UCLA

The evolution of microfabrication has greatly contributed to the advances in biology and medicine, as it can interface with and manipulate the interactions between biological systems and materials with micrometer-scale precision. In addition, microfabrication allows the development of new materials with unique properties by providing the tools to tailor defined topography as well as overall geometry. In the field of tissue engineering, to provide suitable functional microenvironments for cells or tissues, there is a great need to structure artificial tissue constructs at the micrometer scale. In addition, micrometer-sized reactors with defined shape and spatial chemistries can be utilized for diagnostic applications to concentrate or enrich rare biomolecules or cells, otherwise not detectable. The dissertation reports on the development of novel multifunctional biomaterials to overcome current challenges in microfabrication techniques such as 3D bioprinting and microfluidics, highlighted in Chapter 1. In Chapter 2, we present a highly biocompatible and elastic bioink for fabrication of complex biomimetic structures such as vascularized cardiac tissue constructs. The 3D bioprinting of soft tissues has been challenging primarily due to the lack of suitable bioinks. To address these shortcomings, we use recombinant human tropoelastin as a novel bioink with high printability, biocompatibility, biomimicry, and proper mechanical properties. Using the freeform reversible embedding of suspended hydrogels (FRESH) printing method, we demonstrate bioprinting vascularized cardiac constructs using two-nozzles and we extensively characterize their functions in vitro and in vivo. In Chapter 3, we explore a scalable method to fabricate spatially functionalized microparticles for “lab on a particle” applications. For the design of a novel high throughput microfabrication method, we highlight the important role of thermodynamic factors, such as temperature and polymer concentrations, on intermolecular interactions, and therefore, the phase-separation behavior of a polymer mixture. These particles are utilized to analyze secretion phenotypes and heterogeneity of CHO DP-12 cells and to sort rare populations of high-yielding producer cells using fluorescence activated cell sorting (FACS). In Chapter 4, we prove the broad generalizability of this lab-on-a-particle platform by demonstrating their ability to screen and sort primary human T cells as well as genetically engineered chimeric antigen receptor (CAR)-T cells based on cytokine production. Overall, we believe the work presented here demonstrates the importance and utility of microfabrication techniques, especially 3D bioprinting and microfluidics. Combined with novel biomaterials, microfabrication methods can significantly upgrade conventional platforms, such that we can better recapitulate the in vivo microenvironment for tissue engineering or suggest an entirely new technology as with lab-on-a particle technology for single-cell analysis and sorting.