Bioactive additives from the dorsal dermis of mice for enhanced vascularization in 3D bioprinting†

Effective angiogenesis is essential for creating complex vascular networks in tissue engineering; however, there is a scarcity of safe and potent pro-angiogenic factors. Although a decellularized extracellular matrix (dECM) offers excellent biocompatibility and is widely used in tissue engineering as a pro-angiogenic additive, its conventional extraction technique resulting in significant loss of bioactivity limits clinical potential. The dorsal dermal tissue has rich blood perfusion and its dECM is rich in angiogenic factors. In this study, the dECM components from the dorsal dermis of mice (DD) were produced to enhance in vitro and in vivo pro-angiogenic abilities using a novel physical method. Morphological studies showed no significant difference between DD-wild-type (DD-wt) and DD-wild-type-newborn (DD-wtn), and there was also no difference in DNA or RNA concentration. In addition, DD-wtn outperformed DD-wt in maintaining the stemness of MSCs, promoting inflammatory response and facilitating endothelial cell differentiation. It is of greater significance to note that the dermal combined fibrous capsule thickness is greater in the DD-wt treated group than in the DD-wtn group. Furthermore, the number of blood vessels in the subcutaneously implanted scaffold with DD-wtn increased by 233%. Consequently, our current finding provides a promising strategy to produce a novel pro-angiogenic bioink additive for enhancing vascularization in 3D bioprinting.