9 %) compared with NTR (2.3 %) [odds ratio (OR) 1.27; confidence interval (CI) 1.1-1.47; p 0.002]. Both ASCP and LSCP were superior to NTR (ASCP 1.5 %, OR 0.63, CI 0.46-0.86; p 0.003) and LSCP 1.8 % (OR 0.79, CI 0.62-1.01; p 0.07). Overall prolapse recurrence, as indicated by any compartment surgery for prolapse and/or pessary use, was also noted highest in TVMR (5.9 % OR 1.23, CI 1.11-1.36; p <0.0001). Laparoscopic sacrocolpopexies were slightly superior at 4.0 % overall recurrence (OR 0.83, CI 0.7-0.98); p 0.03). Failure of incontinence surgery was higher when the initial procedure combined prolapse and sling surgery (1.97 %) versus sling alone (1.6 %). Reoperation for apical prolapse is more common with TVMR than with sacrocolpopexies and NTR. Incontinence procedures are more likely to fail when performed along with prolapse repair than

  10. Prospective study of single-stage repair of contaminated hernias using a biologic porcine tissue matrix: the RICH Study.

    PubMed

    Itani, Kamal M F; Rosen, Michael; Vargo, Daniel; Awad, Samir S; Denoto, George; Butler, Charles E

    2012-09-01

    In the presence of contamination, the repair of a ventral incisional hernia (VIH) is challenging. The presence of comorbidities poses an additional risk for postoperative wound events and hernia recurrence. To date, very few studies describe the outcomes of VIH repair in this high-risk population. A prospective, multicenter, single-arm, the Repair of Infected or Contaminated Hernias study was performed to study the clinical outcomes of open VIH repair of contaminated abdominal defects with a non-cross-linked, porcine, acellular dermal matrix, Strattice. Of 85 patients who consented to participate, 80 underwent open VIH repair with Strattice. Hernia defects were 'clean-contaminated' (n = 39), 'contaminated' (n = 39), or 'dirty' (n = 2), and the defects were classified as grade 3 (n = 60) or grade 4 (n = 20). The midline was restored, and primary closure was achieved in 64 patients; the defect was bridged in 16 patients. At 24 months, 53 patients (66%) experienced 95 wound events. There were 28 unique, infection-related events in 24 patients. Twenty-two patients experienced seromas, all but 5 of which were transient and required no intervention. No unanticipated adverse events occurred, and no tissue matrix required complete excision. There were 22 hernia (28%) recurrences by month 24. There was no correlation between infection-related events and hernia recurrence. The use of the intact, non-cross-linked, porcine, acellular dermal matrix, Strattice, in the repair of contaminated VIH in high-risk patients allowed for successful, single-stage reconstruction in >70% of patients followed for 24 months after repair. Published by Mosby, Inc.

  11. 3D ultrasound biomicroscopy for assessment of cartilage repair tissue: volumetric characterisation and correlation to established classification systems.

    PubMed

    Schöne, M; Männicke, N; Somerson, J S; Marquaß, B; Henkelmann, R; Mochida, J; Aigner, T; Raum, K; Schulz, R M

    2016-02-08

    Objective and sensitive assessment of cartilage repair outcomes lacks suitable methods. This study investigated the feasibility of 3D ultrasound biomicroscopy (UBM) to quantify cartilage repair outcomes volumetrically and their correlation with established classification systems. 32 sheep underwent bilateral treatment of a focal cartilage defect. One or two years post-operatively the repair outcomes were assessed and scored macroscopically (Outerbridge, ICRS-CRA), by magnetic resonance imaging (MRI, MOCART), and histopathology (O'Driscoll, ICRS-I and ICRS-II). The UBM data were acquired after MRI and used to reconstruct the shape of the initial cartilage layer, enabling the estimation of the initial cartilage thickness and defect volume as well as volumetric parameters for defect filling, repair tissue, bone loss and bone overgrowth. The quantification of the repair outcomes revealed high variations in the initial thickness of the cartilage layer, indicating the need for cartilage thickness estimation before creating a defect. Furthermore, highly significant correlations were found for the defect filling estimated from UBM to the established classification systems. 3D visualisation of the repair regions showed highly variable morphology within single samples. This raises the question as to whether macroscopic, MRI and histopathological scoring provide sufficient reliability. The biases of the individual methods will be discussed within this context. UBM was shown to be a feasible tool to evaluate cartilage repair outcomes, whereby the most important objective parameter is the defect filling. Translation of UBM into arthroscopic or transcutaneous ultrasound examinations would allow non-destructive and objective follow-up of individual patients and better comparison between the results of clinical trials.

  12. Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era

    PubMed Central

    Perry, Christina; Agarwal, Devika; Abdel-Fatah, Tarek M.A.; Lourdusamy, Anbarasu; Grundy, Richard; Auer, Dorothee T.; Walker, David; Lakhani, Ravi; Scott, Ian S.; Chan, Stephen; Ball, Graham; Madhusudan, Srinivasan

    2014-01-01

    Deregulation of multiple DNA repair pathways may contribute to aggressive biology and therapy resistance in gliomas. We evaluated transcript levels of 157 genes involved in DNA repair in an adult glioblastoma Test set (n=191) and validated in ‘The Cancer Genome Atlas’ (TCGA) cohort (n=508). A DNA repair prognostic index model was generated. Artificial neural network analysis (ANN) was conducted to investigate global gene interactions. Protein expression by immunohistochemistry was conducted in 61 tumours. A fourteen DNA repair gene expression panel was associated with poor survival in Test and TCGA cohorts. A Cox multivariate model revealed APE1, NBN, PMS2, MGMT and PTEN as independently associated with poor prognosis. A DNA repair prognostic index incorporating APE1, NBN, PMS2, MGMT and PTEN stratified patients in to three prognostic sub-groups with worsening survival. APE1, NBN, PMS2, MGMT and PTEN also have predictive significance in patients who received chemotherapy and/or radiotherapy. ANN analysis of APE1, NBN, PMS2, MGMT and PTEN revealed interactions with genes involved in transcription, hypoxia and metabolic regulation. At the protein level, low APE1 and low PTEN remain associated with poor prognosis. In conclusion, multiple DNA repair pathways operate to influence biology and clinical outcomes in adult high grade gliomas. PMID:25026297

  13. Preparation and Characterization of Biomimetic Hydroxyapatite-Resorbable Polymer Composites for Hard Tissue Repair

    NASA Astrophysics Data System (ADS)

    Hiebner, Kristopher Robert

    Autografts are the orthopedic "gold standard" for repairing bone voids. Autografts are osteoconductive and do not elicit an immune response, but they are in short supply and require a second surgery to harvest the bone graft. Allografts are currently the most common materials used for the repair of segmental defects in hard tissue. Unlike autografts, allografts can cause an undesirable immune response and the possibility of disease transmission is a major concern. As an alternative to the above approaches, recent research efforts have focused on the use of composite materials made from hydroxyapatite (HA) and bioresorbable polymers, such as poly-L-lactide (PLLA). Recent results have shown that the surface hydroxides on HA can initiate the ring opening polymerization (ROP) of L-lactide and other lactones creating a composite with superior interfacial strength. This thesis demonstrates that the surface of porous biologically derived HA substrates, such as coralline HA and trabecular bone, can be used to initiate the ROP of L-lactide and other lactones from the vapor phase. This process increases the strength of the porous scaffold through the deposition of a thin, uniform polymer coating, while maintaining the porous structure. The kinetics of the chemical vapor deposition polymerization (CVDP) are described using a quartz crystal microbalance (QCM). The reaction temperature and monomer vapor pressure are found to affect the rate of the polymerization. Also described in this thesis is the preparation of a porous polymer scaffold that mimics the structure of demineralized bone matrix (DBM). This demineralized bone matrix simulant (DBMS) is created using anorganic bovine bone as a template to initiate the polymerization of various lactones, followed by the removal of the HA scaffold. This material retained its shape and exhibits mechanical properties superior to DBM. Finally it is shown that HA can be used to initiate the ROP of a-caprolactam and the biocompatibility

  14. The adult brain tissue response to hollow fiber membranes of varying surface architecture with or without cotransplanted cells

    NASA Astrophysics Data System (ADS)

    Zhang, Ning

    A variety of biomaterials have been chronically implanted into the central nervous system (CNS) for repair or therapeutic purposes. Regardless of the application, chronic implantation of materials into the CNS induces injury and elicits a wound healing response, eventually leading to the formation of a dense extracellular matrix (ECM)-rich scar tissue that is associated with the segregation of implanted materials from the surrounding normal tissue. Often this reaction results in impaired performance of indwelling CNS devices. In order to enhance the performance of biomaterial-based implantable devices in the CNS, this thesis investigated whether adult brain tissue response to implanted biomaterials could be manipulated by changing biomaterial surface properties or further by utilizing the biology of co-transplanted cells. Specifically, the adult rat brain tissue response to chronically implanted poly(acrylonitrile-vinylchloride) (PAN-PVC) hollow fiber membranes (HFMs) of varying surface architecture were examined temporally at 2, 4, and 12 weeks postimplantation. Significant differences were discovered in the brain tissue response to the PAN-PVC HFMs of varying surface architecture at 4 and 12 weeks. To extend this work, whether the soluble factors derived from a co-transplanted cellular component further affect the brain tissue response to an implanted HFM in a significant way was critically exploited. The cells used were astrocytes, whose ability to influence scar formation process following CNS injury by physical contact with the host tissue had been documented in the literature. Data indicated for the first time that astrocyte-derived soluble factors ameliorate the adult brain tissue reactivity toward HFM implants in an age-dependent manner. While immature astrocytes secreted soluble factors that suppressed the brain tissue reactivity around the implants, mature astrocytes secreted factors that enhanced the gliotic response. These findings prove the feasibility

  15. Cardiac function in adults following minimally invasive repair of pectus excavatum†

    PubMed Central

    Udholm, Sebastian; Maagaard, Marie; Pilegaard, Hans; Hjortdal, Vibeke

    2016-01-01

    OBJECTIVES To study if minimally invasive repair of pectus excavatum (PE) in adult patients would improve cardiopulmonary function at rest and during exercise as we have found previously in young and adolescent patients with PE. METHODS Nineteen adult patients (>21 year of age) were studied at rest and during bicycle exercise before surgery and 1 year postoperatively. Lung spirometry was performed at rest. Cardiac output, heart rate and aerobic exercise capacity were measured using a photo-acoustic gas-rebreathing technique during rest and exercise. Data are shown as mean ± standard deviation. RESULTS Fifteen patients completed the 1-year follow-up. No significant differences were found in neither cardiac output (14.0 ± 0.9 l min at baseline vs 14.8 ± 1.1 l min after surgery; P = 0.2029), nor maximum oxygen uptake (30.4 ± 1.9 and 33.3 ± 1.6 ml/kg/min; P = 0.0940 postoperatively). The lung spirometry was also unchanged, with no difference in forced expiratory capacity during the first second. CONCLUSIONS Correction of PE in adult patients does not improve the cardiopulmonary function 1 year after surgery as seen in children and adolescents. PMID:26860899

  16. Adult stem cells for cardiac repair: a choice between skeletal myoblasts and bone marrow stem cells.

    PubMed

    Ye, Lei; Haider, Husnain Kh; Sim, Eugene K W

    2006-01-01

    The real promise of a stem cell-based approach for cardiac regeneration and repair lies in the promotion of myogenesis and angiogenesis at the site of the cell graft to achieve both structural and functional benefits. Despite all of the progress and promise in this field, many unanswered questions remain; the answers to these questions will provide the much-needed breakthrough to harness the real benefits of cell therapy for the heart in the clinical perspective. One of the major issues is the choice of donor cell type for transplantation. Multiple cell types with varying potentials have been assessed for their ability to repopulate the infarcted myocardium; however, only the adult stem cells, that is, skeletal myoblasts (SkM) and bone marrow-derived stem cells (BMC), have been translated from the laboratory bench to clinical use. Which of these two cell types will provide the best option for clinical application in heart cell therapy remains arguable. With results pouring in from the long-term follow-ups of previously conducted phase I clinical studies, and with the onset of phase II clinical trials involving larger population of patients, transplantation of stem cells as a sole therapy without an adjunct conventional revascularization procedure will provide a deeper insight into the effectiveness of this approach. The present article discusses the pros and cons of using SkM and BMC individually or in combination for cardiac repair, and critically analyzes the progress made with each cell type.

  17. Should we abandon regional anesthesia in open inguinal hernia repair in adults?

    PubMed

    Bakota, B; Kopljar, M; Baranovic, S; Miletic, M; Marinovic, M; Vidovic, D

    2015-09-17

    Inguinal hernia repair is a common worldwide surgical procedure usually done in the outpatient setting. The purpose of this systematic review is to make an evidence-based meta-analysis to determine the possible benefits of regional (neuraxial block) anesthesia compared to general anesthesia in open inguinal hernia repair in adults. Cochrane Library, Medline, EMBASE, CINAHL, SCI-EXPANDED, SCOPUS as well as trial registries, conference proceedings and reference lists were searched. Only randomized controlled trials (RCT) that compare neuraxial block (spinal or/and epidural) anesthesia (NABA) and general anesthesia (GA) were included. Main outcome measures were postoperative complications, urinary retention and postoperative pain. Seven RCTs were included in this review. A total of 308 patients were analyzed with 154 patients in each group. Overall complications were evenly distributed in NABA and in GA group [OR 1.17, 95 % CI (0.52-2.66)]. Urinary retention was statistically less frequent in GA group compared to NABA group [OR 0.25, 95 % CI (0.08-0.74)]. Movement-associated pain score 24 h after surgery was significantly lower in NABA group [SMD 5.59, 95 % CI (3.69-7.50)]. Time of first analgesia application was shorter in GA group [SMD 8.99, 95 % CI 6.10-11.89]. Compared to GA, NABA appears to be a more adequate technique in terms of postoperative pain control. However, when GA is applied, patients seem to have less voiding problems.

