冻干人骨同种异体移植的聚左旋乳酸涂层用于抗生素的长期释放

PLLA Coating of Lyophilized Human Bone Allograft for Long-term Release of Antibiotics.

作者信息

Barbeck Mike, Zhang Jiawei, Stojanovic Sanja, Radenkovic Milena, Najman Stevo, Foth Anne, Jung Ole, Beuer Florian, Xiong Xin

机构信息

Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, Rostock, Germany;

NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.

出版信息

In Vivo. 2025 Jul-Aug;39(4):1879-1890. doi: 10.21873/invivo.13987.

Abstract

BACKGROUND/AIM: Mineralized allogeneic bone substitutes are ideal biomaterials for bone regeneration in surgeries. Moreover, they are also suitable for releasing antibiotics, delivering initial concentrations many times higher than the minimal inhibitory concentration for relevant bacterial strains, without delaying bone formation. In the present study, the potential of sustained-release long-term antibiotic delivery using allografts was investigated. A broad spectrum of antibiotics, including gentamicin, vancomycin, rifampicin, and clindamycin, was incorporated into the bone blocks using a poly-L-lactic acid (PLLA) polymer coating.

MATERIALS AND METHODS

An model of implantation within the rabbit tibia plateau was used to track the sustained release of single/combined antibiotics for up to 120 days. Bony integration and tissue responses to the PLLA-coated antibiotic-delivery systems were analyzed at 4 months post implantation using histopathological analysis.

RESULTS

The variant loaded with both vancomycin and rifampicin demonstrated the highest activity against methicillin-sensitive and . Histopathological analysis revealed that the tissue responses to the coated allogeneic bone substitutes were comparable in all study groups, with no observable histopathological differences. The coated bone blocks induced a strong foreign-body reaction, including high numbers of multinucleated giant cells and other immune cells but no material-associated bone growth.

CONCLUSION

Based on these results, future optimization can focus on selecting more efficient release of antibiotics and increasing the encapsulated concentration to sustain antibiotic release over 4 months, thereby improving the bacteriostatic effect . Furthermore, biocompatibility and osteoconductivity must be improved.

摘要

背景/目的:矿化同种异体骨替代物是手术中骨再生的理想生物材料。此外,它们还适用于释放抗生素,能提供比相关细菌菌株的最低抑菌浓度高许多倍的初始浓度,且不会延迟骨形成。在本研究中,对使用同种异体移植物进行长效抗生素缓释的潜力进行了研究。使用聚-L-乳酸(PLLA)聚合物涂层将包括庆大霉素、万古霉素、利福平、克林霉素在内的多种广谱抗生素掺入骨块中。

材料与方法

采用兔胫骨平台植入模型来追踪单一/联合抗生素长达120天的缓释情况。在植入后4个月,使用组织病理学分析来分析骨整合以及组织对PLLA涂层抗生素递送系统的反应。

结果

同时负载万古霉素和利福平的变体对甲氧西林敏感菌表现出最高活性。组织病理学分析显示,在所有研究组中,组织对涂层同种异体骨替代物的反应相当,未观察到组织病理学差异。涂层骨块引发了强烈的异物反应,包括大量多核巨细胞和其他免疫细胞,但未观察到与材料相关的骨生长。

结论

基于这些结果,未来的优化可集中在选择更高效的抗生素释放方式以及提高包封浓度以维持4个月以上的抗生素释放,从而增强抑菌效果。此外,必须改善生物相容性和骨传导性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d51/12223631/bd9da7c23cb3/in_vivo-39-1883-g0001.jpg

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