The Experts below are selected from a list of 2184 Experts worldwide ranked by ideXlab platform

Monica Wiig - One of the best experts on this subject based on the ideXlab platform.

Richard H Gelberman - One of the best experts on this subject based on the ideXlab platform.

  • Flexor Tendon Injury and repair the influence of synovial environment on the early healing response in a canine mode
    Journal of Bone and Joint Surgery American Volume, 2021
    Co-Authors: Hua Shen, Susumu Yoneda, Shelly E Sakiyamaelbert, Stavros Thomopoulos, Qiang Zhang, Richard H Gelberman
    Abstract:

    Background Environmental conditions strongly influence the healing capacity of connective tissues. Well-vascularized extrasynovial Tendons typically undergo a robust wound-healing process following transection and repair. In contrast, avascular intrasynovial Tendons do not mount an effective repair response. The current study tests the hypothesis that Flexor Tendons, as a function of their synovial environment, exhibit unique inflammatory, angiogenic, and metabolic responses to Injury and repair. Methods Flexor Tendons present a distinct opportunity to test the study hypothesis, as they have proximal regions that are extrasynovial and distal regions that are intrasynovial. In an internally controlled study design, the second and fifth forepaw Flexor Tendons were transected and repaired in either the extrasynovial or the intrasynovial anatomical region. Histological, gene expression, and proteomics analyses were performed at 3 and 7 days to define the early biological events that drive synovial environment-dependent healing responses. Results Uninjured intrasynovial Tendons were avascular, contained high levels of proteoglycans, and expressed inflammatory factors, complement proteins, and glycolytic enzymes. In contrast, extrasynovial Tendons were well vascularized, contained low levels of proteoglycans, and were enriched in inflammation inhibitors and oxidative phosphorylation enzymes. The response to Injury and repair was markedly different between the 2 Tendon regions. Extrasynovial Tendons displayed a robust and rapid neovascularization response, increased expression levels of complement proteins, and an acute shift in metabolism to glycolysis, whereas intrasynovial Tendons showed minimal vascularity and muted inflammatory and metabolic responses. Conclusions The regional molecular profiles of intact and healing Flexor Tendons revealed extensive early differences in innate immune response, metabolism, vascularization, and expression of extracellular matrix as a function of the synovial environment. These differences reveal mechanisms through which extrasynovial Tendons heal more effectively than do intrasynovial Tendons. Clinical relevance To improve outcomes after operative repair, future treatment strategies should promote features of extrasynovial healing, such as enhanced vascularization and modulation of the complement system and/or glucose metabolism.

  • the effect of adipose derived stem cell sheets and ctgf on early Flexor Tendon healing in a canine model
    Scientific Reports, 2018
    Co-Authors: Hua Shen, Rohith Jayaram, Susumu Yoneda, Stephen W Linderman, Shelly E Sakiyamaelbert, Richard H Gelberman, Stavros Thomopoulos
    Abstract:

    Intrasynovial Tendon injuries are among the most challenging in orthopedics. Despite significant improvements in operative and rehabilitation methods, functional outcomes continue to be limited by adhesions, gap formation, and rupture. Adhesions result from excessive inflammation, whereas Tendon gapping and rupture result from inflammation-induced matrix degradation and insufficient regeneration. Therefore, this study used a combined treatment approach to modulate inflammation with adipose-derived mesenchymal stromal cells (ASCs) while stimulating Tendon regeneration with connective tissue growth factor (CTGF). ASCs were applied to the repair surface via cell sheets and CTGF was delivered to the repair center via porous sutures. The effect of the combined treatment was assessed fourteen days after repair in a canine Flexor Tendon Injury model. CTGF, either alone or with ASCs, reduced inflammatory (IL1B and IL6) and matrix degrading (MMP3 and MMP13) gene expression, while increasing anti-inflammatory gene (IL4) expression and collagen synthesis compared to control repairs. The combined treatment was more effective than CTGF treatment alone, reducing the inflammatory IFNG and scar-associated COL3A1 gene expression and increasing CD146+ Tendon stem/progenitor cells at the Tendon surface and interior along the core suture tracks. Therefore, the combined approach is promising in promoting early Flexor Tendon healing and worthy of further investigation.

