Enhanced Early Vascularization and Tissue Formation in a Biphasic Collagen Hydrogel Dermal Regeneration Template.

Reconstruction of full-thickness wounds remains a major clinical challenge. Full-thickness skin grafts (FTSG) are considered an ideal reconstructive option as they reconstitute both epidermal and dermal layers of skin; however, their use is limited by donor site availability and potential donor site morbidity. Dermal regeneration templates (DRTs) were introduced decades ago to reduce dermal harvesting needs and promote formation of a 'neodermal' layer, improving both functional and cosmetic outcomes. However, current DRTs are limited by slow vascularization, typically requiring 2-4 weeks for integration. To address these limitations, we developed DermiSphere hDRT, a hydrogel dermal regeneration template, a biphasic collagen-based matrix combining a type I collagen hydrogel with densely packed collagen microspheres. The resulting differential-density interfaces generate a gradient microstructure that supports efficient cellular infiltration and neovascularization. Using a swine model, we evaluated early host response and vascular invasion into hDRT without an overlying graft. By Postoperative Day (POD) 3, hDRT was fully integrated with the wound bed and resistant to manual shear, whereas the market-leading DRT (MLT) showed minimal adherence. Quantitative histology revealed significantly greater cellular and endothelial invasion in hDRT, with CD31+ vascular channels penetrating nearly halfway through the construct. By POD 7, hDRT generated thicker neodermal tissue with extensive vascular networks extending into new granulation tissue. By POD 10, hDRT exhibited organised collagen remodelling and interconnected vertical and horizontal vessel growth, while MLT remained incompletely incorporated. These results demonstrate that hDRT's unique microarchitecture accelerates cellular infiltration and neovascularization, enabling faster, more reliable formation of a vascularized neodermal layer for full-thickness skin repair.