Injectable, High Specific Surface Area Cryogel Microscaffolds Integrated with Osteoinductive Bioceramic Fibers for Enhanced Bone Regeneration

Organic-inorganic composites with high specific surface area and osteoinductivity provide a suitable microenvironment for cell ingrowth and effective ossification, which could greatly promote bone regeneration. Here, we report gelatin methacryloyl (GelMA) cryogel microspheres that are reinforced with hydroxyapatite (HA) nanowires and calcium silicate (CS) nanofibers to achieve the goal. The prepared composite cryogel microspheres with open porous structure and rough surface greatly facilitate cell anchoring, simultaneously exhibiting excellent injectability. Compared to the only HA- or CS-containing counterparts, the GelMA cryogel microspheres composited with HA:CS (termed as GMHC) achieve sustained release of bioactive Ca, P, and Si elements, which are conducive to osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). These composite microspheres can prevent from forming peralkalic conditions, which is beneficial for cell growth. After injection of cryogel microspheres into rat calvarial defects, neo-bone tissue grows into their pores, showing tight integration. The embedded bioceramic components significantly promote bone regeneration, with the GMHC achieving the best regenerative outcomes. Promisingly, porous organic-inorganic composite cryogel microspheres, with high specific surface area, biodegradability, and osteoinductivity, can act as injectable microscaffolds to repair bone defects with enhanced efficiency, which may widen the scaffold strategy for bone tissue engineering.