  18. Vascular Endothelial Growth Factor Receptor Expression During Embryogenesis and Tissue Repair Suggests a Role in Endothelial Differentiation and Blood Vessel Growth

    NASA Astrophysics Data System (ADS)

    Peters, Kevin G.; de Vries, Carlie; Williams, Lewis T.

    1993-10-01

    Vascular endothelial growth factor (VEGF) is a polypeptide mitogen that stimulates the growth of endothelial cells in vitro and promotes the growth of blood vessels in vivo. We have recently shown that the fms-like receptor tyrosine kinase (flt) is a receptor for VEGF. Here we used in situ hybridization to show that, in adult mouse tissues, the pattern of flt expression was consistent with localization in endothelium. We also show that flt was expressed in endothelium during neovascularization of healing skin wounds and during early vascular development in mouse embryos. Moreover, flt was expressed in populations of embryonic cells from which endothelium is derived such as early yolk sac mesenchyme. The expression of flt in the endothelium of both developing and mature blood vessels suggests that VEGF might regulate endothelial differentiation, blood vessel growth, and vascular repair.

  19. Exercise capacity, physical activity, and obesity in adults with repaired aortic coarctation.

    PubMed

    Buys, Roselien; Budts, Werner; Delecluse, Christophe; Vanhees, Luc

    2013-01-01

    Patients with aortic coarctation (COA) have a reduced exercise capacity and seem to be more prone to adopt a sedentary lifestyle. During clinical practice, we often observe that patients seem to be overweight. However, data on physical activity and weight status in this population are currently not available. This study aimed to describe weight status, self-reported physical activity levels, and self-perceived health status in adults with repaired COA in comparison with healthy counterparts and to investigate the relationships among exercise capacity, physical activity, weight status, and perceived health status. We studied 103 COA patients who underwent cardiopulmonary exercise testing and who completed the Flemish Physical Activity Computerized Questionnaire and the short-form 36 health survey questionnaire. Patients with COA show a significantly lower exercise tolerance than what would be expected in healthy persons (P < .0001). Weight status was similar to the overall Belgian population, but a tendency toward higher body mass index was present. Patients with COA report a lower level of habitual physical activity (P < .05) as well as reductions in perceived vitality, general health, and mental health (P < .05). Parameters of habitual physical activity are related to exercise capacity (total energy expenditure: r = 0.278, P = .0015). The more active COA patients report higher scores of perceived physical functioning, general health, and mental health. Overweight patients did not perform significantly different than patients with a healthy weight did. Adults with repaired COA have a reduced exercise tolerance, which is related to low physical activity levels. Up to one-third of the COA patients we studied are overweight. As a poor exercise capacity identifies patients at risk for hospitalization and death and obesity might adversely influence the development of cardiovascular disease, it is important to improve the exercise capacity in these patients. Guiding

  20. Tissue adhesives for meniscus tear repair: an overview of current advances and prospects for future clinical solutions.

    PubMed

    Bochyńska, A I; Hannink, G; Grijpma, D W; Buma, P

    2016-05-01

    Menisci are crucial structures in the knee joint as they play important functions in load transfer, maintaining joint stability and in homeostasis of articular cartilage. Unfortunately, ones of the most frequently occurring knee injuries are meniscal tears. Particularly tears in the avascular zone of the meniscus usually do not heal spontaneously and lead to pain, swelling and locking of the knee joint. Eventually, after a (partial) meniscectomy, they will lead to osteoarthritis. Current treatment modalities to repair tears and by that restore the integrity of the native meniscus still carry their drawbacks and a new robust solution is desired. A strong tissue adhesive could provide such a solution and could potentially improve on sutures, which are the current gold standard. Moreover, a glue could serve as a carrier for biological compounds known to enhance tissue healing. Only few tissue adhesives, e.g., Dermabond(®) and fibrin glue, are already successfully used in clinical practice for other applications, but are not considered suitable for gluing meniscus tissue due to their sub-optimal mechanical properties or toxicity. There is a growing interest and research field focusing on the development of novel polymer-based tissue adhesives, but up to now, there is no material specially designed for the repair of meniscal tears. In this review, we discuss the current clinical gold standard treatment of meniscal tears and present an overview of new developments in this field. Moreover, we discuss the properties of different tissue adhesives for their potential use in meniscal tear repair. Finally, we formulate recommendations regarding the design criteria of material properties and adhesive strength for clinically applicable glues for meniscal tears.

  1. Host tissue response by the expression of collagen to cyanoacrylate adhesives used in implant fixation for abdominal hernia repair.

    PubMed

    Pascual, Gemma; Rodríguez, Marta; Pérez-Köhler, Bárbara; Mesa-Ciller, Claudia; Fernández-Gutiérrez, Mar; San Román, Julio; Bellón, Juan M

    2017-04-01

    The less traumatic use of surgical adhesives rather than sutures for mesh fixation in hernia repair has started to gain popularity because they induce less host tissue damage and provoke less postoperative pain. This study examines the host tissue response to a new cyanoacrylate (CA) adhesive (n-octyl, OCA). Partial defects (3 × 5 cm) created in the rabbit anterior abdominal wall were repaired by mesh fixation using OCA, Glubran2(®)(n-butyl-CA), Ifabond(®)(n-hexyl-CA) or sutures. Samples were obtained at 14/90 days for morphology, collagens qRT-PCR/immunofluorescence and biomechanical studies. All meshes were successfully fixed. Seroma was detected mainly in the Glubran group at 14 days. Meshes fixed using all methods showed good host tissue incorporation. No signs of degradation of any of the adhesives were observed. At 14 days, collagen 1 and 3 mRNA expression levels were greater in the suture and OCA groups, and lower in Ifabond, with levels varying significantly in the latter group with respect to the others. By 90 days, expression levels had fallen in all groups, except for collagen 3 mRNA in Ifabond. Collagen I and III protein expression was marked in the suture and OCA groups at 90 days, but lower in Ifabond at both time points. Tensile strengths were similar across groups. Our findings indicate the similar behavior of the adhesives to sutures in terms of good tissue incorporation of the meshes and optimal repair zone strength. The lower seroma rate and similar collagenization to controls induced by OCA suggests its improved behavior over the other two glues. This article deals with a preclinical study to examine different aspects of the repair process in the host of three alkyl cyanoacrylates (n-butyl (GLUBRAN 2), n-hexyl (IFABOND), and n-octyl cyanoacrylate (EVOBOND)) compared to sutures (control), in the fixation of surgical meshes for hernia repair. It goes into detail about collagen deposition in the repair zone at short and medium term. The

  2. Tissue-type plasminogen activator deficiency delays bone repair: roles of osteoblastic proliferation and vascular endothelial growth factor.

    PubMed

    Kawao, Naoyuki; Tamura, Yukinori; Okumoto, Katsumi; Yano, Masato; Okada, Kiyotaka; Matsuo, Osamu; Kaji, Hiroshi

    2014-08-01

    Further development in research of bone regeneration is necessary to meet the clinical demand for bone reconstruction. Recently, we reported that plasminogen is crucial for bone repair through enhancement of vessel formation. However, the details of the role of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) in the bone repair process still remain unknown. Herein, we examined the effects of plasminogen activators on bone repair after a femoral bone defect using tPA-deficient (tPA(-/-)) and uPA-deficient (uPA(-/-)) mice. Bone repair of the femur was delayed in tPA(-/-) mice, unlike that in wild-type (tPA(+/+)) mice. Conversely, the bone repair was comparable between wild-type (uPA(+/+)) and uPA(-/-) mice. The number of proliferative osteoblasts was decreased at the site of bone damage in tPA(-/-) mice. Moreover, the proliferation of primary calvarial osteoblasts was reduced in tPA(-/-) mice. Recombinant tPA facilitated the proliferation of mouse osteoblastic MC3T3-E1 cells. The proliferation enhanced by tPA was antagonized by the inhibition of endogenous annexin 2 by siRNA and by the inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation in MC3T3-E1 cells. Vessel formation as well as the levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were decreased at the damaged site in tPA(-/-) mice. Our results provide novel evidence that tPA is crucial for bone repair through the facilitation of osteoblast proliferation related to annexin 2 and ERK1/2 as well as enhancement of vessel formation related to VEGF and HIF-1α at the site of bone damage. Copyright © 2014 the American Physiological Society.

  3. Irradiation by pulsed Nd:YAG laser induces the production of extracellular matrix molecules by cells of the connective tissues: a tool for tissue repair

    NASA Astrophysics Data System (ADS)

    Monici, Monica; Basile, Venere; Cialdai, Francesca; Romano, Giovanni; Fusi, Franco; Conti, Antonio

    2008-04-01

    Many studies demonstrated that mechanical stress is a key factor for tissue homeostasis, while unloading induce loss of mass and impairment of function. Because of their physiological function, muscle, connective tissue, bone and cartilage dynamically interact with mechanical and gravitational stress, modifying their properties through the continuous modification of their composition. Indeed, it is known that mechanical stress increases the production of extracellular matrix (ECM) components by cells, but the mechanotransduction mechanisms and the optimal loading conditions required for an optimal tissue homeostasis are still unknown. Considering the importance of cell activation and ECM production in tissue regeneration, a proper use of mechanical stimulation could be a powerful tool in tissue repair and tissue engineering. Studies exploring advanced modalities for supplying mechanical stimuli are needed to increase our knowledge on mechanobiology and to develop effective clinical applications. Here we describe the effect of photomechanical stress, supplied by a pulsed Nd:YAG laser on ECM production by cells of connective tissues. Cell morphology, production of ECM molecules (collagens, fibronectin, mucopolysaccharides), cell adhesion and cell energy metabolism have been studied by using immunofluorescence and autofluorescence microscopy. The results show that photomechanical stress induces cytoskeleton remodelling, redistribution of membrane integrins, increase in production of ECM molecules. These results could be of consequence for developing clinical protocols for the treatment of connective tissue dideases by pulsed Nd:YAG laser.

  4. Comparative potential of juvenile and adult human articular chondrocytes for cartilage tissue formation in three-dimensional biomimetic hydrogels.

    PubMed

    Smeriglio, Piera; Lai, Janice H; Dhulipala, Lakshmi; Behn, Anthony W; Goodman, Stuart B; Smith, Robert L; Maloney, William J; Yang, Fan; Bhutani, Nidhi

    2015-01-01

    Regeneration of human articular cartilage is inherently limited and extensive efforts have focused on engineering the cartilage tissue. Various cellular sources have been studied for cartilage tissue engineering including adult chondrocytes, and embryonic or adult stem cells. Juvenile chondrocytes (from donors below 13 years of age) have recently been reported to be a promising cell source for cartilage regeneration. Previous studies have compared the potential of adult and juvenile chondrocytes or adult and osteoarthritic (OA) chondrocytes. To comprehensively characterize the comparative potential of young, old, and diseased chondrocytes, here we examined cartilage formation by juvenile, adult, and OA chondrocytes in three-dimensional (3D) biomimetic hydrogels composed of poly(ethylene glycol) and chondroitin sulfate. All three human articular chondrocytes were encapsulated in the 3D biomimetic hydrogels and cultured for 3 or 6 weeks to allow maturation and extracellular matrix formation. Outcomes were analyzed using quantitative gene expression, immunofluorescence staining, biochemical assays, and mechanical testing. After 3 and 6 weeks, juvenile chondrocytes showed a greater upregulation of chondrogenic gene expression than adult chondrocytes, while OA chondrocytes showed a downregulation. Aggrecan and type II collagen deposition and glycosaminoglycan accumulation were high for juvenile and adult chondrocytes but not for OA chondrocytes. Similar trend was observed in the compressive moduli of the cartilage constructs generated by the three different chondrocytes. In conclusion, the juvenile, adult and OA chondrocytes showed differential responses in the 3D biomimetic hydrogels. The 3D culture model described here may also provide a useful tool to further study the molecular differences among chondrocytes from different stages, which can help elucidate the mechanisms for age-related decline in the intrinsic capacity for cartilage repair.

  5. An in Vitro Study on Tissue Repair: Impact of Unloading on Cells Involved in the Remodelling Phase

    NASA Astrophysics Data System (ADS)

    Monici, Monica; Cialdai, Francesca; Romano, Giovanni; Fusi, Franco; Egli, Marcel; Pezzatini, Silvia; Morbidelli, Lucia

    2011-11-01

    The number of astronauts involved in long-lasting missions and extra-vehicular activities is going to increase in the future. Consequently, the chance of injury due to traumatic events or unexpected emergency surgery will also increase and medical evacuation times to earth will be prolonged. Hence, the need to address requirements for surgery and trauma care in non terrestrial environments will be a priority. Tissue repair in weightlessness should therefore be regarded as a major issue not enough studied to date. Wound healing is a complex multi-step process, crucial to the survival of the organism. It starts with an inflammatory phase followed by a remodelling phase. During repair, the extracellular matrix (ECM) is sequentially remodelled by the concerted action of different cell types, in order to rebuild a functional tissue. The available literature concerning wound healing with mechanical unloading presents controversial results. However, many studies indicate impairment of the healing processes. Here we present a study on the behaviour of cells involved in the remodelling phase of repair, e.g. fibroblasts and endothelial cells, in response to microgravity ( μg). In particular, their adhesion/migration, cytoskeleton organization, production of ECM molecules and receptors have been investigated. Cell response to pulsed Nd: YAG laser irradiation has also been investigated in order to evaluate the possibility to use laser irradiation for counteracting the effect of μg on wound healing. In μg, we observed alterations in production/assembling of ECM molecules. Increased fibronectin (FN) and laminin (LM) could be the cause for impaired ECM rebuilding and altered cell adhesion/migration. Treatment with Nd:YAG laser pulses induced organized fibrillogenesis and favoured endothelial cell spreading and monolayer formation. These findings open the way for a better understanding of tissue repair mechanisms in space and future clinical applications on earth.

