Anti-Infection Efficacy, Osteogenesis Potential, and Biocompatibility of 3D Printed PLGA/Nano-Hydroxyapatite Porous Scaffolds Grafted with Vancomycin/DOPA/rhBMP-2 in Infected Rabbit Bone Defects.
A Li Mu Ke Re Mu, Maimaitiaili Abulikemu, Zhilin Liang, Abudurusuli Abulikemu, Aikebaier Tuxun
{"title":"Anti-Infection Efficacy, Osteogenesis Potential, and Biocompatibility of 3D Printed PLGA/Nano-Hydroxyapatite Porous Scaffolds Grafted with Vancomycin/DOPA/rhBMP-2 in Infected Rabbit Bone Defects.","authors":"A Li Mu Ke Re Mu, Maimaitiaili Abulikemu, Zhilin Liang, Abudurusuli Abulikemu, Aikebaier Tuxun","doi":"10.2147/IJN.S514978","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Given the limitations of traditional therapies, the treatment of infected bone defects (IBD) remains a great challenge. It is urgent to find a novel method that can simultaneously eradicate infection and promote new bone formation. With the increasing application of personalized scaffolds in orthopedics, novel biomaterials with both antibacterial and osteoinductive properties have provided a viable option for IBD treatment. Through the three-dimensional (3D) printing technology, we fabricated a poly(lactic-co-glycolic acid)(PLGA)/nano-hydroxyapatite (n-HA) composite scaffold grafted with the antibiotic vancomycin and loaded with the osteoinductive agent recombinant human bone morphogenic protein-2 (rhBMP-2) via polydopamine (DOPA) chemistry, whose therapeutic effects on IBD were determined.</p><p><strong>Methods: </strong>After examining the hydrophilicity, surface chemical composition, mechanical properties, and drug release of the PLGA/n-HA, PLGA/n-HA/VAN, and PLGA/n-HA/VAN+DOPA/rhBMP-2 composite scaffolds, pre-osteoblast MC3T3-E1 cells were seeded onto the scaffold surface to assess the biocompatibility and osteoconductive properties of the scaffolds in vitro. For in vivo experiments, the composite scaffolds contaminated with <i>Staphylococcus aureus</i> were implanted into the defect sites of rabbit radius. After 12 weeks, micro-CT analysis, H&E and Masson staining, immunohistochemistry, and viable bacteria counting were conducted to compare the effects of three composite scaffolds on new bone formation and bone infection.</p><p><strong>Results: </strong>The surface modification with DOPA/rhBMP-2 increased the hydrophilicity of PLGA/n-HA scaffolds. Vancomycin and BMP-2 were continuously and regularly eluted from the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds. The PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds promoted MC3T3-E1 cell survival and proliferation and enhanced ALP activity and calcium deposition compared with the PLGA/n-HA and PLGA/n-HA/VAN scaffolds. Additionally, the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds significantly facilitated new bone formation and inhibited bone infection in IBD rabbit models. The rabbits implanted with the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited normal heart, lung, and kidney histologies and normal serum biochemical indices, suggesting the safety of the scaffolds.</p><p><strong>Conclusion: </strong>The 3D-printed PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited both antibacterial and osteoinductive activities in IBD.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6399-6421"},"PeriodicalIF":6.6000,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103859/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Nanomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/IJN.S514978","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"NANOSCIENCE & NANOTECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Given the limitations of traditional therapies, the treatment of infected bone defects (IBD) remains a great challenge. It is urgent to find a novel method that can simultaneously eradicate infection and promote new bone formation. With the increasing application of personalized scaffolds in orthopedics, novel biomaterials with both antibacterial and osteoinductive properties have provided a viable option for IBD treatment. Through the three-dimensional (3D) printing technology, we fabricated a poly(lactic-co-glycolic acid)(PLGA)/nano-hydroxyapatite (n-HA) composite scaffold grafted with the antibiotic vancomycin and loaded with the osteoinductive agent recombinant human bone morphogenic protein-2 (rhBMP-2) via polydopamine (DOPA) chemistry, whose therapeutic effects on IBD were determined.
Methods: After examining the hydrophilicity, surface chemical composition, mechanical properties, and drug release of the PLGA/n-HA, PLGA/n-HA/VAN, and PLGA/n-HA/VAN+DOPA/rhBMP-2 composite scaffolds, pre-osteoblast MC3T3-E1 cells were seeded onto the scaffold surface to assess the biocompatibility and osteoconductive properties of the scaffolds in vitro. For in vivo experiments, the composite scaffolds contaminated with Staphylococcus aureus were implanted into the defect sites of rabbit radius. After 12 weeks, micro-CT analysis, H&E and Masson staining, immunohistochemistry, and viable bacteria counting were conducted to compare the effects of three composite scaffolds on new bone formation and bone infection.
Results: The surface modification with DOPA/rhBMP-2 increased the hydrophilicity of PLGA/n-HA scaffolds. Vancomycin and BMP-2 were continuously and regularly eluted from the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds. The PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds promoted MC3T3-E1 cell survival and proliferation and enhanced ALP activity and calcium deposition compared with the PLGA/n-HA and PLGA/n-HA/VAN scaffolds. Additionally, the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds significantly facilitated new bone formation and inhibited bone infection in IBD rabbit models. The rabbits implanted with the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited normal heart, lung, and kidney histologies and normal serum biochemical indices, suggesting the safety of the scaffolds.
Conclusion: The 3D-printed PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited both antibacterial and osteoinductive activities in IBD.
期刊介绍：
The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area.
With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field.
Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
