In view of the lack of a specific drug-sustained release system that is responsive to chronic wounds of the type II diabetic foot, and the demands for frequent movement at the foot wound, pH/glucose dual-responsive metformin-released adhesion-enhanced self-healing easy-removable antibacterial antioxidant conductive hemostasis multifunctional phenylboronic acid and benzaldehyde bifunctional polyethylene glycol-co-poly(glycerol sebacic acid)/dihydrocaffeic acid and l-arginine cografted chitosan (PEGS-PBA-BA/CS-DA-LAG, denoted as PC) hydrogel dressings were constructed based on the double dynamic bond of the Schiff-base and phenylboronate ester. It was further demonstrated that the PC hydrogel promotes wound healing by reducing inflammation and enhancing angiogenesis in a rat type II diabetic foot model. In addition, the addition of metformin (Met) and graphene oxide (GO), as well as their synergy, were confirmed to better promote wound repair in vivo. In summary, adhesion-enhanced self-healing multifunctional PC/GO/Met hydrogels with stimuli-responsive metformin release ability and easy removability have shown a promoting effect on the healing of chronic athletic diabetic wounds and provide a local-specific drug dual-response release strategy for the treatment of type II diabetic feet.

pH/Glucose Dual Responsive Metformin Release Hydrogel Dressings with Adhesion and Self-Healing via Dual-Dynamic Bonding for Athletic Diabetic Foot Wound Healing.

https://doi.org/10.1016/j.ajps.2022.01.001

Antibacterial biomaterials for skin wound dressing

Burns are a common health problem worldwide and are highly susceptible to bacterial infections that are difficult to handle with ordinary wound dressings. Therefore, burn wound repair is extremely challenging in clinical practice. Herein, a series of self-healing hydrogels (QCS/OD/TOB/PPY@PDA) with good electrical conductivity and antioxidant activity were prepared on the basis of quaternized chitosan (QCS), oxidized dextran (OD), tobramycin (TOB), and polydopamine-coated polypyrrole nanowires (PPY@PDA NWs). These Schiff base cross-links between the aminoglycoside antibiotic TOB and OD enable TOB to be slowly released and responsive to pH. Interestingly, the acidic substances during the bacteria growth process can induce the on-demand release of TOB, avoiding the abuse of antibiotics. The antibacterial results showed that the QCS/OD/TOB/PPY@PDA9 hydrogel could kill high concentrations of Pseudomonas aeruginosa (PA), Staphylococcus aureus, and Escherichia coli in a short time and showed a bactericidal effect for up to 11 days in an agar plate diffusion experiment, while showing good in vivo antibacterial activity. Excellent and long-lasting antibacterial properties make it suitable for severely infected wounds. Furthermore, the incorporation of PPY@PDA endowed the hydrogel with near-infrared (NIR) irradiation assisted bactericidal activity of drug-resistant bacteria, conductivity, and antioxidant activity. Most importantly, in the PA-infected burn wound model, the QCS/OD/TOB/PPY@PDA9 hydrogel more effectively controlled wound inflammation levels and promoted collagen deposition, vascular generation, and earlier wound closure compared to Tegaderm dressings. Therefore, the TOB smart release hydrogels with on-demand delivery are extremely advantageous for bacterial-infected burn wound healing.

Bacterial Growth-Induced Tobramycin Smart Release Self-Healing Hydrogel for Pseudomonas aeruginosa-Infected Burn Wound Healing.

In clinical applications, there is a lack of wound dressings that combine efficient resistance to drug-resistant bacteria with good self-healing properties. In this study, a series of adhesive self-healing conductive antibacterial hydrogel dressings based on oxidized sodium alginate-grafted dopamine/carboxymethyl chitosan/Fe3+ (OSD/CMC/Fe hydrogel)/polydopamine-encapsulated poly(thiophene-3-acetic acid) (OSD/CMC/Fe/PA hydrogel) were prepared for the repair of infected wound. The Schiff base and Fe3+ coordination bonds of the hydrogel structure are dynamic bonds that can be repaired automatically after the hydrogel network is disrupted. Macroscopically, the hydrogel exhibits self-healing properties, allowing the hydrogel dressing to adapt to complex wound surfaces. The OSD/CMC/Fe/PA hydrogel showed good conductivity and photothermal antibacterial properties under near-infrared (NIR) light irradiation. In addition, the hydrogels exhibit tunable rheological properties, suitable mechanical properties, antioxidant properties, tissue adhesion properties and hemostatic properties. Furthermore, all hydrogel dressings improved wound healing in the infected full-thickness defect skin wound repair test in mice. The wound size repaired by OSD/CMC/Fe/PA3 hydrogel + NIR was much smaller (12%) than the control group treated with Tegaderm™ film after 14 days. In conclusion, the hydrogels have high antibacterial efficiency, suitable conductivity, great self-healing properties, good biocompatibility, hemostasis and antioxidant properties, making them promising candidates for wound healing dressings for the treatment of infected skin wounds. 

Antibacterial conductive self-healing hydrogel wound dressing with dual dynamic bonds promotes infected wound healing

Hydrogels with multifunctionalities, including sufficient bonding strength, injectability and self-healing capacity, responsive-adhesive ability, fault-tolerant and repeated tissue adhesion, are urgently demanded for invasive wound closure and wound healing. Motivated by the adhesive mechanism of mussel and brown algae, bioinspired dynamic bonds cross-linked multifunctional hydrogel adhesive is designed based on sodium alginate (SA), gelatin (GT) and protocatechualdehyde, with ferric ions added, for sutureless post-wound-closure. The dynamic hydrogel cross-linked through Schiff base bond, catechol-Fe coordinate bond and the strong interaction between GT with temperature-dependent phase transition and SA, endows the resulting hydrogel with sufficient mechanical and adhesive strength for efficient wound closure, injectability and self-healing capacity, and repeated closure of reopened wounds. Moreover, the temperature-dependent adhesive properties endowed mispositioning hydrogel to be removed/repositioned, which is conducive for the fault-tolerant adhesion of the hydrogel adhesives during surgery. Besides, the hydrogels present good biocompatibility, near-infrared-assisted photothermal antibacterial activity, antioxidation and repeated thermo-responsive reversible adhesion and good hemostatic effect. The in vivo incision closure evaluation demonstrated their capability to promote the post-wound-closure and wound healing of the incisions, indicating that the developed reversible adhesive hydrogel dressing could serve as versatile tissue sealant. 

/pdf/bioinspired-injectable-self-healing-hydrogel-sealant-with-1qfl4aq6.pdf

Bioinspired Injectable Self-Healing Hydrogel Sealant with Fault-Tolerant and Repeated Thermo-Responsive Adhesion for Sutureless Post-Wound-Closure and Wound Healing

Injectable stretchable self-healing dual dynamic network hydrogel as adhesive anti-oxidant wound dressing for photothermal clearance of bacteria and promoting wound healing of MRSA infected motion wounds

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Injectable stretchable self-healing dual dynamic network hydrogel as adhesive anti-oxidant wound dressing for photothermal clearance of bacteria and promoting wound healing of MRSA infected motion wounds