Human Tissue Engineered Matrix Constructs for Repair

DESCRIPTION (provided by applicant): The objective of this program is to use a functional tissue engineering approach to develop a construct that will enhance the surgical repair of tendons, in particular the rotator cuff. The objective of this Phase I application is to determine the feasibility of producing tissue engineered constructs possessing the biochemical and biomechanical properties appropriate to enhance the repair of rotator cuff injuries. The working hypothesis is that a tissue engineered construct consisting of a native extracellular matrix and degradable scaffold will support cell attachment and migration, and has tensile properties approaching those of native rotator cuff tendon. The biologic activity of the constructs is expected to be derived largely from the extracellular matrix, and the mechanical (tensile) properties will be derived mostly from the degradable scaffold. In order to achieve this objective, the following four specific aims are proposed: Specific Aim 1: Identify a cell source (tendon cells or dermal fibroblasts) that can be cultured to generate commercially relevant numbers while maintaining its ability to synthesize an extracellular matrix; Specific Aim 2: Identify slowly degradable scaffolds with appropriate mechanical properties; Specific Aim 3: Culture in vitro and characterize the constructs to determine biological and mechanical features important for enhanced in vivo repair; Specific Aim 4: Assess the ability of the device to aid in vivo repair. The successful outcome of these specific aims will be the development of acellular tissue engineered constructs with the potential of enhancing the repair of rotator cuff injuries, and will serve as prototypes for use in further in-vivo animal studies to determine safety and effectiveness in enhancing repair of rotator cuff injuries.