  6. High-dose mode of mortality in Tribolium: A model system for study of radiation injury and repair in non-proliferative tissues

    SciTech Connect

    Cheng, Chihing Christina.

    1989-01-01

    With appropriate doses of ionizing radiation, both the acute, or lethal-midlethal, dose-independent pattern of mortality, and the hyperacute, dose-dependent pattern, were demonstrated within a single insect genus (Tribolium). This demonstration provides resolution of apparently contradictory reports of insect radiation responses in terms of doses required to cause lethality and those based on survival time as a function of dose. A dose-dependent mortality pattern was elicited in adult Tribolium receiving high doses, viz., 300 Gy or greater; its time course was complete in 10 days, before the dose-independent pattern of mortality began. Visual observations of heavily-irradiated Tribolium suggested neural and/or neuromuscular damage, as had been previously proposed by others for lethally-irradiated wasps, flies, and mosquitoes. Results of experiments using fractionated high doses supported the suggestion that the hyperacute or high-dose mode of death is the result of damage to nonproliferative tissues. Relative resistance of a strain to the hyperacute or high-dose mode of death was not correlated with resistance to the midlethal mode, which is believed to be the result of damage to the proliferative cells of the midgut. Using the high-dose mode of death as a model of radiation damage to nonproliferative tissues, the effects of age, and of a moderate priming dose were assessed. Beetles showed age-related increase in sensitivity to the high-dose mode of death, suggesting a decline in capacity to repair radiation damage to postmitotic tissue. This correlated with a decrease (50%) in the amount of repair reflected in the sparing effect of dose-fractionation (SDF) between the age of 1 to 3 months. The age related increase in radiosensitivity was reduced by a moderate priming dose (40 or 65 Gy) given at a young age.

  7. Temporal changes in tissue repair permit survival of diet-restricted rats from an acute lethal dose of thioacetamide.

    PubMed

    Ramaiah, S K; Bucci, T J; Warbritton, A; Soni, M G; Mehendale, H M

    1998-10-01

    Although, diet restriction (DR) has been shown to substantially increase longevity while reducing or delaying the onset of age-related diseases, little is known about the mechanisms underlying the beneficial effects of DR on acute toxic outcomes. An earlier study (S. K. Ramaiah et al., 1998, Toxicol. Appl. Pharmacol. 150, 12-21) revealed that a 35% DR compared to ad libitum (AL) feeding leads to a substantial increase in liver injury of thioacetamide (TA) at a low dose (50 mg/kg, i.p.). Higher liver injury was accompanied by enhanced survival. A prompt and enhanced tissue repair response in DR rats at the low dose (sixfold higher liver injury) occurred, whereas at equitoxic doses (50 mg/kg in DR and 600 mg/kg in AL rats) tissue repair in AL rats was substantially diminished and delayed. The extent of liver injury did not appear to be closely related to the extent of stimulated tissue repair response. The purpose of the present study was to investigate the time course (0-120 h) of liver injury and liver tissue repair at the high dose (600 mg TA/kg, i.p., lethal in AL rats) in AL and DR rats. Male Sprague-Dawley rats (225-275 g) were 35% diet restricted compared to their AL cohorts for 21 days and on day 22 they received a single dose of TA (600 mg/kg, i.p.). Liver injury was assessed by plasma ALT and by histopathological examination of liver sections. Tissue repair was assessed by [3H]thymidine incorporation into hepatonuclear DNA and proliferating cell nuclear antigen (PCNA) immunohistochemistry during 0-120 h after TA injection. In AL-fed rats hepatic necrosis was evident at 12 h, peaked at 60 h, and persisted thereafter until mortality (3 to 6 days). Peak liver injury was approximately twofold higher in DR rats compared to that seen in AL rats. Hepatic necrosis was evident at 36 h, peaked at 48 h, persisted until 96 h, and returned to normal by 120 h. Light microscopy of liver sections revealed progression of hepatic injury in AL rats whereas injury regressed

  8. Microporous calcium phosphate ceramics as tissue engineering scaffolds for the repair of osteochondral defects: biomechanical results.

    PubMed

    Mayr, H O; Klehm, J; Schwan, S; Hube, R; Südkamp, N P; Niemeyer, P; Salzmann, G; von Eisenhardt-Rothe, R; Heilmann, A; Bohner, M; Bernstein, A

    2013-01-01

    This work investigated the suitability of microporous β-tricalcium phosphate (TCP) scaffolds pre-seeded with autologous chondrocytes for treatment of osteochondral defects in a large animal model. Microporous β-TCP cylinders (Ø 7 mm; length 25 mm) were seeded with autologous chondrocytes and cultured for 4 weeks in vitro. Only the upper end of the cylinder was seeded with chondrocytes. Chondrocytes formed a multilayer on the top. The implants were then implanted in defects (diameter 7 mm) created in the left medial femoral condyle of ovine knees. The implants were covered with synovial membrane from the superior recess of the same joint. For the right knees, an empty defect with the same dimensions served as control. Twenty-eight sheep were split into 6-, 12-, 26- and 52 week groups of seven animals. Indentation tests with a spherical (Ø 3mm) indenter were used to determine the biomechanical properties of regenerated tissue. A software-based limit switch was implemented to ensure a maximal penetration depth of 200 μm and maximal load of 1.5 N. The achieved load, the absorbed energy and the contact stiffness were measured. Newly formed cartilage was assessed with the International Cartilage Repair Society Visual Assessment Scale (ICRS score) and histomorphometric analysis. Results were analysed statistically using the t-test, Mann-Whitney U-test and Wilcoxon test. Statistical significance was set at p<0.05. After 6 weeks of implantation, the transplanted area tolerated an indentation load of 0.05±0.20 N. This value increased to 0.10±0.06 N after 12 weeks, to 0.27±0.18 N after 26 weeks, and 0.27±0.11 N after 52 weeks. The increase in the tolerated load was highly significant (p<0.0001), but the final value was not significantly different from that of intact cartilage (0.30±0.12 N). Similarly, the increase in contact stiffness from 0.87±0.29 N mm-(1) after 6 weeks to 3.14±0.86 N mm(-1) after 52 weeks was highly significant (p<0.0001). The absorbed energy

  9. Disrupted G{sub 1} to S phase clearance via cyclin signaling impairs liver tissue repair in thioacetamide-treated type 1 diabetic rats

    SciTech Connect

    Devi, Sachin S.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2005-09-01

    Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute liver injury owing to inhibited hepatic tissue repair, primarily due to blockage of G{sub 0} to S phase progression of cell division cycle. On the other hand, DB rats receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a delay in recovery from liver injury and survival. The objective of the present study was to test the hypothesis that impaired cyclin-regulated progression of G{sub 1} to S phase of the cell cycle may explain inhibited liver tissue repair, hepatic failure, and death, contrasted with delayed liver tissue repair but survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg) exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb, inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg TA/kg exhibited delayed up regulation of MAPK signaling that delayed the expression of CD1 and pRb, explaining delayed stimulation of tissue repair observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent adverse effect on cyclin-regulated pRb signaling: the lower dose causes a recoverable delay, whereas the higher dose inhibits it with corresponding effect on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse effect is substantially shifted to the left of the dose response curve in diabetes.

  10. Zone-specific integrated cartilage repair using a scaffold-free tissue engineered construct derived from allogenic synovial mesenchymal stem cells: Biomechanical and histological assessments.

    PubMed

    Fujie, Hiromichi; Nansai, Ryosuke; Ando, Wataru; Shimomura, Kazunori; Moriguchi, Yu; Hart, David A; Nakamura, Norimasa

    2015-11-26

    The purpose of the present study was to investigate the zone-specific integration properties of articular cartilage defects treated in vivo with scaffold-free three-dimensional tissue-engineered constructs (TECs) derived from allogenic synovial mesenchymal stem cells (MSCs) in a porcine model. The TEC derived from the synovial MSCs was implanted into chondral defects in the medial femoral condyle of the knee. The integration boundary of repair tissue with the adjacent host cartilage was morphologically and biomechanically evaluated at 6 months post-implantation. Histological assessments showed that the repair tissue in each zone was well integrated with the adjacent host cartilage, with an apparent secure continuity of the extracellular matrix. There were no significant differences in histological scores between the integration boundary and the center of the repair tissue at every zone. Nonetheless, in all the specimens subjected to mechanical testing, failure occurred at the integration boundary. The average tensile strength of the integration boundary vs normal cartilage was 0.6 vs 4.9, 3.0 vs 12.6, and 5.5 vs 12.8MPa at the superficial, middle, and deep layers, respectively. Thus, these results indicate the most fragile point in the repair tissue remained at the integration boundary in spite of the apparent secure tissue continuity and equivalent histological quality with the center of the repair tissue. Such tissue vulnerability at the surface integration boundary could affect the long-term durability of the tissue repair, and thus, special consideration will be needed in the post-operative rehabilitation programming to enhance the longevity of such repair tissues in response to normal knee loading.

  11. Effect of Locally Administered Ciliary Neurotrophic Factor on the Survival of Transected and Repaired Adult Sheep Facial Nerve

    PubMed Central

    Al Abri, Rashid; Kolethekkat, Arif Ali; Kelleher, Michael O.; Myles, Lynn M.; Glasby, Michael A.

    2014-01-01

    Objective to determine whether the administration of Ciliary Neurotrophic Factor (CNTF) at the site of repaired facial nerve enhances regeneration in the adult sheep model. Methods Ten adult sheep were divided into 2 groups: control and study group (CNTF group). In the CNTF group, the buccal branch of the facial nerve was transected and then repaired by epineural sutures. CNTF was injected over the left depressor labii maxillaris muscle in the vicinity of the transected and repaired nerve for 28 days under local anesthesia. In the CNTF group, the sheep were again anesthetized after nine months and the site of facial nerve repair was exposed. Detailed electrophysiological, tension experiments and morphometric studies were carried out and then analyzed statistically. Results The skin CV min, refractory period, Jitter and tension parameters were marginally raised in the CNTF group than the control but the difference was statistically insignificant between the two groups. Morphometric indices also did not show any significant changes in the CNTF group. Conclusion CNTF has no profound effect on neuronal regeneration of adult sheep animal model. Keywords CNTF; Neurtrophic factors; Sheep; Facial nerve; Regeneration. PMID:24936272

  12. Effect of locally administered ciliary neurotrophic factor on the survival of transected and repaired adult sheep facial nerve.

    PubMed

    Al Abri, Rashid; Kolethekkat, Arif Ali; Kelleher, Michael O; Myles, Lynn M; Glasby, Michael A

    2014-05-01

    to determine whether the administration of Ciliary Neurotrophic Factor (CNTF) at the site of repaired facial nerve enhances regeneration in the adult sheep model. Ten adult sheep were divided into 2 groups: control and study group (CNTF group). In the CNTF group, the buccal branch of the facial nerve was transected and then repaired by epineural sutures. CNTF was injected over the left depressor labii maxillaris muscle in the vicinity of the transected and repaired nerve for 28 days under local anesthesia. In the CNTF group, the sheep were again anesthetized after nine months and the site of facial nerve repair was exposed. Detailed electrophysiological, tension experiments and morphometric studies were carried out and then analyzed statistically. The skin CV min, refractory period, Jitter and tension parameters were marginally raised in the CNTF group than the control but the difference was statistically insignificant between the two groups. Morphometric indices also did not show any significant changes in the CNTF group. CNTF has no profound effect on neuronal regeneration of adult sheep animal model. CNTF; Neurtrophic factors; Sheep; Facial nerve; Regeneration.

  13. A Tissue-Engineered Muscle Repair Construct for Functional Restoration of an Irrecoverable Muscle Injury in a Murine Model

    PubMed Central

    Machingal, Masood A.; Corona, Benjamin T.; Walters, Thomas J.; Kesireddy, Venu; Koval, Christine N.; Dannahower, Ashley; Zhao, Weixin; Yoo, James J.

    2011-01-01

    There are no effective clinical treatments for volumetric muscle loss (VML) resulting from traumatic injury, tumor excision, or other degenerative diseases of skeletal muscle. The goal of this study was to develop and characterize a more clinically relevant tissue-engineered muscle repair (TE-MR) construct for functional restoration of a VML injury in the mouse lattissimus dorsi (LD) muscle. To this end, TE-MR constructs developed by seeding rat myoblasts on porcine bladder acellular matrix were preconditioned in a bioreactor for 1 week and implanted in nude mice at the site of a VML injury created by excising 50% of the native LD. Two months postinjury and implantation of TE-MR, maximal tetanic force was ∼72% of that observed in native LD muscle. In contrast, injured LD muscles that were not repaired, or were repaired with scaffold alone, produced only ∼50% of native LD muscle force after 2 months. Histological analyses of LD tissue retrieved 2 months after implantation demonstrated remodeling of the TE-MR construct as well as the presence of desmin-positive myofibers, blood vessels, and neurovascular bundles within the TE-MR construct. Overall, these encouraging initial observations document significant functional recovery within 2 months of implantation of TE-MR constructs and provide clear proof of concept for the applicability of this technology in a murine VML injury model. PMID:21548710

  14. Effect of low-level laser therapy on tissue repair after dental extraction in rats administered zoledronic acid and dexamethasone

    NASA Astrophysics Data System (ADS)

    Weber, João Batista Blessmann; Camilotti, Renata Stifelman; Jasper, Juliana; Casagrande, Liliane Cristina Onofre; Maito, Fábio Luiz Dal Moro

    2017-05-01

    Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic and oncological pathologies involving the skeletal system. Because of the severity of the BP associated osteonecrosis of the jaws, the difficulties of treatment, and patient discomfort, additional support methods for their management are needed. Laser therapy has an easy handling, photobiostimulator effect on tissues healing, so it can be considered a preferred therapy. The aim of this study was to evaluate the influence of low-level laser therapy in the 685- and 830-nm wavelength in the healing process of the bone and soft tissues in rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that underwent a surgery for the extraction of upper molars. There were statistically significant differences in the clinical evaluation of the wound and the weight of the animals. Regarding the histological evaluation, it was possible to observe the different maturations of the healing stage between groups. The effect of drug therapy with ZA and dexamethasone in the bone tissue repair process induces osteonecrosis of the jaw in rats and slows down the healing process. In the laser groups, at the stipulated dosimetry, a positive influence on the bone and soft tissue repair process was observed.

