Hyaluronate- and gelatin-based hydrogels encapsulating doxycycline as a wound dressing for burn injury therapy.

Infection is a critical challenge in burn wound therapy. Wound dressings with antibacterial and multifunctional abilities associated with rapid burn wound healing are urgently needed. Here, we developed a bioadhesive and injectable ECM-mimicking hydrogel dressing with antibacterial capacity for burn injury therapy, which is crosslinked by dynamic boronate ester bonds between modified hyaluronate and gelatin (HG). The antibiotic doxycycline (Doxy) was encapsulated in HG networks for drug delivery around the wound sites. The HG/Doxy hydrogel dressing shows biocompatibility and antibacterial activity against Gram-positive and Gram-negative bacteria. Applying to a rat model of burn wound, the HG/Doxy hydrogel significantly speeds up wound closure by reducing the inflammatory reaction. Furthermore, the HG/Doxy hydrogel accelerates the regeneration of the skin structure by promoting collagen deposition, blood vessel regeneration, and hair follicle formation, eventually shortening the healing periods of burn wounds. These findings demonstrated the clinical potential of the HG/Doxy hydrogels as a promising burn wound dressing. STATEMENT OF SIGNIFICANCE: A bioadhesive and injectable hydrogel dressing has been developed for burn injury therapy. The ECM-mimicking hyaluronate-gelatin (HG) hydrogel with antibacterial ability is crosslinked by dynamic boronate ester bonds for delivering antibiotic doxycycline (Doxy). The HG/Doxy hydrogels exhibit bioadhesive, shape-adaptive, and water retention abilities in closing the irregular-shaped wound and providing a moist environment. The HG/Doxy hydrogels significantly shorten the healing periods of burn wounds in rat models within 10~14 days and promote the regeneration of skin structure, which have high potential for clinical applications.

Biomimetic Asymmetric Composite Dressing by Electrospinning with Aligned Nanofibrous and Micropatterned Structures for Severe Burn Wound Healing.

The surface structure and topography of biomaterials play a crucial role in directing cell behaviors and fates. Meanwhile, asymmetric dressings that mimic the natural skin structure have been identified as an effective strategy for enhancing wound healing. Inspired by the skin structure and the superhydrophobic structure of the lotus leaf, an asymmetric composite dressing was obtained by constructing an asymmetric structure and wettability surface modification on both sides of the sponge based on electrospinning. Among them, the collagen and quaternized chitosan sponge was fabricated by freeze-drying, followed by an aligned poly(ε-caprolactone) (PCL)/gelatin nanofiber hydrophilic inner layer and hierarchical micronanostructure PCL/polystyrene microsphere highly hydrophobic outer layer constructed on each side of the sponge. The proposed asymmetric composite dressing combines topological morphology with the material's properties to effectively prevent bacterial colonization/infection and promote wound healing by directing cellular behavior. In vitro experimental results confirmed that the aligned nanofiber inner layer effectively promotes cell adhesion, proliferation, directed cell growth, and migration. Meanwhile, the sponge has good water absorption and antibacterial properties, while the biomimetic hydrophobic outer layer exhibits strong mechanical properties and resistance to bacterial adhesion. In vivo results showed that the composite dressing can reduce inflammatory response, prevent infection, accelerate angiogenesis and epithelial regeneration, and significantly accelerate the healing of severe burns. Thus, the proposed bionic asymmetric dressing is expected to be a promising candidate for severe burn wound healing.

Asymmetric Wettable Composite Wound Dressing Prepared by Electrospinning with Bioinspired Micropatterning Enhances Diabetic Wound Healing.

