Mechanically-adaptive Janus hydrogel enhances scarless tendon healing with tissue-adhesion prevention

Tendon injuries are common orthopedic traumas but often respond poorly to existing surgical treatments, which is largely attributed to the misrouted extracellular matrix (ECM) generation and tendon adhesion formation. Herein, we report a Janus dynamic hydrogel-based patch with asymmetric tissue adhesive property for dressing damaged tendons, leading to scarless restoration of their structural and functional properties. The Janus hydrogel patch (PCP) is prepared by growing a tendon-adhesive layer (CP layer) constituted by dihydrocaffeic acid-containing chitosan (CS-HCA), ureido-pyrimidinone (UPy)-grafted gelatin and catechol-modified waterborne polyurethane atop a pre-semicured anti-adhesive polyurethane layer (PU layer) through in-situ gelatinization, which potentiates firm adhesion to the damaged tendon while avoiding post-surgical adhesion between tendon and surrounding tissues. The heavy mechanical load of tendon would trigger the formation of abundant orderly aligned crystalline domains through stress-induced crystallization that substantially enhances the mechanical strength of PCP, which not only improve its mechanical resilience in the complex biomechanical environment of tendons but also provides optimal biomechanical stimulation to enhance the robustness of the healing tendon through ECM remodeling. Furthermore, the implanted PCP could effectively suppress inflammation-relevant signaling pathways to avoid synechia and further accelerate tendon healing while preventing scar formation. The PCP offers a promising approach for tendon injury treatment in the clinics. STATEMENT OF SIGNIFICANCE: This asymmetric tissue-adhesive double-layer Janus hydrogel patch (PCP) can effectively stabilize dynamic tissue wounds and adequately withstands the mechanical stresses via a strain-induced crystallization (SIC) strategy, thereby preventing its deterioration and rupture in the context of frequent movements and large-amplitude motions. When implanted on damaged tendons, the bio-repelling nature and smooth surface of the anti-adhesive polyurethane (PU) layer effectively prevent postsurgical adhesion and reduce secondary surgery risks. Furthermore, the hydroxycinnamic acid (HCA) component within the CP layer alleviates local inflammation by suppressing inflammation-associated signaling pathways, concurrently inhibiting synechia formation and accelerating tendon regeneration. This integrated system establishes a comprehensive clinical approach for achieving scarless tendon repair while maintaining effective tissue-adhesion prevention.