  15. Spred-2 expression is associated with neural repair of injured adult zebrafish brain.

    PubMed

    Lim, Fei Tieng; Ogawa, Satoshi; Parhar, Ishwar S

    2016-11-01

    Sprouty-related protein-2 (Spred-2) is a negative regulator of extracellular signal-regulated kinases (ERK) pathway, which is important for cell proliferation, neuronal differentiation, plasticity and survival. Nevertheless, its general molecular characteristics such as gene expression patterns and potential role in neural repair in the brain remain unknown. Thus, this study aimed to characterise the expression of spred-2 in the zebrafish brain. Digoxigenin-in situ hybridization showed spred-2 mRNA-expressing cells were mainly seen in the proliferative zones such as the olfactory bulb, telencephalon, optic tectum, cerebellum, and the dorsal and ventral hypothalamus, and most of which were neuronal cells. To evaluate the potential role of spred-2 in neuro-regeneration, spred-2 gene expression was examined in the dorsal telencephalon followed by mechanical-lesion. Real-time PCR showed a significant reduction of spred-2 mRNA levels in the telencephalon on 1-day till 2-days post-lesion and gradually increased to normal levels as compared with intact. Furthermore, to confirm involvement of Spred-2 signalling in the cell proliferation after brain injury, double-labelling of spred-2 in-situ hybridization with immunofluorescence of BrdU and phosphorylated-ERK1/2 (p-ERK1/2), a downstream of Spred-2 was performed. Increase of BrdU and p-ERK1/2 immunoreactive cells suggest that a decrease in spred-2 after injury might associated with activation of the ERK pathway to stimulate cell proliferation in the adult zebrafish brain. The present study demonstrates the possible role of Spred-2 signalling in cell proliferative phase during the neural repair in the injured zebrafish brain.

  16. Plasma Levels of High Sensitivity Cardiac Troponin T in Adults with Repaired Tetralogy of Fallot

    PubMed Central

    Lai, Clare T. M.; Wong, Sophia J.; Ip, Janice J. K.; Wong, Wai-keung; Tsang, Kwong-cheong; Lam, Wendy W. M.; Cheung, Yiu-fai

    2015-01-01

    Detectable low circulating level of cardiac troponin T (cTnT) may reflect subclinical myocardial injury. We tested the hypothesis that circulating levels of hs-cTnT are altered in adults with repaired tetralogy of Fallot (TOF) and associated with ventricular volume load and function. Eighty-eight TOF patients and 48 controls were studied. Plasma hs-cTnT levels were determined using a highly sensitive assay (hs-cTnT). The right (RV) and left ventricular (LV) volumes and ejection fraction (EF) were measured using 3D echocardiography and, in 52 patients, cardiac magnetic resonance (CMR). The median (interquartile range) for male and female patients were 4.87 (3.83–6.62) ng/L and 3.11 (1.00–3.87) ng/L, respectively. Thirty percent of female but none of the male patients had increased hs-cTnT levels. Female patients with elevated hs-cTnT levels, compared to those without, had greater RV end-diastolic and end-systolic volumes and LV systolic dyssynchrony index (all p < 0.05). For patient cohort only, hs-cTnT levels correlated positively with CMR-derived RV end-diastolic volume and negatively with echocardiography-derived LV and RV EF (all p < 0.05). Multiple linear regression identified sex and RV EF as significant correlates of log-transformed hs-cTnT levels. Increased hs-cTnT levels occur in 30% of female patients after TOF repair, and are associated with greater RV volumes and worse RV EF. PMID:26360613

  17. Effects of implantation of three-dimensional engineered bone tissue with a vascular-like structure on repair of bone defects

    NASA Astrophysics Data System (ADS)

    Nishi, Masanori; Matsumoto, Rena; Dong, Jian; Uemura, Toshimasa

    2012-12-01

    Previously, to create an implantable bone tissue associated with blood vessels, we co-cultured rabbit bone marrow mesenchymal stem cells (MSCs) with MSC-derived endothelial cells (ECs) within a porous polylactic acid-based scaffold utilizing a rotating wall vessel (RWV) bioreactor. Here, this engineered tissue was orthotopically implanted into defects made in femurs of immunodeficient rats, and histological analysis were carried out to examine the repair of the damage and the formation of bone around the implant. The bone defects were better repaired in the implanted group than control group after 3 weeks. The results indicate that the engineered bone could repair bone defects.

  18. Adult stem cells from the hyaluronic acid-rich node and duct system differentiate into neuronal cells and repair brain injury.

    PubMed

    Lee, Seung J; Park, Sang H; Kim, Yu I; Hwang, Sunhee; Kwon, Patrick M; Han, In S; Kwon, Byoung S

    2014-12-01

    The existence of a hyaluronic acid-rich node and duct system (HAR-NDS) within the lymphatic and blood vessels was demonstrated previously. The HAR-NDS was enriched with small (3.0-5.0 μm in diameter), adult stem cells with properties similar to those of the very small embryonic-like stem cells (VSELs). Sca-1(+)Lin(-)CD45(-) cells were enriched approximately 100-fold in the intravascular HAR-NDS compared with the bone marrow. We named these adult stem cells "node and duct stem cells (NDSCs)." NDSCs formed colonies on C2C12 feeder layers, were positive for fetal alkaline phosphatase, and could be subcultured on the feeder layers. NDSCs were Oct4(+)Nanog(+)SSEA-1(+)Sox2(+), while VSELs were Oct4(+)Nanog(+)SSEA-1(+)Sox2(-). NDSCs had higher sphere-forming efficiency and proliferative potential than VSELs, and they were found to differentiate into neuronal cells in vitro. Injection of NDSCs into mice partially repaired ischemic brain damage. Thus, we report the discovery of potential adult stem cells that may be involved in tissue regeneration. The intravascular HAR-NDS may serve as a route that delivers these stem cells to their target tissues.

  19. Adult Stem Cells from the Hyaluronic Acid-Rich Node and Duct System Differentiate into Neuronal Cells and Repair Brain Injury

    PubMed Central

    Lee, Seung J.; Park, Sang H.; Kim, Yu I.; Hwang, Sunhee; Kwon, Patrick M.; Han, In S.

    2014-01-01

    The existence of a hyaluronic acid-rich node and duct system (HAR-NDS) within the lymphatic and blood vessels was demonstrated previously. The HAR-NDS was enriched with small (3.0–5.0 μm in diameter), adult stem cells with properties similar to those of the very small embryonic-like stem cells (VSELs). Sca-1+Lin−CD45− cells were enriched approximately 100-fold in the intravascular HAR-NDS compared with the bone marrow. We named these adult stem cells “node and duct stem cells (NDSCs).” NDSCs formed colonies on C2C12 feeder layers, were positive for fetal alkaline phosphatase, and could be subcultured on the feeder layers. NDSCs were Oct4+Nanog+SSEA-1+Sox2+, while VSELs were Oct4+Nanog+SSEA-1+Sox2−. NDSCs had higher sphere-forming efficiency and proliferative potential than VSELs, and they were found to differentiate into neuronal cells in vitro. Injection of NDSCs into mice partially repaired ischemic brain damage. Thus, we report the discovery of potential adult stem cells that may be involved in tissue regeneration. The intravascular HAR-NDS may serve as a route that delivers these stem cells to their target tissues. PMID:25027245

  20. Extensive traumatic anterior skull base fractures with cerebrospinal fluid leak: classification and repair techniques using combined vascularized tissue flaps.

    PubMed

    Archer, Jacob B; Sun, Hai; Bonney, Phillip A; Zhao, Yan Daniel; Hiebert, Jared C; Sanclement, Jose A; Little, Andrew S; Sughrue, Michael E; Theodore, Nicholas; James, Jeffrey; Safavi-Abbasi, Sam

    2016-03-01

    This article introduces a classification scheme for extensive traumatic anterior skull base fracture to help stratify surgical treatment options. The authors describe their multilayer repair technique for cerebrospinal fluid (CSF) leak resulting from extensive anterior skull base fracture using a combination of laterally pediculated temporalis fascial-pericranial, nasoseptal-pericranial, and anterior pericranial flaps. Retrospective chart review identified patients treated surgically between January 2004 and May 2014 for anterior skull base fractures with CSF fistulas. All patients were treated with bifrontal craniotomy and received pedicled tissue flaps. Cases were classified according to the extent of fracture: Class I (frontal bone/sinus involvement only); Class II (extent of involvement to ethmoid cribriform plate); and Class III (extent of involvement to sphenoid bone/sinus). Surgical repair techniques were tailored to the types of fractures. Patients were assessed for CSF leak at follow-up. The Fisher exact test was applied to investigate whether the repair techniques were associated with persistent postoperative CSF leak. Forty-three patients were identified in this series. Thirty-seven (86%) were male. The patients' mean age was 33 years (range 11-79 years). The mean overall length of follow-up was 14 months (range 5-45 months). Six fractures were classified as Class I, 8 as Class II, and 29 as Class III. The anterior pericranial flap alone was used in 33 patients (77%). Multiple flaps were used in 10 patients (3 salvage) (28%)--1 with Class II and 9 with Class III fractures. Five (17%) of the 30 patients with Class II or III fractures who received only a single anterior pericranial flap had persistent CSF leak (p < 0.31). No CSF leak was found in patients who received multiple flaps. Although postoperative CSF leak occurred only in high-grade fractures with single anterior flap repair, this finding was not significant. Extensive anterior skull base

  1. Alkaline diets favor lean tissue mass in older adults1234

    PubMed Central

    Dawson-Hughes, Bess; Harris, Susan S; Ceglia, Lisa

    2008-01-01

    Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women. PMID:18326605

  2. Alkaline diets favor lean tissue mass in older adults.

    PubMed

    Dawson-Hughes, Bess; Harris, Susan S; Ceglia, Lisa

    2008-03-01

    Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid-producing protein and cereal grains relative to their content of net alkali-producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Subjects were 384 men and women > or =65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight/weight x 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. At baseline, the mean urinary potassium excretion was 67.0 +/- 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (beta = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 +/- 3.6%. Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.

  3. Interleukin-10–mediated regenerative postnatal tissue repair is dependent on regulation of hyaluronan metabolism via fibroblast-specific STAT3 signaling

    PubMed Central

    Balaji, Swathi; Wang, Xinyi; King, Alice; Le, Louis D.; Bhattacharya, Sukanta S.; Moles, Chad M.; Butte, Manish J.; de Jesus Perez, Vinicio A.; Liechty, Kenneth W.; Wight, Thomas N.; Crombleholme, Timothy M.; Bollyky, Paul L.; Keswani, Sundeep G.

    2017-01-01

    The cytokine IL-10 has potent antifibrotic effects in models of adult fibrosis, but the mechanisms of action are unclear. Here, we report a novel finding that IL-10 triggers a signal transducer and activator of transcription 3 (STAT3)–dependent signaling pathway that regulates hyaluronan (HA) metabolism and drives adult fibroblasts to synthesize an HA-rich pericellular matrix, which mimics the fetal regenerative wound healing phenotype with reduced fibrosis. By using cre-lox–mediated novel, inducible, fibroblast-, keratinocyte-, and wound-specific STAT3-knockdown postnatal mice—plus syngeneic fibroblast cell-transplant models—we demonstrate that the regenerative effects of IL-10 in postnatal wounds are dependent on HA synthesis and fibroblast-specific STAT3-dependent signaling. The importance of IL-10–induced HA synthesis for regenerative wound healing is demonstrated by inhibition of HA synthesis in a murine wound model by administering 4-methylumbelliferone. Although IL-10 and STAT3 signaling were intact, the antifibrotic repair phenotype that is induced by IL-10 overexpression was abrogated in this model. Our data show a novel role for IL-10 beyond its accepted immune-regulatory mechanism. The opportunity for IL-10 to regulate a fibroblast-specific formation of a regenerative, HA-rich wound extracellular matrix may lead to the development of innovative therapies to attenuate postnatal fibrosis in organ systems or diseases in which dysregulated inflammation and HA intersect.—Balaji, S., Wang, X., King, A., Le, L. D., Bhattacharya, S. S., Moles, C. M., Butte, M. J., de Jesus Perez, V. A., Liechty, K. W., Wight, T. N., Crombleholme, T. M., Bollyky, P. L., Keswani, S. G. Interleukin-10–mediated regenerative postnatal tissue repair is dependent on regulation of hyaluronan metabolism via fibroblast-specific STAT3 signaling. PMID:27903619

  4. Interleukin-10-mediated regenerative postnatal tissue repair is dependent on regulation of hyaluronan metabolism via fibroblast-specific STAT3 signaling.

