The convergence of additive manufacturing (AM) of 3D printed tissues and regenerative medicine offers promise in the high-throughput engineering of tissues and organs with tailored structural, biological and mechanical properties. It can ultimately reduce the complexity of surgical procedures and accelerate post-operative healing by rapidly replicating patient customized, multifaceted designs. To this end, an appropriate AM process capable of fabricating cell-laden fibrous collagen bioinks that mimic the multiscale spatial resolution of the native extracellular matrix is a critical requirement to the successful printing of tissues. However, current AM approaches are not compatible with the 3D bioprinting of fibrous proteins at varying length scales that replicate the complex hierarchical architecture of tissues. Collagen-based hydrogel bioinks are particularly restricted by their narrow printability range, where protein structure, seeded cell viability, and bioactivity of incorporated biomolecules all need to be maintained within physiological boundaries.<br/>In order to overcome these challenges, and by leveraging our research into bioengineered dense collagen gels as tissue models and templates for regenerative engineering, we have developed a unique 3D printing technique based on a gel aspiration-ejection (GAE) process that generates highly defined, fibrous collagen-based hydrogel bioinks for tissue engineering. Our breakthrough development is the AM of tissue structures with varying architectures based on a platform bioink system with a novel 3D bioprinting method. By using naturally derived collagen hydrogels incorporating cells, the printed tissue structures can be tailored to mimic protein fibril density and alignment, as well as cell loading and density according to the intended use. GAE-based bioprinting fabricates bioink hydrogels with tunable meso-structural properties with highly aligned collagen nano-fibrils, anisotropically oriented seeded cells and micro-mechanical properties that provide differentiation modulating cues. It will also enable a fourth dimension to bioprinting where cell-cell communications and cell-extracellular matrix interactions as a function of time in longer term culture can be predicted and modelled.

High-throughput production of physiologically relevant tissue equivalents

2019 Spring National Meeting

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