In the HumanINK project, human methacryloyl platelet lysates (PLMA) and decellularized extracellular matrix (dECM) derived from placental tissues have been combined to create a human bioink with complementary biochemical properties. As newly human biomaterials purposed as great alternatives for the biomaterials of animal origin, the lipidomic profile of human adipose-derived stem cells (hASCs) cultured on PLMA hydrogels was analyzed, revealing a closer correlation to freshly isolated cells than the Matrigel-cultured ones. Pursuing the biological validation of the developed materials for disease modelling, PLMA was explored for the development of complex co-culture tumor models, demonstrating excellent suitability to support native cell functionality. Moreover, a novel placenta-derived biomaterial, the methacryloyl chorionic membrane (CMMA), was produced and tested for its biocompatibility and angio-vasculogenic competence.
Taking into account the exceptional biocompatibility of these protein-rich materials, their potential as bioink was addressed in the HumanINK project through various innovative approaches. To improve the viscoelasticity and shear thinning behavior of platelet lysates (PL)-based solutions, the available amine groups on PL proteins were exploited for coupling with carboxyl groups in PLMA, by leveraging carbodiimide chemistry. The creation of a pre-gel resulted in inks with controlled viscosities and elasticities, which enabled the fabrication of 3D printed multilayered constructs with high shape-fidelity. These PL-based ink scaffolds showcased mechanical robustness and the ability to support hACSs culture.
Building on the recent advancements on granular materials, supramolecular granular materials were prepared from the fragmentation of bulk hydrogels made of human decellularized amniotic membrane (dAM), combined with the proto-responsive acryloyl b-cyclodextrin. Due to the non-covalent interactions between the cyclodextrin and the proteins, the extrudable granular materials exhibited self-healing and self-curing abilities, forming cohesive and stable structures. Using a similar strategy, PLMA microparticles and methacryloyl hAM (AMMA) were combined to produce a jammed microgel ink. In this case, AMMA was incorporated as a photocrosslinkable interstitial matrix that resides between microgels. The jammed ink demonstrated good extrudability and shape fidelity, enabling the production of compartmentalized bulk structures with improved nutrient availability for encapsulated cells.
The outcomes of the HumanINK project highlight the potential of human-based bioinks as a promising technology for creating more physiologically relevant platforms for tissue engineering and more precise disease models. We envision these advancements bridging the gap between fundamental research and drug validation, moving towards an animal-free drug development process.
