초록 |
3D bioprinting is one of the fastest growing state-of-the-art regimes in tissue engineering and regenerative medicine. Bioink, a key material enabling 3D bioprining, mainly consists of either purified materials (e.g. Chitosan, Alginate, and Collagen) or synthetic materials (e.g. PLGA, GelMA, and Pluronic). Although these bioink materials provide a range of viscosity required for printing, they do not contain information/stimulation components to guide cells to form tissue-like structure. We developed a bioink that consists of whole human extraceullar matrix (ECM) derived from human primary cell sheets (i.e. neonatal dermal fibroblasts (NDFBs) grown on hydrogel that matched the native biomechanical environment (i.e. elastic modulus/stiffness). This decellullarized human whole ECM (dh-ECM) contains cell-secreted natural proteins and growth factors that could stimulate ECM production, tissue regeneration and structural organization. Compared to the alginate bioink without dh-ECM, the bioink containing dh-ECM (2.5, 6, and 12.5 mg/ml) showed significantly increased NDFB proliferation and tissue-like structure formation in a 3D printed construct, whereas 12.5 mg/ml dh-ECM did not show highest proliferation and morphological formation compared with 2.5 and 6 mg/ml dh-ECM contained bioninks. To further enhance the regenerative potential of our dh-ECM, we co-cultured NDFBs with activated macrophages with ECM-modulating functions. Gene expression analysis showed the ability of these macrophages to augment de novo collagen production from NDFBs. Taken together, our findings suggest dh-ECM obtained from regenerative capacity-enhanced dermal fibroblasts as a potent multi-purpose material that can be used in wound healing and cosmetic plastic surgery as well as general cosmetics. |