Activation of muscle amine functional groups using eutectic mixture to enhance tissue adhesiveness of injectable, conductive and therapeutic granular hydrogel for diabetic ulcer regeneration

Abstract

Herein, Polydopamine-modified microgels and microgels incorporated with superficial epoxy groups were synthesized and applied as precursors for the fabrication of four granular hydrogels. To enhance the tissue adhesiveness, a ternary deep eutectic solvent was synthesized to activate the muscle amine functional groups facilitating the formation of robust NC bonds at ambient conditions. At a certain shear rate of 10 s(-1), hydrogel DMG displayed a viscosity of 9x10(3) Pa/s, representing the highest complex viscosity among the tested hydrogels primarily driven by quinone groups in PDA which enhanced reversible interactions, thereby increasing particle cohesion. Moreover, the intersection point escalating from about 4x10(3) to approximately 9x10(4) as the concentration of DMG increased from 0 (for MG) to 70 (7D3MG) by weight. There was a decrease in adhesion strength from 0.45 +/- 0.08 N in MG to 0.39 +/- 0.16 N, 0.35+/- 0.18 N, and 0.33 +/- 0.15 N for 3D7MG, 7D3MG, and DMG respectively, suggesting that MG was capable of forming numerous covalent bonds, thereby enhancing its adhesion to the substrate. The type of eutectic mixture affected the electrical conductivity and a very important point was the changes in resistance value with time. For MG catalyzed by DES(AZG), the resistance increased only by 1.3 % (from 3.37 to 3.81 kOmega) at day 3 and 37.09 % (from 3.37 to 4.62 kOmega) at day 5. The 3D7MG hydrogel exhibited superior therapeutic efficacy toward diabetic wound regeneration. The proliferation index value for 3D7MG-DES(AZG) and 3D7MG-DES(AG) were calculated 42.3 % and 58.6 %, respectively, while the control group exhibited a lower value of 37.8 %.