In the field of wound healing, hydrogels have garnered significant attention due to their outstanding biocompatibility and versatile functionality. However, most conventional hydrogels are pre-formed in fixed shapes, limiting their adaptability to complex wound environments. Moreover, the relatively dense structure of these hydrogels can impede cell growth, which, in turn, hinders the wound healing process. Therefore, there is a compelling need to develop a novel hydrogel capable of undergoing shape adjustments and facilitating cell growth, thereby facilitating dynamic wound closure. To address these challenges, we developed a microgel system, gelatin methacryloyl (GelMA)-fibrin microgel scaffolds, composed of two-component microspheres made from GelMA and fibrinogen, which not only facilitates re-cross-linking between microspheres to enhance mechanical properties but also substantially enhances adhesion to the wound site. Gel formation occurs through secondary cross-linking of the microspheres in the presence of thrombin. Notably, GFMs exhibit excellent injectability and can be tailored into various shapes and sizes to suit the specific characteristics of wound. Moreover, the distinct gaps between the microspheres in the GFM structure allow cells to migrate and proliferate, effectively functioning as a “scaffold” for tissue regeneration. In vivo experiments on a mouse full-thickness skin defect model demonstrated the efficacy of this microgel scaffold in promoting cell migration and growth, significantly accelerating wound healing by about 10% compared to fibrin gel. Therefore, we propose that GFMs, as an innovative form of wound dressing, possess broad potential applications and offer substantial research value.

Adhesive hydrogel has drawn great attention for wide applications in wound healing owing to its excellent biocompatibility and lasting adhesiveness. However, traditional adhesive hydrogels only keep the wound moist to promote wound healing. It is still imperative to fabricate adhesive hydrogels that exhibit efficient antibacterial ability, active driving dynamic wound closure, and reactive oxygen species (ROS) scavenging together with excellent mechanical properties. Here, a novel hydrogel based on poly(N-isopropyl acrylamide) (PNIPAAm), a thermoresponsive polymer, and tannic acid (TA)-Ag nanoparticles (TA-Ag NPs) exhibiting active contraction, tissue adhesion, anti-inflammatory and antibacterial functions was developed. TA-Ag dispersed in the hydrogel not only functioned as the catalyst to polymerize the reaction but also provided additional anti-inflammatory and antibacterial properties. Besides, tannic acid containing catechol groups endowed the hydrogel with adhesive ability. More interestingly, the obtained hydrogel exhibited the thermoresponsive shrinkage ability, which could mechanically drive wound closure due to the presence of PNIPAAm network. In vivo mouse full-thickness skin defect model demonstrated that this actively contractible and antibacterial hydrogel is a promising dressing to improve wound healing process by accelerating tissue regeneration and preventing bacterial infection. Therefore, this multi-functional adhesive hydrogel developed here may provide a new possibility for wound healing.

Hair loss can cause psychological distress. Here, red organic light-emitting diode (OLED) light source is first introduced as the photobiomodulation therapy (PBMT) for hair growth and demonstrated as a promising and non-invasive therapeutic modality for alopecia. OLED exhibits unique advantages of homogeneous irradiation, flexible in form factor, and less heat generation. These features enable OLED to be an ideal candidate for wearable PBMT light sources. A systematic study of using red OLEDs to facilitate hair growth was conducted. The results show that OLEDs excellently promote hair regrowth. OLED irradiation can increase the length of the hair by a factor of 1.5 as compared to the control, and the hair regrowth area is enlarged by over 3 times after 20 days of treatments. Moreover, the mechanism of OLED that stimulates hair follicle regeneration is investigated in-vivo by conducting a systematic controlled experiments on mice with or without OLED PBMT. Based on the comprehensive histological and immunofluorescence staining studies, two key factors are identified for red OLEDs to facilitate hair follicle regeneration: (i) increased autophagy during the anagen phase of the hair growth cycle; (ii) increased blood oxygen content promoted by the accelerated microvascular blood flow.

Ultrasound with deep penetration depth and high security could be adopted in sonodynamic therapy (SDT) by activating sonosensitizers to generate cytotoxic reactive oxygen species (ROS). Herein, two-dimensional (2D) coordination nanosheets composed of Zn²⁺ and Tetrakis(4-carboxyphenyl) porphyrin (TCPP) are fabricated. While exhibiting greatly enhanced ultrasound-triggered ROS generation useful for noninvasive SDT, such Zn-TCPP 2D nanosheets show high loading capacity of oligodeoxynucleotides such as cytosine-phosphorothioate-guanine (CpG), which is a potent toll like receptor 9 (TLR9) agonist useful in activating immune responses. Highly effective SDT of primary tumors could release tumor-associated antigens, which working together with Zn-TCPP/CpG adjuvant nanosheets could function like whole-tumor-cell vaccines and trigger tumor-specific immune responses. Interestingly, ultrasound itself could strengthen anti-tumor immune responses by improving the tumor-infiltration of T cells and limiting regulatory T cells in the tumor microenvironment. Thus, SDT using Zn-TCPP/CpG nanosheets after destruction of primary tumors could induce potent antitumor immune responses to inhibit distant abscopal tumors without direct SDT treatment. Moreover, SDT with Zn-TCPP/CpG could trigger strong immunological memory effects to inhibit cancer recurrence after elimination of primary tumors. Therefore, the 2D coordination nanosheet may be a promising platform to deliver potent SDT-triggered immunotherapy for highly effective cancer treatment.