No abstract

Hydrogel microfish featuring biomimetic structures, locomotive capabilities, and functionalized nanoparticles are engineered using a rapid 3D printing platform: microscale continuous ­optical printing (μCOP). The 3D‐printed ­microfish exhibit chemically powered and magnetically guided propulsion, as well as highly efficient detoxification capabilities that highlight the technical versatility of this platform for engineering advanced functional microswimmers for diverse biomedical applications.

Light-assisted 3D direct-printing of biomaterials and cellular-scaffolds has the potential to develop novel lab-on-a-chip devices (LOCs) for a variety of biomedical applications, from drug discovery and diagnostic testing to in vitro tissue engineering and regeneration. Direct-writing describes a broad family of fabrication methods that typically employ computer-controlled translational stages to manufacture structures at multi-length scales. This review focuses on light-assisted direct-write fabrication for generating 3D functional scaffolds with precise micro- and nano-architecture, using both synthetic as well as naturally derived biomaterials. Two bioprinting approaches are discussed in detail - projection printing and laser-based systems - where each method is capable of modulating multiple scaffold parameters, such as 3D architecture, mechanical properties (e.g. stiffness), Poisson's ratio, chemical gradients, biological cell distributions, and porosity. The light-assisted direct-writing techniques described in this review provide the reader with alternative approaches to fabricate 3D biomaterials for utility in LOCs.

Efficient and controlled gene delivery from biodegradable materials can be employed to stimulate cellular processes that lead to tissue regeneration. In this report, a substrate-mediated approach was developed to deliver DNA from hyaluronic acid-collagen hydrogels. The hydrogels were formed by crosslinking HA with poly(ethylene glycol) diglycidyl ether. Poly(ethylene imine)(PEI)/DNA complexes were immobilized to the substrate using either biotin/neutravidin or non-specific adsorption. Complexes were formed in the presence or absence of salt to regulate complex size, and resulted in complexes with z-average diameters of 1221.7 +/- 152.3 and 139.4 +/- 1.3 nm, respectively. During 48-h incubation in PBS or hyaluronidase, DNA was released slowly from the hydrogel substrate (<30% of immobilized DNA), which was enhanced by incubation with conditioned media (approximately 50% of immobilized DNA). Transgene expression mediated by immobilized, large diameter complexes was 3 to 7-fold greater than for small diameter complexes. However, the percentage of cells expressing the transgene was greater for small diameter complexes (48.7%) than for large diameter complexes (22.3%). Spatially controlled gene transfer was achieved by topographically patterning the hydrogel to pattern cell adhesion. Biomaterial-based gene delivery can be applicable to numerous tissue engineering applications, or as a tool to examine tissue formation.

Complex 3D interfacial arrangements of cells are found in several in vivo biosystems such as blood vasculature, renal glomeruli, and intestinal villi. Current tissue engineering techniques fail to develop suitable 3D microenvironments to evaluate the concurrent effects of complex topography and cell encapsulation. There is a need to develop new fabrication approaches that control cell density and distribution within complex 3D features. In this work, we present a dynamic projection printing process that allows rapid construction of complex 3D structures using custom-defined computer-aided-design (CAD) files. Gelatin-methacrylate (GelMA) constructs featuring user-defined spiral, pyramid, flower, and dome micro-geometries were fabricated with and without encapsulated cells. Encapsulated cells demonstrate good cell viability across all geometries both on the scaffold surface and internal to the structures. Cells respond to geometric cues individually as well as collectively throughout the larger-scale patterns. Time-lapse observations also reveal the dynamic nature of mechanical interactions between cells and micro-geometry. When compared to conventional cell-seeding, cell encapsulation within complex 3D patterned scaffolds provides long-term control over proliferation, cell morphology, and geometric guidance. Overall, this biofabrication technique offers a flexible platform to evaluate cell interactions with complex 3D micro-features, with the ability to scale-up towards high-throughput screening platforms.