RESUMEN
Promising wound dressings can achieve rapid soft-tissue filling while refactoring the biochemical and biophysical microenvironment to recruit endogenous cells, facilitating tissue healing, integration, and regeneration. In this study, a tissue biomolecule-responsive hydrogel matrix, employing natural silk fibroin (SF) as a functional biopolymer and haemoglobin (Hb) as a peroxidase-like biocatalyst, was fabricated through cascade enzymatic crosslinking. The hydrogels possessed mechanical tunability and displayed adjustable gelation times. A tyrosine unit on SF stabilised the structure of Hb during the cascade oxidation process; thus, the immobilized Hb in SF hydrogels exhibited higher biocatalytic efficiency than the free enzyme system, which provided a continuously antioxidative system. The regulation of the dual enzyme ratio endowed the hydrogels with favourable biocompatibility, biodegradability, and adhesion strength. These multifunctional hydrogels provided a three-dimensional porous extracellular matrix-like microenvironment for promoting cell adhesion and proliferation. A rat model with a full-thickness skin defect revealed accelerated wound regeneration via collagen deposition, re-epithelialisation and revascularisation. Enzyme-loaded hydrogels are an attractive and high-safety biofilling material with the potential for wound healing, tissue regeneration, and haemostasis.
RESUMEN
Polymer hydrogels are ideal bioprinting scaffolds for cell-loading and tissue engineering due to their extracellular-matrix-like structure. However, polymer hydrogels that are easily printed tend to have poor strength and fragile properties. The gradually polymerized reinforcement after hydrogel printing is a good method to solve the contradiction between conveniently printed and high mechanical strength requirement. Here, a new succinct approach has been developed to fabricate the printable composite hydrogels with tunable strength. We employed the HRP@GOx dual enzyme system to initiate the immediate crosslinking of chondroitin sulfate grafted with tyrosine and the gradual polymerization of monomers to form the composite hydrogels. The detailed two-step gelation mechanism was confirmed by the Fluorescence spectroscopy, Electron paramagnetic resonance spectroscopy and Gel permeation chromatography, respectively. The final composite hydrogel combines the merits of enzymatic crosslinking hydrogels and polymerized hydrogels to achieve adjustable mechanical strength and facile printing performance. The dual-enzyme regulated polymer composite hydrogels are the promising bioscaffolds as organoid, implanted materials, and other biomedical applications.
