Three-dimensional bioprinting combined with natural hydrogels is a promising technology for the treatment of several pathologies and different tissue regeneration. One of the most studied tissues is cartilage, a complex and avascular tissue that displays a limited self-repair capacity after injuries. Herein, the development of alginate-based hydrogels and scaffolds containing different microstructure is presented and the printability of alginate by 3D bioprinting is studied. Rheological characterization was performed for the determination of viscosity and viscoelastic properties of hydrogels and mechanical characterization was carried out for the determination of compressive modulus of alginate hydrogels. All these characteristics were correlated with alginate behaviour during 3D bioprinting process. For the printability evaluation filament diameter, perimeter of the pores, area of the pores and shrinkage of alginate scaffolds were measured. The results demonstrate that alginate microstructure has a great influence on its printability and on hydrogels’ physicochemical properties. Molecular weight of alginate determines its viscosity while M/G ratio determines cross-linking conditions and mechanical properties that vary with cross-linking density. These results suggest the importance of an exhaustive control of the viscoelastic and mechanical properties of alginate hydrogels to obtain structures with high resolution and precision.

One of the emergent regenerative treatments for the restoration of the articular cartilage is tissue engineering (TE), in which hydrogels can functionally imitate the extracellular matrix (ECM) of the native tissue and create an optimal microenvironment for the restoration of the defective tissue. Hyaluronic acid (HA) is known for its potential in the field of TE as a regenerative material for many tissues. It is one of the major components of the articular cartilage ECM contributing to cell proliferation and migration. HA is the only non-sulphated glycosaminoglycan (GAG). However, herein, we use a HA presenting a high amount of sulphated glycosaminoglycans (sGAGs), altering the intrinsic properties of the material particularly in terms of biological response. Alginate (Alg) is another polysaccharide widely used in TE that allows stiff and stable hydrogels to be obtained when crosslinked with CaCl₂. Taking the benefit of the favourable characteristics of each biomaterial, semi-interpenetrating (semi-IPN) hydrogels had been developed by the combination of both materials, in which alginate is gelled, and HA remains uncrosslinked within the hydrogel. Varying the concentration of alginate and HA, the final rheological, viscoelastic, and mechanical properties of the hydrogel can be tailored, always seeking a trade-off between biological and physico-mechanical properties. All developed semi-IPN hydrogels have great potential for biomedical applications.

This work identifies and describes different material-scaffold geometry combinations for cartilage tissue engineering (CTE). Previously reported potentially interesting scaffold geometries were tuned and printed using bioresorbable polycaprolactone and poly(lactide-b-ethylene) block copolymer. Medical grades of both polymers were 3D printed with fused filament fabrication technology within an ISO 7 classified cleanroom. Resulting scaffolds were then optically, mechanically and biologically tested. Results indicated that a few material-scaffold geometry combinations present potential for excellent cell viability as well as for an enhance of the chondrogenic properties of the cells, hence suggesting their suitability for CTE applications.