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Current options for in vivo regeneration of dermal tissue remain limited. The purpose of this study was to engineer a unique scaffold capable of recruiting dermal stem cells from adjacent tissue, thus circumventing the need to seed the scaffolds with stem cells before implantation, leading to skin regeneration.A hydrogel scaffold was created through combination of type I collagen along with fractionated platelet-rich plasma. This was compared to a control hydrogel consisting of type I collagen and fetal bovine serum. Hydrogels were cultured with fresh human skin tissue and incubated with supplemental media. Gels were digested weekly for cellular content as examined by flow cytometry at the 4- and 8-week time points. The fractionated platelet-rich plasma and collagen gels were then implanted onto full-thickness skin defects on the backs of rats and compared to wounds healing by secondary intention. Wound area was evaluated for epithelialization and neovascularization.Platelet-rich plasma fractionation increased platelet-derived growth factors. In contrast to collagen scaffolds, fractionated platelet-rich plasma–supplemented scaffolds recruited more dermal-derived stem cells from fresh skin tissue compared with collagen hydrogels at the 4- and 8-week time points. Furthermore, fractionated platelet-rich plasma–supplemented hydrogels accelerated wound healing, angiogenesis, and hair and sweat gland formation, ultimately regenerating a dermis-like tissue.Generation of hydrogels with fractionated platelet-rich plasma was able to improve cellular recruitment and growth and differentiation of dermal-derived stem cells, leading to hair growth and sweat gland formation. This provides a novel approach to regenerate skin for treating large defects.