Preparation and osteogenesis of a multiple crosslinking silk fibroin/carboxymethyl chitosan/sodium alginate composite scaffold loading with mesoporous silica/poly (lactic acid-glycolic acid) microspheres

Large bone defect repair is a striking challenge in orthopedics. Currently, inorganic-organic composite scaffolds are considered as a promising approach to these bone regeneration. Silicon ions (Si⁴⁺) are bioactive and beneficial to bone regeneration and Si⁴⁺-containing inorganic mesoporous silica (MS) can effectively load drugs for bone repair. To better control the release of drug, we prepared biodegradable MS/PLGA (MP) microspheres. MP loaded organic silk fibroin/carboxymethyl chitosan/sodium alginate (MP/SF/CMCS/SA) composite scaffolds were further constructed by genipin and Ca²⁺ crosslinking. All MP/SF/CMCS/SA scaffolds had good swelling ability, degradation rate and high porosity. The incorporation of 1% MP significantly enhanced the compressive strength of composite scaffolds. Besides, MP loaded scaffold showed a sustained release of Si⁴⁺ and Ca²⁺. Moreover, the release rate of rhodamine (a model drug) of MP/SF/CMCS/SA scaffolds was obviously lower than that of MP. When culturing with rat bone marrow mesenchymal stem cells, scaffolds with 1% MP displayed good proliferation, adhesion and enhanced osteogenic differentiation ability. Based on the results above, the addition of 1% MP in SF/CMCS/SA scaffolds is a prospective way for drug release in bone regeneration and is promising for further in vivo bone repair applications.