Biomimetic Synthesis Of A Novel Antibacterial Nano-composite Materials Of Hydroxyapatite And Gelatin For Bone Repair And Its Biocompatibility In Vitro

Objective To synthesise a new type of antibacterial nano-composite materials for bone repair by biomimetic method and evaluate its cytocompatibility in vitro. To establish a new platform of human hard tissue substitute materials design. The development of a new generation of bio-functional materials may be further applied to bone defects.Methods A certain amount of acidic solution of hydroxyapatite and minocycline solution was added into gelatin solution respectively, and kept the system at about 40℃and pH 8 for 1-2 h, then aged overnight at pH 7-8 to obtain the composite of hydroxyapatite-gelatin-minocycline nano-hydrocolloid. A part of the nano-hydrocolloid was lyophilized to obtain"Gel-HA-M"nano-particles."Gel-HA-M"composite was characterized by FTIR, XRD, SEM, TEM and thermal analysis. The lyophilized nano-composite particles were released in vitro. At appropriate time intervals (1, 3, 5, 7 and 14 day), the release of minocycline was measured by ultraviolet spectrophotometer. Unlyophilized"Gel-HA-M"nano-hydrocolloid was co-cultured with rat bone marrow stromal cells (BMSCs) in vitro to observe the adhesion and growth of BMSCs, and to determine the proliferation and differentiation of BMSCs.Results The FTIR and the XRD spectra showed the formation of low-crystallinity HA, and the effect of minocysline incorporation to the growth of hydroxyapatite crystal. SEM photograph showed that nano-hydroxyapatite distributed evenly in the fibrils of gelatin. TEM micrograph showed that the nano-HA crystals were well-dispersed. Thermal analysis suggested that the content of inorganic component in"Gel-HA-M"composite was about 74%. Minocycline could release from composite materials slowly, and kept the effective antimicrobial concentration in two weeks. The BMSCs response to the material showed that it was considerably cytocompatible."Gel-HA-M"composite could promote BMSCs adhesion, proliferation and differentiation.Conclusions The biomimetic"Gel-HA-M"composite had bone-porous structure. HA crystals distributed evenly in the network of gelatin. The structure of HA crystal was similar with nano-apatite crystals in bone."Gel-HA-M"composite has satisfactory cytocompatibility and biodegradability. It can release antimicrobial agent continuingly, and can promote proliferation and differentiation of bone marrow stromal cells. The composite showed promising as an antibacterial biomaterial for bone repair/regeneration.