Tissue Engineered Meniscus Repair

描述(申请人提供)：半月板部分或全部丧失，极大地改变膝关节功能，使关节容易发生退行性改变。该项目的目标是修复或再生内侧半月板的临界大小的缺陷，以恢复半月板的功能，防止关节损伤。间充质祖细胞是修复半月板损伤的潜在细胞。在这项研究中，自体骨髓间充质祖细胞将在体外创建纤维软骨组织，然后移植到体内用于半月板修复。需要检验的假设是，组织工程软骨将为半月板修复提供更好的植入物。这将在两种不同的半月板修复模型中进行测试： 具体目标1：修复手术造成的半月板中段撕裂。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。该软骨将通过自体骨髓间充质祖细胞种植到可生物降解的支架中并在软骨形成介质中培养而在体外创建。植入物将被缝合成全厚度的纵向撕裂。这种组织工程结构的修复潜力将与空支架和未植入缝合的撕裂进行比较。 具体目标2：在手术创建的半月板部分切除术中再生半月板组织。一种大型组织工程软骨植入物将被用于再生山羊内侧半月板的部分半月板。对于AIM 1，组织工程化植入物将由含有自体间充质祖细胞的可生物降解支架组成，植入前在软骨细胞培养液中培养。 对于这两个目标，半月板植入物将在植入后12周和12个月进行分析。 手术后的膝关节将接受生物力学、形态学、组织学和免疫组织化学分析，以全面评估组织工程植入物在两种修复模式中的成功。

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.