title: The use of injectable sonication-induced silk hydrogel for VEGF(165) and BMP-2 delivery for elevation of the maxillary sinus floor.
abstract: Sonication-induced silk hydrogels were previously prepared as an injectable bone replacement biomaterial, with a need to improve osteogenic features. Vascular endothelial growth factor (VEGF(165)) and bone morphogenic protein-2 (BMP-2) are key regulators of angiogenesis and osteogenesis, respectively, during bone regeneration. Therefore, the present study aimed at evaluating in situ forming silk hydrogels as a vehicle to encapsulate dual factors for rabbit maxillary sinus floor augmentation. Sonication-induced silk hydrogels were prepared in vitro and the slow release of VEGF(165) and BMP-2 from these silk gels was evaluated by ELISA. For in vivo studies for each time point (4 and 12 weeks), 24 sinus floors elevation surgeries were made bilaterally in 12 rabbits for the following four treatment groups: silk gel (group Silk gel), silk gel/VEGF(165) (group VEGF), silk gel/BMP-2 (group BMP-2), silk gel/VEGF(165)/BMP-2 (group V + B) (n = 6 per group). Sequential florescent labeling and radiographic observations were used to record new bone formation and mineralization, along with histological and histomorphometric analysis. At week 4, VEGF(165) promoted more tissue infiltration into the gel and accelerated the degradation of the gel material. At this time point, the bone area in group V + B was significantly larger than those in the other three groups. At week 12, elevated sinus floor heights of groups BMP-2 and V + B were larger than those of the Silk gel and VEGF groups, and the V + B group had the largest new bone area among all groups. In addition, a larger blood vessel area formed in the remaining gel areas in groups VEGF and V + B. In conclusion, VEGF(165) and BMP-2 released from injectable and biodegradable silk gels promoted angiogenesis and new bone formation, with the two factors demonstrating an additive effect on bone regeneration. These results indicate that silk hydrogels can be used as an injectable vehicle to deliver multiple growth factors in a minimally invasive approach to regenerate irregular bony cavities.
authors: Department of Prosthodontics, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China.
authors: Wenjie
authors: W
authors: Zhang
authors: Xiuli
authors: X
authors: Wang
authors: Shaoyi
authors: S
authors: Wang
authors: Jun
authors: J
authors: Zhao
authors: Lianyi
authors: L
authors: Xu
authors: Chao
authors: C
authors: Zhu
authors: Deliang
authors: D
authors: Zeng
authors: Jake
authors: J
authors: Chen
authors: Zhiyuan
authors: Z
authors: Zhang
authors: David L
authors: DL
authors: Kaplan
authors: Xinquan
authors: X
authors: Jiang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007267:Injections; D008297:Male; D008443:Maxillary Sinus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D011817:Rabbits; D047011:Silk / Q000737:chemistry*; D059546:Sinus Floor Augmentation; D013010:Sonication; D013194:Staining and Labeling; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D005456:Fluorescent Dyes; D047011:Silk; D042461:Vascular Endothelial Growth Factor A; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate