Laminin 1 enhances the angiogenic and neurogenic potential of collagen-based scaffolds for complex wound healing applications

Chronic wounds fail to progress through the normal stages of healing, with insufficient vascularisation and dysfunctional neural regrowth playing a key role in their inability to heal. Collagen-glycosaminoglycan scaffolds have shown promise for wound healing as they provide a platform for infiltrating cells to support wound repair, but may require further functionalisation to drive wound closure in chronic wounds. To improve wound healing potential, we sought to enhance the collagen-glycosaminoglycan scaffold's pro-angiogenic and pro-neurogenic capacity through addition of fibronectin, collagen IV, or laminin 1 to the scaffold, key extracellular matrix components known to support angiogenic and neurogenic processes. Laminin 1 functionalised scaffolds showed enhanced angiogenic properties, with human dermal fibroblasts producing significantly more vascular endothelial growth factor (VEGF). Endothelial cell coverage on laminin 1 functionalised scaffolds was also significantly enhanced, with cells forming distinct vascular structures. The individual addition of fibronectin, collagen IV, and laminin 1 also increased the neurogenic potential of the collagen-glycosaminoglycan scaffolds, enhancing neurite outgrowth from neurons, as well as supporting axon outgrowth in ex vivo injured tissue explants. Fibronectin, collagen IV, and laminin 1 were then added in combination to the scaffold, but no additional benefit to angiogenic or neurogenic potential was seen. Taken together, laminin 1 functionalisation of a collagen-glycosaminoglycan scaffold provides a multifaceted enhancement of wound healing potential, supporting both angiogenesis and axon regrowth, two processes essential for healing complex wounds.