    PubMed

    Balaji, Swathi; Wang, Xinyi; King, Alice; Le, Louis D; Bhattacharya, Sukanta S; Moles, Chad M; Butte, Manish J; de Jesus Perez, Vinicio A; Liechty, Kenneth W; Wight, Thomas N; Crombleholme, Timothy M; Bollyky, Paul L; Keswani, Sundeep G

    2017-03-01

    The cytokine IL-10 has potent antifibrotic effects in models of adult fibrosis, but the mechanisms of action are unclear. Here, we report a novel finding that IL-10 triggers a signal transducer and activator of transcription 3 (STAT3)-dependent signaling pathway that regulates hyaluronan (HA) metabolism and drives adult fibroblasts to synthesize an HA-rich pericellular matrix, which mimics the fetal regenerative wound healing phenotype with reduced fibrosis. By using cre-lox-mediated novel, inducible, fibroblast-, keratinocyte-, and wound-specific STAT3-knockdown postnatal mice-plus syngeneic fibroblast cell-transplant models-we demonstrate that the regenerative effects of IL-10 in postnatal wounds are dependent on HA synthesis and fibroblast-specific STAT3-dependent signaling. The importance of IL-10-induced HA synthesis for regenerative wound healing is demonstrated by inhibition of HA synthesis in a murine wound model by administering 4-methylumbelliferone. Although IL-10 and STAT3 signaling were intact, the antifibrotic repair phenotype that is induced by IL-10 overexpression was abrogated in this model. Our data show a novel role for IL-10 beyond its accepted immune-regulatory mechanism. The opportunity for IL-10 to regulate a fibroblast-specific formation of a regenerative, HA-rich wound extracellular matrix may lead to the development of innovative therapies to attenuate postnatal fibrosis in organ systems or diseases in which dysregulated inflammation and HA intersect.-Balaji, S., Wang, X., King, A., Le, L. D., Bhattacharya, S. S., Moles, C. M., Butte, M. J., de Jesus Perez, V. A., Liechty, K. W., Wight, T. N., Crombleholme, T. M., Bollyky, P. L., Keswani, S. G. Interleukin-10-mediated regenerative postnatal tissue repair is dependent on regulation of hyaluronan metabolism via fibroblast-specific STAT3 signaling. © The Author(s).

  5. What We Should Know Before Using Tissue Engineering Techniques to Repair Injured Tendons: A Developmental Biology Perspective

    PubMed Central

    Liu, Chia-Feng; Aschbacher-Smith, Lindsey; Barthelery, Nicolas J.; Dyment, Nathaniel; Butler, David

    2011-01-01

    Tendons connect muscles to bones, and serve as the transmitters of force that allow all the movements of the body. Tenocytes are the basic cellular units of tendons, and produce the collagens that form the hierarchical fiber system of the tendon. Tendon injuries are common, and difficult to repair, particularly in the case of the insertion of tendon into bone. Successful attempts at cell-based repair therapies will require an understanding of the normal development of tendon tissues, including their differentiated regions such as the fibrous mid-section and fibrocartilaginous insertion site. Many genes are known to be involved in the formation of tendon. However, their functional roles in tendon development have not been fully characterized. Tissue engineers have attempted to generate functional tendon tissue in vitro. However, a lack of knowledge of normal tendon development has hampered these efforts. Here we review studies focusing on the developmental mechanisms of tendon development, and discuss the potential applications of a molecular understanding of tendon development to the treatment of tendon injuries. PMID:21314435

  6. What we should know before using tissue engineering techniques to repair injured tendons: a developmental biology perspective.

    PubMed

    Liu, Chia-Feng; Aschbacher-Smith, Lindsey; Barthelery, Nicolas J; Dyment, Nathaniel; Butler, David; Wylie, Christopher

    2011-06-01

    Tendons connect muscles to bones, and serve as the transmitters of force that allow all the movements of the body. Tenocytes are the basic cellular units of tendons, and produce the collagens that form the hierarchical fiber system of the tendon. Tendon injuries are common, and difficult to repair, particularly in the case of the insertion of tendon into bone. Successful attempts at cell-based repair therapies will require an understanding of the normal development of tendon tissues, including their differentiated regions such as the fibrous mid-section and fibrocartilaginous insertion site. Many genes are known to be involved in the formation of tendon. However, their functional roles in tendon development have not been fully characterized. Tissue engineers have attempted to generate functional tendon tissue in vitro. However, a lack of knowledge of normal tendon development has hampered these efforts. Here we review studies focusing on the developmental mechanisms of tendon development, and discuss the potential applications of a molecular understanding of tendon development to the treatment of tendon injuries.

  7. Enhanced potency of cell-based therapy for ischemic tissue repair using an injectable bioactive epitope presenting nanofiber support matrix.

    PubMed

    Tongers, Jörn; Webber, Matthew J; Vaughan, Erin E; Sleep, Eduard; Renault, Marie-Ange; Roncalli, Jerome G; Klyachko, Ekaterina; Thorne, Tina; Yu, Yang; Marquardt, Katja-Theres; Kamide, Christine E; Ito, Aiko; Misener, Sol; Millay, Meredith; Liu, Ting; Jujo, Kentaro; Qin, Gangjian; Losordo, Douglas W; Stupp, Samuel I; Kishore, Raj

    2014-09-01

    The translation of cell-based therapies for ischemic tissue repair remains limited by several factors, including poor cell survival and limited target site retention. Advances in nanotechnology enable the development of specifically designed delivery matrices to address these limitations and thereby improve the efficacy of cell-based therapies. Given the relevance of integrin signaling for cellular homeostasis, we developed an injectable, bioactive peptide-based nanofiber matrix that presents an integrin-binding epitope derived from fibronectin, and evaluated its feasibility as a supportive artificial matrix for bone marrow-derived pro-angiogenic cells (BMPACs) used as a therapy in ischemic tissue repair. Incubation of BMPACs with these peptide nanofibers in vitro significantly attenuated apoptosis while enhancing proliferation and adhesion. Pro-angiogenic function was enhanced, as cells readily formed tubes. These effects were, in part, mediated via p38, and p44/p42 MAP kinases, which are downstream pathways of focal adhesion kinase. In a murine model of hind limb ischemia, an intramuscular injection of BMPACs within this bioactive peptide nanofiber matrix resulted in greater retention of cells, enhanced capillary density, increased limb perfusion, reduced necrosis/amputation, and preserved function of the ischemic limb compared to treatment with cells alone. This self-assembling, bioactive peptide nanofiber matrix presenting an integrin-binding domain of fibronectin improves regenerative efficacy of cell-based strategies in ischemic tissue by enhancing cell survival, retention, and reparative functions.

  8. [Repair of large and deep skin and soft tissue defects around the knee joints with free latissimus dorsi musculocutaneous flaps].

    PubMed

    Zhang, Minghua; Cui, Xu; Zeng, Jizhang; Liu, Xiong; Huang, Mitao; Zhang, Pihong; Huang, Xiaoyuan

    2015-10-01

    To investigate the clinical efficacy of free latissimus dorsi musculocutaneous flaps in repairing large and deep skin and soft tissue defects around the knee joints. Twenty-five patients with large and deep skin and soft tissue defects around the knee joints were hospitalized from March 2005 to March 2014. The area of defects around the knee joints ranged from 10 cm × 8 cm to 43 cm × 23 cm. The free latissimus dorsi musculocutaneous flaps were used to repair the defects, with the area ranging from 12 cm × 10 cm to 45 cm × 25 cm. The thoracodorsal artery and its concomitant vein of the musculocutaneous flap were anastomosed to the descending branch of the lateral circumflex femoral artery and its concomitant vein respectively to reconstruct blood supply. Split-thickness skin grafts around the flap donor sites were harvested to cover the muscle surface of the musculocutaneous flaps. The flap donor sites were closed directly with suture, and the skin donor sites were healed by dressing change. All the 25 flaps survived without vascular crisis. The flaps were in satisfactory appearance. The flap donor sites were healed with linear scar. All the patients were followed up for 3 to 6 months. At last, they were able to stand up and walk. The free latissimus dorsi musculocutaneous flap transplantation is an effective treatment for the repair of large and deep soft tissue defects around the knee joints, and the descending branch of lateral circumflex femoral artery and its concomitant vein are the appropriate recipient vessels.

  9. Single-Walled Carbon Nanotubes Chemically Functionalized with Polyethylene Glycol Promote Tissue Repair in a Rat Model of Spinal Cord Injury

    PubMed Central

    Roman, Jose A.; Niedzielko, Tracy L.; Haddon, Robert C.; Parpura, Vladimir

    2011-01-01

    Abstract Traumatic spinal cord injury (SCI) induces tissue damage and results in the formation of a cavity that inhibits axonal regrowth. Filling this cavity with a growth-permissive substrate would likely promote regeneration and repair. Single-walled carbon nanotubes functionalized with polyethylene glycol (SWNT-PEG) have been shown to increase the length of selected neurites in vitro. We hypothesized that administration of SWNT-PEG after experimental SCI will promote regeneration of axons into the lesion cavity and functional recovery of the hindlimbs. To evaluate this hypothesis, complete transection SCI was induced at the T9 vertebral level in adult female rats. One week after transection, the epicenter of the lesion was injected with 25 μL of either vehicle (saline), or 1 μg/mL, 10 μg/mL, or 100 μg/mL of SWNT-PEG. Behavioral analysis was conducted before injury, before treatment, and once every 7 days for 28 days after treatment. At 28 days post-injection the rats were euthanized and spinal cord tissue was extracted. Immunohistochemistry was used to detect the area of the cyst, the extent of the glial scar, and axonal morphology. We found that post-SCI administration of SWNT-PEG decreased lesion volume, increased neurofilament-positive fibers and corticospinal tract fibers in the lesion, and did not increase reactive gliosis. Additionally, post-SCI administration of SWNT-PEG induced a modest improvement in hindlimb locomotor recovery without inducing hyperalgesia. These data suggest that SWNT-PEG may be an effective material to promote axonal repair and regeneration after SCI. PMID:21303267

  10. Single-walled carbon nanotubes chemically functionalized with polyethylene glycol promote tissue repair in a rat model of spinal cord injury.

    PubMed

    Roman, Jose A; Niedzielko, Tracy L; Haddon, Robert C; Parpura, Vladimir; Floyd, Candace L

    2011-11-01

    Traumatic spinal cord injury (SCI) induces tissue damage and results in the formation of a cavity that inhibits axonal regrowth. Filling this cavity with a growth-permissive substrate would likely promote regeneration and repair. Single-walled carbon nanotubes functionalized with polyethylene glycol (SWNT-PEG) have been shown to increase the length of selected neurites in vitro. We hypothesized that administration of SWNT-PEG after experimental SCI will promote regeneration of axons into the lesion cavity and functional recovery of the hindlimbs. To evaluate this hypothesis, complete transection SCI was induced at the T9 vertebral level in adult female rats. One week after transection, the epicenter of the lesion was injected with 25??L of either vehicle (saline), or 1??g/mL, 10??g/mL, or 100??g/mL of SWNT-PEG. Behavioral analysis was conducted before injury, before treatment, and once every 7 days for 28 days after treatment. At 28 days post-injection the rats were euthanized and spinal cord tissue was extracted. Immunohistochemistry was used to detect the area of the cyst, the extent of the glial scar, and axonal morphology. We found that post-SCI administration of SWNT-PEG decreased lesion volume, increased neurofilament-positive fibers and corticospinal tract fibers in the lesion, and did not increase reactive gliosis. Additionally, post-SCI administration of SWNT-PEG induced a modest improvement in hindlimb locomotor recovery without inducing hyperalgesia. These data suggest that SWNT-PEG may be an effective material to promote axonal repair and regeneration after SCI.

  11. Generation of hyaline cartilaginous tissue from mouse adult dermal fibroblast culture by defined factors

    PubMed Central

    Hiramatsu, Kunihiko; Sasagawa, Satoru; Outani, Hidetatsu; Nakagawa, Kanako; Yoshikawa, Hideki; Tsumaki, Noriyuki

    2011-01-01

    Repair of cartilage injury with hyaline cartilage continues to be a challenging clinical problem. Because of the limited number of chondrocytes in vivo, coupled with in vitro de-differentiation of chondrocytes into fibrochondrocytes, which secrete type I collagen and have an altered matrix architecture and mechanical function, there is a need for a novel cell source that produces hyaline cartilage. The generation of induced pluripotent stem (iPS) cells has provided a tool for reprogramming dermal fibroblasts to an undifferentiated state by ectopic expression of reprogramming factors. Here, we show that retroviral expression of two reprogramming factors (c-Myc and Klf4) and one chondrogenic factor (SOX9) induces polygonal chondrogenic cells directly from adult dermal fibroblast cultures. Induced cells expressed marker genes for chondrocytes but not fibroblasts, i.e., the promoters of type I collagen genes were extensively methylated. Although some induced cell lines formed tumors when subcutaneously injected into nude mice, other induced cell lines generated stable homogenous hyaline cartilage–like tissue. Further, the doxycycline-inducible induction system demonstrated that induced cells are able to respond to chondrogenic medium by expressing endogenous Sox9 and maintain chondrogenic potential after substantial reduction of transgene expression. Thus, this approach could lead to the preparation of hyaline cartilage directly from skin, without generating iPS cells. PMID:21293062

  12. Adult Tissue Sources for New β-cells

    PubMed Central

    Nichols, Robert J.; New, Connie; Annes, Justin P.

