Chronic wound management represents a significant healthcare challenge, with an estimated global prevalence of 1.47 to 2.2 per 1,000 population. In the UK alone, NHS data from 2017/2018 revealed 3.8 million skin wound patients, with more than 1.5 million suffering from chronic wounds including diabetic foot ulcers (DFU), venous leg ulcers (VLU), and pressure ulcers.
Revolutionary Hydrogel Compositions Drive Superior Outcomes
Recent advances in hydrogel technology have demonstrated remarkable improvements in wound healing efficacy. Composite hydrogels combining multiple polymer networks show particularly promising results. Yang and colleagues developed a multifunctional hydrogel that induced wound healing 25% faster than commercially available wound dressings, exhibiting limited immune activation and no infections across 14 days of treatment. Their approach combined synthetic polyethylene glycol (PEG) with natural chitosan polymer, integrating functional antibacterial compounds including methacrylamide dopamine and zinc ions.
Similarly, Bakadia's research group achieved exceptional outcomes with their hybrid composite silk sericin/polyvinyl alcohol/azithromycin (SS/PVA/AZM) hydrogel. This formulation promoted wound healing to achieve 100% wound closure at day 24, compared to 60-75% closure rates for control and commercially available dressing groups during the same timeframe.
Injectable Hydrogels Address Complex Wound Geometries
Traditional wound dressings face significant limitations when treating irregular wounds with complex geometries. Injectable in-situ forming hydrogels offer transformative solutions by conforming to wound shapes and eliminating surgical implantation requirements. These formulations can be pre-seeded with viable cells such as fibroblasts and mesenchymal stem cells, or incorporated with bioactive molecules including epidermal growth factor and vascular endothelial growth factor without compromising biological activity during polymerization.
Balitaan and colleagues demonstrated the effectiveness of hybrid composite hydrogels created by combining acrylamide-modified β-chitin with alginate dialdehyde. When tested in zebrafish models, wounds treated with these injectable hydrogels showed approximately 87% healing of wound area, while untreated wounds achieved only 50% closure.
Advanced Biomimetic Properties Enhance Tissue Integration
Modern hydrogel designs increasingly focus on replicating native skin's viscoelastic properties, which allow tissue to recover its original shape after force application through stress relaxation mechanisms. This biomimetic approach sends crucial mechanical cues to cells, supporting tissue homeostasis and proper wound healing progression.
Wang and colleagues developed a gelatin-hyaluronic acid hydrogel exhibiting Young's moduli between 20 and 140 kPa, comparable to human skin properties. By adjusting the gelatin-to-hyaluronic acid ratio, researchers successfully tuned the viscoelastic properties. In vitro and in vivo studies using this gel as a scaffold for bilayer skin constructs in murine models showed improved cell proliferation, adhesion, and overall healing properties.
Controlled Drug Delivery Systems Optimize Treatment Phases
The complex nature of wound healing, involving hemostasis, inflammation, proliferation, and remodeling phases, requires sophisticated drug delivery approaches. Advanced hydrogels now incorporate controlled-release mechanisms that respond to specific wound conditions.
Huang and colleagues developed pH and reactive oxygen species (ROS)-responsive injectable hydrogels by attaching phenylboronic acid to alginate polymer side chains. This modification provided antibacterial and anti-inflammatory capabilities while enclosing antibiotic amikacin and anti-inflammatory naproxen in micelles for targeted release during inflammatory stages.
Zhang and colleagues created injectable hydrogels using carboxymethyl chitosan and oxidized hyaluronic acid containing blueberry anthocyanins, known for antioxidant and anti-inflammatory effects. The hydrogel significantly accelerated wound healing in rat models with full-thickness skin wounds by stimulating new tissue growth, reducing inflammation, and facilitating collagen production and blood vessel formation.
Addressing Diabetic Wound Complications
Diabetic wounds present particular challenges due to multi-drug resistant bacterial infections and microenvironments characterized by high glucose levels and oxidative stress. Wang and colleagues developed a multifunctional injectable hydrogel through Schiff-based reactions between ε-polylysine-coated MnO2 nanosheets and insulin-loaded self-assembled aldehyde Pluronic F127 micelles.
This innovative system demonstrated exceptional antimicrobial abilities against multi-drug resistant bacteria. The MnO2 nanoenzyme catalyzed decomposition of endogenous H2O2 into H2O and molecular O2, effectively controlling harmful oxidative conditions in wound microenvironments. The pH and redox-sensitive hydrogel exhibited controlled, sustained insulin release with spatial and temporal management capabilities.
Commercial Applications and Future Directions
Current commercially available skin substitutes face limitations including requirements for multiple surgeries, graft fragility, inadequate engraftment, and surgical implantation needs for deeper irregular wounds. Advanced hydrogel technologies address these challenges through enhanced biocompatibility, improved mechanical properties, and minimally invasive application methods.
The development of hybrid biomaterials has enabled composition adaptation and enhanced biocompatibility to improve tissue repair and regeneration. Research demonstrates that hybrid hydrogels exhibit more effective structural integrity and enhanced biocompatibility when acellular tissue is conjugated with polymers such as polyvinyl alcohol and alginate.
Injectable hydrogels represent a paradigm shift in wound care, offering solutions for complex wound defects with multi-tunnel formations through appropriate formulation and delivery methods. Their ability to conform to irregular wound geometries ensures uniform coverage and adhesion while supporting controlled release of embedded therapeutic factors.
The integration of growth factors, antimicrobial agents, and cellular components into hydrogel matrices continues to drive innovation in chronic wound management, offering hope for improved patient outcomes and reduced healthcare costs associated with prolonged wound care.
