Researchers Unveil Bioprinting Technique in Tissue Fabrication

Introduction to 3D Bioprinting Challenges and Opportunities

A novel bioprinting technique developed by researchers at Penn State promises to advance tissue fabrication by overcoming longstanding challenges in scalability and cell density. Published in Nature Communications, this innovative approach introduces the High-throughput Integrated Tissue Fabrication System for Bioprinting (HITS-Bio), which leverages clusters of cells known as spheroids to build complex tissues efficiently. The findings were summarized in an article published on Innovations-Report.

Bioprinting, a subset of 3D printing, constructs three-dimensional structures from living cells combined with biomaterials like hydrogels. These bioinks serve as the “cement” for the cells, which mature into tissue over time. However, conventional methods struggle to replicate the high cell density required for functional tissue or scale production for clinical applications. As Ibrahim T. Ozbolat, professor and chair in 3D Bioprinting and Regenerative Medicine at Penn State, explained, “It’s like constructing a brick wall where the cells are the bricks and the bioink is the cement or mortar.”

Overcoming Limitations with the HITS-Bio Technique

Spheroids present a promising solution for achieving cell density akin to natural human tissue. However, existing technologies for 3D bioprinting spheroids often fall short due to slow processing times, cell damage, and limited precision. In previously published research, the team’s aspiration-assisted bioprinting system could place spheroids with high precision but lacked scalability, requiring days to create even a small tissue sample.

HITS-Bio addresses these issues through its digitally controlled nozzle array, enabling simultaneous manipulation of multiple spheroids. With a four-by-four nozzle configuration, the system can pick up 16 spheroids in customized patterns and deposit them rapidly. As Ozbolat highlighted, “It’s 10-times faster than existing techniques and maintains more than 90% high cell viability.”

Demonstrating Scalability and Efficiency

The researchers tested the HITS-Bio platform by fabricating cartilage tissue, creating a one-cubic-centimeter structure with approximately 600 spheroids in under 40 minutes—a stark improvement over traditional methods. The system also demonstrated its utility in surgical settings. In a rat model, the researchers printed spheroids directly into a skull wound, using microRNA technology to prompt the cells to transform into bone tissue. This innovative approach enabled the wound to heal by 91% within three weeks and 96% within six weeks.

“Since we delivered the cells in high dosages with this technique, it actually sped up the bone repair,” Ozbolat noted.

Future Directions and Applications

The success of the HITS-Bio system represents a step toward scalable tissue and organ fabrication, with implications for regenerative medicine, transplantation, and pharmaceutical research. Expanding the nozzle array could enable the production of larger and more intricate tissues, such as liver or kidney structures. The researchers are also exploring the integration of blood vessels into fabricated tissues, a critical component for more complex organ production.

While these developments are still in progress, the lack of blood vessels was not a limitation in their current applications. Cartilage, for example, is naturally avascular, and in surgical settings, surrounding blood vessels can support bioprinted bone tissue.

Collaborative Efforts and Funding

The study’s multidisciplinary team included researchers from Penn State’s Huck Institutes of the Life Sciences, the Materials Research Institute, and the College of Medicine, among others. Collaborators also hailed from Johns Hopkins University. The work received funding from the National Institute of Biomedical Imaging and Bioengineering and the National Institute of Dental and Craniofacial Research.

Conclusion

By enabling faster, more precise, and scalable tissue fabrication, the HITS-Bio technique has the potential to significantly advance the field of bioprinting. As Ozbolat remarked, “This technique is a significant advancement in rapid bioprinting of spheroids,” setting the stage for future innovations in creating functional human tissues.

For more details, the original study can be accessed via Nature Communications (DOI: 10.1038/s41467-024-54504-7).