Engineered multi-functional, pro-angiogenic collagen-based scaffolds loaded with endothelial cells promote large deep burn wound healing.

The inability to create new blood vessels in deep burns delays the construction of wound beds, increases the risks of infection, and leads to disfigurement or the formation of raised or thickened scars, also known as hypertrophic scars. To address this challenge, we have created a multi-functional molecule that promotes new blood vessel growth by an integrin named avb3 attached to a ligand named LXW7 and collagen-binding peptides named SILY attached to a backbone of a long chain of sugar molecules called dermatan sulfate (DS) glycosaminoglycan. This multi-functional molecule was then named LXW7-DS-SILY (LDS), which will be the basis for the collagen-based Integra scaffolds. Using a large deep burn wound model in mice, we demonstrated that LDS-modified collagen-based Integra modified scaffolds loaded with endothelial cells (ECs) accelerate wound healing rate, promote blood vessel growth, and collagen production. Specifically, a 2 cm x 3 cm full-thickness skin burn wound was created. 48h after the burn and the wounds were treated with four groups of different dressing scaffolds, including Integra + ECs, Integra + LDS, and Integra + LDS + ECs with Integra-only as the control. Digital photos were taken for wound healing measurement on post-treatment days 1, 7, 14, 21, 28, and 35. Post-treatment photos revealed that treatment with the Integra + LDS + ECs scaffold exhibited a higher wound healing rate when the cells rapidly divide and replicate. When examining the tissues of the scaffold, the results showed significantly increased re-epithelialization, increased collagen production, increased thin and mixed collagen fiber content, increased formation of blood vessels, and shorter wound length within the Integra + LDS + ECs group at Day 35. On Day 14, the Integra + LDS + ECs group showed the same trend. The relative proportions of collagen changed from Day 14 to Day 35 in the Integra + LDS + ECs and Integra + ECs groups demonstrated decreased thick collagen fiber production and greater thin and mixed collagen fiber production. LDS-modified Integra scaffolds represent a promising newly invented treatment to accelerate deep burn wound healing, thereby potentially reducing the illness associated with open burn wounds. These scaffolds can also potentially reduce the need for taking tissue from another part of the patient’s body to repair the wound and illness in patients with already limited areas of harvestable skin.