The treatment of difficult-to-heal wounds remains a substantial clinical challenge due to deteriorative tissue microenvironment including the loss of extracellular matrix (ECM), excessive inflammation, impaired angiogenesis, and bacterial infection. Inspired by the chemical components, fibrous structure, and biological function of natural ECM, antibacterial and tissue environment–responsive glycopeptide hybrid hydrogel was developed for chronic wound healing. The hydrogel can facilitate the cell proliferation and macrophage polarization to M2 phenotype, and show potent antibacterial efficacy against both Gram-negative and Gram-positive bacteria. Significantly, the glycopeptide hydrogel accelerated the reconstruction of methicillin-resistant Staphylococcus aureus (MRSA)–infected full-thickness diabetic and scalding skin by orchestrating a pro-regenerative response indicated by abundant M2-type macrophages, attenuated inflammation, and promoted angiogenesis. Collectively, ECM-mimetic and immunomodulatory glycopeptide hydrogel is a promising multifunctional dressing to reshape the damaged tissue environment without additional drugs, exogenous cytokines, or cells, providing an effective strategy for the repair and regeneration of chronic cutaneous wounds.

Clinical wound management remains a major challenge due to massive bleeding, bacterial infection, and difficult wound healing after tissue trauma. To simultaneously address these issues, composite polymer sponges for accelerating drug-resistant bacterial infected wound healing are fabricated by facilely mixing sodium polyacrylate (PAAS), double quaternary ammonium salts-conjugated chitosan (QAS-CS), and collagen (COL) in aqueous solution, followed by lyophilization. Composite sponges (PAAS/QAS-CS/COL, PQC) show highly porous microstructures (porosity ≈90%) with moderate compress modulus (≈0.3 MPa), tensile strength (0.004 MPa), and high swelling ratio (≈3500%). Importantly, PQC sponge demonstrates superior hemostasis ability over commercially available CS sponge by inducing rapid hemagglutination, and exhibits significantly better antibacterial activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli by destroying cell membrane and causing the leakage of bioactive components such as potassium ion and 𝜷-galactosidase from treated bacterial. Furthermore, PQC sponge can efficiently promote cell proliferation. Significantly, the sponge greatly expedites the regeneration of MRSA-infected full-thickness skin wound in rabbit by successfully eradicating bacterial infection, and reducing inflammation. PQC sponge also improves both early angiogenesis and blood vessel maturation at the wound site. Overall, this multifunctional sponge is a promising wound dressing for clinical use and holds great potential for rapid clinical translation.

No abstract

Abdominal adhesion is a common complication after surgery, which causes pain to patient and increases the risks of reoperation. Electrospinning polyester membrane serving as a physical barrier is used for preventing abdominal adhesion; however, the efficacy is limited due to the lacking of bioactivity necessary for antiadhesion. Here, hydrophobic poly(l‐lactide‐co‐caprolactone) (PLCL) electrospinning membranes are hydrophilized with photo‐crosslinked methacrylic anhydride gelatin (GelMA) hydrogel for postoperative abdominal adhesion prevention. The composite membranes show fibrous network architecture, good cytocompatibility, and hydrophilicity than commercial poly(d,l‐lactide acid) (PDLLA) film. Importantly, the composite membrane provides superior antiadhesion effect over PLCL membrane alone or commercial PDLLA film, against abdominal wall–cecum adhesion models in Sprague Dawley (SD) rats. The underlying mechanism is that PLCL/GelMA membrane successfully promotes the secretion of matrix metalloproteinases 9 (MMP‐9) that can reduce the collagen deposition in extracellular matrix (ECM). Furthermore, the composite membrane significantly upregulates the expression of tissue‐type plasminogen activator (t‐PA) and downregulates the production of plasminogen activator inhibitor‐1 (PAI‐1), leading to the activation of fibrinolytic system, which inhibits the formation of adhesive tissues. Collectively, gelatinized PLCL electrospun membrane is a promising bioactive barrier for preventing postsurgery abdominal adhesions.

Titanium alloy has been widely used in orthopedic surgeries as bone defect filling. However, the regeneration of high-quality new bones is limited due to the pro-inflammatory microenvironment around implants, resulting in a high occurrence rate of implant loosening or failure in osteological therapy. In this study, extracellular matrix (ECM)-mimetic polysaccharide hydrogel co-delivering BMP-2 and IL-4 was composited with 3D printed titanium alloy to promote the osseointegration and regulate macrophage response to create a pro-healing microenvironment in bone defect. Notably, it is discovered from the bioinformatics data that IL-4 and BMP-2 could affect each other through multiple signal pathways to achieve a synergistic effect towards osteogenesis. The composite scaffold significantly promoted the osteoblast differentiation and proliferation of human bone marrow mesenchyme stem cells (hBMSCs). The repair of large-scale femur defect in rat indicated that the dual-cytokine-delivered composite scaffold could manipulate a lower inflammatory level in situ by polarizing macrophages to M2 phenotype, resulting in superior efficacy of mature new bone regeneration over the treatment of native titanium alloy or that with an individual cytokine. Collectively, this work highlights the importance of M2-type macrophages-enriched immune-environment in bone healing. The biomimetic hydrogel-metal implant composite is a versatile and advanced scaffold for accelerating in vivo bone regeneration, holding great promise in treating orthopedic diseases.

Clinical wound management of radiation-induced skin injury (RSI) remains a great challenge due to acute injuries induced by excessive reactive oxygen species (ROS), and the concomitant repetitive inflammatory microenvironment caused by an imbalance in macrophage homeostasis. Herein, a cutaneous extracellular matrix (ECM)-inspired glycopeptide hydrogel (GK@TA gel ) is rationally designed for accelerating wound healing through modulating the chronic inflammation in RSI. The glycopeptide hydrogel not only replicates ECM-like glycoprotein components and nanofibrous architecture, but also displays effective ROS scavenging and radioprotective capability that can reduce the acute injuries after exposure to irradiation. Importantly, the mannose receptor (MR) in GK@TA gel exhibits high affinity and bioactivity to drive the M2 macrophage polarization, thereby overcoming the persistent inflammatory microenvironment in chronic RSI. The repair of RSI in mice demonstrates that GK@TA gel significantly reduces the hyperplasia of epithelial, promotes appendage regeneration and angiogenesis, and decreased the proinflammatory cytokine expression, which is superior to the treatment of commercial radioprotective drug amifostine. Collectively, the ECM-mimetic hydrogel dressing can protect the tissue from irradiation and heal the chronic wound in RSI, holding great potential in clinical wound management and tissue regeneration.