  • cell and biologic based treatment of Flexor Tendon injuries
    Operative Techniques in Orthopaedics, 2016
    Co-Authors: Stephen W Linderman, Richard H Gelberman, Stavros Thomopoulos, Hua Shen
    Abstract:

    The 2 primary factors leading to poor clinical results after intrasynovial Tendon repair are adhesion formation within the digital sheath and repair-site elongation and rupture. As the outcomes following modern Tendon multistrand repair and controlled rehabilitation techniques are often unsatisfactory, alternative approaches, such as the application of growth factors and mesenchymal stem cells, have become increasingly attractive treatment options. Successful biological therapies require carefully controlled spatiotemporal delivery of cells, growth factors, and biocompatible scaffold matrices to simultaneously (1) promote matrix synthesis at the Tendon repair site leading to increased biomechanical strength and stiffness and (2) suppress matrix synthesis along the Tendon surface and synovial sheath preventing adhesion formation. This article summarizes recent cell and biologic-based experimental treatments for Flexor Tendon Injury, with an emphasis on large animal translational studies.

  • the effect of muscle loading on Flexor Tendon to bone healing in a canine model
    Journal of Orthopaedic Research, 2008
    Co-Authors: Stavros Thomopoulos, Matthew J Silva, Emmanouil Zampiakis, Richard H Gelberman
    Abstract:

    Previous Tendon and ligament studies demonstrated a role for mechanical loading in tissue homeostasis and healing. In uninjured musculoskeletal tissues, increased loading leads to an increase in mechanical properties, while decreased loading leads to a decrease in properties. The role of loading on healing tissues is less clear. We studied Tendon-to-bone healing in a canine Flexor Tendon-to-bone Injury and repair model. To examine the effect of muscle loading on healing, repaired Tendons were either cut proximally to remove all load from the distal phalanx repair site (unloaded group) or left intact proximally (loaded group). All paws were cast post-operatively and subjected to daily passive motion rehabilitation. Specimens were tested to determine functional properties, biomechanical properties, repair-site gapping, and bone mineral density. Loading across the repair site led to improved functional and biomechanical properties (e.g., stiffness for the loaded group was 8.2 ± 3.9 vs. 5.1 ± 2.5 N/mm for the unloaded group). Loading did not affect bone mineral density or gapping. The formation of a gap between the healing Tendon and bone correlated with failure properties. Using a clinically relevant model of Flexor Tendon Injury and repair, we found that muscle loading was beneficial to healing. Complete removal of load by proximal transection resulted in Tendon-to-bone repairs with less range of motion and lower biomechanical properties compared to repairs in which the muscle-Tendon-bone unit was left intact.

  • nonviral in vivo gene therapy for tissue engineering of articular cartilage and Tendon repair
    Clinical Orthopaedics and Related Research, 2000
    Co-Authors: Randal S Goomer, Richard H Gelberman, Matthew J Silva, Thira M Maris, Marty Boyer, David Amiel
    Abstract:

    Heretofore, nonviral methods have been used primarily for in vitro transfection of cultured cell lines. These methods were substantially less efficient when compared with the use of viruses, particularly when used in vivo. Herein a three-step, highly efficient method of nonviral gene delivery is presented. Using this method, genes have been delivered successfully into tissues of orthopaedic importance with high-efficiency by nonviral means. Transforming growth factor-beta 1, parathyroid hormone related protein, and a marker gene were transfected into primary perichondrium and cartilage cells with efficiencies in excess of 70%. They overexpressed their cognate gene products showing efficacy of expression in a rabbit model of osteochondral defect repair. Using the same method, a marker gene was delivered into a canine model for intrasynovial Flexor Tendon Injury and repair. This was achieved by direct gene delivery during surgery. An estimated 5 additional minutes were required during surgery to complete the transfection steps. High efficiency gene delivery was achieved in the Flexor Tendons, Tendon sheaths, Tendon pulleys, surrounding tissues, and skin. The efficiency of transfection approached 100% in the exposed superficial tissue layers and transfected cells were found several layers below the exposed tissue surfaces. The data show the potential of direct nonviral gene therapy in orthopaedics for ex vivo and in vivo applications.

Stavros Thomopoulos - One of the best experts on this subject based on the ideXlab platform.

  • Flexor Tendon Injury and repair the influence of synovial environment on the early healing response in a canine mode
    Journal of Bone and Joint Surgery American Volume, 2021
    Co-Authors: Hua Shen, Susumu Yoneda, Shelly E Sakiyamaelbert, Stavros Thomopoulos, Qiang Zhang, Richard H Gelberman
    Abstract:

