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3D打印万古霉素/多巴胺/重组人骨形态发生蛋白-2接枝的PLGA/纳米羟基磷灰石多孔支架在感染兔骨缺损中的抗感染疗效、成骨潜力及生物相容性

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.

作者信息

Ke Re Mu A Li Mu, Abulikemu Maimaitiaili, Liang Zhilin, Abulikemu Abudurusuli, Tuxun Aikebaier

机构信息

Department of Orthopedic, First People's Hospital of Kashgar, Kashgar, Xinjiang, 844000, People's Republic of China.

Department of Trauma Orthopaedics, First People's Hospital of Kashgar, Kashgar, Xinjiang, 844000, People's Republic of China.

出版信息

Int J Nanomedicine. 2025 May 21;20:6399-6421. doi: 10.2147/IJN.S514978. eCollection 2025.

DOI:10.2147/IJN.S514978
PMID:40416730
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12103859/
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 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.

摘要

背景

鉴于传统疗法的局限性，感染性骨缺损（IBD）的治疗仍然是一项巨大挑战。迫切需要找到一种能够同时根除感染并促进新骨形成的新方法。随着个性化支架在骨科领域的应用日益增加，具有抗菌和骨诱导特性的新型生物材料为IBD治疗提供了一种可行选择。通过三维（3D）打印技术，我们制备了一种接枝抗生素万古霉素并通过聚多巴胺（DOPA）化学负载骨诱导剂重组人骨形态发生蛋白-2（rhBMP-2）的聚乳酸-乙醇酸共聚物（PLGA）/纳米羟基磷灰石（n-HA）复合支架，并确定了其对IBD的治疗效果。

方法

在检测PLGA/n-HA、PLGA/n-HA/VAN和PLGA/n-HA/VAN+DOPA/rhBMP-2复合支架的亲水性、表面化学成分、力学性能和药物释放后，将前成骨细胞MC3T3-E1接种到支架表面，以评估支架在体外的生物相容性和骨传导性能。对于体内实验，将污染有[具体细菌]的复合支架植入兔桡骨缺损部位。12周后，进行显微CT分析、苏木精-伊红（H&E）和Masson染色、免疫组织化学以及活菌计数，以比较三种复合支架对新骨形成和骨感染的影响。

结果

用DOPA/rhBMP-2进行表面改性提高了PLGA/n-HA支架的亲水性。万古霉素和BMP-2从PLGA/n-HA/VAN+DOPA/rhBMP-2支架中持续且有规律地释放。与PLGA/n-HA和PLGA/n-HA/VAN支架相比，PLGA/n-HA/VAN+DOPA/rhBMP-2支架促进了MC3T3-E1细胞的存活和增殖，并增强了碱性磷酸酶（ALP）活性和钙沉积。此外，PLGA/n-HA/VAN+DOPA/rhBMP-2支架在IBD兔模型中显著促进了新骨形成并抑制了骨感染。植入PLGA/n-HA/VAN+DOPA/rhBMP-2支架的兔子表现出心脏、肺和肾脏组织学正常以及血清生化指标正常，表明支架具有安全性。

结论

3D打印的PLGA/n-HA/VAN+DOPA/rhBMP-2支架在IBD中表现出抗菌和骨诱导活性。

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