A novel hydrogel-collagen composite improves functionality of an injectable extracellular matrix

Cellular transplantation is now closer to becoming a practical clinical strategy to repair, regenerate or restore the function of skin, muscle, nerves and pancreatic islets. In this study we sought to develop a simple injectable collagen matrix that would preserve the normal cellular organization of skin cells. Three different scaffolds were created and compared: collagen-glycosaminoglycan (GAG) scaffolds, crosslinked collagen-GAG scaffolds without polyvinyl alcohol (PVA) and crosslinked collagen-GAG scaffolds containing PVA hydrogel. Importantly, all scaffolds were found to be non-cytotoxic. PVA-containing gels exhibited a higher tensile strength (P<0.05), faster fibril formation (P<0.001) and reduced collagenase digestion (P<0.01) compared with other gels. Free floating fibroblast-populated, PVA-borate scaffolds resisted contraction over a 10 day period (P<0.001). The fibroblast-populated scaffolds containing PVA demonstrated a 3-fold reduction in cellularity over 10 days compared with the control gels (P<0.001). Multicellular skin substitutes containing PVA-borate networks display a linear cellular organization, reduced cellularity and the formation of a keratinized epidermis that resembles normal skin. In conclusion, these data underscore the multifunctionality of a simple PVA-borate-collagen matrix as an injectable composite for tissue engineering or cell transplantation.