Engineered Anterior Cruciate Ligaments

描述：每年有超过20万美国人撕裂或断裂他们的前十字韧带(ACL)。部分原因是， 前交叉韧带的复杂力学特性，以前的重建技术 (例如，人造材料)未能提供完全恢复的功能 受伤的膝盖。组织工程为改善患者护理提供了新的选择 通过为受损的韧带提供更快、更有效的替代。在我们的 初步研究我们已经解决了机械力的假设 在本质上是生理的，强度和频率可以引导骨骼 骨髓基质细胞(BMSC)向韧带形成细胞分化 导致在体外形成与本地ACL功能等效的ACL。这个 我们的初步研究结果表明，这是一种新的可行的 体外形成前交叉韧带的方法探讨。 第一阶段研究的总体目标是建立一个工程化的 具有合适的力学、结构和生化性能的韧带 随后的活体第二阶段研究。在第一阶段研究中，我们建议延长 我们之前的体外韧带形成工作包括了 生化参数、机械负荷制度和培养时间， 按顺序寻址，以每一轮数据为基础，以达到 ‘通过/不通过决定。评估特定的前交叉韧带标记、机械性能 形态评估将是这些研究的组成部分。 可生物降解材料包埋骨髓间充质干细胞的体外培养 矩阵，结合机械力，可能是一条可行的途径 本土韧带的功能性置换。开发出组织工程化ACL 来自患者自身祖细胞的干细胞可能会成为一种 体内无限量的自体组织等效物池 移植，以替代韧带患者的受损组织 撕裂或破裂。 建议的商业应用： 存在对不会导致自体组织丢失或引起免疫反应，而是完全恢复膝关节功能的ACL假体的巨大需求。无论是在膝关节损伤之前还是之后，从患者自身的BMSCs体外构建的ACL将向每年至少20多万名ACL断裂或撕裂的美国人销售，平均每位患者的成本为25,000美元。这项拟议的技术将创造一个门诊程序，并将手术时间、康复周期和总成本减少80%。分别为80%和40%，消除了与前交叉韧带签名重建相关的肌腱炎和关节炎。

DESCRIPTION (Verbatim from Applicant): Each year more than 200,000 Americans tear or rupture their anterior cruciate ligaments (ACL). Due, in part, to the complex mechanical properties of the ACL, previous reconstructive techniques (e.g., artificial materials) have failed to provide fully restored function to the damaged knee. Tissue engineering avails new options to improve patient care by offering more rapid and effective replacements for damaged ligaments. In our preliminary studies we have addressed the hypothesis that mechanical forces that are physiological in nature, intensity and frequency can direct bone marrow stromal cell (BMSC) differentiation into ligament-forming cells and result in the in vitro formation of functional equivalents of native ACLs. The results of our preliminary studies suggest that this is a new and viable approach to ACL formation in vitro. The overall objective of the Phase I study is to establish an engineered ligament with suitable mechanical, structural and biochemical properties for subsequent Phase II studies in vivo. In Phase I studies, we propose to extend our previous work of ligament formation in vitro to include matrices of biochemical parameters, mechanical loading regimes and time of culture, addressed sequentially to build on each round of data, in order to reach a 'go/no go decision. Assessment of ACL-specific markers, mechanical properties and morphological evaluation will be components of these studies. In vitro cultivation of progenitor BMSC cells embedded within a biodegradable matrix, in conjunction with mechanical forces could be a viable path toward functional replacements of native ligaments. Tissue engineered ACLs developed from the patient's own progenitor stem cells could potentially serve as an essentially unlimited pool of autologous tissue equivalents for in vivo transplantation, to replace damaged tissues in patients suffering from ligament tear or rupture. PROPOSED COMMERCIAL APPLICATION: An immense need exists for ACL prostheses that do not result in the loss of autologous tissue or cause an immune response but rather fully restore knee functionality. An ACL engineered from a patient's own BMSCs in vitro, either prior to or immediately after knee joint trauma, would be marketable to at least the 200,000+ Americans a year who rupture or tear their ACL at an average cost of $25,000 per patient. The proposed technology would create an outpatient procedure and reduce surgical time, rehabilitation period and total cost cost by 80%. 80% and 40%, respectively, and eliminate tendinitis and arthritis associated with ACL autograph reconstruction.