Peng Ziyue, Du Yuqi, Song Mingrui, Sun Chongkai, Xu Yuan, Qian Jikun, Guan Xin, Yang Mankai, Zhang Xin, Dai Fangfang, Wan Haoyang, Chen Yuhang, Liu Chun, Yu Bin
Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
ACS Appl Mater Interfaces. 2024 Dec 18;16(50):68794-68815. doi: 10.1021/acsami.4c10912. Epub 2024 Dec 8.
Implant-associated infections frequently complicate orthopedic surgeries, resulting in challenging issues. The current therapy of antibiotic treatment and surgical debridement often leads to drug resistance and bone defect. The development of pH-responsive antimicrobial and pro-osteogenic materials is a promising approach to controlling infections and repairing infected bone defects, especially given the weakly acidic pH of the bacterial infection area. Solid peroxides have the potential to provide a sustained release of hydrogen peroxide (HO), rendering them applicable for antimicrobial purposes. Additionally, their chemical properties render them inherently responsive to pH. Here, we propose a novel GelBA/PVA/MgO hydrogel composed of gelatin (Gel), benzeneboronic acid (BA), poly(vinyl alcohol) (PVA), and magnesium peroxide (MgO) with self-healing ability and pH-responsiveness. The borate ester bond formed between PVA and BA is a dynamic chemical bond with properties of dynamic formation and dissociation, making the hydrogel both self-healable and pH-responsive. Meanwhile, the addition of MgO improves the network structure of the hydrogel and gives the hydrogel the ability to perform sustained release of HO and Mg. Experimentally, the GelBA/PVA/MgO hydrogel exhibits controlled and pH-dependent HO and Mg release, sustained over time at physiological pH (7.4) and significantly increased at infection pH (5.5). In vitro and in vivo outcomes revealed that this hydrogel is able to inhibit growth and accelerate bone regeneration, improving bone healing without cytotoxic effects on normal tissues. These findings suggest that the GelBA/PVA/MgO hydrogel is a unique and efficient approach for anti-infection and therapeutic implant-associated infections.
植入物相关感染常常使骨科手术复杂化，引发诸多棘手问题。目前的抗生素治疗和手术清创疗法常常导致耐药性和骨缺损。开发pH响应性抗菌和成骨材料是控制感染和修复感染性骨缺损的一种有前景的方法，特别是考虑到细菌感染区域的弱酸性pH值。固体过氧化物有潜力实现过氧化氢（H₂O₂）的持续释放，使其适用于抗菌目的。此外，它们的化学性质使其本身对pH有响应。在此，我们提出一种新型的GelBA/PVA/MgO水凝胶，它由明胶（Gel）、苯硼酸（BA）、聚乙烯醇（PVA）和过氧化镁（MgO）组成，具有自愈能力和pH响应性。PVA和BA之间形成的硼酸酯键是一种具有动态形成和解离特性的动态化学键，使水凝胶既具有自愈性又具有pH响应性。同时，MgO的添加改善了水凝胶的网络结构，并赋予水凝胶持续释放H₂O₂和Mg的能力。实验表明，GelBA/PVA/MgO水凝胶表现出可控的、pH依赖性的H₂O₂和Mg释放，在生理pH值（7.4）下随时间持续释放，在感染pH值（5.5）下显著增加。体外和体内实验结果表明，这种水凝胶能够抑制细菌生长并加速骨再生，促进骨愈合且对正常组织无细胞毒性作用。这些发现表明，GelBA/PVA/MgO水凝胶是一种独特且有效的抗感染及治疗植入物相关感染的方法。