    2014-01-01

    The diabetes pandemic incurs extraordinary public health and financial costs that are projected to expand for the foreseeable future. Consequently, the development of definitive therapies for diabetes is a priority. Currently, a wide spectrum of therapeutic strategies, from implantable insulin-delivery devices to transplantation-based cell replacement therapy, to β-cell regeneration, focus on replacing the lost insulin-production capacity of diabetics. Among these, β-cell regeneration remains promising but heretofore unproven. Indeed, recent experimental work has uncovered surprising biology that underscores the potential therapeutic benefit of β-cell regeneration. These studies have elucidated a variety of sources for the endogenous production of new β-cells from existing cells. First, β-cells, long thought to be post-mitotic, have demonstrate potential for regenerative capacity. Second, the presence of pancreatic facultative endocrine progenitor cells has been established. Third, the malleability of cellular identity has availed the possibility of generating β-cells from other differentiated cell types. Here, we will review the exciting developments surrounding endogenous sources of β-cell production and consider the potential of realizing a regenerative therapy for diabetes from adult tissues. PMID:24345765

  13. Expression of heparanase in soft tissue sarcomas of adults

    PubMed Central

    2014-01-01

    Background Heparanase is an endo-β-D-glucuronidase that cleaves heparan sulfate chains of proteoglycans, resulting in the disassembly of the extracellular matrix. Heparanase has a central role in the development of various tumors, and its expression has been associated with increased tumor growth, angiogenesis and metastasis, but there is insufficient information about the function of heparanase in sarcomas. Study aims 1) To evaluate heparanase levels in adult soft tissue sarcomas (STS); 2) To examine the correlation between heparanase levels and pathological and clinical parameters and treatment outcome. Methods Pathological specimens of primary or metastatic STS were subjected to immunohistochemical analysis applying an anti-heparanase antibody. The clinical and the pathological data, together with the data of heparanase levels, were evaluated in a logistic regression model for tumor recurrence and survival. Results One hundred and one samples were examined, 55 from primary tumors and 46 from metastatic sites. A high expression of heparanase was observed in 29 (52.7%) and 22 specimens (47.8%), respectively. There was no statistically significant difference between heparanase expressions in the primary vs. metastatic sites of tumors. Moreover, no correlation was observed between heparanase staining and tumor aggressiveness, tumor recurrence or patient survival in various groups of patients. Conclusion Expression of heparanase was observed in 50% of the STS, in various histological subtypes. A larger study with homogenous groups of specific sub-types of STS or stages of disease is required to validate over-expression of heparanase as a marker of disease aggressiveness. PMID:24887057

  14. In-situ crosslinkable and self-assembling elastin-like polypeptide block copolymers for cartilage tissue repair

    NASA Astrophysics Data System (ADS)

    Lim, Dong Woo

    This work describes the development of genetically engineered elastin-like polypeptide (ELP) block copolymers as in-situ gelling scaffolds for cartilage tissue repair. The central hypothesis underlying this work is that ELP based biopolymers can be exploited as injectable biomaterials by rapid chemical crosslinking. To prove this, gene libraries encoding ELP having different molecular weights and amino acid sequences, and ELP block copolymers composed of various ELP blocks having diverse amino acid composition, length, and phase transition behavior were synthesized by recursive directional ligation, expressed in E. Coli and purified by inverse transition cycling. Mannich-type condensation of hydroxymethylphosphines (HMPs) with primary- and secondary-amines of amino acids was developed as a new crosslinking method of polypeptides. Chemically crosslinked ELP hydrogels were formed rapidly in an aqueous solution by reaction of ELPs containing periodic lysine residues with HMPs. The crosslinking density and mechanical property of the ELP hydrogels were controlled at the sequence level by varying the Lys density in ELPs composed of mono-block as well as by segregation of the Lys residues within specific blocks of tri-block architectures. Fibroblasts embedded in ELP hydrogels survived the crosslinking process and were viable after in vitro culture for at least 3 days. The DNA content of fibroblasts within the tri-block gels was significantly higher than that in the mono-block gels at day 3. These results suggest that the HMP crosslinked ELP block copolymer hydrogels show finely tuned mechanical properties and different microenvironments for cell viability as well as potential as in-situ crosslinkable biopolymers for tissue repair applications with load-bearing environments. As an alternative, rheological behavior of the ELP block copolymers and ELP-grafted hyaluronic acids (HAs) as artificial extracellular matrices (ECMs) showed that they were thermally aggregated into

  15. Loss of DNA mismatch repair imparts a selective advantage in planarian adult stem cells.

    PubMed

    Hollenbach, Jessica P; Resch, Alissa M; Palakodeti, Dasaradhi; Graveley, Brenton R; Heinen, Christopher D

    2011-01-01

    Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis.

  16. Loss of DNA Mismatch Repair Imparts a Selective Advantage in Planarian Adult Stem Cells

    PubMed Central

    Hollenbach, Jessica P.; Resch, Alissa M.; Palakodeti, Dasaradhi; Graveley, Brenton R.; Heinen, Christopher D.

    2011-01-01

    Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis. PMID:21747960

  17. Fan1 deficiency results in DNA interstrand cross-link repair defects, enhanced tissue karyomegaly, and organ dysfunction

    PubMed Central

    Thongthip, Supawat; Bellani, Marina; Gregg, Siobhan Q.; Sridhar, Sunandini; Conti, Brooke A.; Chen, Yanglu; Seidman, Michael M.; Smogorzewska, Agata

    2016-01-01

    Deficiency of FANCD2/FANCI-associated nuclease 1 (FAN1) in humans leads to karyomegalic interstitial nephritis (KIN), a rare hereditary kidney disease characterized by chronic renal fibrosis, tubular degeneration, and characteristic polyploid nuclei in multiple tissues. The mechanism of how FAN1 protects cells is largely unknown but is thought to involve FAN1's function in DNA interstrand cross-link (ICL) repair. Here, we describe a Fan1-deficient mouse and show that FAN1 is required for cellular and organismal resistance to ICLs. We show that the ubiquitin-binding zinc finger (UBZ) domain of FAN1, which is needed for interaction with FANCD2, is not required for the initial rapid recruitment of FAN1 to ICLs or for its role in DNA ICL resistance. Epistasis analyses reveal that FAN1 has cross-link repair activities that are independent of the Fanconi anemia proteins and that this activity is redundant with the 5′–3′ exonuclease SNM1A. Karyomegaly becomes prominent in kidneys and livers of Fan1-deficient mice with age, and mice develop liver dysfunction. Treatment of Fan1-deficient mice with ICL-inducing agents results in pronounced thymic and bone marrow hypocellularity and the disappearance of c-kit+ cells. Our results provide insight into the mechanism of FAN1 in ICL repair and demonstrate that the Fan1 mouse model effectively recapitulates the pathological features of human FAN1 deficiency. PMID:26980189

  18. Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues.

    PubMed

    Cohen, Shahar; Leshansky, Lucy; Zussman, Eyal; Burman, Michael; Srouji, Samer; Livne, Erella; Abramov, Natalie; Itskovitz-Eldor, Joseph

    2010-10-01

    The use of stem cells for tissue engineering (TE) encourages scientists to design new platforms in the field of regenerative and reconstructive medicine. Human embryonic stem cells (hESC) have been proposed to be an important cell source for cell-based TE applications as well as an exciting tool for investigating the fundamentals of human development. Here, we describe the efficient derivation of connective tissue progenitors (CTPs) from hESC lines and fetal tissues. The CTPs were significantly expanded and induced to generate tendon tissues in vitro, with ultrastructural characteristics and biomechanical properties typical of mature tendons. We describe a simple method for engineering tendon grafts that can successfully repair injured Achilles tendons and restore the ankle joint extension movement in mice. We also show the CTP's ability to differentiate into bone, cartilage, and fat both in vitro and in vivo. This study offers evidence for the possibility of using stem cell-derived engineered grafts to replace missing tissues, and sets a basic platform for future cell-based TE applications in the fields of orthopedics and reconstructive surgery.

  19. Estimation of dynamic, in vivo soft-tissue deformation: experimental technique and application in a canine model of tendon injury and repair.

    PubMed

    Bey, Michael J; Kline, Stephanie K; Baker, Andrew R; McCarron, Jesse A; Iannotti, Joseph P; Derwin, Kathleen A

    2011-06-01

    Outcomes after rotator cuff surgery are typically assessed with measures of strength, joint motion, or pain, but these measures do not provide a direct assessment of tissue function as healing progresses. To address this limitation, this manuscript describes biplane X-ray analysis as a technique for quantifying in vivo soft-tissue deformation. Tantalum beads were implanted in the humerus and infraspinatus tendon in a canine model of tendon injury and repair. Biplane X-ray images were acquired during treadmill trotting and tissue deformation was estimated from the three-dimensional bead positions. Changes over time were characterized by the mean, range, and normalized range (i.e., range/mean) of interbead distance. Intact tendon repair tissue demonstrated significant decreases over time in the mean (p = 0.003), range (p = 0.001), and normalized range (p = 0.001) of interbead distance. Failed tendon repair tissue demonstrated significant decreases over time in the range (p =  0.05) and normalized range (p = 0.04) of interbead distance. In an uninjured control, differences over time in the interbead distance parameters were not detected. This approach is a promising technique for estimating changes over time in soft-tissue deformation. These preliminary data indicate appreciable differences between normal tendons, intact repairs, and failed repairs. Copyright © 2010 Orthopaedic Research Society.

  20. Laser scanning microscopy as a means to assess the augmentation of tissue repair by exposition of wounds to tissue tolerable plasma

    NASA Astrophysics Data System (ADS)

    Vandersee, Staffan; Richter, Heike; Lademann, Jürgen; Beyer, Marc; Kramer, Axel; Knorr, Fanny; Lange-Asschenfeldt, Bernhard

    2014-11-01

    Confocal laser scan microscopy (CLSM) has emerged as a tool for in vivo assessment of cutaneous conditions. In particular, its use in wound healing assessment has increasingly moved into focus. In this context, the application of tissue tolerable plasma (TTP) for wound treatment has recently become one of the most innovative therapeutic modalities. We analyzed wound healing parameters such as area decline and histomorphological characteristics of tissue repair in six subjects with vacuum-generated wounds on the forearm with a four-armed design: (A) no treatment, (B) treatment with TTP, (C) treatment with octenidine, and (D) sequential treatment with TTP and octenidine. Assessment of the wounds was conducted during six visits over the course of two weeks. The wounds were analyzed by photography and CLSM. TTP treatment led to a more rapid area decline that was statistically significant in comparison to other treatment groups. Besides mild pain, it was well tolerated. Morphologically, wound healing was found to initiate from the edges with the formation of dendritic structures consisting of keratinocytes. CLSM is a valuable tool for assessing the dynamics of wound healing. TTP, for reasons that still need to be investigated, can accelerate wound repair.

  1. Sox2+ adult stem/progenitor cells are important for tissue regeneration and survival of mice

    PubMed Central

    Arnold, Katrin; Sarkar, Abby; Yram, Mary Anna; Polo, Jose M.; Bronson, Rod; Sengupta, Sumitra; Seandel, Marco; Geijsen, Niels; Hochedlinger, Konrad

    2012-01-01

    Summary The transcription factor Sox2 maintains the pluripotency of early embryonic cells and regulates the formation of several epithelia during fetal development. Whether Sox2 continues to play a role in adult tissues remains largely unknown. We here show that Sox2 marks adult cells in several epithelial tissues where its expression has not previously been characterized, including the stomach, cervix, anus, testes, lens and multiple glands. Genetic lineage tracing and transplantation experiments demonstrate that Sox2-expressing cells continuously give rise to mature cell types within these tissues, documenting their self-renewal and differentiation potentials. Consistent with these findings, ablation of Sox2+ cells in mice results in a disruption of epithelial tissue homeostasis and lethality. Developmental fate mapping reveals that Sox2+ adult stem cells originate from fetal Sox2+ tissue progenitors. Thus, our results identify Sox2 expression in numerous adult ectodermal and endodermal stem cell compartments, which are critical for normal tissue regeneration and survival. PMID:21982232

  2. Osteochondral repair using a scaffold-free tissue-engineered construct derived from synovial mesenchymal stem cells and a hydroxyapatite-based artificial bone.

    PubMed

    Shimomura, Kazunori; Moriguchi, Yu; Ando, Wataru; Nansai, Ryosuke; Fujie, Hiromichi; Hart, David A; Gobbi, Alberto; Kita, Keisuke; Horibe, Shuji; Shino, Konsei; Yoshikawa, Hideki; Nakamura, Norimasa

    2014-09-01

    For an ideal osteochondral repair, it is important to facilitate zonal restoration of the subchondral bone and the cartilage, layer by layer. Specifically, restoration of the osteochondral junction and secure integration with adjacent cartilage could be considered key factors. The purpose of the present study was to investigate the feasibility of a combined material comprising a scaffold-free tissue-engineered construct (TEC) derived from synovial mesenchymal stem cells (MSCs) and a hydroxyapatite (HA) artificial bone using a rabbit osteochondral defect model. Osteochondral defects were created on the femoral groove of skeletally mature rabbits. The TEC and HA artificial bone were hybridized to develop a combined implant just before use, which was then implanted into defects (N=23). In the control group, HA alone was implanted (N=18). Histological evaluation and micro-indentation testing was performed for the evaluation of repair tissue. Normal knees were used as an additional control group for biomechanical testing (N=5). At hybridization, the TEC rapidly attached onto the surface of HA artificial bone block, which was implantable to osteochondral defects. Osteochondral defects treated with the combined implants exhibited more rapid subchondral bone repair coupled with the development of cartilaginous tissue with good tissue integration to the adjacent host cartilage when assessed at 6 months post implantation. Conversely, the control group exhibited delayed subchondral bone repair. In addition, the repair cartilaginous tissue in this group had poor integration to adjacent cartilage and contained clustered chondrocytes, suggesting an early osteoarthritis (OA)-like degenerative change at 6 months post implantation. Biomechanically, the osteochondral repair tissue treated with the combined implants at 6 months restored tissue stiffness, similar to normal osteochondral tissue. The combined implants significantly accelerated and improved osteochondral repair

  3. Assessment of DNA Damage and Repair in Adults Consuming AllylIsothiocyanate or Brassica Vegetables

    PubMed Central

    Charron, Craig S.; Clevidence, Beverly A.; Albaugh, George A.; Kramer, Matthew H.; Vinyard, Bryan T.; Milner, John A.; Novotny, Janet A.

