Integrating bioprinting, cell therapies and drug delivery towards in vivo regeneration of cartilage, bone and osteochondral tissue

Abstract

The biological and biomechanical functions of cartilage, bone and osteochondral tissue are naturally orchestrated by a complex crosstalk between zonally dependent cells and extracellular matrix components. In fact, this crosstalk involves biomechanical signals and the release of biochemical cues that direct cell fate and regulate tissue morphogenesis and remodelling in vivo. Three-dimensional bioprinting introduced a paradigm shift in tissue engineering and regenerative medicine, since it allows to mimic native tissue anisotropy introducing compositional and architectural gradients. Moreover, the growing synergy between bioprinting and drug delivery may enable to replicate cell/extracellular matrix reciprocity and dynamics by the careful control of the spatial and temporal patterning of bioactive cues. Although significant advances have been made in this direction, unmet challenges and open research questions persist. These include, among others, the optimization of scaffold zonality and architectural features; the preservation of the bioactivity of loaded active molecules, as well as their spatio-temporal release; the in vitro scaffold maturation prior to implantation; the pros and cons of each animal model and the graft-defect mismatch; and the in vivo non-invasive monitoring of new tissue formation. This work critically reviews these aspects and reveals the state of the art of using three-dimensional bioprinting, and its synergy with drug delivery technologies, to pattern the distribution of cells and/or active molecules in cartilage, bone and osteochondral engineered tissues. Most notably, this work focuses on approaches, technologies and biomaterials that are currently under in vivo investigations, as these give important insights on scaffold performance at the implantation site and its interaction/integration with surrounding tissues. Graphical Abstract

Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions

“… 745 The integration of drug delivery systems within 3D bioprinted scaffolds represents a promising trend. 746 Hydrogel bioink can construct complex biological tissue structures, enabling relatively accurate drug delivery by modulating the release rate. This precision allows for the targeted release of factors at specific sites or concentrations within the 3D structure, mimicking complex cell interactions and signaling processes within the body.…”

“…This precision allows for the targeted release of factors at specific sites or concentrations within the 3D structure, mimicking complex cell interactions and signaling processes within the body. 746 Additionally, the synergistic effect of combining cell therapy and drug delivery in 3D printed hydrogels has been demonstrated to promote cartilage formation in vivo. 747 – 749 …”