Tissue Engineered Meniscus Repair

描述（由申请人提供）：半月板部分或全部丧失会极大地改变膝关节功能，并使关节易于发生退行性变化。该项目的目标是修复或再生内侧半月板的临界尺寸缺损，以恢复关节功能并防止关节损伤。间充质祖细胞是骨缺损的潜在修复细胞。在这项研究中，自体骨髓来源的间充质祖细胞将用于体外创建纤维软骨组织，然后将其植入用于体内修复。有待检验的假设是，组织工程软骨将提供一个上级植入物用于关节修复。这将在两种不同的骨修复模型中进行测试： 具体目标1：修复手术造成的中间物质韧带撕裂。其目的是使用组织工程软骨修复手术造成的内侧半月板撕裂。将自体骨髓来源的间充质祖细胞接种到可生物降解的支架中并在软骨形成培养基中培养，在体外产生软骨。将植入物缝合成全层纵向撕裂。这种组织工程结构的修复潜力将与空支架和无植入物缝合撕裂的修复潜力进行比较。 具体目标2：在手术创建的部分直肠切除术中再生直肠组织。一个大的组织工程软骨植入物将用于再生山羊内侧半月板的部分半月板切除术。至于目标1，组织工程植入物将由含有自体间充质祖细胞的生物可降解支架组成，在植入前在软骨形成培养基中培养。 对于这两个目的，将在植入后12周和12个月对髋臼植入物进行分析。 对手术后的膝关节进行生物力学、形态学、组织学和免疫组化分析，以全面评估组织工程植入物在两种修复模型中的成功率。

DESCRIPTION (provided by applicant): Loss of the meniscus, in part or in total, greatly alters knee function and predisposes the joint to degenerative changes. The goal of this project is the repair or regeneration of critical-sized defects in the medial meniscus to restore meniscal function and prevent joint damage. Mesenchymal progenitor cells are potential repair cells for meniscal defects. In this study, autologous bone marrow-derived mesenchymal progenitor cells will used to create a fibrocartilaginous tissue in vitro that is then implanted for meniscal repair in vivo. The hypothesis to be tested is that tissue-engineered cartilage will provide a superior implant for meniscal repair. This will be tested in two different meniscal repair models: Specific Aim 1: To repair a surgically created mid-substance meniscal tear. The aim is to use a tissue-engineered cartilage to repair a surgically created tear in the medial meniscus. The cartilage will be created in vitro with autologous marrow-derived mesenchymal progenitor cells seeded into a biodegradable scaffold and cultured in a chondrogenic medium. The implant will be sutured into a full-thickness longitudinal tear. The repair potential of this tissue-engineered construct will be compared with those of empty scaffolds and no-implant sutured tears. Specific Aim 2: To regenerate meniscal tissue in a surgically created partial meniscectomy. A large tissue-engineered cartilaginous implant will be used to regenerate a partial meniscectomy of the goat medial meniscus. As for aim 1, the tissue-engineered implant will be composed of the biodegradable scaffold containing autologous mesenchynial progenitor cells, cultured in chondrogenic medium prior to implantation. For both aims, the meniscal implant will be analyzed at 12 weeks and 12 months after implantation. The operated knee joints will be subjected to biomechanical, morphological, histological and immunohistochemical analyses to provide a comprehensive assessment of the success of the tissue-engineering implants in the two repair models.