A dual-cross-linked hydrogel based on hyaluronic acid/gelatin tethered via tannic acid: mechanical properties' enhancement and stability control

Extracellular matrix (ECM) as a network is mainly composed of glycosaminoglycans and proteins. Among these glycosaminoglycans and proteins that naturally occur in ECM, hyaluronic acid (HA) and gelatin attract more attentions. In this work, a chemically cross-linked HA/gelatin hydrogel (HG hydrogel) was firstly fabricated, and then, tannic acid (TA) was introduced as a physical cross-linker, to form a dual-cross-linked network (HG-TA(x) hydrogels). The strong hydrogen bonding between TA and HG hydrogel resulted in lower swelling ratio, decreasing from 220% (pristine HG hydrogels) to 7.5% (HG-TA(25) hydrogels) and stronger mechanical properties increasing from 6 kPa (HG hydrogel) to 160 kPa (HG-TA(25) hydrogel). The hydrogel stability in enzyme was significantly improved, attributing to the hyaluronidase inhibition activity of TA. The degradation time significantly increased along with the addition of TA (from 7 up to 21 days). Furthermore, the HG-TA(x) hydrogels exhibited good cleavage ability to reactive oxygen species (ROS) that could be generated in human tissues, and the antioxidant capacity increased up to 24.2 mg/mL of L-ascorbic acid standard. The improved mechanical properties, prolonged degradation time, and potential antioxidant ability of the HG-TA(x) hydrogels could pave the way for the design of biomaterials. Furthermore, TA has shown potential biological functions properties and brought the great potential of the HG-TA(x) hydrogels for implant applications.