Hyaluronic acid (HA), a naturally occurring linear polysaccharide, has been widely used as a key biomaterial in a range of cosmetic and therapeutic applications. Its excellent biocompatibility and bio-functions related to tissue regeneration encourage the development of HA-based hydrogels to expand its applications. This study details an in situ forming surgical glue based on photocrosslinkable HA, providing tunable mechanical properties and firm tissue adhesion under wet and dynamic conditions. Depending on the degree of photocrosslinkable methacrylate groups in HA polymer chains, the mechanical properties of hyaluronate methacrylate (HAMA) hydrogels prepared by UV photocrosslinking was improved. Ex vivo adhesion tests revealed that HAMA hydrogels exhibited 3-fold higher shear adhesive strength compared to gelatin methacryloyl hydrogels and achieved firm adherence to the porcine skin tissue for several weeks. The high adhesive strength of HAMA hydrogels, under dry and wet conditions, suggests that it may have great promise as a tissue adhesive.Additional supporting information may be found in the online version of this article.

Chitosan has been widely used as a nature-derived polymeric biomaterial due to its high biocompatibility and abundance. However, poor solubility in aqueous solutions of neutral pH and multiple fabrication steps for the molding process limit its application to microneedle technology as a drug delivery carrier. Here, we present a facile method to prepare water-soluble chitosan and its application for sustained transdermal drug delivery. The water-soluble chitosan was prepared by acid hydrolysis using trifluoroacetic acid followed by dialysis in 0.1 M NaCl solutions. We successfully fabricated bullet-shaped microneedle (MN) arrays by the single molding process with neutral aqueous chitosan solutions (pH 6.0). The chitosan MN showed sufficient mechanical properties for skin insertion and, interestingly, exhibited slow dissolving behavior in wet conditions, possibly resulting from a physical crosslinking of chitosan chains. Chitosan MN patches loading rhodamine B, a model hydrophilic drug, showed prolonged release kinetics in the course of the dissolving process for more than 72 h and they were found to be biocompatible to use. Since the water-soluble chitosan can be used for MN fabrication in the mild conditions (neutral pH and 25 °C) required for the loading of bioactive agents such as proteins and achieve a prolonged release, this biocompatible chitosan MN would be suitable for sustained transdermal drug delivery of a diverse range of drugs.

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Stem cell therapies offer great promise in regenerative medicine to reinstate the normal function of diseased tissue, thereby avoiding the need for replacement. In stem cell therapies, damaged cells are replaced or restored by regulating inflammation and the immune system. However, the low survival rate and local retention of transplanted cells pose a significant challenge. In this study, injectable selfcrosslinkable hydrogels using thiol-functionalized hyaluronic acid (HA-SH) were developed to improve the efficacy of mesenchymal stem cells (MSCs) for treating atopic dermatitis (AD)-related inflammatory lesions. The gelation kinetics and mechanical properties of HA-SH hydrogels were easily tuned by varying the concentration of the polymer in the precursor solution before injection. The MSC-laden HA-SH hydrogels exhibited high cell viability (>80%) for 1 week and good in vivo biocompatibility after implantation beneath the mouse skin. Moreover, the MSC-laden HA-SH hydrogel showed increased expression of anti-inflammatory cytokines, which can alleviate the immune response. In an AD animal model, a reduction in epidermal thickness and mast cell infiltration was achieved by applying a self-crosslinkable HA-SH solution including MSCs. This HA-based injectable hydrogel represents a potential carrier of stem cells, and its strong immunomodulation capabilities can be utilized for treating inflammation-related diseases.

Achieving fast and secure wound closure without ocular foreign body sensation is highly desired in ophthalmologic surgery. Sutureless approaches using tissue adhesives are gaining popularity, but their practical use is limited by the difficulty in controlling adhesion time and satisfying safety standards without compromising adhesive performance. Herein, we report user-demand hydrogel-forming ocular glues based on multilength photo-crosslinkable hyaluronic acid (HA), achieving firm tissue adhesion under wet and dynamic conditions and possessing cornea-like optical transparency.The HA-based photocurable glue (HA photoglue) quickly seals wounds upon nontoxic low-energy light exposure (320-500 nm, < 5 s, < 1 J cm À2 ), and its mechanical and adhesive properties are improved by introducing short and long crosslinkable moieties into HA through one-step synthesis, forming multilength networks. Furthermore, the HA photoglue provides stable sealing in wet environments like ocular mucous surface, a clear vision with a light transmittance of more than 95% over the entire visible range, and a lubricating surface with minimal ocular sensation (generating less than 10% frictional force than suture groups). In a rabbit corneal incision model, the HA photoglue showed improved wound healing efficacy based on histological evaluation compared to control groups.