title: A novel method for the direct fabrication of growth factor-loaded microspheres within porous nondegradable hydrogels: controlled release for cartilage tissue engineering.
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±0.02MPa, compared to 0.17-0.2MPa 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.
authors.affiliation: Biomaterials and Drug Delivery Laboratory, Dept. of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USA. kls2174@columbia.edu
authors.forename: Kara L
authors.initials: KL
authors.lastname: Spiller
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Julianne L
authors.initials: JL
authors.lastname: Holloway
authors.forename: Suzanne A
authors.initials: SA
authors.lastname: Maher
authors.forename: Yilin
authors.initials: Y
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Guangdong
authors.initials: G
authors.lastname: Zhou
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Lowman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008863:Microspheres; D010539:Permeability; D016062:Porosity / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D013552:Swine; D023822:Tissue Engineering / Q000379:methods* / Q000639:trends
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I