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具有粘附侧和高载药能力的坚韧水凝胶增强肌腱愈合。

Enhanced tendon healing by a tough hydrogel with an adhesive side and high drug-loading capacity.

机构信息

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

出版信息

Nat Biomed Eng. 2022 Oct;6(10):1167-1179. doi: 10.1038/s41551-021-00810-0. Epub 2022 Jan 3.

Abstract

Hydrogels that provide mechanical support and sustainably release therapeutics have been used to treat tendon injuries. However, most hydrogels are insufficiently tough, release drugs in bursts, and require cell infiltration or suturing to integrate with surrounding tissue. Here we report that a hydrogel serving as a high-capacity drug depot and combining a dissipative tough matrix on one side and a chitosan adhesive surface on the other side supports tendon gliding and strong adhesion (larger than 1,000 J m) to tendon on opposite surfaces of the hydrogel, as we show with porcine and human tendon preparations during cyclic-friction loadings. The hydrogel is biocompatible, strongly adheres to patellar, supraspinatus and Achilles tendons of live rats, boosted healing and reduced scar formation in a rat model of Achilles-tendon rupture, and sustainably released the corticosteroid triamcinolone acetonide in a rat model of patellar tendon injury, reducing inflammation, modulating chemokine secretion, recruiting tendon stem and progenitor cells, and promoting macrophage polarization to the M2 phenotype. Hydrogels with 'Janus' surfaces and sustained-drug-release functionality could be designed for a range of biomedical applications.

摘要

水凝胶可以提供机械支撑并可持续释放治疗药物,已被用于治疗肌腱损伤。然而,大多数水凝胶的韧性不足,药物释放呈爆发式,并且需要细胞渗透或缝合才能与周围组织整合。在这里,我们报告了一种水凝胶,它作为一个高容量的药物库,结合了一侧的耗散韧性基质和另一侧的壳聚糖粘合表面,能够支持肌腱滑动和在水凝胶的相对表面之间产生强大的附着力(大于 1000 J m),我们在猪和人肌腱标本的循环摩擦负荷实验中证明了这一点。该水凝胶具有生物相容性,能够强烈附着于活鼠的髌腱、冈上肌腱和跟腱,在跟腱断裂的大鼠模型中促进愈合并减少疤痕形成,并在髌腱损伤的大鼠模型中持续释放皮质类固醇曲安奈德,从而减轻炎症、调节趋化因子分泌、招募肌腱干/祖细胞,并促进巨噬细胞向 M2 表型极化。具有“双面”表面和持续药物释放功能的水凝胶可以设计用于多种生物医学应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd4c/9250555/09702c95aa78/nihms-1740314-f0008.jpg

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