Biology

Researchers use lasers to grow biological tissue in the lab to produce microfilaments

Filament optical 3D bioprinters can be used to create aligned tissue structures. Credit: Zurich University of the Arts / Samuel Thalmann

Pioneer Fellow Hao Liu uses lasers to generate microfilament structures to grow living tissue in the lab for research and medical purposes, from muscle tissue to cartilage. He is currently working on getting this technology ready for the market.

It was in Japan that Hao Liu first encountered the production of living tissue in cell culture dishes. “While studying for my master’s degree at Osaka University, I worked on a project to cultivate Wagyu beef using a 3D printer,” says Liu.

Wagyu beef is considered some of the most tender, juicy and most expensive meat in the world. So researchers set out to recreate it in the lab. “At that time, I learned that by growing an organization you can develop relevance and make a difference.”

Mr. Liu began his studies in China. He moved to Osaka to pursue his master’s degree and has been working as a PhD student at ETH Zurich since 2020. I just finished my Ph.D. He has already won an ETH Pioneer Fellowship, which he will use to develop a new device to fabricate microfilament-structured tissues and prepare them for market.

Tissue is made up of microstructures

These microstructures are found throughout our bodies. The cells in our muscles, tendons, connective tissue, and nervous system are not randomly arranged, but follow a definite pattern. They give the organization both stability and flexibility and help it perform a variety of functions.

For example, the cells and fibers in muscle tissue are highly aligned to allow muscles to contract. Tendons, which connect muscle and bone, require cells to be organized so that the tendon can withstand enormous tension. Nerve tissue must also be aligned so that signals can be transmitted between cells.

When researchers create such tissues in the laboratory, they need to reproduce such arrangements. Often, they accomplish this by first fabricating artificial but biocompatible 3D scaffolds with aligned microstructures. The researchers then grow cells on and within this scaffold, forming a fully structured tissue.

In the future, this could be used as an alternative material in surgery, for example in the regeneration of peripheral nerves after severe injuries. Additionally, such tissue constructs can be used as in vitro tissue models for disease research and drug testing, reducing animal testing. Or it could be used to produce cultured meat in a laboratory, as Liu has done in Japan.

A lucky decision to store the workpiece

At ETH, Liu’s hard work and a bit of luck led to the discovery of a new way to fabricate tissue scaffolds with highly aligned, ultra-thin filaments. He used a chemically modified gelatin that was sensitive to light, based on a well-known process.

Gelatin is initially a liquid. “When irradiated with a laser, the hydrogel solidifies. In areas that the laser cannot reach, the gelatin remains liquid,” Liu explains. Targeted application of laser can generate customized three-dimensional hydrogel structures.

His delicate filament scaffold allows cells to grow perfectly

Hydrogel scaffolds and cells that generate connective tissue, neural tissue, and muscle tissue (left to right, microscopic images). Credit: ETH Zurich

Liu continued testing this printing process. He almost threw out some of the hydrogel artifacts, but instead set them aside. When I took it out again, I noticed first with the naked eye and then with a microscope that the structure of the hydrogel was not uniform, but instead consisted of very thin filaments.

“Professor Marcy Zenobi-Wong, who supervised my doctoral thesis, and I were very happy,” Liu recalls. He created microfilaments within the hydrogel with diameters similar to the fibrous components found in many body tissues. He then grew cells within this hydrogel scaffold to generate aligned tissue constructs. “If I had given up on work then, I wouldn’t be where I am today.”

Liu began studying the physics literature and realized that a well-known optical phenomenon creates microfilaments within the hydrogel scaffold. The light intensity of the laser beam is not the same throughout. Analyzing a cross-section of a laser beam with microscopic resolution reveals that the light intensity resembles a spot pattern. The intensity is very high in some places and very low in others.

When a photosensitive material is hardened with a laser beam, it does not harden uniformly, but instead shows a parallel thread-like gel structure. Channel-like spaces exist between these gel filaments. Both filament and channel diameters are approximately 2 to 20 micrometers. When cells are encapsulated in this hydrogel scaffold, they can grow within the channels. The result is an aligned tissue structure that closely resembles the natural structure of many body tissues.

“The optical phenomenon that creates filament microstructures within gels has been known to physicists and materials scientists for a long time,” Liu said. “But it hadn’t been used in biology yet. We were the first.”

Liu’s team, in collaboration with industrial design students at the Zurich University of the Arts, completed the design of a prototype printer to produce filamentary hydrogel scaffolds for aligned tissues. With the help of a Pioneer Fellowship, Liu now hopes to bring a compact bioprinter to market.

Drug discovery and nerve regeneration

“As a first step, we want to make this technology and printer available to other scientists so they too can create aligned tissues like this and use them in their research,” Liu said. say. “Several labs have already expressed interest.”

At the same time, we would like to develop various tissue models such as muscle tissue and tendons. “Our goal is to create human tissue models for high-throughput drug screening and other applications.” As a result, he is not only selling the devices, but also developing and developing tissues for research and medical use. We believe that there is also potential for future business in sales.

Using this technology, Liu’s lab has already successfully constructed muscle, tendon, nerve, and cartilage tissue. This technology has been patented by ETH Zurich. “Our technology is suitable for a wide range of applications,” says Liu.

“It’s even conceivable that in the future this could be used to create nerve conduits that could be implanted into patients suffering from nerve damage.” Or, as he learned in Japan, lab-grown It can also produce meat.

The scientist, who travels frequently, wants to stay in Switzerland for the next few years to watch the development of technology. And after that? Is he looking to move elsewhere? That’s certainly a possibility. Maybe he’ll go to America “In each country, I learned about different research focuses and different research cultures. Going to a new environment is very stimulating. It helps you question what you’ve been doing. ‘And to grow as a person,’ he explains.

Japan is known for its stem cell research, Liu said. There he saw how governments commission research projects and how research groups deliver those projects to exacting specifications. In Switzerland, he experienced just the opposite. It was the great academic freedom that was given to me by my supervisor Zenobi Wong during my doctoral thesis. This allowed me to easily adjust my work focus after discovery.

He also appreciates the European scientific culture and ETH, especially its emphasis on engineering approaches. From his point of view, these are the perfect conditions to work with teams and partners to develop technology and bring it to market, as he is currently doing.

Citation: Researchers use lasers to grow biological tissue in lab to generate microfilaments (October 28, 2024) https://phys.org/news/2024-10-biological-tissue-lab Retrieved October 28, 2024 from -lasers-microfilaments.html

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