Fibrous tissue (blood vessels, muscles, nerves, etc.) is a common tissue structure. Is it possible to construct basic microfibrillar units in vitro and then assemble them into fibrous tissue? In addition to discussing microsphere-based mini-tissues in recent years, the research group has also developed a strong interest in fiber-based mini-tissue fabrication. At present, the biggest challenge in the fabrication of mini-fibrous tissues is how to fabricate hydrogel microfilaments that have both biological activity and processability. The high biological activity ensures that the cell-laden microfibrils can establish cell connections and induce tissue function in subsequent cultures.
Limited by the manufacturing process, many microfibers based on alginate system are currently reported, but the hydrogel of alginate system hinders subsequent cell development, making it impossible to develop into microtissues. GelMA hydrogel is a hydrogel material with very good bioactivity and fast photocuring, but the curing time of GelMA is slightly longer (3-5s), and the viscosity of GelMA loaded with cells is low, which makes it difficult to directly manufacture. larger. If the fabrication of GelMA microfibers can be realized efficiently, it is expected to develop microfiber-based mini-tissues.
Inspired by the spinning rope effect, the research group developed a coaxial bioprinting technology, using the high-performance hydrogel GelMA industrialized by the research group to realize the manufacture of heterogeneous microfibers of GelMA material, which can print a variety of components, Various morphologies of fibrous mini-tissues. The research group wrapped endothelial cells in microfibrils, and endothelial cells migrated to the surface of the fibers in a very short time to form a microvascular-like structure.
Fibrous tissue (blood vessels, muscles, nerves, etc.) is also a common tissue structure, and the reconstruction of fibrous tissue in vitro requires materials with strong processability and excellent biocompatibility at the same time. The alginate system hydrogel used in the current study has good processability but weak biological properties, which limits the induction of tissue function after printing.
Methacrylated hydrogel gelatin methacrylate (GelMA) is a photosensitive biohydrogel with strong processability and biocompatibility. It is a popular material in the fields of tissue engineering, biomedicine, and biomanufacturing. , has great potential. A detailed introduction to this material can be found in my previous blog post.
Recently, the team of Professor He Yong from the School of Mechanical Engineering of Zhejiang University used the GelMA material jointly developed by the research group and the Suzhou Intelligent Manufacturing Research Institute to develop GelMA microfibers with controllable functional morphology, and at the same time realized the functional induction of fibrous tissue.
A related paper, Fiber-based Mini Tissue with Morphology-Controllable GelMA Microfibers, was recently published in WILLY's SMALL magazine. The first authors are doctoral student Shao Lei and postdoctoral fellow Gao Qing, and the corresponding author is Professor He Yong.
GelMA Microfiber Coaxial Bioprinting
In this paper, based on the fluid sling effect, the research team used a coaxial nozzle fluid control system to prepare continuous microfibers (as shown in the above figure), and the microfibers had alginate hydrogel as the shell and GelMA as the core. The core GelMA is the first to be photo-crosslinked into GelMA fibers. When the shell alginate enters the calcium chloride water bath, it rapidly reacts and gels to form the shell layer. The role of alginate is to quickly set the shape and fix the incompletely cured GelMA. After the GelMA is cured, the alginate hydrogel can be digested and removed. Using fluid control technology and precise manipulation, the adjustment of the size and morphology of GelMA microfibers was achieved, and the GelMA microfibers prepared by this method were long, thin, and flexible. Due to the diversity of tissue components in living organisms, it is necessary to prepare multi-material heterogeneous fibers. The research team improved the fabrication system and fabricated a variety of multi-material heterofiber structures (as shown in the figure below), such as Janus structure, multilayer GelMA structure, double-parallel and double-helical GelMA structure.
Multicomponent Heterogeneous GelMA Fiber
The research team printed straight and spiral vascular mini-tissues (as shown below) wrapped in human umbilical vein endothelial cells (HUVECs), and the cells could proliferate, stretch and migrate in GelMA. Interestingly, with the prolongation of culture time, endothelial cells migrated to the outer wall of GelMA fibers and established connections to form endothelial lumen like blood vessels, which was the result of more adequate nutrition of the outer wall of GelMA fibers leading to cell migration.
straight blood vessel
spiral vessel
angiogenesis
Household Electrical Appliances
gree , https://www.greegroups.com