Soft, flexible hydrogels have enabled significant advancements in engineering biological tissue by mimicking the natural scaffolding that provides structure and support to cells. Existing engineered hydrogels, however, fall short in a significant way. Unlike in nature, they do not have the dynamic ability to change their structure or support depending on what the biological tissue needs. The answer may rest in shining a light on the problem — literally, according to a team led by researchers at YOKOHAMA National University.
The researchers found that precisely applying light to a gelatin-based hydrogel they developed allows them to accurately control the shape of the gel, which allowed them to direct the growth direction and shape of nearby cells. The team published their work, which they said could have implications for tissue growth in health and in disease, on Sept. 2 in ACS Biomaterials Science & Engineering .
"The ability to control the morphology of pre-encapsulated cells on demand is useful for mimicking tissues, such as blood vessels and nerves, which change their growth direction according to their environment," said corresponding author Kazuhiro Iijima, associate professor, Faculty of Engineering, YOKOHAMA National University. "This approach may also be applied to create anisotropic metastasis models for cancer and tumor cells, which help elucidate how the composition of the cellular environment's natural scaffolding — called the extracellular matrix — and vascular systems guide how cancer cells develop and spread in the body."
In this study, the researchers incorporated a photoreactive molecule into a gelatin network, resulting in what they called a photodegradable acrylate-modified gelatin (Gelatin-PDA). When initially developed, the Gelatin-PDA hydrogel adds crosslinks to the gelatin network, strengthening it. But when the Gelatin-PDA is irradiated with two photons — two individual particles of light — the crosslinks degrade, loosening the network. Exposing the Gelatin-PDA with ultraviolet light further degrades the hydrogel, enabling the researchers to change its shape.
In tests of the Gelatin-PDA hydrogel, the team found that precisely irradiating the hydrogel's surface and interior allowed them to control the directional growth of stem cells derived from human bone marrow. They also found they could elongate the naturally spherical shape of mouse cells, demonstrating three-dimensional control.
"In this study, we achieved the dynamic and precise control of the cell elongation direction within a three-dimensional cell scaffold by combining a Gelatin-PDA hydrogel with advanced two-photon excitation technology," Iijima said. "This contributes significantly to complex and dynamic biological tissue mimicry and paves the way for advances in regenerative medicine."
Co-authors include Chisato Handa, Shoma Miura, Noemi Bata Hikuma, Reira Ishige, Taichi Urasakit, Shogo Oishi and Yuki Hatta, Graduate School of Engineering, YOKOHAMA National University; Shoji Maruo, Faculty of Engineering, YOKOHAMA National University; Hiroki Miyajima, Department of Frontier Fiber Technology and Sciences, University of Fukui; and Masaru Mukai, Department of Applied Chemistry, Tokyo University of Science.
The Japan Society for the Promotion of Science and the Japan Science and Technology Agency funded this research.
