Construction of enzyme digested holes on hydrogel surface inspired by cell migration processes

The construction of in vitro capillary network models for drug testing and toxicity evaluation has become a major challenge in the field of tissue engineering. Previously, we discovered a novel phenomenon of hole formation by endothelial cell migration on the surface of fibrin gels. Interestingly, the hole char-acteristics, such as depth and number, were strongly influenced by the gel stiffness, but the details of hole formation are not to be clarified.In this study, we tried to understand the effect of hydrogel stiffness on the hole formation by dropping collagenase solution onto the surface of the hydrogels because the endothelial cell migration was made possible by the metalloproteinases' digestion. We found that smaller hole structures were formed on stiffer fibrin gels, but larger ones were formed on softer fibrin gels after the hydrogel digestion of the collagenase. This is consistent with our previous results in experiments on hole structures formed by endothelial cells. Furthermore, deep and small hole structures were successfully obtained by optimizing the volume of collagenase solution and incubation time. This unique approach inspired by endothelial cell hole formation may provide new methods of fabricating hydrogels with opening hole structures.& COPY; 2023 Elsevier Inc. All rights reserved.

Automated summary

The construction of in vitro capillary network models for drug testing and toxicity evaluation is a major challenge in tissue engineering. This study explored the effect of hydrogel stiffness on hole formation and found that smaller hole structures were formed on stiffer fibrin gels, while larger ones were formed on softer fibrin gels. By optimizing the volume of collagenase solution and incubation time, deep and small hole structures were successfully obtained.