MCL Healing: Interdisciplinary Studies

MCL 治疗：跨学科研究

• 批准号: 6864440
• 负责人: SAVIO L-Y. WOO
• 金额: $ 33.79万
• 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 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6864440
• 关键词: arthroplasty; biomechanics; biotechnology; collagen; combination chemotherapy; gene therapy; goats; joint ligament; knee; laboratory rabbit; light microscopy; longitudinal animal study; medical rehabilitation related tag; musculoskeletal disorder therapy; musculoskeletal injury; nonhuman therapy evaluation; polymerase chain reaction; tensile strength; tissue /cell culture; tissue engineering; tissue support frame; transmission electron microscopy; western blottings; wound healing

DESCRIPTION (provided by applicant): Injuries to knee ligaments are becoming more frequent and more extensive, demanding increased understanding of the healing process and methods to enhance it. Clinically, the injured medial collateral ligament (MCL) has been found to heal without surgical intervention; however, laboratory studies have shown that the quality of the healed tissue remains far from the normal tissue, even after one year. There are serious concerns about the suboptimal biomechanical, biochemical, and histomorphological properties of healing tissue, especially in the case of more severe injuries that involve both the MCL and anterior cruciate ligament (ACL), which may lead to the early development of osteoarthritis. There is yet no consensus of opinion on the therapeutic approach to such combined MCL/ACL injuries. New and innovative approaches, such as antisense gene therapy and functional tissue engineering, have become available. Thus, the overall objective of this study is to explore novel ways to enhance MCL healing. The proposed study involves four Specific Aims: (1) antisense oligodeoxynucleotides (ODNs) specific for collagen types V and III, alone and in combination, will be delivered to the healing MCL to reduce the ratios of collagen types V/I and III/I, thereby increasing the collagen fibril diameter; (2) a tissue-engineered small intestinal submucosa (SIS) scaffold will be applied to aid the healing MCL after rupture by improving the collagen fiber alignment; (3) the optimal treatments from above will be applied concurrently to further enhance the healing process; and (4) this treatment modality will be extended to improve MCL healing in the more severe combined MCL/ACL injury. Using an interdisciplinary approach, the biomechanical, biochemical, and histomorphological properties of the healing MCL will be evaluated. Biomechanical testing will assess joint instability, as well as the tensile and viscoelastic behaviors of the healing MCL. Biochemical analysis will include determination of collagen and proteoglycan contents, as well as typing of collagen and collagen crosslinking. Histomorphological analysis will measure the changes in collagen fibril diameter and fiber alignment. It is anticipated that increasing the diameter of collagen fibril and improving collagen fiber alignment of the healing MCL will lead to improved biomechanical properties, thereby enhancing the quality of the healing tissue. The knowledge gained from this study will enhance the understanding of the mechanisms of ligament healing, which in turn, could be applied to aid in the healing of other ligaments (ACL) and tendons (flexor tendon).

描述（由申请人提供）：膝关节韧带损伤正在成为 更频繁、更广泛，要求加深对 愈合过程和方法，以提高它。临床上，受伤的内侧 侧副韧带（MCL）已被发现愈合没有手术干预; 然而，实验室研究表明，愈合组织的质量 即使在一年后，仍然远离正常组织。存在严重 关注次优的生物力学，生物化学， 愈合组织的组织形态学特性，特别是在更多的情况下 涉及MCL和前交叉韧带（ACL）的严重损伤， 这可能导致骨关节炎的早期发展。目前还没有 关于这种MCL/ACL联合治疗方法的共识 受伤新的和创新的方法，例如反义基因治疗和 功能性组织工程已经成为可能。由此可见，总体 本研究的目的是探索促进MCL愈合的新方法。的 拟开展的研究涉及四个具体目标：（1）反义寡核苷酸 单独和组合的对V型和III型胶原特异性的寡核苷酸（ODN）将被用于治疗和/或预防。 递送至愈合的MCL以降低V/I型胶原蛋白的比率， III/I，从而增加胶原原纤维直径;（2）组织工程化的 小肠粘膜下层（SIS）支架将用于帮助愈合 MCL破裂后通过改善胶原纤维排列;（3）最佳 上述处理将同时应用，以进一步增强 （4）这种治疗方式将得到扩展，以改善 在更严重的MCL/ACL联合损伤中MCL愈合。 使用跨学科的方法，生物力学，生物化学， 将评价愈合MCL的组织形态学特性。 生物力学测试将评估关节不稳定性，以及拉伸和 愈合的MCL的粘弹行为。生化分析将包括 胶原蛋白和蛋白多糖含量的测定，以及 胶原和胶原交联。组织形态学分析将测量 胶原纤维直径和纤维排列的变化。预计 增加胶原纤维的直径和改善胶原纤维的 愈合的MCL的对齐将导致改善的生物力学性能， 从而提高愈合组织的质量。知识来自于 本研究将加深对韧带损伤机制的认识， 治疗，这反过来，可以应用于帮助其他愈合 韧带（ACL）和肌腱（屈肌腱）。