Programmable Engineered Human Tissues using Living Materials

Cells are often called the building blocks of life. Programming them to create living organisms is an active area of scientific research, with potential applications in areas like tissue regeneration or generating organs to address medical needs. While significant strides have been made in developing synthetic materials that mimic the behavior of natural biological systems, using multi-cellular organisms (e.g. mammalian cells) as building blocks remains largely uncharted due to their complexity. Current research is trying to use interactions between mammalian cells to help them come together and form structures. However, the current state of the art is limited to the formation of small clusters. Despite the tremendous achievements here, additional research is required to understand how cells control their behavior and make them suitable for building larger, more complex structures.

In a recent study published in Nature Materials, researchers from the University of Aveiro in Portugal developed complex 3D structures known as ‘Cellgels’ using mammalian cells. To create these tissue-like structures, they applied Nobel Prize-winning chemistry to modify the glycocalyx — a gel-like layer of proteins and lipids on the cell membrane responsible for mediating cell-environment interactions and housing key signaling functions. Similar to natural tissues, these 3D Cellgels can mature over time, acquiring mechanical properties akin to real tissue. Unlike synthetic materials, they can also self heal, reattaching and regenerating lost mass. To evaluate their efficacy, the researchers implanted the Cellgels into mice, where they significantly improved wound healing compared to hybrid materials without interfering with the scarring process.

This approach opens up the potential to create materials that can develop into human-like tissue over time, with similar structures and customizable features. Through advanced techniques like genetic engineering, Cellgels can be designed at the cellular level to perform specific functions or introduce new capabilities. Additionally, combining them with synthetic materials makes them even more adaptable, enabling the creation of complex materials with targeted strengths. This breakthrough could significantly advance tissue repair and medicine by providing self-healing materials that mimic the behavior of real living tissues.

This study was led by researchers at University of Aveiro, Portugal under the guidance of João F. Mano.

Managing Correspondent: Gurminder K. Paink

Press article: Cells as active crosslinkers in living materials (Nature Bioengineering)

Original Journal Article: Engineered nascent living human tissues with unit programmability (Nature Materials) 
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