    2012-01-01

    Allylisothiocyanate (AITC) is a dietary component with possible anti-cancer effects, though much information about AITC and cancer has been obtained from cell studies. To investigate the effect of AITC on DNA integrity in vivo, a crossover study was conducted. Adults (n=46) consumed AITC, AITC-rich vegetables (mustard and cabbage), or a control treatment with a controlled diet for 10 days each. On day 11, volunteers provided blood and urine before and after consuming treatments. Volunteers were characterized for genotype for GSTM1 and GSTT1 (glutathione S-transferases) and XPD (DNA repair). DNA integrity in peripheral blood mononuclear cells (PBMCs) was assessed by single cell gel electrophoresis. Urine was analyzed for 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) and creatinine. Ten day intake of neither AITC nor mustard/cabbage(M/C) resulted in statistically significant differences in DNA strand breaks (LS mean % DNA in tail ± SEM: 4.8 ± 0.6 for control, 5.7 ± 0.7 for AITC, 5.3 ± 0.6 for M/C) or urinary 8-oxodG (LS mean µg 8-oxodG/g creatinine ± SEM: 2.95 ± 0.09 for control, 2.88 ± 0.09 for AITC, 3.06 ± 0.09 for M/C). Both AITC and M/C increased DNA strand breaks 3h post-consumption (LS mean % DNA in tail ± SEM: 3.2 ± 0.7 for control, 8.3 ± 1.7 for AITC, 8.0 ± 1.7 for M/C), and this difference disappeared at 6h (4.2 ± 0.9 for control, 5.7 ± 1.2 for AITC, 5.5 ± 1.2 for M/C). Genotypes for GSTM1, GSTT1, and XPD were not associated with treatment effects. In summary, DNA damage appeared to be induced in the short term by AITC and AITC-rich products, but that damage disappeared quickly, and neither AITC nor AITC-rich products affected DNA base excision repair. PMID:22902324

  4. Biomaterials/scaffolds. Design of bioactive, multiphasic PCL/collagen type I and type II-PCL-TCP/collagen composite scaffolds for functional tissue engineering of osteochondral repair tissue by using electrospinning and FDM techniques.

    PubMed

    Schumann, Detlef; Ekaputra, Andrew K; Lam, Christopher X F; Hutmacher, Dietmar W

    2007-01-01

    Current clinical therapies for traumatic or chronic injuries involving osteochondral tissue result in temporary pain reduction and filling of the defect but with biomechanically inferior repair tissue. Tissue engineering of osteochondral repair tissue using autologous cells and bioactive biomaterials has the potential to overcome the current limitations and results in native-like repair tissue with good integration capabilities. For this reason, we applied two modem biomaterial design techniques, namely, electrospinning and fused deposition modeling (FDM), to produce bioactive poly(epsilon-caprolactone)/collagen (PCL/Col) type I and type II-PCL-tri-calcium phosphate (TCP)/Col composites for precursor cell-based osteochondral repair. The application of these two design techniques (electrospinning and FDM) allowed us to specifically produce the a suitable three-dimensional (3D) environment for the cells to grow into a particular tissue (cartilage and bone) in vitro prior to in vivo implantation. We hypothesize that our new designed biomaterials, seeded with autologous bone marrow-derived precursor cells, in combination with bioreactor-stimulated cell-culture techniques can be used to produce clinically relevant osteochondral repair tissue.

  5. Furcation Perforation: Periradicular Tissue Response to Biodentine as a Repair Material by Histopathologic and Indirect Immunofluorescence Analyses.

    PubMed

    Silva, Lea Assed Bezerra; Pieroni, Karina Alessandra Michelão Grecca; Nelson-Filho, Paulo; Silva, Raquel Assed Bezerra; Hernandéz-Gatón, Patrícia; Lucisano, Marília Pacífico; Paula-Silva, Francisco Wanderley Garcia; de Queiroz, Alexandra Mussolino

    2017-07-01

    The purpose of this study was to evaluate the in vivo response of periradicular tissues after sealing of furcation perforations with Biodentine, mineral trioxide aggregate (MTA), and gutta-percha by means of histopathologic and indirect immunofluorescence analyses. Thirty teeth of 3 dogs were divided into 3 groups: Biodentine (n = 14 teeth), MTA (negative control, n = 10 teeth), and gutta-percha (positive control, n = 6 teeth). After endodontic treatment, perforations were made on the center of the pulp chamber floor and filled with the materials. After 120 days, the animals were killed, and blocks containing the teeth and periradicular tissues were processed histotechnically for histopathologic semiquantitative (new mineralized tissue formation and bone resorption at the perforation site) and quantitative (thickness and area of newly formed mineralized tissue and number of inflammatory cells) analyses and RUNX2 immunofluorescence assay. Data were analyzed by χ(2), Fisher exact test, Mann-Whitney test, one-way analysis of variance, Kruskal-Wallis test, and Dunn posttest (α = 0.05). MTA and Biodentine induced the formation of significantly more new mineralized tissue (P < .0001) than gutta-percha, which did not induce the formation of mineralized tissue in any case. Complete sealing of the perforations was more frequent with MTA, which formed mineralized tissue with greater thickness and area. Biodentine and MTA exhibited no bone resorption in the furcation region, fewer inflammatory cells, and greater RUNX2 immunostaining intensity than gutta-percha. Although MTA presented higher frequency of complete sealing and greater thickness and area of newly formed mineralized tissue, Biodentine also had good histopathologic results and can be considered as an adequate furcation perforation repair material. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  6. [Repair of skin and soft tissue defects on the wrist with reverse bi-pedicle posterior interosseous artery perforator flap].

    PubMed

    Li, Xiuquan; Sun, Guangfeng; Wang, Dali; Wei, Zairong; Qi, Jianping; Nie, Kaiyu; Jin, Wenhu; Deng, Chengliang; Li, Hai

    2014-10-01

    To explore the curative effect of reverse bi-pedicle posterior interosseous artery perforator flap in repairing skin and soft tissue defects on the wrist. Seven patients with soft tissue defects on the wrist, including simple skin and soft tissue defects in 4 cases and skin and soft tissue defects combined with radial tendon injury in 3 cases, were hospitalized from December 2010 to March 2012. The area of skin defect on the volar side of the wrist ranged from 4.8 cm x 4.0 cm to 6.2 cm x 4.5 cm, while that on the dorsal side ranged from 3.5 cm x 3.2 cm to 6. 5 cm x 5.4 cm. These wounds were respectively caused by traffic injury (3 cases), reamer injury (2 cases), burn (1 case), and tumor resection (1 case). Reverse bi-pedicle posterior interosseous artery perforator flaps were used to repair these defects, with area of one pedicle ranging from 2.5 cm x 2.0 cm to 3.5 cm x 2.5 cm and the area of the other pedicle ranging from 2.5 cm x 2.5 cm to 4.0 cm x 3.0 cm. The donor sites were closed by suturing. All flaps survived completely. Patients were followed up for 6 to 36 months. The color, texture, and appearance of all flaps were satisfactory. At last follow-up, distances of two-point discrimination of flaps ranged from 9 to 13 mm. The dorsal extension and palmar flexion functions of wrist were satisfactory. The results of function evaluation of 7 wrists were excellent in 6 cases and good in 1 case according to the tentative standards for the evaluation of upper extremity function of Society of Hand Surgery of Chinese Medical Association. A linear scar was formed at the donor site. The reverse bi-pedicle posterior interosseous artery perforator flap, with advantages of flexible design, easy to achieve, less injury to donor site, and reliable blood supply, etc., is another choice for repairing skin and soft tissue defects over the wrist.

  7. Fast Absorbing Gut Suture versus Cyanoacrylate Tissue Adhesive in the Epidermal Closure of Linear Repairs Following Mohs Micrographic Surgery

    PubMed Central

    Kim, June; Cool, Alicia J.; Hanlon, Allison M.; Leffell, David J.

    2015-01-01

    Background: Cyanoacrylate topical adhesives and fast absorbing gut sutures are increasingly utilized by dermatologic surgeons as they provide satisfactory surgical outcomes while eliminating an additional patient visit for suture removal. To date, no head-to-head studies have compared the wound healing characteristics of these epidermal closure techniques in the repair of facial wounds after Mohs micrographic surgery. Objective: To compare the cosmetic outcome of epidermal closure by cyanoacrylate topical adhesive with fast absorbing gut suture in linear repairs of the face following Mohs micrographic surgery. Methods: Fourteen patients with wound length greater than 3cm who underwent Mohs micrographic surgery for nonmelanoma skin cancer of the face were enrolled in this randomized right-left comparative study. Following placement of dermal sutures, half of the wound was randomly selected for closure with cyanoacrylate and the contralateral side with fast absorbing gut suture. Using photographs from the three-month postoperative visit, six blinded individuals rated the overall cosmetic outcome. Results: The present study shows no significant difference in cosmetic outcomes between cyanoacrylate and fast absorbing gut suture for closure of linear facial wounds resulting from Mohs micrographic surgery. Cyanoacrylate tissue adhesive may not be as effective in achieving optimal cosmesis for wounds on the forehead or of longer repair lengths. The majority of patients did not have a preference for wound closure techniques, but when a preference was given, cyanoacrylate was significantly favored over sutures. Conclusion: Cyanoacrylate tissue adhesive and fast absorbing gut suture both result in comparable aesthetic outcomes for epidermal closure of linear facial wounds following Mohs micrographic surgery. Consideration should be given to factors such as need for eversion, hemostasis, and wound tension when selecting an epidermal wound closure method. (Clinical

  8. 3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair.

    PubMed

    Jang, Jinah; Park, Hun-Jun; Kim, Seok-Won; Kim, Heejin; Park, Ju Young; Na, Soo Jin; Kim, Hyeon Ji; Park, Moon Nyeo; Choi, Seung Hyun; Park, Sun Hwa; Kim, Sung Won; Kwon, Sang-Mo; Kim, Pum-Joon; Cho, Dong-Woo

    2017-01-01

    Stem cell therapy is a promising therapeutic method for the treatment of ischemic heart diseases; however, some challenges prohibit the efficacy after cell delivery due to hostile microenvironment of the injured myocardium. 3D printed pre-vascularized stem cell patch can enhance the therapeutic efficacy for cardiac repair through promotion of rapid vascularization after patch transplantation. In this study, stem cell-laden decellularized extracellular matrix bioinks are used in 3D printing of pre-vascularized and functional multi-material structures. The printed structure composed of spatial patterning of dual stem cells improves cell-to-cell interactions and differentiation capability and promotes functionality for tissue regeneration. The developed stem cell patch promoted strong vascularization and tissue matrix formation in vivo. The patterned patch exhibited enhanced cardiac functions, reduced cardiac hypertrophy and fibrosis, increased migration from patch to the infarct area, neo-muscle and capillary formation along with improvements in cardiac functions. Therefore, pre-vascularized stem cell patch provides cardiac niche-like microenvironment, resulting in beneficial effects on cardiac repair.

  9. Modeling the functional repair of nervous tissue in spinal cord injury

    NASA Astrophysics Data System (ADS)

    Mantila, Sara M.; Camp, Jon J.; Krych, Aaron J.; Robb, Richard A.

    2004-05-01

    Functional repair of traumatic spinal cord injury (SCI) is one of the most challenging goals in modern medicine. The annual incidence of SCI in the United States is approximately 11,000 new cases. The prevalence of people in the U.S. currently living with SCI is approximately 200,000. Exploring and understanding nerve regeneration in the central nervous system (CNS) is a critical first step in attempting to reverse the devastating consequences of SCI. At Mayo Clinic, a preliminary study of implants in the transected rat spinal cord model demonstrates potential for promoting axon regeneration. In collaborative research between neuroscientists and bioengineers, this procedure holds promise for solving two critical aspects of axon repair-providing a resorbable structural scaffold to direct focused axon repair, and delivery of relevant signaling molecules necessary to facilitate regeneration. In our preliminary study, regeneration in the rat's spinal cord was modeled in three dimensions utilizing an image processing software system developed in the Biomedical Imaging Resource at Mayo Clinic. Advanced methods for image registration, segmentation, and rendering were used. The raw images were collected at three different magnifications. After image processing the individual channels in the scaffold, axon bundles, and macrophages could be identified. Several axon bundles could be visualized and traced through the entire volume, suggesting axonal growth throughout the length of the scaffold. Such information could potentially allow researchers and physicians to better understand and improve the nerve regeneration process for individuals with SCI.

  10. A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.

    PubMed

    Guenther, Catherine A; Wang, Zhen; Li, Emma; Tran, Misha C; Logan, Catriona Y; Nusse, Roel; Pantalena-Filho, Luiz; Yang, George P; Kingsley, David M

    2015-08-01

    Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an "injury response" control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals.

  11. Alcohol-induced One-carbon Metabolism Impairment Promotes Dysfunction of DNA Base Excision Repair in Adult Brain*

    PubMed Central

    Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G.; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J.; Bergeson, Susan E.; Henderson, George I.; Kruman, Inna I.

    2012-01-01

    The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr+/− mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain. PMID:23118224

  12. Alcohol-induced one-carbon metabolism impairment promotes dysfunction of DNA base excision repair in adult brain.

    PubMed

    Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J; Bergeson, Susan E; Henderson, George I; Kruman, Inna I

    2012-12-21

    The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr(+/-) mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain.

