Bio-ink has gradually transited from ionic-crosslinking to photocrosslinking due to photocurable bio-hydrogel having good formability and biocompatibility. It is very important to understand and quantify the crosslinking process of photocurable hydrogels, otherwise, bioprinting cannot be standardized and scalable. However, there are few studies on hydrogel formation process and its photocrosslinking behavior which cannot be accurately predicted. Herein, the photoinitiated radical polymerized bio-hydrogels are taken as an example to establish the formation theory. Three typical crosslinking reactions are first distinguished. It is further proposed that not all double-bonds consumed during crosslinking contributeequally to polymerization. Then the concept of effective double-bond conversion (EDBC) is elicited. Deriving from EDBC, several important formation indices are defined. According to theory, it is predicted that slow crosslinking can improve the crosslinking degree. Furthermore, based on the slow crosslinking effect, a new strategy of projectionbased 3D printing (PBP) is proposed, which significantly improved printing quality and efficiency. Overall, this work will fill the gap in hydrogel's formation theory, making it possible to accurately quantify the formation process.
The functional blood–brain barrier (BBB) model can provide a reliable tool for better understanding BBB transport mechanisms and in vitro preclinical experimentation. However, recapitulating microenvironmental complexities and physiological functions in an accessible approach remains a major challenge. Here, a new BBB model with a high‐cell spatial density and tightly connected biomimetic minitissue is presented. The minitissue, pivotal functional structure of the BBB model, is fabricated by a novel and easy‐to‐use liquid substrate culture (LSC) method, which allows cells to self‐assemble and self‐heal into macrosized, tightly connected membranous minitissue. The minitissue with uniform thickness can be easily harvested in their entirety with extracellular matrix. Attributed to the tightly connected minitissue formed by LSC, the fabricated BBB biomimetic model has 1 to 2 orders of magnitude higher transendothelial electric resistance than the commonly reported BBB model. It also better prevents the transmission of large molecular substances, recapitulating the functional features of BBB. Furthermore, the BBB biomimetic model provides feedback regarding BBB‐destructive drugs, exhibits selective transmission, and shows efflux pump activity. Overall, this model can serve as an accessible tool for life science or clinical medical researchers to enhance the understanding of human BBB and expedite the development of new brain‐permeable drugs.
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