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The management of diabetic wounds remains a critical therapeutic challenge. Platelet-rich plasma (PRP) gel, PRP-derived exosomes (PRP-Exos), and mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated therapeutic potential in wound treatment. Unfortunately, their poor mechanical properties, the short half-lives of growth factors (GFs), and the burst release of GFs and exosomes have limited their clinical applications. Furthermore, proteases in diabetic wounds degrade GFs, which hampers wound repair. Silk fibroin is an enzyme-immobilization biomaterial that could protect GFs from proteases. Herein, we developed novel dual-crosslinked hydrogels based on silk protein (SP) (sericin and fibroin), including SP@PRP, SP@MSC-Exos, and SP@PRP-Exos, to promote diabetic wound healing synergistically. SP@PRP was prepared from PRP and SP using calcium gluconate/thrombin as agonist, while SP@PRP-Exos and SP@MSC-Exos were derived from exosomes and SP with genipin as crosslinker. SP provided improved mechanical properties and enabled the sustained release of GFs and exosomes, thereby overcoming the limitations of PRP and exosomes in wound healing. The dual-crosslinked hydrogels displayed shear-induced thinning, self-healing, and eradication of microbial biofilms in a bone-mimicking environment. In vivo, the dual-crosslinked hydrogels contributed to faster diabetic wound healing than PRP and SP by upregulating GFs expression, down-regulating matrix metalloproteinase-9 expression, and by promoting an anti-NETotic effect, angiogenesis, and re-epithelialization. Hence, these dual-crosslinked hydrogels have the potential to be translated into a new generation of diabetic wound dressings.

Hydrogel-based burn wound dressings with excellent antibacterial, antifungal, and mechanical properties are ideal biomaterials to promote infected large burn wound healing. In this study, the hydrogel synthesized by repetitive freezing-thawing consists of poly (vinyl alcohol) (PVA), silk sericin (SS), and azithromycin (AZM), with genipin (GNP) as crosslinker. The FTIR showed that all hydrogel components were successfully blended. The swelling ratio, porosity, cell attachment, and proliferation improved with SS incorporation, while increased PVA content enhanced the mechanical performance of the hydrogel. The inclusion of AZM improved the antimicrobial property of the hydrogel towards Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. The hydrogel showed sustained SS and AZM releases as well as cytocompatibility on keratinocytes and fibroblasts. Furthermore, the hydrogel displays skin adhesion ability when freeze-dried. In the in vivo study using an infected mouse full-thickness burn model with a 10% total body surface area, it was shown that burn injury led to increased inflammatory cytokine responses and macroscopic and microscopic alterations in the spleen and liver. The kidneys, on the other hand, revealed neither change. Interestingly, the prepared hydrogel had a better burn wound healing effect than the commercial Tegaderm™ film dressing, minimizing systemic burn effects. Hence, this novel hydrogel is projected to be a promising candidate for accelerated healing of infected burn wounds.

Glycolic acid (GA), as an anti-aging skincare ingredient, plays a pivotal role in anti-aging treatment. However, its benefits could be overshadowed due to its side effects including skin burning and irritation when overused. Bacterial cellulose (BC) is a highly pure form of cellulose, biosynthesized in the form of a swollen membrane by several kinds of bacteria that was demonstrated to modulate the release of model drugs owing to its porous and 3D fibrous network structure, and glycerol (GL), as a plasticizer, could enhance the controlled drug delivery. Herein, we report a topical controlled drug delivery system based on BC membrane, GA and GL for controlling sustainable release of GA to reduce its side effects on the skin, while maintaining its prolonged and maximum therapeutic effect. The results showed that the incorporation of GL increased the malleability and flexibility of BC/GA/GL membrane, as compared with BC/GA membrane. In addition, the GL enhanced the control of the GA delivery, as evidenced by a higher swelling capacity and thereby a slower release of the GA from BC/GA/GL membrane. More importantly, in vitro study indicated that both BC/GA and BC/GA/GL membranes could effectively stimulate endogenous collagen synthesis in NIH3T3 cells owing to the release of GA, and that BC/GA/GL membrane is more conducive to a long-term cell adhesion, spreading, and proliferation of NIH3T3 and HaCaT cells due to its lower and sustainable release of GA than BC/GA membrane. This study suggests the BC/GL/GA composite membrane holds great promise as an appealing platform to control the release of GA to greatly promote renewal of skin cells for effective anti-aging treatment.