Transgenic PDGF-BB/sericin hydrogel supports for cell proliferation and osteogenic differentiation

• Published in: Biomaterials science 2020-01, Vol.8 (2), p.657-672
• Main Authors: Wang, Feng, Hou, Kai, Chen, Wenjing, Wang, Yuancheng, Wang, Riyuan, Tian, Chi, Xu, Sheng, Ji, Yanting, Yang, Qianqian, Zhao, Ping, Yu, Ling, Lu, Zhisong, Zhang, Huijie, Li, Fushu, Wang, Han, He, Baicheng, Kaplan, David L, Xia, Qingyou
• Format: Article
• Language: English
• Subjects: Animals; Becaplermin - chemistry; Becaplermin - pharmacology; Biocompatibility; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biodegradability; Biomedical materials; Bombyx; Cell adhesion; Cell adhesion & migration; Cell Differentiation - drug effects; Cell growth; Cell Line; Cell Proliferation - drug effects; Crosslinking; Differentiation (biology); Growth factors; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; In vivo methods and tests; Mice; Modulus of elasticity; NIH 3T3 Cells; Organic chemistry; Osteoblasts; Osteogenesis - drug effects; Particle Size; Platelet-derived growth factor; RAW 264.7 Cells; Sericins - chemistry; Sericins - metabolism; Silk; Silk fibroin; Silkworms; Stem cells
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/c9bm01478k

Sericin has been exploited as a biomaterial due to its biocompatibility, biodegradability, and low-immunogenicity as an isolated polymer and support for cell adhesion. In the present study, human platelet-derived growth factor (PDGF-BB)-functionalized sericin hydrogels were generated using transgenic silkworms, where the as-spun silk incorporated engineered PDGF-BB (termed PDGFM) in the sericin layers of the cocoons. Sericin and PDGFM were simultaneously extracted from the silk fibroin cocoon fibers, and the soluble extract was then formed into a hydrogel via thermal exposure. The PDGFM sericin hydrogels exhibited increased β-sheet content and a compressive modulus of 74.91 ± 2.9 kPa comparable to chemically crosslinked sericin hydrogels (1.68-55.53 kPa) and a porous microstructure, which contributed to cell adhesion and growth. A 13.1% of total extracted PDGFM from the initial silk fibers was incorporated and immobilized in the sericin hydrogels during material processing, and 1.33% of PDGFM was released over 30 days from the hydrogels in vitro . The remaining PDGFM achieved long-term storage/stability in the sericin hydrogels for more than 42 days at 37 °C. In addition, the PDGFM sericin hydrogels were not immunogenic, were biocompatible and bioactive in promoting the support of cell proliferation. When combined with BMP-9, the PDGFM sericin hydrogels provided synergy to support the osteoblastic differentiation of mesenchymal stem cells (hMSCs) in vitro and in vivo . This study demonstrates that genetically functionalized PDGFM sericin hydrogels can provide useful biomaterials to support cell and tissue outcomes, here with a focus on osteogenesis. The present study demonstrates fabrication of PDGF-BB functionalized sericin hydrogel to explore biomaterials-related utility in bone tissue engineering.