Calcium phosphate incorporated in silk fibroin/methylcellulose based injectable hydrogel: Preparation, characterization, and in vitro biological evaluation for bone defect treatment

Bone defect is still a challenging problem in orthopedic practice. Injectable bone substitutes that can fill different geometry of bone defect and improve biological environment for bone regeneration are attracting attention. Herein, silk fibroin (SF) is noticeable polymer regarding its biocompatible and biodegradable properties. Thus, the calcium phosphate particles incorporated in silk fibroin/methylcellulose (CAPs-SF/MC) and only methylcellulose (CAPs-MC) hydrogels are developed and compared their physicochemical properties. Both CAPs-hydrogels solutions can be administered with a low injectability force of ~6 N, and they require ~40-min to change to hydrogel at physiological temperature (37°C). The CAPs are evenly distributed throughout the hydrogel matrix and are capable transformed to bioactive hydroxyapatite at pH 7.4. The CAPs in CAPs-SF/MC have a smaller size than those in CAPs-MC. Moreover, CAPs-SF/MC exhibit gradual degradation, as prediction of the degradation mechanism by the Peppas-Sahlin model and show a greater ability to sustain CAPs release. CAPs-SF/MC has good biocompatibility with less cytotoxicity in a dose-dependent manner on mouse preosteoblast cell line (MC3T3-E1) when compared to CAPs-MC. CAPs-SF/MC hydrogels also have better possibility for promoting cell proliferation and differentiation. In conclusion SF incorporated into composite injectable hydrogel potentially improve biological characteristics and may provide clinical advantages.