Department of Biomaterials, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
ACS Infect Dis. 2022 Jan 14;8(1):159-169. doi: 10.1021/acsinfecdis.1c00480. Epub 2021 Dec 7.
Fracture-related infections require both treatments for bacteria removal and bone reconstruction. The use of combined broad-spectrum antibacterial silver compounds and artificial bone with high osteogenic activity is considered to be an effective strategy for achieving these treatments in one surgery. However, silver compounds are toxic for living tissues even at low concentrations. Herein, we investigated the no-observed-effect level (NOEL) of silver phosphate (AgPO) in a bone substitute composed of carbonate apatite (COAp), a bone mineral, using in vitro and in vivo experiments. In vitro experiments demonstrated that the COAp artificial bone containing ≥0.1 wt % AgPO exerted antibacterial effects against , while those containing ≤0.3 wt % AgPO did not affect cellular adhesion, proliferation, differentiation, and calcification of osteoblast-like MC3T3-E1 cells. In vivo experiments demonstrated that the COAp artificial bone containing ≤0.3 wt % AgPO replaced a new bone to the same levels as those without AgPO 4 weeks after implantation into the bone defect of the rabbit femur condyle. However, the COAp artificial bone containing 0.3 wt % AgPO caused an inflammatory reaction, whereas those containing ≤0.1 wt % AgPO did not. Thus, both bone regeneration and infection control without any adverse effects were achieved using the COAp artificial bone containing 0.1 wt % AgPO, indicating that the NOEL of AgPO was 0.1 wt %. Our results provide an effective strategy for the treatments of fracture-related infections.
骨折相关感染需要同时进行细菌清除和骨重建治疗。使用广谱抗菌银化合物和具有高成骨活性的人工骨的组合被认为是在一次手术中实现这些治疗的有效策略。然而，即使在低浓度下，银化合物对活组织也具有毒性。在此，我们使用体外和体内实验研究了由碳酸盐磷灰石（COAp）组成的骨替代物中磷酸银（AgPO）的无观察到效应水平（NOEL）。体外实验表明，含有≥0.1wt%AgPO 的 COAp 人工骨对 具有抗菌作用，而含有≤0.3wt%AgPO 的人工骨不影响成骨细胞样 MC3T3-E1 细胞的细胞黏附、增殖、分化和钙化。体内实验表明，植入兔股骨髁骨缺损 4 周后，含有≤0.3wt%AgPO 的 COAp 人工骨可替代新骨，与不含 AgPO 的人工骨水平相同。然而，含有 0.3wt%AgPO 的 COAp 人工骨引起了炎症反应，而含有≤0.1wt%AgPO 的人工骨则没有。因此，使用含有 0.1wt%AgPO 的 COAp 人工骨实现了无需任何不良反应的骨再生和感染控制，表明 AgPO 的 NOEL 为 0.1wt%。我们的结果为骨折相关感染的治疗提供了一种有效的策略。