Wound dressings with asymmetric wettability surfaces can effectively prevent bacterial colonization and tissue dehydration and have shown great potential for diabetic wound healing applications. However, the construction of a highly hydrophobic outer surface with high biocompatibility and permeability is still the major challenge in the preparation of asymmetric wettable dressings. Inspired by the superhydrophobic surface structures existing in nature, an asymmetric wettable composite wound dressing with a highly hydrophobic outer layer was successfully prepared for diabetic wound healing in this study. The hydrophobic outer layer was fabricated by the electrospinning of poly(ε-caprolactone) (PCL) on a micron-pore-size nylon mesh template, and the hydrophilic inner layer was obtained by the electrospinning of pioglitazone-incorporated gelatin (Gel-pio). The hydrophobic outer layer of the dressing with a hierarchical micro-nanostructure exhibits excellent ability to waterproof and prevent bacterial adhesion, whereas the hydrophilic inner layer can promote cell proliferation, migration, and angiogenesis by its nanofiber structure and biocompatible gelatin composition. The presented dressing has good mechanical properties, permeability, and high biocompatibility. More importantly, the results of full-thickness skin wound model evaluation on db/db mice (type 2 diabetes) and STZ rats (type 1 diabetes) indicate that the developed dressing can promote wound healing by stimulating cell proliferation, angiogenesis, collagen deposition, and re-epithelialization. The findings of this study suggest that the bioinspired asymmetric wettable composite wound dressing can be used as a promising candidate for diabetic wound healing.

Preparation of biocompatible wound dressings with long-term antimicrobial activity through covalent bonding of antibiotic agents to natural polymers.

Wound dressings with long-term antimicrobial activity are highly desired for treatment of chronic wound infections. Herein, the sustained antimicrobial wound dressings were developed by using antibiotic agents, ciprofloxacin HCL (CIP) and gentamicin sulfate (GS), covalent bonding to natural polymer matrix composites, carboxymethyl chitosan (CMC) and collagen (COL). By amide bond formation between antibiotic agents and polymer chains, two antimicrobial wound dressings CMC-COL-CIP and CMC-COL-GS were prepared. The presented wound dressings exhibited high water absorption capacity, excellent water vapor transmission rate (WVTR), appropriate mechanical properties, and impressive stability. Cytocompatibility of the dressings was demonstrated by in vitro human skin fibroblast (HSF) cells culture study. The results of in vitro and in vivo studies indicated that the two antimicrobial wound dressings have effective antimicrobial activity and prolonged antimicrobial period. Furthermore, the antimicrobial dressings could promote the wound healing, reepithelialization, collagen deposition, and angiogenesis. It also displays superiority wound healing effects compared to commercially available silver-based dressings (Aguacel Ag). This work indicates that the prepared antimicrobial wound dressings have great potential application in chronic wound healing, such as severe wound cure and diabetic foot ulcers.

Transglutaminase-catalyzed preparation of crosslinked carboxymethyl chitosan/carboxymethyl cellulose/collagen composite membrane for postsurgical peritoneal adhesion prevention.

Peritoneal adhesion is a general complication following pelvic and abdominal surgery, which may lead to chronic abdominal pain, bowel obstruction, organ injury, and female infertility. Biodegradable polymer membranes have been suggested as physical barriers to prevent peritoneum adhesion. In this work, a transglutaminase (TGase)-catalyzed crosslinked carboxymethyl chitosan/carboxymethyl cellulose/collagen (CMCS/CMCL/COL) composite anti-adhesion membrane with various proportions of CMCS, CMCL, and COL (40/40/20, 35/35/30, 25/25/50) was developed. After crosslinking by TGase, the composite anti-adhesion membranes shown enhanced mechanical properties and improved biodegradability. Meanwhile, the high cytocompatibility of anti-adhesion membranes was proved by in vitro cell culture study. Moreover, the anti-adhesion membrane with the proportion of 25/25/50 was implanted between the artificially defected cecum and peritoneal wall in rats and following by general observation, histological examination, and inflammatory factors assay. The results indicated that the anti-adhesion membrane can significantly prevent peritoneal adhesion with negligible immunogenicity. Therefore, the composite membrane crosslinked by TGase had satisfactory anti-adhesive effects with high biocompatibility and low antigenicity, which could be used as a preventive barrier for peritoneal adhesion.