Synergistic effects of the dual release of stromal cell-derived factor-1 and bone morphogenetic protein-2 from hydrogels on bone regeneration

• Published in: Biomaterials Vol. 32; no. 11; pp. 2797 - 2811
• Main Authors: Ratanavaraporn, Juthamas, Furuya, Hiroyuki, Kohara, Hiroshi, Tabata, Yasuhiko
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-04-2011
• Subjects: Advanced Basic Science; Animals; Bone Morphogenetic Protein 2 - chemistry; Bone Morphogenetic Protein 2 - pharmacology; Bone morphogenetic protein-2 (BMP-2); Bone regeneration; Bone Regeneration - drug effects; Cells, Cultured; Chemokine CXCL12 - chemistry; Chemokine CXCL12 - pharmacology; Combined release; Core Binding Factor Alpha 1 Subunit - metabolism; Dentistry; Female; Flow Cytometry; Gelatin - chemistry; Gelatin hydrogels; Hydrogels - chemistry; Male; Mice; Mice, Inbred C57BL; Osteocalcin - metabolism; Rats; Rats, Wistar; Receptors, CXCR4 - metabolism; Stromal cell-derived factor-1 (SDF-1); Tissue Engineering - methods; X-Ray Microtomography; Stromal cell-derived factor-1 (SDF-1); Combined release; Gelatin hydrogels; Bone morphogenetic protein-2 (BMP-2); Bone regeneration
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2010.12.052

Abstract The objective of this study is to evaluate the activity of gelatin hydrogels incorporating combined stromal cell-derived factor-1 (SDF-1) and bone morphogenetic protein-2 (BMP-2) on the in vivo bone regeneration at an ulna critical-sized defect and subcutaneous site of rats, and compared with that of those incorporating either SDF-1 or BMP-2. The similar release profile of SDF-1 and BMP-2 from the hydrogels was observed with or without the combination of BMP-2 and SDF-1, respectively. An enhanced bone regeneration by the hydrogels incorporating combined SDF-1 and BMP-2 was observed. In addition, the implantation of hydrogels incorporating combined SDF-1 and BMP-2 enhanced the expression level of CXC chemokine cell-surface receptor-4 ( Cxcr4 ), Runt-related factor-2 ( Runx2 ), and Osteocalcin genes. The experiments with green fluorescent protein (GFP)-positive Chimeric mice revealed that the recruitment of bone marrow-derived cells was promoted and a vascular-like structure together with strong accumulation of CD31- and CD34-positive cells was observed at the site of hydrogels incorporating combined SDF-1 and BMP-2 implanted. In addition, a large fraction of CD29- and CD44-positive non-hematopoietic cells was detected. It is concluded that the combined release of SDF-1 and BMP-2 enhanced the recruitment of osteogenic cells and angiogenesis, resulting in the synergistic effect on bone regeneration.