    Background Environmental conditions strongly influence the healing capacity of connective tissues. Well-vascularized extrasynovial Tendons typically undergo a robust wound-healing process following transection and repair. In contrast, avascular intrasynovial Tendons do not mount an effective repair response. The current study tests the hypothesis that Flexor Tendons, as a function of their synovial environment, exhibit unique inflammatory, angiogenic, and metabolic responses to Injury and repair. Methods Flexor Tendons present a distinct opportunity to test the study hypothesis, as they have proximal regions that are extrasynovial and distal regions that are intrasynovial. In an internally controlled study design, the second and fifth forepaw Flexor Tendons were transected and repaired in either the extrasynovial or the intrasynovial anatomical region. Histological, gene expression, and proteomics analyses were performed at 3 and 7 days to define the early biological events that drive synovial environment-dependent healing responses. Results Uninjured intrasynovial Tendons were avascular, contained high levels of proteoglycans, and expressed inflammatory factors, complement proteins, and glycolytic enzymes. In contrast, extrasynovial Tendons were well vascularized, contained low levels of proteoglycans, and were enriched in inflammation inhibitors and oxidative phosphorylation enzymes. The response to Injury and repair was markedly different between the 2 Tendon regions. Extrasynovial Tendons displayed a robust and rapid neovascularization response, increased expression levels of complement proteins, and an acute shift in metabolism to glycolysis, whereas intrasynovial Tendons showed minimal vascularity and muted inflammatory and metabolic responses. Conclusions The regional molecular profiles of intact and healing Flexor Tendons revealed extensive early differences in innate immune response, metabolism, vascularization, and expression of extracellular matrix as a function of the synovial environment. These differences reveal mechanisms through which extrasynovial Tendons heal more effectively than do intrasynovial Tendons. Clinical relevance To improve outcomes after operative repair, future treatment strategies should promote features of extrasynovial healing, such as enhanced vascularization and modulation of the complement system and/or glucose metabolism.

  • the effect of adipose derived stem cell sheets and ctgf on early Flexor Tendon healing in a canine model
    Scientific Reports, 2018
    Co-Authors: Hua Shen, Rohith Jayaram, Susumu Yoneda, Stephen W Linderman, Shelly E Sakiyamaelbert, Richard H Gelberman, Stavros Thomopoulos
    Abstract:

    Intrasynovial Tendon injuries are among the most challenging in orthopedics. Despite significant improvements in operative and rehabilitation methods, functional outcomes continue to be limited by adhesions, gap formation, and rupture. Adhesions result from excessive inflammation, whereas Tendon gapping and rupture result from inflammation-induced matrix degradation and insufficient regeneration. Therefore, this study used a combined treatment approach to modulate inflammation with adipose-derived mesenchymal stromal cells (ASCs) while stimulating Tendon regeneration with connective tissue growth factor (CTGF). ASCs were applied to the repair surface via cell sheets and CTGF was delivered to the repair center via porous sutures. The effect of the combined treatment was assessed fourteen days after repair in a canine Flexor Tendon Injury model. CTGF, either alone or with ASCs, reduced inflammatory (IL1B and IL6) and matrix degrading (MMP3 and MMP13) gene expression, while increasing anti-inflammatory gene (IL4) expression and collagen synthesis compared to control repairs. The combined treatment was more effective than CTGF treatment alone, reducing the inflammatory IFNG and scar-associated COL3A1 gene expression and increasing CD146+ Tendon stem/progenitor cells at the Tendon surface and interior along the core suture tracks. Therefore, the combined approach is promising in promoting early Flexor Tendon healing and worthy of further investigation.

  • cell and biologic based treatment of Flexor Tendon injuries
    Operative Techniques in Orthopaedics, 2016
    Co-Authors: Stephen W Linderman, Richard H Gelberman, Stavros Thomopoulos, Hua Shen
    Abstract:

    The 2 primary factors leading to poor clinical results after intrasynovial Tendon repair are adhesion formation within the digital sheath and repair-site elongation and rupture. As the outcomes following modern Tendon multistrand repair and controlled rehabilitation techniques are often unsatisfactory, alternative approaches, such as the application of growth factors and mesenchymal stem cells, have become increasingly attractive treatment options. Successful biological therapies require carefully controlled spatiotemporal delivery of cells, growth factors, and biocompatible scaffold matrices to simultaneously (1) promote matrix synthesis at the Tendon repair site leading to increased biomechanical strength and stiffness and (2) suppress matrix synthesis along the Tendon surface and synovial sheath preventing adhesion formation. This article summarizes recent cell and biologic-based experimental treatments for Flexor Tendon Injury, with an emphasis on large animal translational studies.

