MCL Healing: Interdisciplinary Studies

描述(申请人提供)：膝关节韧带损伤 更频繁、更广泛，要求更多地了解 治愈过程和增强它的方法。临床上，受伤的内侧 侧副韧带(MCL)已被发现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 即使在一年后，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特性，特别是在更多 涉及MCL和前十字韧带(ACL)的严重损伤， 这可能导致骨性关节炎的早期发展。目前还没有 对MCL/前交叉韧带联合治疗的共识 受伤。新的和创新的方法，如反义基因治疗和 功能组织工程，已经成为可能。因此，总体上， 本研究的目的是探索促进MCL愈合的新方法。这个 建议的研究涉及四个具体目标：(1)反义寡核苷酸 (ODN)V型和III型胶原蛋白的特异性，单独和组合将是 提供给正在愈合的MCL以降低V/I型胶原和 III/I，从而增加胶原原纤维直径；(2)组织工程化 将应用小肠粘膜下层(SIS)支架来帮助愈合 MCL断裂后通过改善胶原纤维的排列；(3)最佳 上述治疗方法将同时应用，以进一步提高 治愈过程；以及(4)这种治疗方式将得到推广，以改善 严重的MCL/前交叉韧带联合损伤的MCL愈合。 使用跨学科的方法，生物力学、生化和 愈合的MCL的组织形态特性将被评估。 生物力学测试将评估关节不稳定，以及拉伸和 愈合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 胶原蛋白和胶原蛋白交联剂。组织形态分析将测量 胶原纤维直径和纤维排列的变化。这是意料之中的 增加胶原原纤维直径，改善胶原纤维 愈合的MCL的对准将导致生物力学性能的改善， 从而提高愈合组织的质量。从以下方面获得的知识 本研究将加深对韧带形成机制的认识。 治疗，这反过来又可以用来帮助治疗其他 韧带(前交叉韧带)和肌腱(屈肌腱)。

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).