A novel method for the direct fabrication of growth factor-loaded microspheres within porous nondegradable hydrogels: Controlled release for cartilage tissue engineering |
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Authors: | Kara L Spiller Yu Liu Julianne L HollowaySuzanne A Maher Yilin CaoWei Liu Guangdong Zhou Anthony M Lowman |
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Institution: | a Biomaterials and Drug Delivery Laboratory, Dept. of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USAb School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, USAc Shanghai Key Tissue Engineering Laboratory, Dept. of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR Chinad Laboratory of Functional Tissue Engineering, Hospital for Special Surgery, New York, NY, USA |
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Abstract: | Because of similar mechanical properties to native cartilage, synthetic hydrogels based on poly(vinyl alcohol) (PVA) have been proposed for replacement of damaged articular cartilage, but they suffer from a complete lack of integration with surrounding tissue. In this study, insulin-like growth factor-1 (IGF-1), an important growth factor in cartilage regeneration, was encapsulated in degradable poly(lactic-co-glycolic acid) (PLGA) microparticles embedded in the PVA hydrogels in a single step based on a double emulsion. The release of IGF-1 from these hydrogels was sustained over 6 weeks in vitro. Poly(glycolic acid) (PGA) fiber scaffolds were wrapped around the hydrogels, seeded with chondrocytes, and implanted subcutaneously in athymic mice. The release of IGF-1 enhanced cartilage formation in the layers surrounding the hydrogels, in terms of the content of extracellular matrix components and mechanical properties, and increased integration between the cartilage layers and the hydrogels, according to gross observation of the cross-sections and histology. The compressive modulus of the cartilage-hydrogel constructs without IGF-1 was 0.07 ± 0.02 MPa, compared to 0.17-0.2 MPa for hydrogels that contained IGF-1. The biochemical and mechanical markers of cartilage formation were not different between the low and high concentrations of IGF-1, despite an order of magnitude difference in concentration. This study shows that the sustained release of IGF-1 can enhance tissue formation and points to a possible strategy for effecting integration with surrounding tissue. |
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Keywords: | Insulin-like growth factor-1 Cartilage tissue engineering Hydrogel Microparticle |
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