(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.
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.