  13. Vascularisation to improve translational potential of tissue engineering systems for cardiac repair.

    PubMed

    Dilley, Rodney J; Morrison, Wayne A

    2014-11-01

    Cardiac tissue engineering is developing as an alternative approach to heart transplantation for treating heart failure. Shortage of organ donors and complications arising after orthotopic transplant remain major challenges to the modern field of heart transplantation. Engineering functional myocardium de novo requires an abundant source of cardiomyocytes, a biocompatible scaffold material and a functional vasculature to sustain the high metabolism of the construct. Progress has been made on several fronts, with cardiac cell biology, stem cells and biomaterials research particularly promising for cardiac tissue engineering, however currently employed strategies for vascularisation have lagged behind and limit the volume of tissue formed. Over ten years we have developed an in vivo tissue engineering model to construct vascularised tissue from various cell and tissue sources, including cardiac tissue. In this article we review the progress made with this approach and others, together with their potential to support a volume of engineered tissue for cardiac tissue engineering where contractile mass impacts directly on functional outcomes in translation to the clinic. It is clear that a scaled-up cardiac tissue engineering solution required for clinical treatment of heart failure will include a robust vascular supply for successful translation. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Adults with repaired tetralogy: low mortality but high morbidity up to middle age.

    PubMed

    Dennis, Mark; Moore, Ben; Kotchetkova, Irina; Pressley, Lynne; Cordina, Rachael; Celermajer, David S

    2017-01-01

    Survival of patients with repaired tetralogy of Fallot (rToF) into young adulthood is very good. Concerns exist, however, over long-term morbidity and mortality as these subjects reach middle age. We aimed to assess survival and the prevalence of complications in patients with rToF seen in our Adult Congenital Heart Disease (ACHD) service. One hundred and sixty-eight consecutive patients with 'simple rToF', aged over 16 years, followed up at our tertiary-level ACHD service in Sydney, Australia since 2000, were included. We documented mortality and analysed the prospectively defined composite end points of (a) 'Serious adverse events', including death, heart failure hospitalisation and/or documented ventricular arrhythmia and (b) 'Adverse events' inclusive of the above and endocarditis, atrial arrhythmia, defibrillator and/or pacemaker implantation. Mean age at the last follow-up was 34±12 years, and 55% were men. There were 10 (6%) deaths, and 26 patients (16%) experienced a 'serious adverse event'. Fifty-one patients (30%) experienced an 'adverse event' and 29 patients had atrial arrhythmias. One hundred and one (61%) patients had at least one pulmonary valve replacement. By age 40 years, 93% were free of serious adverse events, and 83% were free of any adverse event. By age 50 years, only 56% had not had an adverse event. Older age and history of atrial arrhythmia were predictive of serious adverse events. Survival into mid-adulthood in patients with rToF is very good; however, a substantial number of survivors have adverse events by the age of 50 years.

  15. Impaired arm development after Blalock-Taussig shunts in adults with repaired tetralogy of Fallot.

    PubMed

    Le Gloan, Laurianne; Marcotte, François; Leduc, Hugues; Mercier, Lise-Andrée; Dore, Annie; Mongeon, François-Pierre; Ibrahim, Reda; Miro, Joaquim; Asgar, Anita; Poirier, Nancy; Khairy, Paul

    2013-09-30

    Many adults with repaired tetralogy of Fallot have had prior Blalock-Taussig shunts. These shunts may theoretically hinder growth and development of the ipsilateral arm. We prospectively enrolled consecutive patients with tetralogy of Fallot in a cross-sectional study to measure arm length and assess handgrip strength. Bilateral handgrip strength was quantified by a dynamometer in a standing position after instructing patients to clench each hand tightly in succession. The maximum force achieved, in kilograms, was measured. A total of 80 consecutive adults with tetralogy of Fallot, aged 36.0 ± 12.5 years, 49% female, were prospectively enrolled. Thirty-eight (47.5%) patients had prior Blalock-Taussig shunts at a median age of 1.0 year. Twenty-one (55.3%) were left-sided and 23 (60.5%) were classic shunts. All but six patients with right-sided shunts and one without a prior shunt were right-handed. The shunts were present for a median of 4.0 years prior to takedown during corrective surgery. The arm ipsilateral to the shunt was significantly shorter than the contralateral arm (71.5 ± 6.1 versus 73.6 ± 5.6 cm, P<0.0001). Handgrip strength was significantly weaker on the ipsilateral versus contralateral side (median [IQR], 26.5 [14.0-41.5] versus 31.0 [18.0-46.0] kg, P<0.0001) and the ipsilateral-to-contralateral handgrip ratio was lower with classic versus modified shunts (median [IQR], 1.05 [1.02-1.14] versus 1.19 [1.07-1.33] kg, P=0.0541). In patients with tetralogy of Fallot, Blalock-Taussig shunts may impair normal development of the ipsilateral arm with repercussions in adulthood that include shorter limb length and reduced handgrip strength. These changes are most pronounced in patients with classic end-to-side anastomoses. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Comparison of sutures and cyanoacrylate tissue adhesives for wound repair in a rat model of corneal laceration.

    PubMed

    Nuhoglu, Fadime; Altiparmak, Ugur E; Hazirolan, Dicle O; Kasim, Remzi; Duman, Sunay

    2013-01-01

    The aim of the present study was to evaluate the cicatricial repair of a corneal artificial perforation in rats with 10-0 nylon suture, N-butyl-2-cyanoacrylate (NBCA) adhesive, or NBCA + methacryloxysulfolane (NBCA-MS) adhesive through microscopic and histological assays. Twenty Wistar rats were randomly divided into 4 groups each containing 5 rats: (1) control group (corneal trauma without suturing and tissue adhesives), (2) suture group, (3) NBCA group and (4) NBCA-MS group. A central full-thickness 2-mm laceration was performed in the left eyes of the studied rats in all 4 groups. The presence of corneal edema, corneal neovascularization and tissue adhesive/suture were evaluated. On the 21st day, the rats were sacrificed and histological examination was performed to determine irregularity of corneal layers, superficial epithelization, polymorphonuclear leucocytes and neovascularization. Tissue adhesives were as effective as suturing in closing full-thickness corneal wounds and no difference in postoperative healing was observed clinically. As for the histological results, suture-treated eyes had persistent corneal irregularity that can limit visual acuity and may also lead to astigmatism. The use of tissue adhesives constitutes a viable alternative clinical procedure to conventional sutures. Possible influences on astigmatism are hypothetical, as no objective measure of astigmatism was performed in the test animals. Copyright © 2013 S. Karger AG, Basel.

  17. Effect on the contour of bone and soft tissue one year after harvesting chin bone for alveolar cleft repair.

    PubMed

    Dik, E A; de Ruiter, A P; van der Bilt, A; Koole, R

    2010-10-01

    In this study the authors evaluate and quantify the residual bony defect in the mandibular symphysis and its effect on the soft tissue contour a minimum of 1 year after harvesting chin bone. 59 ASA I cleft lip and palate patients, aged 8-19 years were included. In all patients an autologous bone graft from the mandibular symphysis was harvested for transplantation to the alveolar cleft. Lateral cephalograms were used to measure the donor site defects, and the effects on the soft tissue contour. An evident residual defect was measured at the donor site 1 year after harvesting chin bone. A significant relation was seen between age at time of surgery and size of the defect 1 year postoperatively. In older patients a larger defect remained. Using the current surgical technique of harvesting chin bone, complete bony repair of the defect was not achieved. This study shows postoperatively persisting defects that comprise on average 14% of the original peroperative defects. A significant increase in soft tissue thickness was seen at the mandibular symphysis at a minimum of 1 year postoperatively. These changes in the soft tissue chin contour 1 year after harvesting bone are similar to normal growth changes. Copyright © 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. Cytotoxicity of Cyanoacrylate-Based Tissue Adhesives and Short-Term Preclinical In Vivo Biocompatibility in Abdominal Hernia Repair

    PubMed Central

    Rodríguez, Marta; Pérez-Köhler, Bárbara; Kühnhardt, Andreé; Fernández-Gutiérrez, Mar; San Román, Julio; Bellón, Juan Manuel

    2016-01-01

    Background Cyanoacrylate(CA)-based tissue adhesives, although not widely used, are a feasible option to fix a mesh during abdominal hernia repair, due to its fast action and great bond strength. Their main disadvantage, toxicity, can be mitigated by increasing the length of their alkyl chain. The objective was to assess the in vitro cytotoxicity and in vivo biocompatibility in hernia repair of CAs currently used in clinical practice (Glubran(n-butyl) and Ifabond(n-hexyl)) and a longer-chain CA (OCA(n-octyl)), that has never been used in the medical field. Methods Formaldehyde release and cytotoxicity of unpolymerized(UCAs) and polymerized CAs(PCAs) were evaluated by macroscopic visual assessment, flow cytometry and Alamar Blue assays. In the preclinical evaluation, partial defects were created in the rabbit abdominal wall and repaired by fixing polypropylene prostheses using the CAs. At 14 days post-surgery, animals were euthanized for morphology, macrophage response and cell damage analyses. Results Formaldehyde release was lower as the molecular weight of the monomer increased. The longest side-chain CA(OCA) showed the highest cytotoxicity in the UCA condition. However, after polymerization, was the one that showed better behavior on most occasions. In vivo, all CAs promoted optimal mesh fixation without displacements or detachments. Seroma was evident with the use of Glubran, (four of six animals: 4/6) and Ifabond (2/6), but it was reduced with the use of OCA (1/6). Significantly greater macrophage responses were observed in groups where Glubran and Ifabond were used vs. sutures and OCA. TUNEL-positive cells were significantly higher in the Glubran and OCA groups vs. the suture group. Conclusions Although mild formaldehyde release occurred, OCA was the most cytotoxic during polymerization but the least once cured. The CAs promoted proper mesh fixation and have potential to replace traditional suturing techniques in hernia repair; the CAs exhibited good tissue

  19. [Repair of lower extremity soft tissue defect with free musculo-cutaneous flaps bridging with healthy contralateral posterior tibial vessel].

    PubMed

    Chengde, Xia; Haiping, Di; Jidong, Xue; Yaohua, Zhao; Xiaoliang, Li; Qiang, Li; Xihua, Niu; Yonglin, Li; Hongkai, Lian

    2015-05-01

    To observe the clinical effects of free musculo-cutaneous flap bridging with contralateral posterior tibial vessel on repair of lower extremity soft tissue defect. From February 2006 to June 2013, 10 patients with soft tissue defect on lower shank and foot were included. The posterior tibial vessel on healthy lower extremity was chosen as recipient vessel and anastomosed with free latissimus dorsi musculo-cutaneous flap, or free latissimus dorsi musculo-cutaneous flap combined with thoracic-umbilical skin flap or anterolateral femoral musculo-cutaneous flap. The retrograde bridged flap was transposed to repair defect on contralateral lower shank and foot. The wound area ranged from 40 cm x 21 cm to 22 cm x 15 cm, with flap size from 48 cm x 26 cm to 25 cm x 18 cm. Meanwhile the defects on donor sites were covered with skin graft and both lower extremities were fixed with kirschner wires at middle tibia and calcaneus. The kirschner wires were removed at 4 weeks and pedicles were cut off 5-8 weeks postoperatively. Six patients received posterior tibial vessel reanastomosis at the same time of pedicle cutting. All the 10 flaps survived and 3 patients received thinning of flaps due to excessive thickness. During the follow-up period of 3 months to 2 years follow up, the ambulatory function of injured legs recovered gradually with satisfactory appearance. The reanastomosed posterior tibial vessel on the healthy side was recovered. Appropriate bridged musculo-cutaneous flaps is suitable for extensive soft tissue defect of lower shank and foot. It is a safe and effective method for limb salvage.

  20. Peripheral nerve repair of transplanted undifferentiated adipose tissue-derived stem cells in a biodegradable reinforced nerve conduit.

    PubMed

    Shen, Chiung-Chyi; Yang, Yi-Chin; Liu, Bai-Shuan

    2012-01-01

    This study proposes a biodegradable nerve conduit containing genipin-cross-linked gelatin annexed with tricalcium phosphate ceramic particles (genipin-gelatin-tricalcium phosphate, GGT) in peripheral nerve regeneration. Firstly, cytotoxicity tests revealed that the GGT-extracts were not toxic, and promoted the proliferation and neuronal differentiation of adipose tissue-derived stem cells (ADSCs). Secondly, the GGT composite film effectively supported ADSCs attachment and growth. Additionally, the GGT substrate was biocompatible with the neonatal rat sciatic nerve and produced a beneficial effect on peripheral nerve repair through in vitro tissue culture. Finally, the experiments in this study confirmed the effectiveness of a GGT/ADSCs nerve conduit as a guidance channel for repairing a 10-mm gap in a rat sciatic nerve. Eight weeks after implantation, the mean recovery index of compound muscle action potentials (CMAPs) was significantly different between the GGT/ADSCs and autografts groups (p < 0.05), both of which were significantly superior to the GGT group (p < 0.05). Furthermore, walking track analysis also showed a significantly higher sciatic function index (SFI) score (p < 0.05) and better toe spreading development in the GGT/ADSCs group than in the autograft group. Histological observations and immunohistochemistry revealed that the morphology and distribution patterns of nerve fibers in the GGT/ADSCs nerve conduits were similar to those of the autografts. The GGT nerve conduit offers a better scaffold for the incorporation of seeding undifferentiated ADSCs, and opens a new avenue to replace autologous nerve grafts for the rapid regeneration of damaged peripheral nerve tissues and an