TY - JOUR
T1 - No-Observed-Effect Level of Silver Phosphate in Carbonate Apatite Artificial Bone on Initial Bone Regeneration
AU - Shimabukuro, Masaya
AU - Hayashi, Koichiro
AU - Kishida, Ryo
AU - Tsuchiya, Akira
AU - Ishikawa, Kunio
N1 - Funding Information:
This study was supported partially by JSPS KAKENHI (grant numbers JP20K23032 and JP21K18057), AMED (grant number JP21im0502004h), and The Foundation for The Promotion of Ion Engineering.
Publisher Copyright:
©
PY - 2022/1/14
Y1 - 2022/1/14
N2 - 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 (Ag3PO4) in a bone substitute composed of carbonate apatite (CO3Ap), a bone mineral, using in vitro and in vivo experiments. In vitro experiments demonstrated that the CO3Ap artificial bone containing ≥0.1 wt % Ag3PO4 exerted antibacterial effects against Staphylococcus epidermidis, while those containing ≤0.3 wt % Ag3PO4 did not affect cellular adhesion, proliferation, differentiation, and calcification of osteoblast-like MC3T3-E1 cells. In vivo experiments demonstrated that the CO3Ap artificial bone containing ≤0.3 wt % Ag3PO4 replaced a new bone to the same levels as those without Ag3PO4 4 weeks after implantation into the bone defect of the rabbit femur condyle. However, the CO3Ap artificial bone containing 0.3 wt % Ag3PO4 caused an inflammatory reaction, whereas those containing ≤0.1 wt % Ag3PO4 did not. Thus, both bone regeneration and infection control without any adverse effects were achieved using the CO3Ap artificial bone containing 0.1 wt % Ag3PO4, indicating that the NOEL of Ag3PO4 was 0.1 wt %. Our results provide an effective strategy for the treatments of fracture-related infections.
AB - 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 (Ag3PO4) in a bone substitute composed of carbonate apatite (CO3Ap), a bone mineral, using in vitro and in vivo experiments. In vitro experiments demonstrated that the CO3Ap artificial bone containing ≥0.1 wt % Ag3PO4 exerted antibacterial effects against Staphylococcus epidermidis, while those containing ≤0.3 wt % Ag3PO4 did not affect cellular adhesion, proliferation, differentiation, and calcification of osteoblast-like MC3T3-E1 cells. In vivo experiments demonstrated that the CO3Ap artificial bone containing ≤0.3 wt % Ag3PO4 replaced a new bone to the same levels as those without Ag3PO4 4 weeks after implantation into the bone defect of the rabbit femur condyle. However, the CO3Ap artificial bone containing 0.3 wt % Ag3PO4 caused an inflammatory reaction, whereas those containing ≤0.1 wt % Ag3PO4 did not. Thus, both bone regeneration and infection control without any adverse effects were achieved using the CO3Ap artificial bone containing 0.1 wt % Ag3PO4, indicating that the NOEL of Ag3PO4 was 0.1 wt %. Our results provide an effective strategy for the treatments of fracture-related infections.
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U2 - 10.1021/acsinfecdis.1c00480
DO - 10.1021/acsinfecdis.1c00480
M3 - Article
C2 - 34875165
AN - SCOPUS:85121133698
VL - 8
SP - 159
EP - 169
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
SN - 2373-8227
IS - 1
ER -