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Hydrogels have long been used for encapsulating stem cell-derived conditioned mediums to achieve skin regeneration after wounding. However, inappropriate mechanical strength, low adhesion and low elasticity limit their clinical application. To address these challenges, we engineered a hyaluronic acid-based hydrogel grafted with methacrylic anhydride and N-(2-aminoethyl)-4-[4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy]-butanamide (NB) groups to encapsulate a lyophilized amnion-derived conditioned medium (AM-CM). This hydrogel can photopolymerize in situ within 3 s by photo-initiated free-radical crosslinking between methacrylate moieties. Meanwhile, the formed o-nitrosobenzaldehyde groups by photo-irradiation could covalently bond with the amino groups of tissue surface, which allowed strong tissue adhesion. Furthermore, the hydrogel possessed excellent mechanical properties, high elasticity, favorable biocompatibility and prolonged AM-CM release. Our further vitro and in vivo studies showed that the hydrogel significantly accelerated diabetic wound healing by regulating macrophage polarization and promoting angiogenesis. The engineered hydrogel with AM-CM release has high potential to treat chronic wounds in clinics., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The wet and highly dynamic environment of the mouth makes local treatment of oral mucosal diseases challenging. To overcome this, a photo-crosslinking hydrogel adhesive is developed inspired by the success of light-curing techniques in dentistry. The adhesive operates on a fast (within 5 s) phototriggered S-nitrosylation coupling reaction and employs imine anchoring to connect to host tissues. Unlike other often-used clinical agents that adhere weakly and for short durations, this thin, elastic, adhesive, and degradable cyclic o-nitrobenzyl-modified hyaluronic acid gel protects mucosal wounds from disturbance by liquid rinsing, oral movement, and friction for more than 24 h. The results from both rat and pig oral mucosa repair models demonstrate that this new gel adhesive creates a favorable microenvironment for tissue repair and can shorten tissue healing time. This study thus illustrates a therapeutic strategy with the potential to advance the treatment of oral mucosal defects in the clinic., (© 2021 Wiley-VCH GmbH.)

In this study, we developed an injectable antibacterial hydrogel based on hyaluronic acid (HA) and chlorhexidine (CHX) for cardiovascular implantable electronic device (CIED) infection treatment. To balance stability and moldability, the HA scaffold was pre-crosslinked by 1,4-butanediol diglycidyl ether (BDDE) and then ground to form an HA microgel (CHA). Then, the antibacterial agent CHX was further crosslinked in the CHA microgel through electrostatic interactions between CHA and CHX to obtain hybrid crosslinked hydrogels (CHA/CHX). These hydrogels exhibited shear-thinning/self-recovery behavior, allowing easy injection into the CIED pocket and good matching with the pocket shape without extra space requirements, which represents an improvement on previously reported methods. In vitro and in vivo antibacterial tests showed that the CHA/CHX hydrogels had both good biocompatibility and very effective antibacterial action. The above results indicated that the CHA/CHX hydrogels would be an excellent candidate for CIED pocket infection treatment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Reconstructing segmental costal cartilage defects resulting from autologous cartilage grafts in plastic surgery remains a challenge. The present study focused on a biomimetic strategy for in situ costal cartilage regeneration that did not rely on an autogenous/xenogenous tissue graft. A multifunctional biomimetic SGII/HA-DN hydrogel based on a "chemical-curing, shaping, and light-curing" gelation system was developed and evaluated for its mechanical properties, clinical applications and biological functions. This hydrogel showed good suitability to repair defects and a high mechanical support strength (11 MPa, which is close to the natural strength of costal cartilage). Biologically, the hydrogel exhibited dual-immunomodulatory effects on the pro-inflammatory/anti-inflammatory phenotypes of neutrophils and M1/M2 macrophage polarization and subsequently promoted the chondrogenesis of cartilage stem/progenitor cells through both direct induction and indirect stimulation by the M2 macrophage-mediated TGF-β/Smad pathway. Furthermore, this SGII/HA-DN hydrogel could regulate the local microenvironment, inducing new costal cartilage regeneration in vivo. Our findings demonstrate that the newly developed multifunctional SGII/HA-DN hydrogel provides a strategy with high prospect for the biomimetic repair of segmental costal cartilage defects in clinical practice., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Uncontrollable bleeding is a major problem in surgical procedures and after major trauma. Existing hemostatic agents poorly control hemorrhaging from traumatic arterial and cardiac wounds because of their weak adhesion to wet and mobile tissues. Here we design a photo-reactive adhesive that mimics the extracellular matrix (ECM) composition. This biomacromolecule-based matrix hydrogel can undergo rapid gelling and fixation to adhere and seal bleeding arteries and cardiac walls after UV light irradiation. These repairs can withstand up to 290 mm Hg blood pressure, significantly higher than blood pressures in most clinical settings (systolic BP 60-160 mm Hg). Most importantly, the hydrogel can stop high-pressure bleeding from pig carotid arteries with 4~ 5 mm-long incision wounds and from pig hearts with 6 mm diameter cardiac penetration holes. Treated pigs survived after hemostatic treatments with this hydrogel, which is well-tolerated and appears to offer significant clinical advantage as a traumatic wound sealant.