Researchers from the Vall d’Hebron Research Institute (VHIR), the biotechnology company REGEMAT3D, and CEU Cardenal Herrera University (CEU UCH) have launched the research project ‘4D CARE, 4D Bioprinting of Living Implants for Cartilage Regeneration’, funded under the 2024 Public-Private Collaboration call of the State Research Agency (AEI) of the Ministry of Science, Innovation and Universities, due to its strategic nature and its potential scientific, clinical, and industrial impact.

According to Dr José Manuel Baena, researcher at CEU UCH and REGEMAT3D, “biofabrication technologies are redefining the healthcare sector by enabling the development of biomedical solutions tailored to the specific needs of each patient. In this context, the evolution from conventional 3D printing to 4D bioprinting, based on the use of bioinks composed of living cells, biomaterials, and bioactive molecules, has opened new opportunities for the generation of functional tissues. However, significant challenges still exist regarding scalability, structural complexity, and the long-term functionality of the generated tissues.”

The new project addresses these limitations through an innovative approach based on 4D bioprinting, an emerging technology that gives biofabricated constructs the ability to evolve over time in response to biological or mechanical stimuli applied in a bioreactor. As highlighted by Dr Nayana Joshi, principal investigator of the musculoskeletal tissue engineering group at VHIR, “this advance is particularly significant in the field of cartilage regeneration, a tissue with limited self-repair capacity whose degeneration is closely associated with conditions such as osteoarthritis, which is becoming increasingly prevalent worldwide.”

4D biofabrication for clinical translation

To achieve this objective, the 4D CARE project is structured around three main lines, as explained by Dr Iván López, researcher at REGEMAT3D: “These lines are the development of advanced bioinks and hybrid scaffolds, with optimized mechanical and biological properties to promote tissue regeneration; the validation of a 4D biofabrication station, which will integrate bioprinting technologies and advanced bioreactors under conditions compatible with GMP standards; and functional evaluation in preclinical models, led by VHIR, with the aim of demonstrating the regenerative potential of the implants and facilitating their future clinical translation.”

The consortium developing the 4D CARE research project is made up of three entities that currently lead the development of this innovative technology and are complementary in the fields of biofabrication and regenerative medicine. The biotechnology company REGEMAT3D coordinates the project due to its experience in the development of bioprinting systems. CEU Cardenal Herrera University (CEU UCH) participates in biomaterial characterization and technological validation. VHIR contributes its clinical expertise in preclinical validation.

According to Dr José Manuel Baena, “we expect the project’s results to lead to solutions with a high transfer potential, especially in the fields of tissue engineering and regenerative medicine. Through this initiative, the project partners aim to contribute to the development of innovative therapies capable of addressing an unmet clinical need, positioning 4D bioprinting as one of the key technologies in the future of personalized medicine.”

This June, the Biofabrication Research Group at CEU UCH and REGEMAT3D published an article on their advances in the development of mechanobiology strategies for the maturation of biofabricated cartilage constructs, applicable to the 4D CARE project, in the journal Frontiers in Bioengineering and Biotechnology.