Silver phosphate-modified carbonate apatite honeycomb scaffolds for anti-infective and pigmentation-free bone tissue engineering.

ABSTRACT

Bone regeneration using synthetic materials has a high rate of surgical site infection, resulting in severe pain for patients and often requiring revision surgery. We propose Ag3PO4-based surface modification and structural control of scaffolds for preventing infections in bone regeneration. We demonstrated the differences in toxicity and antibacterial activity between in vitro and in vivo studies and determined the optimal silver content in terms of overall anti-infection effects, bone regeneration, toxicity, and pigmentation. A honeycomb structure comprising osteoconductive and resorbable carbonate apatite (CAp) was used as the base scaffold. CAp in the scaffold surface was partially replaced with different concentrations of Ag3PO4 via controlled dissolution-precipitation reactions in an AgNO3 solution. Both bone regeneration and infection prevention were achieved at 860-2300 ppm of silver. Despite the absence of Ag3PO4, honeycomb scaffolds were less susceptible to infection, even under conditions where infection occurs in clinically used three-dimensional porous scaffolds. Regardless of in vitro cytotoxicity at >5200 ppm of silver, increasing the silver content to 21,000 ppm did not adversely affect in vivo bone formation and scaffold resorption or cause acute systemic toxicity. Rather, bone formation was enhanced with 5200 ppm of silver. However, pigmentation was observed at that concentration. Hence, we concluded that the optimal silver concentration range is 860-2300 ppm for anti-infective and pigmentation-free bone regeneration. Bone regeneration was achieved via surface modification, resulting in the rapid release of silver ions immediately after implantation, followed by gradual release over several months. The scaffold structure may also aid in preventing bacterial growth within the scaffolds.