Compared with traditional gel-based bio-inks, decellularized matrices (dECMs) can better mimic the cell microenvironment and can promote cell survival, adhesion, proliferation, proliferation, migration, differentiation, and tissue formation and repair.But because its physical properties are not adjustable, resulting in poor printability, so in the biological3D printingThe application of complex functional bionic tissue is restricted.
Recently, the Shaochen Chen team of the University of California, San Diego proposed a non-scanning continuous biological ink using photo-crosslinked dECM bio-ink and digital light processing (DLP).3D printingMachine to create a new method of micro-scale biomimetic tissue. This method can generate very complex microstructures in just a few seconds. The research used DLP printing to manufacture hiPSCs-derived cells and tissue-matched dECM bio-inks, and constructed bionic human heart and liver striated muscles and striated muscles. The lobular liver structure, and then through the biophysical clues to guide the spontaneous cell reorganization into the pre-designed structure, so that the cells can survive and mature well in the printed structure. The related paper “Scanningless and continuous 3D bioprinting of human tissues with decellularized extracellular matrix” has been published in the journal “Biomaterials”.
First, prepare two photocrosslinkable dECM bio-inks: For the heart tissue structure, the bio-ink is composed of 5% (w/v) GelMA + 5% (w/v) HdECM + 0.25% (w/w/ v) The final solution of LAP; the final concentration of bio-ink for liver tissue is 5% (w/v) GelMA + 5% (w/v) LdECM + 0.25% (w/v) LAP.Then through digital light processing (DLP) biological3D printingMachine (Figure 1) to manufacture biomimetic microstructures based on tissue-specific dECM.Light-cured biological3D printingThe process enables complex micro-scale geometric figures with both good mechanical properties and high resolution to be generated in just a few seconds.
In this study, two different bionic models were designed to simulate the key histological features of the natural heart and liver (Figure 2). The pattern that simulates the myocardial tissue structure is parallel equidistant lines, and structural stimulation is used to promote the formation of myocardial tissue; the pattern that simulates the liver tissue structure is a small hexagonal structure. The printed acellular tissue structure has a high degree of pattern accuracy and exhibits long-term fidelity within 28 days. The exposure time for printing of heart and liver dECM tissue constructs is selected based on the shortest time required to obtain high resolution and structural stability. The research results show that in the printed tissue structure, the soft mechanical properties are very important to ensure the diffusion and remodeling of the wrapped cells. The micro acellular dECM structure printed for each tissue type in the study is very similar to the established digital model, and its matching size can reach the order of micrometers.
The live/dead staining results showed that the cell survival rate of the two constructs was very high (Figure 3). Further experimental results showed that the cardiomyocytes resumed beating at 72h without external stimulation. Live/dead staining results in liver tissue construction also confirmed that within 7 days, both LdECM and type I collagen maintained high cell viability and had similar levels of metabolic activity. Current research shows that micro-scale geometric structures play an important role in cell function, migration, differentiation, and organization. The internal reason is that it is regulated by contact guidance through the interaction between the cell and the biophysical signals of the surrounding environment. In this study, two separate models were designed for the bioprinting of cellularized bionic heart and liver tissue construction. The tissue-specific dECM bio-ink provides a good environment for supporting hiPSC-derived culture that matches with the tissue, so that the cell survival rate in HdECM and LdECM tissues is higher. The hiPSC-derived cells are cultured in the stimulating environment provided by their natural dECM to promote cell maturation, and the printed pattern shape can have a natural feeling and response to the surrounding biophysical environment according to the cells, thus the development of their tissues Realize induction. These microstructures produced in this research reflect the detailed geometric shapes of various tissues and provide physical guidance clues for promoting tissue-specific morphology.
In general, the research is based on the combination of dECM bio-ink and DLP-based3D bioprintingThe combination of technologies provides a new method for quickly constructing biomimetic human tissues with tissue-specific biochemical components, micro-scale structure and adjustable modulus. The method described in the study can be used to develop specific dECM bio-inks suitable for other tissues, and to rationally design biomimetic tissues with tissue-like cell density and high-resolution topological structure to guide cell organization and well control mechanical properties. These dECM-based liver and heart tissue constructs can open the door for future research on the long-term stability and functional maturity of hiPSC-derived cells in complex biomimetic tissue systems. In subsequent applications, this method can be used to merge multiple cell types to create a heterogeneous tissue structure based on dECM, which can be used as a new way to study biological disease mechanisms, develop personalized drugs, and screen applications for diagnostic drugs.
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