Writing 3D In Vitro Models of Human Tendon within a Biomimetic Fibrillar Support Platform.

Tendinopathies are poorly understood diseases for which treatment remains challenging. Relevant in vitro models to study human tendon physiology and pathophysiology are therefore highly needed. Here we propose the automated 3D writing of tendon microphysiological systems (MPSs) embedded in a biomimetic fibrillar support platform based on cellulose nanocrystals (CNCs) self-assembly. Tendon decellularized extracellular matrix (dECM) was used to formulate bioinks that closely recapitulate the biochemical signature of tendon niche. A monoculture system recreating the cellular patterns and phenotype of the tendon core was first developed and characterized. This system was then incorporated with a vascular compartment to study the crosstalk between the two cell populations. The combined biophysical and biochemical cues of the printed pattern and dECM hydrogel were revealed to be effective in inducing human-adipose-derived stem cells (hASCs) differentiation toward the tenogenic lineage. In the multicellular system, chemotactic effects promoted endothelial cells migration toward the direction of the tendon core compartment, while the established cellular crosstalk boosted hASCs tenogenesis, emulating the tendon development stages. Overall, the proposed concept is a promising strategy for the automated fabrication of humanized organotypic tendon-on-chip models that will be a valuable new tool for the study of tendon physiology and pathogenesis mechanisms and for testing new tendinopathy treatments.

Engineering next-generation bioinks with nanoparticles: moving from reinforcement fillers to multifunctional nanoelements.

The application of additive manufacturing in the biomedical field has become a hot topic in the last decade owing to its potential to provide personalized solutions for patients. Different bioinks have been designed trying to obtain a unique concoction that addresses all the needs for tissue engineering and drug delivery purposes, among others. Despite the remarkable progress made, the development of suitable bioinks which combine printability, cytocompatibility, and biofunctionality is still a challenge. In this sense, the well-established synthetic and functionalization routes to prepare nanoparticles with different functionalities make them excellent candidates to be combined with polymeric systems in order to generate suitable multi-functional bioinks. In this review, we briefly discuss the most recent advances in the design of functional nanocomposite hydrogels considering their already evaluated or potential use as bioinks. The scientific development over the last few years is reviewed, focusing the discussion on the wide range of functionalities that can be incorporated into 3D bioprinted constructs through the addition of multifunctional nanoparticles in order to increase their regenerative potential in the field of tissue engineering.