The cartilage part of the developed implants, consists of a reinforced composite hydrogel structure containing regenerative cells. Gel-MA based hydrogels were already proven to be highly performant both as bioinks for printing and for abundant neo-cartilage synthesis from encapsulated cells. The optimal bioprinting window for GelMA, unmodified or supplemented with the rheology-modifier gellan gum, was identified, while preserving abundant and homogenous cartilage deposition into the hydrogel matrix .
Additionally, the key role of the yield behavior of the hydrogel as determinant of printability and capability to mix cells was elucidated. Chondrocytes, MSCs, and the recently identified Articular Cartilage-derived Progenitor Cells (ACPCs) were embedded into the bioink, and chondrogenic differentiation confirmed, underscoring the potential of these materials to print zonal-like constructs.
To understand the observed mechanical performance and reinforcement mechanism of the manufactured micro-fibre reinforced hydrogels, two FE models were developed. We revealed that the reinforcement mechanism of the composite constructs is governed by the fibres being pulled in tension by the lateral expansion of the hydrogel, as well as by the fibre cross-section interconnections. The model has been used to predict the response of the 3D-JOINT constructs in other relevant mechanical situations that are difficult to mimic in laboratory.
A printable bone substitute was generated from a printable calcium phosphate cement based on osteoconductive materials that is able to set at room temperature and neutral pH; compatible with labile materials and biological components. Several porous scaffold designs have been produced, with increasing range of porosity. We have demonstrated the ability of the material to support attachment, proliferation and osteogenic differentiation of MSCs in vitro. Additionally, a first in vivo study was performed to assess the osteoconductive performance of these porous scaffolds.
In the effort the generate and print full osteochondral constructs (and eventually larger joint structures), an approach to enhance integration of the biomaterials intended for the cartilage region (microfiber reinforced, cell-laden GelMA bioinks), and the underlying subchondral bone substitutes was developed. We demonstrated the necessity of providing stable anchoring into the subchondral bone for tissue engineered cartilage constructs. As such, the MEW-fabricated microfibers used to reinforce the GelMA hydrogels have been used as anchoring system between the engineered bone-cartilage compartments in osteochondral constructs.
One of the technologies developed during this project is the converged printing of microfibres and extrusion based printing. Further understanding of the underlying physical principles of the MEW process allowed for accurate fibre deposition on anatomical relevant structures and materials. This study established the groundwork for translating MEW from planar to anatomically relevant geometries. This resurfacing approach allowed us to translate from the relatively small plug to larger and clinically more relevant (patient-specific) implants.
