Evaluation of Demineralized Bone Matrix Particles Delivered by Alginate Hydrogel for a Bone Graft Substitute: An Animal Experimental Study.

ABSTRACT

BACKGROUND Our objective was to explore a synthetic alginate hydrogel delivery system for the delivery of demineralized bone matrix (DBM) particles for bone graft substitutes. MATERIAL AND METHODS The physiochemical properties of surface morphology, porosity measurements, in vitro degradation, equilibrium swelling, and mechanical testing of combined DBM powder and alginate in amounts of 0 mg/1 mL, 25 mg/1 mL, 50 mg/1 mL, and 100 mg/1 mL were detected. In vitro cell culture and in vivo studies using Sprague-Dawley rats were performed to evaluate the biocompatibility and osteoinductivity of DBM-alginate (ADBM) composites. RESULTS DBM particles were uniformly scattered in all composites, and macro-scale pores were omnipresent. All composites showed a similar low degradation rate, with approximately 85% of weight remaining after 15 days. As the concentration of DBM particles in composites increased, degradation in collagenase and elastic modulus increased and the pore area and swelling ratio significantly decreased. No cytotoxicity of ADBM or alginate on mesenchymal stem cells (MSCs) was observed. Cell cultivation with ADBM showed greater osteogenic potential, evidenced by the upregulation of alkaline phosphatase and alizarin red staining activity and the mRNA expression level of marker genes RUNX2, OCN, OPN, and collagen I compared with the cells grown in alginate. Evaluation of ectopic bone formation revealed the osteoinductivity of the ADBM composites was significantly greater than that of DBM particles. Osteoinduction of the composites was demonstrated by a cranial defect model study. CONCLUSIONS The delivery of DBM particles using a synthetic alginate hydrogel carrier may be a promising approach in bone tissue engineering for bone defects.