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电纺胶原纤维膜介导肝素载药及其体内抗生素控释研究

Heparin-mediated antibiotic delivery from an electrochemically-aligned collagen sheet.

机构信息

Case Western Reserve University (CWRU) School of Medicine, Cleveland, OH, USA.

Department of Otolaryngology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.

出版信息

Biomed Mater Eng. 2021;32(3):159-170. doi: 10.3233/BME-201133.

Abstract

BACKGROUND

Implantable medical devices and hardware are prolific in medicine, but hardware associated infections remain a major issue.

OBJECTIVE

To develop and evaluate a novel, biologic antimicrobial coating for medical implants.

METHODS

Electrochemically compacted collagen sheets with and without crosslinked heparin were synthesized per a protocol developed by our group. Sheets were incubated in antibiotic solution (gentamicin or moxifloxacin) overnight, and in vitro activity was assessed with five-day diffusion assays against Pseudomonas aeruginosa. Antibiotic release over time from gentamicin-infused sheets was determined using in vitro elution and high performance liquid chromatography (HPLC).

RESULTS

Collagen-heparin-antibiotic sheets demonstrated larger growth inhibition zones against P. aeruginosa compared to collagen-antibiotic alone sheets. This activity persisted for five days and was not impacted by rinsing sheets prior to evaluation. Rinsed collagen-antibiotic sheets did not produce any inhibition zones. Elution of gentamicin from collagen-heparin-gentamicin sheets was gradual and remained above the minimal inhibitory concentration for gentamicin-sensitive organisms for 29 days. Conversely, collagen-gentamicin sheets eluted their antibiotic load within 24 hours. Overall, heparin-associated sheets demonstrated larger inhibition zones against P. aeruginosa and prolonged elution profile via HPLC.

CONCLUSION

We developed a novel, local antibiotic delivery system that could be used to coat medical implants/hardware in the future and reduce post-operative infections.

摘要

背景

植入式医疗器械和硬件在医学中广泛应用,但硬件相关感染仍然是一个主要问题。

目的

开发和评估一种新型的、具有生物抗菌性的医疗植入物涂层。

方法

根据我们小组制定的方案,电化学压缩含有和不含有交联肝素的胶原片。将片材在抗生素溶液(庆大霉素或莫西沙星)中孵育过夜,并通过 5 天的扩散试验对铜绿假单胞菌进行体外活性评估。使用体外洗脱和高效液相色谱法(HPLC)测定庆大霉素输注片的抗生素随时间释放情况。

结果

与仅含抗生素的胶原片相比,胶原-肝素-抗生素片对铜绿假单胞菌的生长抑制区更大。这种活性持续了五天,在评估前冲洗片材不会影响其活性。冲洗后的胶原-抗生素片没有产生任何抑制区。从胶原-肝素-庆大霉素片中洗脱的庆大霉素逐渐释放,并且在 29 天内仍保持在庆大霉素敏感菌的最小抑菌浓度之上。相比之下,胶原-庆大霉素片在 24 小时内就洗脱了它们的抗生素负荷。总的来说,肝素相关的片材对铜绿假单胞菌表现出更大的抑制区和通过 HPLC 延长的洗脱曲线。

结论

我们开发了一种新型的局部抗生素递送系统,将来可用于涂覆医疗器械/硬件,以减少术后感染。

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