In this study, we developed an injectable system of hydroxyapatite and poly (lactic-co-glycolic acid) (HA/PLGA) with an in situ-solidification property and appropriate initial mechanical strength through the phase separation of a water-miscible solvent. Gelatin microspheres (GMs) were fabricated and utilized as porogen and a potential cargo loading of the biological substance of bone morphogenetic protein 2 (BMP-2). The injectability, compression strength, and microstructure of the injectable implants were systematically characterized by screening the molecule weight (Mw) and concentration of PLGA solution and the proportion of PLGA, HA, and GMs. It was noticed that a higher Mw and concentration of PLGA matrix and a moderate content of HA and GMs resulted in a satisfactory injectable force and mechanical property. In vivo evaluation demonstrated that the injectable materials could significantly repair skull defects, especially via efficient loading with BMP-2, which implied these could serve as a potential vehicle of biological substances for bone tissue regeneration. Although there was acute cytotoxicity after injection, no damage was observed for the main organs by these injectable materials. In all, the GM-incorporated injectable implants present a promising aspect for realizing innovative minimally invasive treatment for clinical orthopedics.
