Achieving rapid and effective hemostasis on irregularly shaped, non‐compressible visceral, and high‐pressure arterial bleeding wounds remains a critical clinical challenge. Herein, an ultrafast self‐gelling and wet adhesive polyethyleneimine/polyacrylic acid/quaternized chitosan (PEI/PAA/QCS) powder is reported as the hemostatic material and wound dressing. PEI/PAA/QCS powder deposited on bleeding wounds can rapidly absorb a large amount of blood to concentrate coagulation factors. Meanwhile, the powder can form an adhesive hydrogel in situ within 4 s upon hydration to form a pressure‐resistant physical barrier. Furthermore, PEI/PAA/QCS hydrogels can aggregate blood cells and platelets to enhance hemostasis. Depositing PEI/PAA/QCS powder on various bleeding wounds, including at the liver and heart, high‐pressure femoral artery and tail vein of rats, arrests the bleeding around 10 s with no rebleeding after ten minutes. Excellent hemostasis of PEI/PAA/QCS powder is further demonstrated against massive hemorrhage in porcine spleen and liver in vivo, which are non‐compressible organs with abundant blood supply. In addition, the powder can be used as a wound dressing to promote the healing of the full‐thickness skin wounds. The advantages of PEI/PAA/QCS powder including rapid and effective hemostasis, effective wound healing, easy usage, low cost, and adaptability to fit complex target sites make it a promising biomaterial for surgical applications.

Noncanonical Wnt signaling in stem cells is essential to numerous developmental events. However, no prior studies have capitalized on the osteoinductive potential of noncanonical Wnt ligands to functionalize biomaterials in enhancing the osteogenesis and associated skeleton formation. Here, we investigated the efficacy of the functionalization of biomaterials with a synthetic Wnt5a mimetic ligand (Foxy5 peptide) to promote the mechanosensing and osteogenesis of human mesenchymal stem cells by activating noncanonical Wnt signaling. Our findings showed that the immobilized Wnt5a mimetic ligand activated noncanonical Wnt signaling via the up-regulation of Disheveled 2 and downstream RhoA-ROCK signaling, leading to enhanced intracellular calcium level, F-actin stability, actomyosin contractility, and cell adhesion structure development. This enhanced mechanotransduction in stem cells promoted the in vitro osteogenic lineage commitment and the in vivo healing of rat calvarial defects. Our work provides valuable guidance for the developmentally inspired design of biomaterials for a wide array of therapeutic applications.

A key challenge for the effective treatment of gastrointestinal diseases including inflammatory bowel disease is to develop an orally administered drug delivery system capable of prolonged retention in the gastrointestinal tract. Herein we report a bioadhesive liquid coacervate based on hydrogen bonding-driven nanoparticle assembly. Free from electrostatic interactions, our fluid nanoparticle-assembled coacervate demonstrates significant pH- and salt-independent structural stability and forms a physically adhesive coating on a large surface area of intestinal tract with an extended residence time of more than 2 days to mediate the sustained release of preloaded water-soluble small molecule drugs in vivo. The orally administered drug-laden nanoparticle-assembled coacervate significantly mitigates the symptoms of inflammatory bowel disease, restores the diversity of gut microbiota, reduces systemic drug exposure, and improves the therapeutic efficacy in a rat acute colitis model compared with the oral administration of the same amount of drug in solution form. We suggest that the nanoparticle-assembled coacervate provides a promising drug delivery platform for management and treatment of numerous gastrointestinal diseases where controlled drug release with extended residence time is desired.

Achieving robust underwater adhesion by bioadhesives remains a challenge due to interfacial water. Herein a coacervate-to-hydrogel strategy to enhance interfacial water repulsion and bulk adhesion of bioadhesives is reported. The polyethyleneimine/thioctic acid (PEI/TA) coacervate is deposited onto underwater substrates, which can effectively repel interfacial water and completely spread into substrate surface irregularities due to its liquid and water-immiscible nature. The physical interactions between coacervate and substrate can further enhance interfacial adhesion. Furthermore, driven by the spontaneous hydrophobic aggregation of TA molecules and strong electrostatic interaction between PEI and TA, the coacervate can turn into a hydrogel in situ within minutes without additional stimuli to develop enhanced matrix cohesion and robust bulk adhesion on diverse underwater substrates. Molecular dynamics simulations further reveal atomistic details of the formation and wet adhesion of the PEI/TA coacervate via multimode physical interactions. Lastly, it is demonstrated that the PEI/TA coacervate-derived hydrogel can effectively repel blood and therefore efficiently deliver the carried growth factors at wound sites, thereby enhancing wound healing in an animal model. The advantages of the PEI/TA coacervate-derived hydrogel including body fluid-immiscibility, strong underwater adhesion, adaptability to fit irregular target sites, and excellent biocompatibility make it a promising bioadhesive for diverse biomedical applications.

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