Tendon-Bone Construct Tissue Engineering for Extremity Reconstuction

用于四肢重建的肌腱-骨结构组织工程

• 批准号: 8971507
• 负责人: James Chang
• 金额: --
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8971507
• 关键词: Accidents; Allografting; Anatomy; Animal Model; Area; Athletic Injuries; Biocompatible; Biocompatible Materials; Biological Assay; Biological Preservation; Biomechanics; Biomedical Engineering; Blood Platelets; Body Temperature; Bone Regeneration; Bone Tissue; Bone Transplantation; Cadaver; Caring; Cell Proliferation; Cell Survival; Cells; Clinical; Complex; DNA; Defect; Degenerative Disorder; Distal; Early Mobilizations; Extracellular Matrix Proteins; Fatty acid glycerol esters; Flexor; Gel; Goals; Grant; Healed; Histology; Human; Human Development; Hydrogels; Immunohistochemistry; Implant; In Situ; In Situ Hybridization; In Vitro; Injury; Lead; Limb structure; Liquid substance; Measurement; Medical; Methods; Migration Assay; Military Personnel; Modeling; Molecular; Motion; Operating Rooms; Operative Surgical Procedures; Outcome; Patients; Phalanx; Plasma; Postoperative Period; Powder dose form; Process; Production; Proliferating; Property; Protocols documentation; Rattus; Rehabilitation therapy; Research; Resected; Resolution; Roentgen Rays; Rotator Cuff; Rupture; Sampling; Seeds; Site; Soldier; Solid; Solutions; Stem cells; Structure; Supplementation; Surgeon; Surgical sutures; Survival Rate; System; Techniques; Tendon structure; Testing; Time; Tissue Banking; Tissue Banks; Tissue Engineering; Tissues; Training; Translating; Translations; Upper Extremity; Veterans; achilles tendon; anterior cruciate ligament rupture; base; biomaterial compatibility; bone; bone healing; bone strength; calcaneum; cell motility; clinical application; combat; healing; human tissue; improved; in vivo; injured; joint function; microCT; migration; novel; public health relevance; reconstitution; reconstruction; repaired; tissue culture

 DESCRIPTION (provided by applicant): When soldiers and Veterans injure their extremities, tendons are likely to be disrupted. Without intact tendon-bone units, extremities cannot function properly. These injuries may be mid-substance tendon ruptures, or tears at the tendon-bone interface (TBI). The most difficult aspect of tendon reconstruction is adequate healing of this interface with bone. To date, the healing process of the TBI is poorly understood. The goals of this project are to determine the cellular and molecular mechanisms of TBI healing, and to develop tissue engineered TBI constructs that can be used for extremity reconstruction. It is hypothesized that tissue-engineered composite constructs consisting of tendon and bone would allow reconstruction with tendon-to-tendon and bone-to-bone healing. This would be faster and stronger, thus offering earlier mobilization and improved outcomes. Because there is a paucity of research on the process of TBI healing and tissue engineered TBI composite constructs, the following research objectives are proposed: The initial objective is to use an animal model of TBI healing based on the rat Achilles tendon to develop tendon-bone constructs. Decellularization of rat Achilles tendon-calcaneal bone segments and reseeding with adipoderived stem cells (ASCs) will be performed to create tissue engineered composite constructs. This process will be optimized with platelet-rich plasma (PRP) supplementation and the use of a novel tendon hydrogel as a carrier. The hydrogel is produced from decellularized tendon powder, is reconstituted into liquid form, and becomes a solid, yet porous gel at body temperature. It is hypothesized that the strength of bone-bone healing and tendon-tendon healing will exceed that of tendon-bone healing. Furthermore, repairs made with reseeded TBI grafts would be stronger than repairs performed with decellularized TBI grafts. In order to test this, tissue engineered rat Achilles TBI constructs will be re-implanted to assess fo short-term and long-term biocompatibility and repair strength. Techniques to assess healing will include immunohistochemistry, in situ hybridization, MTS measurement of tendon and bone-tendon junction biomechanical strength, high resolution Xray, and micro CT. Lastly, the ultimate goal would be translation to the production of human TBI composite grafts for clinical use in the reconstruction of extremity injuries. Human tissue engineered TBI constructs will be created based on optimized decellularization and reseeding techniques from the previous objectives. The specific anatomic structure to be produced initially is the distal phalanx-flexor tendon graft. The strength of native versus decellularized composite grafts will be tested. This proposal will ultimately allow the development of human composite TBI grafts for use in the reconstruction of traumatic and degenerative conditions of the extremities in soldiers and Veterans.

 描述（由申请人提供）： 当士兵和退伍军人的四肢受伤时，如果没有完整的肌腱-骨单位，四肢就无法正常工作，这些损伤可能是肌腱中部断裂或肌腱-骨界面撕裂（TBI）。肌腱重建的困难在于该界面与骨骼的充分愈合，迄今为止，人们对 TBI 的愈合过程知之甚少，该项目的目标是确定 TBI 愈合的细胞和分子机制。开发可用于四肢重建的组织工程 TBI 结构 人们认为，由肌腱和骨骼组成的组织工程复合结构将允许肌腱到肌腱和骨骼到骨骼的愈合进行重建。由于对 TBI 愈合过程和组织工程 TBI 复合结构的研究很少，因此提出以下研究目标： 最初的目标是使用 TBI 动物模型。基于大鼠跟腱的愈合以开发肌腱-骨结构 对大鼠跟腱-跟骨段进行脱细胞化并用脂肪干细胞（ASC）重新接种，以创建组织工程复合结构。富血浆（PRP）补充和使用新型肌腱水凝胶作为载体该水凝胶由脱细胞肌腱粉末制成，被重组为液体形式，并成为一种新型肌腱水凝胶。在体温下呈固体但多孔的凝胶，骨-骨愈合和肌腱-肌腱愈合的强度将超过肌腱-骨愈合。此外，用重新接种的TBI移植物进行的修复将比用脱细胞进行的修复更强。为了测试这一点，将重新植入组织工程大鼠跟腱 TBI 结构，以评估短期和长期生物相容性以及评估愈合强度的技术。免疫组织化学、原位杂交、肌腱和骨肌腱连接处生物力学强度的 MTS 测量、高分辨率 X 射线和显微 CT 最终目标是转化为用于临床四肢重建的人类 TBI 复合移植物。人体组织工程 TBI 构建体将基于先前目标的优化脱细胞和重新接种技术来创建，最初生成的具体解剖结构是远端指骨屈肌腱。接枝。 天然复合移植物与脱细胞复合移植物的强度将得到测试，该提案最终将允许开发人类复合 TBI 移植物，用于重建士兵和退伍军人的四肢创伤和退行性疾病。