HEALING OF THE MCL--INTERDISCIPLINARY STUDIES

内侧副韧带的治愈——跨学科研究

• 批准号: 2732850
• 负责人: SAVIO L-Y. WOO
• 金额: $ 28.28万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-20 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2732850
• 关键词: arthroplasty; biomechanics; collagen; combination chemotherapy; dosage; drug screening /evaluation; epidermal growth factor; fibroblast growth factor; gene therapy; goats; growth factor; insulinlike growth factor; joint ligament; knee; light microscopy; longitudinal animal study; musculoskeletal injury; nonhuman therapy evaluation; platelet derived growth factor; protein biosynthesis; skeletal disorder chemotherapy; tensile strength; tissue /cell culture; transforming growth factors; transmission electron microscopy; wound healing

The annual incidence of medial collateral ligament (MCL) injuries in the U.S. is estimated to be greater than 60,000, one-third of which have concomitant anterior cruciate ligament (ACL) injuries. Clinically, the injured MCL can heal without operative intervention; however, animal studies have shown that the quality of the healed tissue does not return to pre-injury levels, even after one year. There are concerns that suboptimal healing, especially of combined MCL+ACL injuries, can lead to knee disability. Although many treatment methods have been recommended, there is no consensus of opinion regarding the therapeutic approach to MCL+ACL ligament injuries. Thus, the objective of this study is to systematically identify methods for improving the healing of the injured MCL with growth factors. Four specific aims are proposed: 1) EGF, PDGF-BB, betaFGF and TGF-beta1 will be applied to goat MCL fibroblasts and then isolated MCL injuries to identify the best growth factor and optimal dose. 2) The effects of the optimal growth factor treatment on MCL healing will then be explored in a combined- MCL+ACL injury with ACL reconstruction. 3) Gene transfer technology, which allows repeated percutaneous delivery of growth factors to the injury site, will be explored. 4) The combined MCL+ACL injury with ACL reconstruction will be used to study the effects of growth factors on MCL healing and remodeling up to 2 years post-injury. Using an interdisciplinary approach, the morphological, biochemical, and biomechanical properties of MCL healing will be evaluated and correlated. Morphological analyses will consist of gross, histological, and ultra examination. Biomechanical evaluation will consist of measurements of joint instability as well as tensile and viscoelastic behaviors. Biochemical evaluation will involve the quantification and classification of proteoglycans and the determination of content, typing and cross-linking of collagen. Based on published and ongoing studies, growth factors will aid MCL healing and remodeling, while gene transfer technology offers an exciting opportunity for repeated percutaneous delivery of growth factors. The knowledge gained from this study will increase our understanding of the mechanisms of MCL healing, which could be applied to other ligaments.

内侧副韧带（MCL）损伤的年发病率 在美国，估计超过60，000，三分之一的 前交叉韧带（ACL）损伤。 临床上，损伤的MCL可不经手术而愈合 然而，动物研究表明， 愈合组织的损伤不会恢复到损伤前的水平，即使在 一年有人担心，次优愈合，特别是 MCL+ACL联合损伤可导致膝关节残疾。 虽然有很多治疗方法， 关于治疗方法没有共识， MCL+ACL韧带损伤。 因此，本研究的目的是 为了系统地确定方法，以改善愈合的 用生长因子损伤MCL。四个具体目标是 建议：1）EGF，PDGF-BB，betaFGF和TGF-β 1将被 应用于山羊MCL成纤维细胞，然后分离MCL损伤， 确定最佳生长因子和最佳剂量。2)的影响 那么对MCL愈合的最佳生长因子治疗将是 在MCL+ACL联合损伤中进行了探索， 重建3)基因转移技术，它允许重复 将生长因子经皮递送至损伤部位， 探讨了4)MCL+ACL联合损伤 重建将用于研究生长因子的影响 受伤后2年内MCL的愈合和重塑。使用 一种跨学科的方法，形态学，生物化学， 将评价MCL愈合的生物力学特性， 相关的形态学分析将包括大体， 组织学和超微结构检查。生物力学评价将 包括关节不稳定性的测量以及拉伸和 粘弹性行为生化评估将涉及 蛋白聚糖的定量和分类， 胶原蛋白的含量测定、分型和交联。 根据已发表和正在进行的研究，生长因子将有助于 MCL愈合和重塑，而基因转移技术 提供了一个令人兴奋的机会， 的生长因子。从这项研究中获得的知识将 增加我们对MCL愈合机制的理解， 其可以应用于其它韧带。