ARI research pearls

ARI project is revolutionizing tissue engineering

The AO Research Institute Davos (ARI) and mimiX team with the 3D SIM patterning instrument: Mauro Alini, Geraldine Guex, Tiziano Serra, Nicola Di Marzio, Marc Thurner

A new technology developed by an AO Research Institute Davos (ARI) research scientist has been licensed to a Switzerland-based startup and is revolutionizing tissue engineering. The result is mimiX Biotherapeutics’ CymatiX, the world’s first acoustic bioprinter, making it possible to create biological architectures with sound.

Sound-Wave Induced Morphogenesis (3D SIM), the brainchild of ARI research scientist Tiziano Serra, PhD, uses sound waves to generate a network of cells in a matter of seconds, providing a self-assembled substrate for vascularization. This has potential to make tissue-engineered constructs based on autologous materials that are widely available in a laboratory environment. In 2020, the technology was licensed to newly created mimiX Biotherapeutics from Switzerland.

SIM is a gentle, fast, and easy method used to generate multi-cellular, spatially orchestrated tissue constructs using sound waves. It has excellent potential for use in operation rooms in the future due to its speed, and as no needles are involved in the printing process, there is no fluid stress on the cells printed and consequently no cell damage or death.

Serra’s project was supported by AO resources—including funding and know-how—through the Technology Transfer office at the AO Innovation Translation Center (AO ITC), which partners with inventors to achieve proof of concept (POC) and bring them to market.

Vascular tissue engineering—the generation of tissue that includes vessels—has the potential to significantly impact the treatment of a wide variety of medical conditions. It could provide in vitro-generated vascularized tissue and be useful for in vitro models for diagnostic and drug discovery indications. However, developing a large-scale, functional, vascularized construct is still a major challenge and an unsolved clinical problem.

3D SIM technology aims to make artificial tissues a true therapeutic option by providing affordable, life-transforming treatment for patients. This intraoperative method for generating vascularized constructs has potential to disrupt and trigger development across the entire field of regenerative, personalized, and precision medicine. He began working on the 3D SIM project when he joined ARI in October 2016 and went on to earn CHF 180,000 in support from BRIDGE, a joint program with the Swiss National Science Foundation and Innosuisse – Swiss Innovation Agency.

3D SIM technology resolves an array of challenges—difficulties in rapid and mild recreation of the natural complex morphology of tissues and organs during surgery—presented by other promising tissue engineering technologies, such as 3D printing. In less than a minute, the system generates large-size, cell-patterned constructs (from a few millimeters to 150 square centimeters) to guide the formation of vascularized tissues—a real breakthrough. The technology can pattern cells and build tissue layer upon layer, meaning that it can be used to generate specially orchestrated tissue models for use in screening drugs, creating patient-specific tissue or disease models.

That means scientists, pharma companies, and clinicians can simply use a pipette to put cells into the mimiX system’s labware and then apply sound for a few seconds, leading to the formation of a patterning of cells that can then be extracted and used to treat the patient. In principle, this technology could be used to produce skin, bone, cartilage, even organs. The system, Serra said, could revolutionize the way 3D organs and tissues are generated and the way of working in the operating room by offering a cost-efficient, point-of-care tissue engineering approach to regenerative, patient-tailored precision medicine.

Human umbilical vein endothelial cells(HUVEC) patterned within fibrin gel in a circle shape in order to assemble aproto-vessel structure after 72 hours