MCL Healing: Interdisciplinary Studies

MCL 治疗：跨学科研究

• 批准号: 6766696
• 负责人: SAVIO L-Y. WOO
• 金额: $ 41.84万
• 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/6766696
• 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变得越来越严重 更频繁、更广泛，要求加深对 愈合过程和增强它的方法。临床上，受伤的内侧 研究发现，副韧带 (MCL) 无需手术干预即可愈合； 然而，实验室研究表明，愈合组织的质量 即使一年后，仍然远离正常组织。有严重的 对次优生物力学、生化和 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 和前十字韧带 (ACL) 的严重损伤， 这可能会导致骨关节炎的早期发展。目前还没有 此类合并MCL/ACL的治疗方法达成共识 受伤。新的和创新的方法，例如反义基因疗法和 功能性组织工程已成为现实。因此，总体 本研究的目的是探索增强 MCL 愈合的新方法。这 拟议的研究涉及四个具体目标：（1）反义寡脱氧核苷酸 (ODN) 特异性针对 V 型和 III 型胶原蛋白，单独或组合，将 输送至正在愈合的 MCL，以降低 V/I 型胶原蛋白的比例， III/I，从而增加胶原原纤维直径； (2)组织工程 将应用小肠粘膜下层 (SIS) 支架来帮助愈合 MCL破裂后通过改善胶原纤维排列； (3)最优 上述治疗方法将同时应用，以进一步增强 愈合过程； (4) 这种治疗方式将得到推广，以改善 更严重的 MCL/ACL 联合损伤中的 MCL 愈合。 采用跨学科方法，生物力学、生物化学和 将评估愈合中 MCL 的组织形态学特性。 生物力学测试将评估关节的不稳定性以及拉伸和 愈合中 MCL 的粘弹性行为。生化分析将包括 胶原蛋白和蛋白多糖含量的测定，以及分型 胶原蛋白和胶原蛋白交联。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 增加胶原纤维直径，改善胶原纤维 愈合中的 MCL 的对齐将导致生物力学特性的改善， 从而提高愈合组织的质量。所获得的知识来自 这项研究将增强对韧带机制的理解 治愈，反过来又可以用来帮助治愈其他人 韧带（ACL）和肌腱（屈肌腱）。