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W9.04 - Mechanical Adjustable and Biodegradable Implant Materials for the Treatment of Articular Cartilage Defects 
April 25, 2014   9:15am - 9:30am

Osteoarthritis (OA) is a debilitating disease that affects the articular cartilage (AC) and the underlying bone in joints. It is the leading cause of both disability and chronic pain in elderly people, with approximately 35 to 40 million Europeans currently affected with OA. Trauma and abnormal joint loading also contribute to AC defects. Due to the limited self-repair ability of adult AC, defects that are not treated properly can develop into secondary (late-stage) OA. Numerous surgical interventions and biomaterials have been introduced over the last decades but none has been successful in restoring the structure, composition and biomechanical function of AC to its native state. Our research aims to provide a long-term solution for the treatment of AC defects by investigating a temporary structural support that is able to sustain in vivo joint loading forces, and hence, assist the body to regenerate functional competent AC. Three dimensional scaffolds were produced by electrospinning biocompatible polyhydroxyalkanoates blends, i.e. poly(3-hydroxybutyrate)/poly(3-hydroxyoctanoate) [P(3HB)/P(3HO)] into nanometre-sized fibrils that exhibit a similar structure compared to the collagen fibril meshwork in native cartilage. Structure of the electrospun P(3HB)/P(3HO) fibrils was stable in liquid condition due to “pseudo crosslinking” represented by the hydrogen bonding formed between the included water molecules and carbonyl groups of the polyhydroxyalkanoates backbone. The stiffness of P(3HB)/P(3HO) nanofibrous scaffolds can be adjusted by controlling the composition of P(3HB) and P(3HO) in the polymer blends. Indentation-type atomic force microscopy (IT-AFM) employing hard borosilicate glass spherical probes revealed a stiffness of the P(3HB)/P(3HO) nanofibrous scaffold of 0.87 ± 0.54 MPa for a ratio of P(3HB)/P(3HO) = 1:0.25, which is a factor of two lower compared to the stiffness of 1.86 ± 0.50 MPa of native AC and needs to be further optimised. After culturing the scaffold with human articular chondrocytes for 3 weeks, the stiffness of the construct increased to 1.06 ± 0.60 MPa. Matrix formation within the construct was confirmed by Alcian blue and Sirius red staining of the proteoglycan and total collagen content, respectively. Higher total collagen and less proteoglycan contents were produced on the stiffer P(3HB)/P(3HO) scaffolds compared to those on the softer scaffolds. The nanofibrous structure provides a large surface area that promotes good chondrocytes attachment and the cells were observed to successfully penetrate into the voids between fibrils. A major advantage of employing polyhydroxyalkanoates blends compared to similar approaches in cartilage repair is that the polymer scaffolds are biodegradable, which allows ingrowth and formation of new cartilage into the defect site. Our future work is to investigate the in vivo performance of these constructs by implanting them into the joints of immunosuppressed mice.

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