Optimized Bone Regeneration in Calvarial Bone Defect Based on Biodegradation-Tailoring Dual-shell Biphasic Bioactive Ceramic Microspheres

Bioceramic particulates capable of filling bone defects have gained considerable interest over the last decade. Herein, dual-shell bioceramic microspheres (CaP@CaSi@CaP, CaSi@CaP@CaSi) with adjustable beta-tricalcium phosphate (CaP) and beta-calcium silicate (CaSi) distribution were fabricated using a co-concentric capillary system enabling bone repair via a tailorable biodegradation process. The in vitro results showed the optimal concentration (1/16 of 200 mg/ml) of extracts of dual-shell microspheres could promote bone marrow mesenchymal cell (BMSC) proliferation and enhance the level of ALP activity and Alizarin Red staining. The in vivo bone repair and microsphere biodegradation in calvarial bone defects were compared using micro-computed tomography and histological evaluations. The results indicated the pure CaP microspheres were minimally resorbed at 18 weeks post-operatively and new bone tissue was limited; however, the dual-shell microspheres were appreciably biodegraded with time in accordance with the priority from CaSi to CaP in specific layers. The CaSi@CaP@CaSi group showed a significantly higher ability to promote bone regeneration than the CaP@CaSi@CaP group. This study indicates that the biphasic microspheres with adjustable composition distribution are promising for tailoring material degradation and bone regeneration rate, and such versatile design strategy is thought to fabricate various advanced biomaterials with tailorable biological performances for bone reconstruction.