A macromolecular cross-linked alginate aerogel with excellent concentrating effect for rapid hemostasis.

Alginate-based materials present promising potential for emergency hemostasis due to their excellent properties, such as procoagulant capability, biocompatibility, low immunogenicity, and cost-effectiveness. However, the inherent deficiencies in water solubility and mechanical strength pose a threat to hemostatic efficiency. Here, we innovatively developed a macromolecular cross-linked alginate aerogel based on norbornene- and thiol-functionalized alginates through a combined thiol-ene cross-linking/freeze-drying process. The resulting aerogel features an interconnected macroporous structure with remarkable water-uptake capacity (approximately 9000 % in weight ratio), contributing to efficient blood absorption, while the enhanced mechanical strength of the aerogel ensures stability and durability during the hemostatic process. Comprehensive hemostasis-relevant assays demonstrated that the aerogel possessed outstanding coagulation capability, which is attributed to the synergistic impacts on concentrating effect, platelet enrichment, and intrinsic coagulation pathway. Upon application to in vivo uncontrolled hemorrhage models of tail amputation and hepatic injury, the aerogel demonstrated significantly superior performance compared to commercial alginate hemostatic agent, yielding reductions in clotting time and blood loss of up to 80 % and 85 %, respectively. Collectively, our work illustrated that the alginate porous aerogel overcomes the deficiencies of alginate materials while exhibiting exceptional performance in hemorrhage, rendering it an appealing candidate for rapid hemostasis.

An Injectable, Adhesive, and Self-Healing Hydrogel with Inherently Antibacterial Property for Wound Dressing.

Antibacterial hydrogel has emerged as an excellent candidate for wound dressing with the ability to eliminate infection and promote wound healing. Herein, a dynamic hydrogel is developed by Schiff base reaction of mixed charged polypeptides and oxidized dextran (ODex). Specifically, biodegradable polypeptides of 1-(propylthio)acetic acid-3-butylimidazole-modified poly(L-lysine) (PLL-PBIM) and adipate dihydrazide-modified poly(L-glutamic acid) (PLG-ADH) are achieved with tunable substitution and charge. By mixing with ODex, charged polypeptides of PLL-PBIM and PLG-ADH led to an injectable and self-healing hydrogel in seconds. The injectable and self-healing performances of the hydrogels are ascribed to the reversible imine and hydrazone bonds formed between polypeptides and ODex. The positively charged hydrogels exhibited over 95% antibacterial activity against E. coli and S. aureus. An optimized balancing of PLG-ADH and PLL-PBIM significantly reduced the hemolysis rate and cytotoxicity of hydrogels. Therefore, the dynamic hydrogel with excellent biocompatibility and inherently antibacterial ability can have potential application for wound dressing.

Sequential Release of Small Extracellular Vesicles from Bilayered Thiolated Alginate/Polyethylene Glycol Diacrylate Hydrogels for Scarless Wound Healing.

Excessive scar formation has adverse physiological and psychological effects on patients; therefore, a therapeutic strategy for rapid wound healing and reduced scar formation is urgently needed. Herein, bilayered thiolated alginate/PEG diacrylate (BSSPD) hydrogels were fabricated for sequential release of small extracellular vesicles (sEVs), which acted in different wound healing phases, to achieve rapid and scarless wound healing. The sEVs secreted by bone marrow derived mesenchymal stem cells (B-sEVs) were released from the lower layer of the hydrogels to promote angiogenesis and collagen deposition by accelerating fibroblast and endothelial cell proliferation and migration during the early inflammation and proliferation phases, while sEVs secreted by miR-29b-3p-enriched bone marrow derived mesenchymal stem cells were released from the upper layer of the hydrogels and suppressed excessive capillary proliferation and collagen deposition during the late proliferation and maturation phases. In a full-thickness skin defect model of rats and rabbit ears, the wound repair rate, angiogenesis, and collagen deposition were evaluated at different time points after treatment with BSSPD loaded with B-sEVs. Interestingly, during the end of the maturation phase in the in vivo model, tissues in the groups treated with BSSPD loaded with sEVs for sequential release (SR-sEVs@BSSPD) exhibited a more uniform vascular structure distribution, more regular collagen arrangement, and lower volume of hyperplastic scar tissue than tissues in the other groups. Hence, SR-sEVs@BSSPD based on skin repair phases was successfully designed and has considerable potential as a cell-free therapy for scarless wound healing.