Cell driven elastomeric particle packing in composite bioinks for engineering and implantation of stable 3D printed...

Geometric and structural integrity often deteriorate in 3D printed cell-laden constructs over time due to cellular compaction and hydrogel shrinkage. This study introduces a new approach that synergizes the advantages of cell compatibility of biological hydrogels and mechanical stability of elastomeric polymers for structure fidelity maintenance upon stereolithography and extrusion 3D printing. Enabling this advance is the composite bioink, formulated by integrating elastomeric microparticles from poly(octamethylene maleate (anhydride) citrate) (POMaC) into biologically derived hydrogels (fibrin, gelatin methacryloyl (GelMA), and alginate). The composite bioink enhanced the elasticity and plasticity of the 3D printed constructs, effectively mitigating tissue compaction and swelling. It exhibited a low shear modulus and a rapid crosslinking time, along with a high ultimate compressive strength and resistance to deformation from cellular forces and physical handling; this was attributed to packing and stress dissipation of elastomeric particles, which was confirmed via mathematical modelling. Enhanced functional assembly and stability of human iPSC-derived cardiac tissues and primary vasculature proved the utility of the composite bioink in tissue engineering. In vivo implantation studies revealed that constructs containing POMaC particles exhibited improved resilience against host tissue stress, enhanced angiogenesis, and infiltration of pro-reparative macrophages.