Fibrous-Hydrogel Composites for Cartilage Repair in an Osteoarthritic Environment

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DESCRIPTION (provided by applicant): Lesions of the articular surface do not heal spontaneously and are often intractable clinical problems that are managed symptomatically. The progressive loss of articular cartilage is a pathologic hallmark of the degenerative joint disease osteoarthritis (OA). OA is one of the most common joint disorders afflicting humans, and it is estimated that over 60% of the United States population develop radiographic evidence of OA by 55 years of age. Given the aging American population and increasing physical activity among the elderly this estimate is likely to increase over time. The objective of this proposal is to design and characterize a novel fibrous-hydrogel composite to enhance the repair of cartilage defects in a normal and OA environment. The goals of this proposal are both hypothesis and design driven and will be addressed in the following specific aims: Aim 1. Development and characterization of novel fibrous-hydrogel composites to promote cartilage repair. Specifically, we will incorporate a three dimensional electrospun poly(caprolactone) fibrous network into a photopolymerizable polyethylene-glycol hydrogel. Fiber diameter and density within the hydrogel will be modulated in order to optimize the bulk properties and chondrogenic potential of the composite. Physical properties of the composite will be evaluated. The chondrogenic potential will be studied in vitro through encapsulation experiments with primary chondrocytes and MSCs. The regenerative potential of this material will be investigated using an in vitro OA model based on Interleukin 1B exposure. Cartilage formation will be assessed on the basis of ECM production, gene expression, and histology. Aim 2. Translate the fiber-hydrogel composites and cell-based repair strategies to a rodent model of a normal and osteoarthritic joint. The appropriate material from Aim 1 will be applied to a critical sized cartilage defect on the rat femoral trochlea in combination with a marrow stimulation procedure. A rat surgical destabilization model of OA will be used to evaluate the repair potential of these materials in the context of a degradative joint environment. Cartilage development and integration of our constructs will be evaluated by gross lesion grading scales and histology. PUBLIC HEALTH RELEVANCE: Load bearing joint surfaces do not heal spontaneously and over time small cartilage lesions progress to full blown osteoarthritis which adversely affects the lives of 60% of people over 55 years of age. The aims of this proposal seek to develop a novel technology platform for the treatment of cartilage defects both in a healthy joint and in the context of a diseased joint environment.