Materials Science, Biomedical engineering, Chemical engineering, 3D Printing, Elastomer, Hydrogel, Mechanical Properties, Polyurethane, and Tissue Engineering
Understanding the physical and chemical properties of biomaterials in rapid 3D printing could pave a way for the construction of complex structures with specific functionalities. Both the material conditions and printing techniques play crucial roles in modulating these properties. This dissertation was dedicated to answering the basic questions about how to engineer and improve the mechanical performance of rapidly 3D printed structure from synthesis and printing process. Three distinct groups of materials, namely plastic, soft hydrogels, and elastomeric polymers were used as case studies to reveal their relationships. Additionally, the toughening mechanism of networks with different mechanical properties was discovered and tested. These results could help future studies in rapid prototyping of medical devices, as well as adapting 3D printing in tissue engineering as a new direction.
Chemical engineering, Biomedical engineering, bijel, composite, hydrogel, implant, microstructure, and self-assembly
Biomaterials are engaged ubiquitously to regenerate or replace damaged or diseased tissues. Numerous processing techniques aim to impart interconnected, porous structures within biomaterials to support cell delivery, direct tissue growth, and increase the acceptance of foreign materials in the body. Many processing techniques lack predictable control of scaffold architecture, and rapid prototyping methods are often limited by time-consuming, layer-by-layer fabrication of micro-features appropriate for biomaterials applications. Further, scaffold architecture is implicated in the body’s innate ability to isolate foreign substances making mitigation of this foreign body response (FBR) essential to ensuring the longevity of implanted biomaterials and devices. Bicontinuous interfacially jammed emulsion gels (bijels) offer a robust, self-assembly-based platform for synthesizing a new class of morphologically distinct biomaterials. Bijels form via kinetic arrest of temperature-driven spinodal decomposition in partially miscible binary liquid systems. These non-equilibrium soft materials comprise co-continuous, fully percolating, non-constricting liquid domains separated by a nanoparticle monolayer. In this dissertation, fluid incompatibility in bijels is exploited to process biocompatible precursors to form hydrogel scaffolds displaying the morphological characteristics of the parent bijel template. Bijel-derived materials are first used to generate structurally unique, fibrin-loaded polyethylene glycol hydrogel composites to demonstrate a new, robust cell delivery system. Next, bijel-derived materials are investigated as tissue integrating implants with high vascularization and FBR mitigation potential stemming from their uniquely arranged pore morphology, presenting a new paradigm for designing long-lasting biomaterials.
Humans, Proteomics, Genomics, Chemistry, Analytic, Biomarkers, Analytical Chemistry, Chemical Engineering, and Other Chemical Sciences
Perhaps paradoxically, we argue that the biological sciences are "data-limited". In contrast to the glut of DNA sequencing data available, high-throughput protein analysis is expensive and largely inaccessible. Hence, we posit that access to robust protein-level data is inadequate. Here, we use the framework of the formal engineering design process to both identify and understand the problems facing measurement science in the 21st century. In particular, discussion centers on the notable challenge of realizing protein analyses that are as effective (and transformative) as genomics tools. This Perspective looks through the lens of a case study on protein biomarker validation and verification, to highlight the importance of iterative design in realizing significant advances over currently available measurement capabilities in the candidate or targeted proteomics space. The Perspective follows a podium presentation given by the author at The 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences (μTAS 2012), specifically focusing on novel targeted proteomic measurement tools based in microfluidic design. The role of unmet needs identification, iteration in concept generation and development, and the existing gap in rapid prototyping tools for separations are all discussed.
Chemical engineering, cytochrome p450, natural products, plant bacterial fusion, and protein engineering
The objective of this work was to engineer plant Cytochrome P450s to be self-sufficient in Escherichia coli, as a proof-of-concept of a novel protein engineering platform, termed ProtoVitro. The P450 reaction of interest was the hydroxylation of limonene for its potential to produce cancer therapeutics.1 The reaction can be performed naturally by plant P450s but not bacterial ones,2 so we created 28 fusion protein variants that each contained a plant P450 heme domain and either a bacterial or eukaryotic reductase domain. The heme domains were selected based on previously observed activity on limonene, and the reductase domains were selected as the maximally informative set from a list of thousands of prokaryotic and eukaryotic sequences. The rapid prototyping of diverse sequences facilitated by ProtoVitro allowed us to identify optimal protein variants in a more robust fashion than alternative protein engineering methods.