Exogenous factors aimed at promoting fibroblast activity might hold the key to improving the clinical outcome of chronic wounds. The current study explores the feasibility to use a collagen-based scaffold as a delivery system for a niacinamide dominated formulation in vivo. The combined use of niacinamide, L-carnosine, hesperidin and a HSP70 homologue is known to promote fibroblast activity in vitro. Scaffold mediated wound healing was assessed in 16 female Sprague-Dawley rats that received both a control scaffold and an enhanced scaffold. The test scaffolds presented with a higher fibroblast count (60.49 ± 9.90% of the total cell infiltrate) on day 7 compared that of the control scaffolds (42.62 ± 13.60%) but was found to be statistically insignificant. However, the addition of these active components did not compromise the in vivo resistance against enzymatic degradation nor alter the scaffold microenvironment deleteriously.