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交联海藻酸钠/明胶湿法纺丝多孔纤维的尼生素 Z 功能化用于抑制-诱导的感染。

Functionalization of Crosslinked Sodium Alginate/Gelatin Wet-Spun Porous Fibers with Nisin Z for the Inhibition of -Induced Infections.

机构信息

Centre for Textile Science and Technology (2C2T), Department of Textile Engineering, University of Minho, Campus of Azurém, 4800-058 Guimarães, Portugal.

出版信息

Int J Mol Sci. 2021 Feb 16;22(4):1930. doi: 10.3390/ijms22041930.

Abstract

Nisin Z, an amphipathic peptide, with a significant antibacterial activity against Gram-positive bacteria and low toxicity in humans, has been studied for food preservation applications. Thus far, very little research has been done to explore its potential in biomedicine. Here, we report the modification of sodium alginate (SA) and gelatin (GN) blended microfibers, produced via the wet-spinning technique, with Nisin Z, with the purpose of eradicating -induced infections. Wet-spun SAGN microfibers were successfully produced at a 70/30% / of SA (2 wt%)/GN (1 wt%) polymer ratio by extrusion within a calcium chloride (CaCl) coagulation bath. Modifications to the biodegradable fibers' chemical stability and structure were then introduced via crosslinking with CaCl and glutaraldehyde (SAGNCL). Regardless of the chemical modification employed, all microfibers were labelled as homogeneous both in size (≈246.79 µm) and shape (cylindrical and defect-free). SA-free microfibers, with an increased surface area for peptide immobilization, originated from the action of phosphate buffer saline solution on SAGN fibers, were also produced (GNCL). Their durability in physiological conditions (simulated body fluid) was, however, compromised very early in the experiment (day 1 and 3, with and without Nisin Z, respectively). Only the crosslinked SAGNCL fibers remained intact for the 28 day-testing period. Their thermal resilience in comparison with the unmodified and SA-free fibers was also demonstrated. Nisin Z was functionalized onto the unmodified and chemically altered fibers at an average concentration of 178 µg/mL. Nisin Z did not impact on the fiber's morphology nor on their chemical/thermal stability. However, the peptide improved the SA fibers (control) structural integrity, guaranteeing its stability for longer, in physiological conditions. Its main effect was detected on the time-kill kinetics of the bacteria . SAGNCL and GNCL loaded with Nisin Z were capable of progressively eliminating the bacteria, reaching an inhibition superior to 99% after 24 h of culture. The peptide-modified SA and SAGN were not as effective, losing their antimicrobial action after 6 h of incubation. Bacteria elimination was consistent with the release kinetics of Nisin Z from the fibers. In general, data revealed the increased potential and durable effect of Nisin Z (significantly superior to its free, unloaded form) against -induced infections, while loaded onto prospective biomedical wet-spun scaffolds.

摘要

乳链菌肽 Z 是一种两亲性肽,对革兰氏阳性菌具有显著的抗菌活性,对人体的毒性较低,因此被研究用于食品保鲜。迄今为止,很少有研究探索其在生物医学中的潜力。在这里,我们报告了通过湿法纺丝技术对海藻酸钠 (SA) 和明胶 (GN) 共混微纤维进行乳链菌肽 Z 修饰,以根除耐甲氧西林金黄色葡萄球菌 (MRSA) 诱导的感染。通过在氯化钙 (CaCl) 凝固浴中挤出,成功地以 SA(2wt%)/GN(1wt%)聚合物比为 70/30%的比例生产出 SAGN 湿纺微纤维。然后通过与氯化钙和戊二醛交联(SAGNCL)对可生物降解纤维的化学稳定性和结构进行改性。无论采用哪种化学改性方法,所有微纤维的尺寸(≈246.79µm)和形状(圆柱形且无缺陷)都均匀一致。也生产了源自于 SAGN 纤维的磷酸盐缓冲盐水溶液作用下的无 SA 微纤维(GNCL),其具有用于肽固定化的更大表面积。然而,在实验早期(分别为第 1 天和第 3 天,有无乳链菌肽 Z 时),它们在生理条件(模拟体液)下的耐用性就受到了损害。只有交联的 SAGNCL 纤维在 28 天的测试期内保持完整。与未改性和无 SA 纤维相比,还证明了它们的热弹性。乳链菌肽 Z 以平均浓度 178µg/mL 功能化到未改性和化学改性的纤维上。乳链菌肽 Z 既没有影响纤维的形态,也没有影响它们的化学/热稳定性。然而,该肽改善了 SA 纤维(对照)的结构完整性,确保了其在生理条件下更长时间的稳定性。其主要作用是检测到耐甲氧西林金黄色葡萄球菌的时间杀伤动力学。负载乳链菌肽 Z 的 SAGNCL 和 GNCL 能够逐渐消除细菌,在 24 小时的培养后达到超过 99%的抑制率。负载乳链菌肽 Z 的 SA 和 SAGN 效果并不理想,孵育 6 小时后失去抗菌作用。细菌的消除与纤维中乳链菌肽 Z 的释放动力学一致。总的来说,数据显示负载到有前途的生物医学湿纺支架上的乳链菌肽 Z(明显优于其游离的未负载形式)对耐甲氧西林金黄色葡萄球菌诱导的感染具有增强的潜力和持久的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6628/7919837/615364532fe1/ijms-22-01930-g001.jpg

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