Biologic Scaffold Prostheses to Enhance Meniscus Repair

摘要

Abstract Menisci play critical roles in stabilization and load transmission in the knee joint. Meniscal damage or loss often results in progressive osteoarthritic degeneration of the articular cartilage and other joint tissues, leading to significant pain and disability. We need better methods to repair or replace damaged menisci. However, most tissue engineering approaches for meniscal replacement require significant culture time for the newly formed tissue to develop functional properties that could withstand joint loading. We have demonstrated the usefulness of three dimensional (3-D) woven scaffolds for tissue engineering purposes. These scaffolds provide physiologic mechanical properties prior to implantation. We have also shown that mechanical stress and cytokines alter the metabolism of menisci and inhibit repair of meniscal injury. The overall goal of our study is to develop a new 3-D composite scaffold for use in the functional tissue engineering of the meniscus. A special advantage of 3-D weaving is that constructs can be designed and built with predetermined control of site-dependent variations in mechanical properties. Also, certain growth factors that may enhance meniscus-bone molding and annealing can be incorporated into the matrix. We will develop the device and also determine effects of soluble mediators such as cytokines, nitric oxide (NO), and prostaglandins (PG) on development, integrity, and function of the prostheses. We will accomplish 4 aims. Aim 1. Design and construct 3-D woven composite scaffolds for use in the functional tissue engineering of the knee meniscus. We will develop a composite scaffold that promotes meniscal fibrochondrocyte development and tissue organization, while effectively replicating the structural and functional mechanical properties of a natural meniscus. Aim 2: Incorporate bioactive factors into the 3-D matrix that will allow fibrochondrocyte differentiation and attachment to bone. We will incorporate growth factors into the materials used in Aim 1 to construct the 3-D woven composite scaffolds. Aim 3: Perform mechanical testing of the composite scaffolds to assess their potential in vitro functionality. Tension, compression, and shear testing will be used to evaluate the critical biomechanical parameters of the developed scaffolds and resulting neomeniscus. We will assess the importance of certain cytokines, growth factors, and other natural mediators such as NO and PG on the development and biomechanical properties of the meniscus prostheses. Aim 4: Test the ability of the meniscus scaffold prosthesis to attach to bone and function in vivo. We will place the in vitro-generated meniscus prostheses into sites of fresh-ly resected medial menisci in dogs and leave the prostheses in place for up to 12 weeks, after which we will evaluate their function and their effects on development of pathology in the joint. Our work will have a direct effect on veterans with meniscal injuries, facilitating a more rapid recovery and reducing long term morbidity. Also, for active-duty military personnel, it may result in more rapid return to active duty.