Wound healing is known as one of the most complicated biological processes for injured skin caused by surgical, trauma, burns, or diabetic diseases, which causes a nonfunctioning mass of fibrotic tissue. Recent reports have suggested that exosomes (EXOs) secreted by this type of stem cells may contribute to their paracrine effect. In this study, the EXOs were isolated from the supernatant of cultured adipose-derived stem cells (ADSCs) via ultracentrifugation and filtration. The EXO loaded in the alginate-based hydrogel was used as a bioactive scaffold to preserve the EXO in the wound site in the animal model. The physical and biochemical properties of EXO loaded Alg hydrogel were characterized and results proved that fabricated structure was biodegradable and biocompatible. This bioactive wound dressing technique has significantly improved wound closure, collagen synthesis, and vessel formation in the wound area. Results offer a new viewpoint and a cell-free therapeutic strategy, for wound healing through the application of the composite structure of EXO encapsulated in alginate hydrogel. K E Y W O R D S adipose-derived stem cells, alginate based hydrogel, exosomes, wound dressing, wound healing

Hydrogels catalyzed by horseradish peroxidase (HRP) serve as an efficient and effective platform for biomedical applications due to their mild reaction conditions for cells, fast and adjustable gelation rate in physiological conditions, and an abundance of substrates as water-soluble biocompatible polymers. In this review, we highlight the tunable characteristics and use of the HRP-catalyzed hydrogels and provide a brief overview of various substrates employed in the HRP system for different biomedical applications of the resultant hydrogels. In addition, we discuss and summarize the biocompatibility, possible functionalization, and biofabrication process. Finally, the future prospective of the HRP crosslinking system is highlighted with biomedical applications.

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This article describes the preparation of cell-enclosing hyaluronic acid (HA) microparticles with solid core and microcapsules with liquid core through cell-friendly horseradish peroxidase (HRP)-catalyzed hydrogelation. The spherical vehicles were made from HA derivative possessing phenolic hydroxyl moieties (HA-Ph) cross-linkable through the enzymatic reaction by extruding cellsuspending HA-Ph aqueous solution containing HRP from a needle of 180 lm in inner diameter into the ambient coaxial flow of liquid paraffin containing H 2 O 2 in a microtubule of 600 lm in diameter. By altering the flow rate of liquid paraffin, the diameters of gelatin and HA-Ph microparticles were varied in the range of 120-220 lm and 100-300 lm, respectively. The viability of the enclosed human hepatoma HepG2 cells in the HA-Ph microparticles of 180 lm in diameter was 94.2 6 2.3%. The growth of the enclosed HepG2 cells was enhanced by decreasing the HRP concentration. The microcapsules of 200 lm in diameter were obtained by extruding HA-Ph aqueous solution containing thermally liquefiable cell-enclosing gelatin microparticles of 150 lm in diameter using the same microfluidic system. The enclosed cells grew and filled the cavity within 10 days. Spherical tissues covered with a heterogeneous cell layer were obtained by degrading the microcapsule membrane using hyaluronidase after covering the surface with a heterogeneous cell layer.

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