Abstract

3D Printed Programmable Release Capsules for Dynamic Tissue Engineering Applications

Michael McAlpine, Associate Professor, University of Minnesota

The development of methods for achieving spatiotemporal control over biomolecular gradients could enable advances in areas such as synthetic tissue engineering, biotic-abiotic interfaces, and bionanotechnology. Living organisms guide tissue development through orchestrated gradients of biomolecules that direct cell growth, migration, and differentiation. Our group has previously presented a method to 3D print stimuli-responsive core/shell capsules for programmable release of multiplexed gradients within hydrogel matrices. These capsules are comprised of an aqueous core, which can be formulated to maintain the activity of payload biomolecules, and a PLGA shell. The shell can be loaded with plasmonic gold nanorods (AuNRs), which permits selective rupturing of the capsule when irradiated with a laser wavelength determined by the lengths of the nanorods. This precise control over space, time, and selectivity allows for the ability to pattern 2D and 3D multiplexed arrays of content-loaded capsules, along with tunable laser-triggered rupture and release of payloads into a hydrogel ambient – allowing for dynamic tissue engineering applications. One particular example includes the use of these capsules in the development of 3D in vitro models capable of recapitulating native tumor microenvironments. Here, we build tumor constructs via the co-3D printing of living cells, natural hydrogels, and programmable release capsules. This enables the spatiotemporal control over signaling molecular gradients, thereby dynamically modulating cellular behaviors at the local level. Vascularized tumor models are created to mimic key steps of cancer dissemination (invasion, intravasation, and angiogenesis), based on guided migration of tumor cells and endothelial cells in the context of stromal cells and growth factors. These ‘4D printed’ vascularized tumor tissues provide a proof-of-concept dynamic tissue engineering platform to i) explore the molecular mechanisms of tumor progression and metastasis, and ii) preclinically identify therapeutic agents and screen anticancer drugs.