A self-responsive insulin delivery system is highly desirable because of its high sensitivity dependent on blood glucose levels. Herein, a smart pH-triggered and glucose-mediated transdermal delivery system, insulin-loaded and ZnO quantum dots (ZnO QDs) capped mesoporous bioactive glasses (MBGs) integrated with microneedles (MNs), was developed to achieve control and painless administration. ZnO QDs as a promise pH-responsive switch were employed to cap the nanopores of MBGs via electrostatic interaction. The drug (insulin) and glucose-responsive factor (glucose oxidase/catalase, GO x /CAT) were sealed into the pores of MBGs. GO x /CAT in the MBGs could catalyze glucose to form gluconic acid, resulting decrease in the local pH. The ZnO QDs on the surface of the MBGs could be dissolved in the acidic condition, leading to disassembly of the pH-sensitive MBGs and then release of preloaded insulin from the MBGs. As a result of administration in a diabetic model, an excellent hypoglycemic effect and lower hypoglycemia risk were obtained. These results indicate that as-prepared pH-triggered and glucose-mediated transdermal delivery systems have hopeful applications in the treatment of diabetes.

Development of proper skin wound dressing is a vital step for wound repair, especially for those patients with serious skin injuries. Herein, zinc-doped bioactive glass (ZBG)/succinyl chitosan (SCS)/oxidized alginate (OAL) composite hydrogels (Gel-ZBG) have been developed as wound dressings to accelerate wound closure. Schiff-based linkages have been introduced into the composite hydrogels, which provide a humid microenvironment for the proliferation of cells on wound sites. The amino groups from SCS and Zn 2+ released from ZBG exhibited excellent antibacterial properties to composite hydrogels, confirmed by the antibacterial tests in vitro. Si 4+ and Ca 2+ ions are essential factors that stimulate fibroblasts to secrete beneficial factors for angiogenesis and wound closure. The epidermal growth factor (EGF) was further embedded into the hydrogels to improve cell proliferation and tissue remodeling in the wound bed. Finally, the formation of granulation tissue, deposition of collagen and myofibril, the release of anti-inflammatory factors, and angiogenesis have been investigated to determine the healing mechanism of the composite hydrogels as the wound dressings.

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Near-infrared (NIR) light-triggered and separable segmented microneedles (MNs), consisting of lauric acid and polycaprolactone (LA/PCL) arrowheads and poly­(vinyl alcohol) and polycaprolactone (PVA/PVP) supporting bases, have been fabricated. A hypoglycemic drug (metformin) and photothermal conversion factor (Cu7S4 nanoparticles) are encapsulated into LA/PCL arrowheads. Due to the dissolution of soluble supporting bases after the absorption of tissue fluid, the separable MNs arrowheads can be embedded into skin after insertion. Under the NIR-light irradiation, the LA/PCL arrowheads exhibit an excellent thermal-ablation change with a low amount of Cu7S4 nanoparticles (0.1 wt %) due to the low melting point of LA and PCL, thus enabling the release behavior of the encapsulated model drug to be photothermally triggered. Compared to the hypodermic injection of metformin, the thermal ablation of separable MNs triggered by NIR irradiation in the current research exhibit an excellent hypoglycemic effect in vivo. It suggests that the NIR-induced thermal-ablation MNs comprise a prospective transdermal drug-delivery system for the precise control of the timing and dosage of a drug that is dependent on NIR administration.

Wound dressing has been used for decades to be effective for accelerating skin wound healing. However, practical applications are still limited due to their lower cell affinity, tissue adhesiveness, and biocompatibility. Natural polymers are the important biomaterials because of their excellent biodegradability, biocompatibility, and low immunogenicity. In this work, the composite bioadhesives (PLS-CS/RSF) were prepared from regenerated silk fibroin (RSF) and polylysine-modified chitosan (PLS-CS) that were cross-linked by Ca 2+ ions. The adhesion property tests showed that the PLS-CS/RSF exhibited excellent bonding potentials for various substrates, and the adhesive strength was up to 70 kPa for isolated porcine skin by the extension test. The as-prepared PLS-CS/RSF was nontoxic, displayed obvious antibacterial effects against Staphylococcus aureus and Escherichia coli in vitro, and their bacteriostasis rates were 100% after 120 min treatment. In addition, the PLS-CS/RSF exhibited favorable cytocompatibility by cell counting kit-8 assay. The animal model of wound closure results showed that PLS-CS/ RSF can promote wound closure and the integrity of wound healing, inhibiting the secretion of inflammatory factor and tumor necrosis factor and stimulating vascular factor and α-smooth muscle actin to the release of vascular growth factor and promote angiogenesis during the process of wound healing by immunohistochemical assay.