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

通过具有粘性面和高载药量的坚韧水凝胶增强肌腱愈合

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作者:Benjamin R Freedman, Andreas Kuttler, Nicolau Beckmann, Sungmin Nam, Daniel Kent, Michael Schuleit, Farshad Ramazani, Nathalie Accart, Anna Rock, Jianyu Li, Markus Kurz, Andreas Fisch, Thomas Ullrich, Michael W Hast, Yann Tinguely, Eckhard Weber, David J Mooney

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-2) 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.

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