Design of a non-oxidative adhesive dopamine-grafted hyaluronic acid/NOCC hydrogel for enhanced cell spheroid formation and soft tissue regeneration

Abstract

Tissue adhesive hydrogels from dopamine represent a compelling material with diverse applications across engineering and medical fields. Although numerous designed adhesive hydrogels have been developed, significant limitations have arisen from the reliance on hydrogen peroxide as an activating agent for crosslinking hydrogels. To address this, our study investigates an innovative approach to create an adhesive and biocompatible hydrogel from dopamine conjugated-hyaluronic acid (Da-HA) and N, O-Carboxymethyl Chitosan (NOCC) without the need for oxidative agent treatment for use in biomedical engineering application. The reactions were performed under mild alkaline conditions, vigorous stirring, and curing, resulting in DHC hydrogels. Proper modification and reactions in the hydrogel matrix were confirmed by NMR spectroscopy and Fourier transform infrared spectroscopy (FTIR). The gelling and tissue adhesive properties of the produced DHC hydrogel are proportional to the Da-HA content in the hydrogel. Scanning electron microscopy revealed changes in pore walls among samples and pore diameters ranging from 100 to 300 nm. Rheological analysis demonstrated a high visco-elastic material and self-healing properties. Importantly, the growth of L929 cell spheroids was noted upon their cultivation atop the designed hydrogel. The material holds significant promise for 3D printing and cell encapsulation therapies, as well as in situ tissue repair, particularly for mechanically dynamic tissues like the dermis.