Wound healing and tissue regeneration are orchestrated by the cellular microenvironment, e.g. the extracellular matrix (ECM). Including ECM components in biomaterials is a promising approach for improving regenerative processes, e.g. wound healing in skin. This review addresses recent findings for enhanced epidermal-dermal regenerative processes on collagen (coll)/glycosaminoglycan (GAG)-based matrices containing sulfated GAG (sGAG) in simple and complex in vitro models. These matrices comprise 2D-coatings, electrospun nanofibrous scaffolds, and photo-crosslinked acrylated hyaluronan (HA-AC)/coll-based hydrogels. They demonstrated to regulate keratinocyte and fibroblast migration and growth, to stimulate melanogenesis in melanocytes from the outer root sheath (ORS) of hair follicles and to enhance the epithelial differentiation of human mesenchymal stem cells (hMSC). The matrices' suitability for delivery of relevant growth factors, like heparin-binding epidermal growth factor like growth factor (HB-EGF), further highlights their potential as bioinspired, functional microenvironments for enhancing skin regeneration.