Scaffold-Free 3D Cell Printing Using the Kenzan Method for Tissue Regeneration and Clinical Translation

Scaffold-free 3D cell printing provides a biomanufacturing approach to tissue regeneration using living cells and their self-produced extracellular matrix. The Kenzan Method uses multicellular spheroids as building blocks, robotically positioning them on a temporary microneedle array according to a digital 3D design. The spheroids fuse into continuous tissues, and removal of the needles yields constructs without permanent synthetic scaffolds. This presentation connects the fabrication process with vascular and musculoskeletal applications and their progress toward clinical translation.

For vascular applications, human dermal fibroblast spheroids are assembled into tubular grafts. Preclinical studies have demonstrated mechanical strength, host remodeling, endothelialization, and repair of puncture sites. Clinical research has begun using grafts fabricated from autologous skin-derived cells as vascular access for hemodialysis. These studies are evaluating the clinical potential of living conduits as alternatives to synthetic prostheses.

For musculoskeletal regeneration, mesenchymal stem cell constructs have shown promising results in long bone and osteochondral defect repair. Within osteochondral defects, deeper regions form bone while superficial regions form hyaline cartilage, supporting reconstruction of the osteochondral interface. Human induced pluripotent stem cell-derived chondrocytes provide abundant extracellular matrix and enable fabrication of centimeter-scale cartilage constructs with stiffness and elasticity comparable to native cartilage. Anatomically shaped, cell-based joint implants are being investigated in animal models.

Additional applications include peripheral nerve regeneration and ongoing cardiac and hepatic tissue research. Together, these projects illustrate how digital tissue design, robotic spheroid assembly, and cellular self-organization can be integrated into a biomanufacturing platform. The lecture will discuss the transition from fabrication technology to preclinical validation and early clinical application, with the long-term goal of producing living tissues that integrate and remodel after transplantation.

Koichi Nakayama, M.D., Ph.D., is an orthopedic surgeon and Professor and Director of the Regenerative Medicine Research Center, Faculty of Medicine, Saga University, Japan. He graduated from Kyushu University School of Medicine in 1997 and received his Ph.D. in Medicine from Kyushu University in 2005. He became a professor in engineering at Saga University in 2009, joined its Faculty of Medicine as a professor in 2015, and became Center Director in 2019. His research focuses on scaffold-free 3D cell printing for tissue and organ regeneration. He organized ISBF2024, an international conference of the International Society for Biofabrication, serving as Conference Chair.