Flexor tendon intrinsic healing and intervention strategy development

屈肌腱内在愈合和干预策略的制定

• 批准号: 10436789
• 负责人: Chunfeng Zhao
• 金额: $ 50.8万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10436789
• 关键词: Address; Adhesions; Affect; Anatomy; Animal Model; Antibodies; Area; Autologous; Basic Science; Biological; Biological Products; Canis familiaris; Carbodiimides; Cells; Chickens; Chondrocytes; Cicatrix; Client satisfaction; Clinic; Clinical; Clinical Trials; Data; Development; Domestic Fowls; Economic Burden; Effectiveness; Elements; Fibrocartilages; Flexor; Future; Gelatin; Genetic Markers; Glues; Gold; Hand; Hand functions; Human; Injury; Intervention; Intrinsic factor; Knowledge; Lead; Leg; Meleagris gallopavo; Minerals; Modeling; Molecular; Motion; Natural regeneration; Necrosis; Operative Surgical Procedures; Outcome; Patients; Play; Postoperative Period; Productivity; Recovery of Function; Regenerative Medicine; Reporting; Research; Rodent; Role; Rupture; Second Look Surgery; Structure; Surface; Synovial Fluid; Techniques; Tendon Injuries; Tendon structure; Testing; Therapeutic; Time; Tissues; Vascular blood supply; Work; aging population; base; cDNA Library; cell type; clinical application; clinical practice; clinical translation; clinically relevant; crosslink; digital; disability; disability impact; economic impact; exosome; foot; functional outcomes; functional restoration; genome sequencing; healing; improved; molecular marker; novel; prevent; progenitor; regeneration potential; repair model; repaired; response; severe injury; stem cells; tendon graft; therapy development; tool

ABSTRACT Hand flexor tendon injuries are common and often occur in a young working-age population resulting in considerable disability and economic impact. Surgical direct repair immediately after tendon injury is the clinical standard in practice. However, clinical and functional outcomes following tendon repair remain unsatisfactory due to restrictive adhesions and poor digital motion, often resulting in multiple surgical revisions, such as tenolysis or tendon grafting. It is known that both intrinsic and extrinsic healing mechanisms are involved in flexor tendon healing. Intrinsic healing is accomplished by cellular productivities from the cells within the tendon resulting in fewer adhesions and better function. In contrast, extrinsic healing relies on the healing from outside tissues, leading to adhesion and scar formations that bond to the tendon with surrounding tissues and diminish hand function. Therefore, research strategies to improve clinical outcomes have focused on either enhancing intrinsic healing or eliminating extrinsic healing, or a combination of both. It is also recognized that some intrinsic healing elements (IHE) involve tendon intrinsic healing capacity including flexor vinculum (FV) for tendon blood supply and epitenon cells (ECs) within the tendon for tendon regeneration. However, it is still unknown if and how these IHEs would affect the intrinsic healing ability. Since the IHEs can be damaged during tendon injury, it is critical to better understand the intrinsic healing associated with IHEs, which not only help to bridge the scientific gap between clinic and research in this field, but also improve the intervention strategy development. Recently, we have successfully developed a novel turkey animal model, which is similar to the human flexor tendon in size, anatomy, structure, function, and most importantly the intrinsic healing capacity. This unique animal model provides an ideal opportunity to investigate the effects of the IHE on tendon intrinsic healing. Furthermore, we have recently explored a purified exosome product (PEP) developed by Mayo Center for Regenerative Medicine in the ISO-5 Good Manufacturing Practice (GMP) Facility to improve tendon intrinsic healing with promising results. We have also developed a lubricating barrier material using carbodiimide derivatized synovial fluid plus gelatin (cd-SF-G) to reduce adhesions in the tendon graft; but it has not been tested in flexor repair model. Therefore, Aim 1 of this proposal is to determine the role of two major factors of IHEs including FV and ECs on tendon healing and functional restoration using our novel turkey flexor tendon injury model. This specific aim, if successful, we will address a critical barrier for the understanding of flexor tendon intrinsic healing mechanism and advance the current knowledge in hand surgery. Aim 2 will define the effectiveness of our novel interventions using PEP for enhancing intrinsic healing ability and cd-SF-G for preventing extrinsic healing to reduce scar and adhesion formations using our new turkey animal model. If successful, we will have developed and validated the clinically translational interventions to improve functional outcomes following flexor tendon repair, since both our therapeutics, GMP grade PEP and native SF based material, are one step close to a clinical trial. Thus, the proposal has a significant impact on both basic science research and clinical translation.

摘要