Abstract
Surgical site infection (SSI) is a severe complication associated with orthopedic bone reconstruction. For both infection prevention and bone regeneration, the framework surface of osteoconductive and bioresorbable scaffolds must be locally modified by minimum antibacterial substances, without sacrificing the osteoconductivity of the scaffold framework. In this study, we fabricated antibacterial honeycomb scaffolds by replacing carbonate apatite, which is the main component of the scaffold, with silver phosphate locally on the scaffold surface via dissolution-precipitation reactions. When the silver content was 9.9 × 10-4 wt %, the honeycomb scaffolds showed antibacterial activity without cytotoxicity and allowed cell proliferation, differentiation, and mineralization. Furthermore, the antibacterial honeycomb scaffolds perfectly prevented bacterial infection in vivo in the presence of methicillin-resistant Staphylococcus aureus, formed new bone at 2 weeks after surgery, and were gradually replaced with a new bone. Thus, the antibacterial honeycomb scaffolds achieved both infection prevention and bone regeneration. In contrast, severe infection symptoms, including abscess formation, osteolytic lesions, and inflammation, occurred 2 weeks after surgery when honeycomb scaffolds without silver phosphate modification were implanted. Nevertheless, the unmodified honeycomb scaffolds eliminated bacteria and necrotic bone through their scaffold channels, resulting in symptom improvement and bone formation. These results suggest that the honeycomb structure is inherently effective in hindering bacterial growth. This novel insight may contribute to the development of antibacterial scaffolds. Moreover, our modification method is useful for providing antibacterial activity to various biomaterials.
Highlights
In orthopedic bone reconstruction, surgical site infection (SSI)is a severe complication that causes treatment hardships, longer hospitalization, increased medical expenditure, and diseased limb amputation in the worst cases.[1−5] Depending on the surgical site and disorder, the rate and number of SSIs are 3−45% and 1.5 million per year, respectively
Providing antibacterial activity to scaffolds is an effective approach to prevent SSI.[3−5] various antibacterial scaffolds have previously been reported, in terms of bone regeneration, the preferred scaffold framework is composed of osteoconductive bioceramics, rather than organics and composites, and has a porous structure.[3−5] antibacterial substances within the scaffold framework have little effect on SSI prevention and negatively affect the longterm outcomes of bone regeneration.[3−5] minimum antibacterial substances should preferably be located on the scaffold surface without sacrificing the osteoconductivity of the scaffold framework
To modify the carbonate apatite (CAp) HC frameworks with Ag3PO4 via dissolution−precipitation reactions, the CAp HC frameworks were immersed in AgNO3 solutions of 0, 0.01, 0.1, 1, and 10 mmol/L, which were designated as HC-0, HC-0.01, HC-0.1, HC-1, and HC-10, respectively
Summary
Surgical site infection (SSI)is a severe complication that causes treatment hardships, longer hospitalization, increased medical expenditure, and diseased limb amputation in the worst cases.[1−5] Depending on the surgical site and disorder, the rate and number of SSIs are 3−45% and 1.5 million per year, respectively. We fabricated honeycomb (HC) materials with uniaxial macropores, that is, channels that penetrate the material.[6,7] The HC materials were constructed from interconnecting spheres composed of carbonate apatite (CAp) crystals,[8−10] analogous to bone minerals, and contained micropores and nanopores in the HC struts.[11,12] the CAp HC materials are multiscale porous structures Owing to these characteristics, CAp HC materials are osteoconductive and osteoinductive.[13] the CAp HC materials substantially surpass various calcium phosphate materials in osteogenesis.[14,15] in most previously reported porous materials, large portions of the macropores are closed, making modification of the pore surface with antibacterial substances difficult.[16−21] In contrast, modification of the pore
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