TY - JOUR
T1 - A novel method for the direct fabrication of growth factor-loaded microspheres within porous nondegradable hydrogels
T2 - Controlled release for cartilage tissue engineering
AU - Spiller, Kara L.
AU - Liu, Yu
AU - Holloway, Julianne L.
AU - Maher, Suzanne A.
AU - Cao, Yilin
AU - Liu, Wei
AU - Zhou, Guangdong
AU - Lowman, Anthony M.
N1 - Funding Information:
This research was supported by the National Basic Research Program of China ( 2005CB522702, 2010CB944804 ), Hi-Tech Research and Development Program of China ( 2006AA02A126 ), National Natural Science Foundation of China ( 50830105, 30973131, 30973130, and 81000677 ), Shanghai Aurora Program ( 08SG19 ), and Shanghai Rising-star Program ( 09QH1401600 ). The authors would like to thank Lingling Xia (Shanghai Key Tissue Engineering Laboratory) for help with surgeries, Dr. Peter Lelkes (Drexel University) for lab space and helpful discussions, and Demin Yin, Lijuan Zong, and Juanjuan Wu for technical support in the laboratory. The authors would also like to acknowledge use of the Drexel University Centralized Research Facilities. K.L.S. is grateful to the U.S. National Science Foundation for a Graduate Research Fellowship and the Doctoral Dissertation Enhancement Program (Award No. 0935871).
PY - 2012/1/10
Y1 - 2012/1/10
N2 - 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.
AB - 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.
KW - Cartilage tissue engineering
KW - Hydrogel
KW - Insulin-like growth factor-1
KW - Microparticle
UR - http://www.scopus.com/inward/record.url?scp=84855842640&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855842640&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2011.09.057
DO - 10.1016/j.jconrel.2011.09.057
M3 - Article
C2 - 21930167
AN - SCOPUS:84855842640
SN - 0168-3659
VL - 157
SP - 39
EP - 45
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -