Disorders of skin wound healing and the repair of full-thickness skin defects remain significant clinical challenges. Natural polysaccharide-based hydrogels, with their excellent biocompatibility, tunable degradability, and multifunctional properties (e.g., antibacterial, antioxidant, and pro-angiogenic), have emerged as key materials for designing wound dressings and skin tissue engineering scaffolds. This review systematically summarizes recent advances in polysaccharide hydrogels—including chitosan, hyaluronic acid, and alginate—focusing on material types, crosslinking strategies, and functional modifications, with particular emphasis on their dual applications in wound healing (acute and chronic wounds) and skin tissue engineering. In wound healing, these hydrogels regulate the microenvironment through multiple mechanisms, including anti-inflammatory, antioxidant, pro-angiogenic, and immunomodulatory effects. In skin tissue engineering, their three-dimensional porous structures mimic the extracellular matrix, supporting cell adhesion, proliferation, and tissue regeneration. Finally, we discuss the challenges and future prospects for the clinical translation and commercialization of natural polysaccharide hydrogels.

Diabetic wound healing is often hindered by poor outcomes, prolonged recovery, and high recurrence. To address this, a new therapy approach was demonstrated in this study, in which ginsenoside (GS) molecules are incorporated into small extracellular vesicles (sEV) secreted by mesenchymal stem cells (MSCs), and the formed complexes are then anchored in DNA hydrogels via aptamer‐CD63 affinity as “GS/sEV@DNAgels”. Besides the tissue‐restorative ability that sEVs inherit from MSCs, in GS/sEV@DNAgels, GS molecules provide a superior antimicrobial/anti‐inflammatory environment at wound sites, while DNA hydrogels serve as wound dressings to ensure sustained release kinetics and enhanced skin penetration. An innovative ultrasonic stimulation was developed to promote the massive production of sEVs. By triggering multiple cellular responses that alter membrane fluidity, calcium levels, and relevant protein expression, our approach achieves a 57.7‐fold increase in sEV yield. The synergistic effects of GS and sEVs enhance cell viability, migration, and angiogenesis, as well as local anti‐inflammatory and antibacterial conditions during diabetic wound healing. The upregulation of miR‐424/322 is confirmed as an essential mechanism of this GS/sEV@DNAgel system in accelerating skin restoration. Our work provides a new and promising strategy for diabetic tissue regeneration.

Background: Skin injuries, such as chronic wounds and inflammatory skin diseases, often face limitations in treatment efficacy due to the low efficiency of transdermal drug delivery and insufficient local concentrations. Curcumin (CUR), a natural compound with anti-inflammatory and antioxidant properties, has demonstrated potential in the repair of skin damage; however, its clinical application is hindered by its physicochemical characteristics. This study constructs a novel nanocomposite drug delivery system: CUR-loaded micellar nanocomposite gel (CUR-M-DMNs-Gel). A composite system is used to achieve the efficient solubilization and enhanced transdermal permeation of CUR, thereby providing a novel formulation approach for the treatment of skin diseases. Methods: CUR-loaded micellar (CUR-M) utilizes CUR as the core active ingredient, which possesses multiple pharmacological effects including anti-inflammatory and antioxidant properties. TPGS serves as a micellar carrier that not only enhances the solubility and stability of CUR through its amphiphilic structure but also facilitates drug absorption and transport within the body. In dissolvable microneedles (DMNs), PVP K30 forms a stable three-dimensional network structure through entanglement of polymer chains, ensuring sufficient mechanical strength for effective penetration of the skin barrier. Meanwhile, PVP K90, with its higher molecular weight, enhances the backing’s support and toughness to prevent needle breakage during application. The incorporation of hyaluronic acid (HA) improves both the moisture retention and adhesion properties at the needle tips, ensuring gradual dissolution and release of loaded CUR-M within the skin. In CUR-loaded micellar gel (CUR-M-Gel), PVP K30 increases both adhesive and cohesive forces in the gel through chain entanglement and hydrogen-bonding interactions. Tartaric acid precisely regulates pH levels to adjust crosslinking density; glycerol provides a long-lasting moisturizing environment for the gel; aluminum chloride enhances mechanical stability and controlled drug-release capabilities; NP-700 optimizes dispersion characteristics and compatibility within the system. Results: In vitro experiments demonstrated that the CUR-M-DMNs-Gel composite system exhibited enhanced transdermal penetration, with a cumulative transdermal efficiency significantly surpassing that of single-component formulations. In the mouse skin defect model, CUR-M-DMNs-Gel facilitated collagen deposition and effectively inhibited the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1β). In the mouse skin photoaging model, CUR-M-DMNs-Gel markedly reduced dermal thickness, alleviated damage to elastic fibers, and suppressed inflammatory responses. Conclusions: The CUR-M-DMNs-Gel system can enhance wound healing through subcutaneous localization, achieving long-term sustained efficacy. This innovative approach offers new insights into the treatment of skin injuries.

Diabetes is a global disease that can lead to a range of complications. Currently, the treatment of type 2 diabetes focuses on oral hypoglycemic drugs and insulin analogues. Studies have shown that drugs such as oral metformin are useful in the treatment of diabetes but can limit the liver’s ability to release sugar. The development of glucose-lowering peptides has provided new options for the treatment of type 2 diabetes. Peptide drugs have low oral utilization due to their easy degradation, short half-life, and difficulty passing through the intestinal mucosa. Therefore, improving the oral utilization of peptide drugs remains an urgent problem. This paper reviews the research progress of peptide drugs in the treatment of diabetes mellitus and proposes that different types of nano-formulation carriers, such as liposomes, self-emulsifying drug delivery systems, and polymer particles, should be combined with peptide drugs for oral administration to improve their absorption in the gastrointestinal tract.