Wound healing is a complex biological process that requires coordinated cell proliferation, migration, and extracellular matrix production/remodeling, all of which are inhibited/delayed in chronic
wounds. In this study, a formulation was developed that marries a
fibrin-based, provisional-like matrix with
collagen mimetic
peptide (
CMP)/PDGF gene-modified
collagens, leading to the formation of robust
gels that supported temporally controlled PDGF expression and facile application within the
wound bed. Analysis employing in vitro co-gel scaffolds confirmed sustained and temporally controlled gene release based on
matrix metalloproteinase (
MMP) activity, with ~30% higher PDGF expression in
MMP producing fibroblasts as-compared with non-
MMP-expressing cells. The integration of
fibrin with the gene-modified
collagens resulted in co-
gels that strongly supported both fibroblast cell recruitment/invasion as well as multiple aspects of the longer-term healing process. The excisional wound healing studies in mice established faster
wound closure using
CMP-modified PDGF polyplex-loaded co-
gels, which exhibited up to 24% more
wound closure (achieved with ~2 orders of magnitude lower
growth factor dosing) after 9 days as compared to PDGF-loaded co-
gels, and 19% more
wound closure after 9 days as compared to
CMP-free polyplex loaded co-
gels. Moreover, minimal
scar formation as well as improved
collagen production, myofibroblast activity, and
collagen orientation was observed following
CMP-modified PDGF polyplex-loaded co-gel application on
wounds. Taken together, the combined properties of the co-
gels, including their stability and capacity to control both cell recruitment and cell phenotype within the murine
wound bed, strongly supports the potential of the co-gel scaffolds for improved treatment of chronic non-healing
wounds.