Biomaterials for Chronic Wound Healing

Wound healing is a multi-stage process of repairing damaged tissue and restoring its integrity. This dynamic, interactive process involves soluble mediators, numerous cell types including blood cells and parenchymal cells, and their associated extracellular matrix (ECM). This process involves a series of biochemical and physiological events which follow four distinct, sometimes overlapping healing phases: hemostasis, inflammation, proliferation, and remodeling. Non-healing chronic wounds (e.g., diabetic, pressure, and venous ulcers) are an important and persistent problem in dermatology. They are characterized by an elevated and prolonged inflammatory phase, which leads to the destruction of the ECM and in turn affects resident fibroblast populations. This includes altering fibroblast abilities to proliferate and to synthesize/remodel the ECM as the chronic wound-associated fibroblasts develop a senescent phenotype. Finally, the chronic wound environment impairs angiogenesis and stalls epithelialization. Presence of diverse pathological conditions may further adversely affect healing and lead to several complications. The resulting delayed or impaired wound healing have become a major therapeutic challenge.

Once a trauma occurs, the damaged skin should be immediately covered with a dressing, capable of maintaining a moderately moist environment for regeneration of the skin, prevent infection, alleviate pain, and remove excessive exudates. The wound-healing material should ideally satisfy the following requirements: flexibility and softness, elasticity and high mechanical strength, chemical and physical stability, biocompatibility, biodegradability, antibacterial activity and facile applicability. In addition, wound dressings should be easily sterilized, have a long shelf life, and be cost-effective. Today’s commercially available dressings can only satisfy a few of the above specifications. Hence, new frontiers for wound healing should include multi-functional antimicrobial approaches that can overcome the current challenges and promote healing. These should be suitable for treating impaired and hard-to-heal wounds, like diabetic ulcers, and ensure faster healing by reducing infection, preventing hypoxia, stimulating the healing mechanisms, speeding up wound closure, and reducing scar formation.

The Research Topic focuses on the design of novel approaches and the synthesis of advanced materials, including but not limited to biofunctional hydrogels, exhibiting resistance to external strain and enhanced antibacterial properties, capable of regulating the inflammatory phase of wound healing, promoting angiogenesis, and accelerating tissue formation.

The topic welcomes, but is not limited to, original research, reviews, and mini reviews in the following research areas:

• Synthesis of macromolecules as building blocks for the formation of bio-functional hydrogels;
• Design and Applications of antimicrobial and/or wound healing peptides;
• (Bio)functionalization of the novel building blocks with cell binding epitopes and antimicrobial/wound healing peptides;
• Delivery systems with sustained oxygenation;
• Stimuli-responsive biopolymer hydrogels and composites for wound healing applications;
• 3D/4D (bio)printing of scaffolds for use in wound healing;
• Controlled release of bioactive factors from hydrogels via tuning the hydrogel cross-linking density and swelling behavior;
• Controlled release of bioactive agents (e.g., growth factors, platelet activating agents, angiogenic factors, miRNA) from nanoparticles encapsulated within wound dressings;
• Construction of engineered stem cells producing angiogenic factors continuously or on demand;
• Small extra-cellular vesicles (SEVs) exhibiting pro-healing and anti-scarring properties;
• In vitro assessment of biocompatibility-cytotoxicity, genotoxicity, and antibacterial properties of the hydrogels;
• In vivo evaluation of the wound healing efficacy of bio-functional hydrogels.