Abstract
The field of tissue engineering aims to restore the function of damaged or missing tissues by combining cells and/or a supportive biomaterial scaffold into an engineered tissue construct. The construct’s design requirements are typically set by native tissues – the gold standard for tissue engineers. Closely observing native tissues from an engineering perspective reveals a complex multiscale modular design. This natural architecture is essential for proper tissue functioning, but not trivial to manufacture. Recapitulating the complexity of native tissues requires high-resolution manufacturing technologies such as microfluidics. However, increasing resolution is typically at the cost of production throughput and vice versa, which hampers the clinical translation of complex tissue engineering strategies. New advanced concepts that integrate both high-resolution and rapid additive manufacturing techniques are thus prerequisite to upgrade the field of modular tissue engineering. This thesis describes: i) the development of various innovative biomaterials and microfluidic platforms for the production of (cell-laden) hydrogel microparticles (i.e. microgels) that act as tissue engineering building blocks; ii) the modification of microgels with in situ tunable biomechanical and biochemical properties to enable specific tailoring of the cellular microenvironment; iii) their incorporation into modular bio-inks, which is a novel concept to enable the facile engineering of complex tissues using standard biofabrication methods; and iv) the invention of a platform technology called ‘in-air microfluidics’ (IAMF), which uniquely enables the chip-free micromanufacturing of droplets, particles, and 3D modular biomaterials at rates that are readily compatible with clinical applications. Together, this thesis introduces a number of innovative biomaterial modifications and microfluidics-based manufacturing concepts that facilitate the development and clinical translation of modular tissue engineering applications.
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