A Biomimetic, Bilayered Antimicrobial Collagen-Based Scaffold for Enhanced Healing of Complex Wound Conditions

Abstract

Chronic, nonhealing wounds in the form of diabetic foot ulcers (DFUs) are a major complication for diabetic patients. The inability of a DFU to heal appropriately leads to an open wound with a high risk of infection. Current standards of care fail to fully address either the underlying defective wound repair mechanism or the risk of microbial infection. Thus, it is clear that novel approaches are needed. One such approach is the use of multifunctional biomaterials as platforms to direct and promote wound healing. In this study, a biomimetic, bilayered antimicrobial collagen-based scaffold was developed to deal with the etiology of DFUs. An epidermal, antimicrobial collagen/chitosan film for the prevention of wound infection was combined with a dermal collagen−glycosaminoglycan scaffold, which serves to support angiogenesis in the wound environment and ultimately accelerate wound healing. Biophysical and biological characterization identified an 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide cross-linked bilayered scaffold to have the highest structural stability with similar mechanical properties to products on the market, exhibiting a similar structure to native skin, successfully inhibiting the growth and infiltration of Staphylococcus aureus and supporting the proliferation of epidermal cells on its surface. This bilayered scaffold also demonstrated the ability to support the proliferation of key cell types involved in vascularization, namely, induced pluripotent stem cell derived endothelial cells and supporting stromal cells, with early signs of organization of these cells into vascular structures, showing great promise for the promotion of angiogenesis. Taken together, the results indicate that the bilayered scaffold is an excellent candidate for enhancement of diabetic wound healing by preventing wound infection and supporting angiogenesis.

Collagen-Based Scaffolds for Chronic Skin Wound Treatment

“…The scaffold exhibited a functional stratum corneum, improved re-epithelialization, and the presence of elastin in the dermis, not typically present in wound healing. An improvement in mimicking the skin's architecture was obtained by creating a bilayer scaffold consisting of a collagen/chitosan film to emulate the epidermis and a collagen-glycosaminoglycan scaffold to simulate the dermis features [92]. In vitro tests revealed that the epidermal layer exhibited not only antibacterial properties but also the ability to support keratinocyte proliferation for epidermal reformation.…”

Biomimetic Materials for Skin Tissue Regeneration and Electronic Skin

“…These chronic wounds can become open wounds that are at high risk of infection if they do not heal properly. To address this issue, bilayer scaffolds have been developed to mimic the structure of the epidermal and dermal layers of the skin (Figure 4a) [90]. The bilayer scaffolds can be designed to promote angiogenesis and wound healing, which are the functions of endothelial cells.…”

“…The traditional approach to wound dressings has limitations in supporting complex wound healing processes, as they primarily focus on sealing the wound, absorbing exudate, and maintaining a moist environment. However, by incorporating ECM components like collagen, glycosaminoglycan, or hyaluronic acid into traditional dressings, it can actively promote epithelialization, angiogenesis, and collagen deposition, thereby enhancing the overall wound healing process [90,237,238]. (2) Biomimetics presents a promising approach to wound care technology and has the potential to extend its benefits to the treatment of other diseases and conditions.…”

Current status and progress in research on dressing management for diabetic foot ulcer

“…The dressing exhibits a structure similar to that of natural skin, successfully inhibiting bacterial growth and promoting angiogenesis. This dressing is an excellent candidate for enhancing diabetic wound healing ( 111 ).…”