Abstract

Integrating Multiple Biofabrication Technologies To Create Complex and Functional Musculoskeletal Tissue Grafts

Riccardo Levato, Assistant Professor of Biofabrication and Regenerative Medicine, University Medical Center Utrecht and Regenerative Medicine Center Utrecht

Major challenges in musculoskeletal tissue engineering revolve around recapitulating the architecture, and therefore the function, of native tissues. Present strategies to treat chondral and osteochondral defects, including tissue engineering and cell implantation, prevalently result in repair tissue with poor mechanical properties, which is prone to degeneration, and can only delay the insurgence of severe pathologies like osteoarthritis.

Biofabrication is opening new avenues for the restoration of impaired joints tissues. Multi-material bioprinting enables to fabricate composite structures combining cell-laden, soft hydrogels with mechanically strong polymers for structural support. By the accurate 3D patterning of stem and tissue-specific progenitor cells, salient features of the native zonal and depth dependent organization of articular cartilage can be replicated. Alongside hydrogel extrusion and bioprinting, different additive manufacturing technologies, such as melt electrowriting of polymeric microfibers, ceramic plotting and digital light processing lithographic printing of hydrogels, can be combined to create composite, cell-laden constructs that enable integration between engineered cartilage hydrogels and bone scaffolds. These bioartificial osteochondral grafts exhibit improved interfacial mechanical strength, favouring their integration in vivo.

Herein, the latest development in the field of bioink printing to create zonal-biomimetic cartilage constructs will be discussed, together with the integration of multiple (bio)printing strategies (i.e. co-fabrication of hydrogels, reinforcing polymers and bioceramics), and the impact of these technologies towards the generation of fully biofabricated, high-performance engineered osteochondral grafts, with potential application for regenerative medicine. Finally, technological advances and challenges towards the biofabrication of large, clinically-relevant multi-tissue constructs will be discussed.