  • the effect of muscle loading on Flexor Tendon to bone healing in a canine model
    Journal of Orthopaedic Research, 2008
    Co-Authors: Stavros Thomopoulos, Matthew J Silva, Emmanouil Zampiakis, Richard H Gelberman
    Abstract:

    Previous Tendon and ligament studies demonstrated a role for mechanical loading in tissue homeostasis and healing. In uninjured musculoskeletal tissues, increased loading leads to an increase in mechanical properties, while decreased loading leads to a decrease in properties. The role of loading on healing tissues is less clear. We studied Tendon-to-bone healing in a canine Flexor Tendon-to-bone Injury and repair model. To examine the effect of muscle loading on healing, repaired Tendons were either cut proximally to remove all load from the distal phalanx repair site (unloaded group) or left intact proximally (loaded group). All paws were cast post-operatively and subjected to daily passive motion rehabilitation. Specimens were tested to determine functional properties, biomechanical properties, repair-site gapping, and bone mineral density. Loading across the repair site led to improved functional and biomechanical properties (e.g., stiffness for the loaded group was 8.2 ± 3.9 vs. 5.1 ± 2.5 N/mm for the unloaded group). Loading did not affect bone mineral density or gapping. The formation of a gap between the healing Tendon and bone correlated with failure properties. Using a clinically relevant model of Flexor Tendon Injury and repair, we found that muscle loading was beneficial to healing. Complete removal of load by proximal transection resulted in Tendon-to-bone repairs with less range of motion and lower biomechanical properties compared to repairs in which the muscle-Tendon-bone unit was left intact.

Regis J Okeefe - One of the best experts on this subject based on the ideXlab platform.

  • bone marrow derived matrix metalloproteinase 9 is associated with fibrous adhesion formation after murine Flexor Tendon Injury
    PLOS ONE, 2012
    Co-Authors: Alayna E Loiselle, Benjamin J Frisch, Matthew Wolenski, Justin A Jacobson, Laura M Calvi, Edward M Schwarz, Hani A Awad, Regis J Okeefe
    Abstract:

    The pathogenesis of adhesions following primary Tendon repair is poorly understood, but is thought to involve dysregulation of matrix metalloproteinases (Mmps). We have previously demonstrated that Mmp9 gene expression is increased during the inflammatory phase following murine Flexor digitorum (FDL) Tendon repair in association with increased adhesions. To further investigate the role of Mmp9, the cellular, molecular, and biomechanical features of healing were examined in WT and Mmp9−/− mice using the FDL Tendon repair model. Adhesions persisted in WT, but were reduced in Mmp9−/− mice by 21 days without any decrease in strength. Deletion of Mmp9 resulted in accelerated expression of neo-Tendon associated genes, Gdf5 and Smad8, and delayed expression of collagen I and collagen III. Furthermore, WT bone marrow cells (GFP+) migrated specifically to the Tendon repair site. Transplanting myeloablated Mmp9−/− mice with WT marrow cells resulted in greater adhesions than observed in Mmp9−/− mice and similar to those seen in WT mice. These studies show that Mmp9 is primarily derived from bone marrow cells that migrate to the repair site, and mediates adhesion formation in injured Tendons. Mmp9 is a potential target to limit adhesion formation in Tendon healing.

Lee A Osterman - One of the best experts on this subject based on the ideXlab platform.

  • distal radius volar locking plate design and associated vulnerability of the Flexor pollicis longus
    Journal of Hand Surgery (European Volume), 2014
    Co-Authors: Roongsak Limthongthang, Abdo Bachoura, Sidney M Jacoby, Lee A Osterman
    Abstract:

    Purpose Flexor pollicis longus (FPL) Tendon rupture is a well-documented complication related to the use of distal radius volar locking plates (VLPs). The final common pathway of Flexor Tendon rupture appears to involve implants prominent at the watershed line. We hypothesized that significant differences in VLP prominence exist between various plate designs. Methods Ten fresh frozen specimens were dissected to identify the path of the FPL in relationship to the distal radius at the watershed line. Five VLP designs were fixed to each specimen based on their anatomic fit, and slid distally until the distal edge of the plate reached the watershed line. The position of each fixed plate was evaluated by fluoroscopy. We used a 3-dimensional laser scanner to create computer models. The total surface area of plate prominence volar to the watershed line and the prominent area beneath the FPL were measured in the axial plane using computer software. Results At the watershed line, the FPL was located at 54% of the maximal width of the radius, as measured from its volar-ulnar corner. There were no significant differences in the location of plate fixation on lateral view radiographs according to the classification of Soong et al. The mean total surface area of plate prominence was 36 mm 2 . The mean prominent area beneath the FPL was 10 mm 2 . Significant differences in plate prominence were noted for various designs. Conclusions Despite optimal plate placement, various VLP designs were observed to have prominent profiles volar to the watershed line, to varying extents. Clinical relevance The results raise concerns regarding interference between all of the analyzed VLP designs and the FPL. This study may help guide both implant design considerations and assist the surgeon in better understanding implant morphology as it relates to iatrogenic Flexor Tendon Injury.