A Novel Crosslinking Approach for Biomanufacturing of a Collagen-Based Skin Dermal Template

Abstract

Third-degree burns result in extensive damage to the skin's epidermal and dermal layers, with limited treatment options available. Currently, xenogeneic collagen-based skin grafts are used as scaffolds to integrate into the wound bed and provide a template for neodermis formation. Existing commercial products like Integra dermal templates rely on a time-consuming and variable dehydrothermal (DHT) crosslinking process. This study presents a novel crosslinking process for collagen sponges, utilizing UV irradiation followed by glutaraldehyde (GA) crosslinking. This UV method allows to fine-tune the template's crosslink density and degradation profile while significantly reducing the total crosslinking time from 48 to 24 h compared to DHT/GA crosslinking. In vitro characterization and in vivo validation are conducted using a full-thickness skin wound mouse model. The collagen template supports the human dermal fibroblast cell line WS-1 proliferation more effectively than the Integra template after 2 weeks in culture. Additionally, in vivo data indicate a similar level of regeneration of full-thickness skin wounds in mouse models between the sponge and Integra templates. Furthermore, the sponge template does not elicit any abnormal angiogenic or immune responses. The crosslinking approach offers a promising alternative production process for collagen sponge scaffolds.

Keywords: collagen sponge; dehydrothermal treatment; dermal template; glutaraldehyde; skin regeneration; ultraviolet irradiation.