| 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 novel mode of ECM preparation in which unmodified and undamaged whole human dermal ECM was extracted from primary neonatal dermal fibroblasts (NDFBs) growing on hydrogel in vitro. The hydrogel-based NDFB culture was designed to simulate the native biomechanical environment (i.e. elastic modulus/stiffness), and found to have significant effects on cell phenotype and function. This whole human ECM (AlloECM) contained bioactive cell-secreted natural proteins that amplified ECM production and promoted tissue regeneration as well as structural reorganization. We fomulated an AlloECM preparation suitable for use as a bioink (AlloECM admixed in hydrogel) and verified its efficacy in vitro. Compared to an alginate bioink containing purified bovine collagen (2.5-6 mg/ml), the same type of bioink reinforced with AlloECM (2.5-6 mg/ml) showed a significantly increased ability to support NDFB proliferation and tissue-like structure formation in a 3D printed construct (Figure not shown). To further demonstrate the regenerative potential of our AlloECM, we cultured M2-type pro-repair macrophages on AlloECM-coated fibrin hydrogel. Gene expression analysis revealed that AlloECM enhanced the expression of macrophage genes that play a critical role in skin regeneration within 36 hrs of culture (Figure not shown). Large animal test (porcine) indeed confirmed the regenerative potential of AlloECM in vivo (Figure not shown). Taken together, our findings suggest AlloECM as a potent multi-purpose material that promotes wound healing in the setting of cosmetic plastic surgery as well as general cosmetics. |
