Journal
BIOMATERIALS
Volume 33, Issue 30, Pages 7613-7620Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.06.075
Keywords
Bone regeneration; Drug delivery; Recombinant human fibroblast growth; factor 18 (FGF18); Recombinant human bone morphogenetic; protein 2 (BMP2); Osteoblasts; Acryloyl group-modified cholesterol-bearing; pullulan (CHPOA)
Funding
- Japan Society for the Promotion of Science [20390510, 23.8114]
- Grants-in-Aid for Scientific Research [20240047, 20390510] Funding Source: KAKEN
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To create a drug delivery system that allows the controlled release of proteins, such as growth factors, over a long-term period, cholesteryl group- and acryloyl group-bearing pullulan (CHPOA) nanogels were aggregated to form fast-degradable hydrogels (CHPOA/hydrogels) by cross-linking with thiol-bearing polyethylene glycol. The gold standard of clinical bone reconstruction therapy with a physiologically active material is treatment with recombinant human bone morphogenetic protein 2 (BMP2); however, this approach has limitations, such as inflammation, poor cost-efficiency, and varying interindividual susceptibility. In this study, two distinct growth factors, BMP2 and recombinant human fibroblast growth factor 18 (FGF18), were applied to a critical-size skull bone defect for bone repair by the CHPOA/hydrogel system. The CHPOA-FGF18/hydrogel displayed identical results to the control CHPOA-PBS/hydrogel, and the CHPOA-BMP2/hydrogel treatment imperfectly induced bone repair. By contrast, the CHPOA-FGF18 + BMP2/hydrogel treatment strongly enhanced and stabilized the BMP2-dependent bone repair, inducing osteoprogenitor cell infiltration inside and around the hydrogel. This report indicates that the CHPOA/hydrogel system can successfully deliver two different proteins to the bone defect to induce effective bone repair. The combination of the CHPOA/hydrogel system with the growth factors FGF18 and BMP2 might be a step towards efficient bone tissue engineering. (C) 2012 Elsevier Ltd. All rights reserved.
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