Chronic wounds, burns, and other large full-thickness skin wounds are a significant source of morbidity and mortality and thus a challenging clinical problem in human and veterinary medicine alike. Wound healing therapies are a multi-billion-dollar industry, and yet effective treatments for regenerating functional skin remain elusive. Scarless skin regeneration is observed in nature in that fetal wounds and some oral mucosal wounds heal without scar. However, deep partial thickness and full thickness wounds in adult mammals heal predominantly through robust scar formation. This is largely the result of the scar-forming reparative response of a specific lineage of dermal fibroblasts located within the reticular (deep) dermis. Of recent interest, investigations into the diversity of dermal fibroblasts have revealed that multiple populations exist, each with a different phenotypic response to injury. Interestingly, one specific population of fibroblast progenitor cells exists within the mammalian hair follicle mesenchyme and functions to regenerate the hair follicle throughout the human or animal’s lifetime. Following isolation and expansion in culture, these dermal progenitor cells (DPCs) have been shown to contribute to dermal repair as well as function to induce neogenic hair follicle formation. Considering this inherent regenerative phenotype, I hypothesized that cultured DPCs could be transplanted to generate a more functional neodermis following skin injury. In Chapter 2, I asked whether addition of DPCs could improve the outcome of split-thickness skin grafts (STSG, the current mainstay of care for deep skin wounds and burns). After 3 months, I found that DPCs repopulated the dermal layer underneath the STSG, supported improved viscoelastic properties, and lead to a modest reduction in itch. In doing this, I found that modifications in cell delivery methods were necessary to improve cell survival and distribution within the graft and avoid the negative consequences observed following utilization of a collagen scaffold. Therefore, in Chapter 3, I investigated the utility of a fully synthetic, flowable hydrogel platform and discovered that indeed DPCs survived and maintained their inductive phenotype even after in vitro culture in 2-3% TG-PEG hydrogel. Not only does this substrate show promise for ease of cell delivery in wound healing applications, it also affords us the opportunity to fully tailor the environment of the cells to further drive dermal regeneration. Finally, in Chapter 4, I demonstrate that adult reindeer antler velvet is capable of near-complete skin regeneration, thus providing a novel mammalian platform to understand the cellular and molecular processes that underlie tissue regeneration as opposed to scar formation. Taken together, this work highlights the potential therapeutic value of DPCs for skin wound healing, a unique biomaterial adjunct to improve cell transplantation and new insight into the mechanisms underlying skin regeneration and mitigation of scar.