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

Abstract

Hydrogels that provide mechanical support and sustainedly 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/m2) 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 sustainedly 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.

Multifunctional “Janus‐Type” Bilayer Films Combine Broad‐Range Tissue Adhesion with Guided Drug Release

“…To cope with this problem, medical materials with asymmetric functionalities were recently introduced, and they were indeed successful in promoting tissue repair in vivo. [22][23][24][25] For example, Cui et al [22] presented a Janus structure with oppositely charged surfaces, which enables the overall material to seal tissue perforations and-at the same time-prevents undesired adhesions to its exterior part. Very recently, a three-layered Janus adhesive with asymmetric wetting properties developed by Xu et al [23] was found to be successful in keeping the wound area dry while absorbing the wound exudate.…”

“…Other very recent and highly promising examples from this area are peritoneuminspired porous poly(vinyl alcohol) (PVA) hydrogels for canalizing cellular growth at the desired site, [26] and double-layered (ionically and covalently cross-linked) alginate/chitosan films for advanced tendon healing. [25] These asymmetric materials provide a set of distinct functions for the wound-healthy tissue interface. However, these materials exhibit a long lifetime, which limits their use to specific applications that are strictly controlled under medical care.…”

Supramolecular assemblies based on natural small molecules: Union would be effective

“…Vesicular self-assemblies of NSMs are expected to mimic cellular membranes for delivering drugs better and catalyze nano-reactions as microreactors more efficiently [ 77 , 78 ]. The gels naturally formed by self-assembled NSMs, especially glycoside, can be redesigned as bioadhesive patch in place of handsewn closure of gastrointestinal defects or medical dressing to enhance tendon or wound healing [ 3 , [152] , [153] , [154] ]. Compared to synthetic substrates, natural hydrogels may be better suited to simulate the internal environment for 3D cell culture and organogenesis [ 155 , 156 ].…”

Advances in Cellulose-Based Hydrogels for Biomedical Engineering: A Review Summary

“…The outstanding feature of these hydrogels is that the swelling behavior changes significantly in response to the environment. They are used as actuators [ 21 ], sensors [ 22 ], plantable and biodegradable ion batteries [ 23 ], thermally insulating materials [ 24 ], for tissue transformation [ 25 , 26 ], in controlled-release switches [ 27 , 28 ] or in precise topical administration regimens [ 29 ] and programmable and bioinstructive materials systems [ 30 ], etc. Therefore, functional/smart stimuli-responsive hydrogels have been one of the most interesting topics for scientific researchers in recent years.…”