This thesis describes the production of advanced materials comprising a wide array of polymer-based building blocks. These materials include bio-hybrid polymer-peptide conjugates, based on phenylalanine and poly(ethylene oxide), and polymers with intrinsic microporosity (PIMs). Polymer-peptides conjugates were previously synthesised using click chemistry. Due to the inherent disadvantages of the reported synthesis, a new, simpler, inexpensive protocol was sought. Three synthetic methods based on amidation chemistry were investigated for both oligopeptide and polymerpeptide coupling. The resulting conjugates produced were then assessed by various analytical techniques, and the new synthesis was compared with the established protocol. An investigation was also carried out focussing on polymer-peptide coupling via ester chemistry, involving deprotection of the carboxyl terminus of the peptide. Polymer-peptide conjugates were also assessed for their propensity to self-assemble into thixotropic gels in an array of solvent mixtures. Determination of the rules governing this particular self-assembly (gelation) was required. Initial work suggested that at least four phenylalanine peptide units were necessary for self-assembly, due to favourable hydrogen bond interactions. Quantitative analysis was carried out using three analytical techniques (namely rheology, FTIR, and confocal microscopy) to probe the microstructure of the material and provided further information on the conditions for self-assembly. Several polymers were electrospun in order to produce nanofibres. These included novel materials such as PIMs and the aforementioned bio-hybrid conjugates. An investigation of the parameters governing successful fibre production was carried out for PIMs, polymer-peptide conjugates, and for nanoparticle cages coupled to a polymer scaffold. SEM analysis was carried out on all material produced during these electrospinning experiments.

Peptides are the building blocks of the natural world; with varied sequences and structures, they enrich materials producing more complex shapes, scaffolds and chemical properties with tailorable functionality. Essentially based on self-assembly and self-organization and mimicking the strategies that occur in Nature, peptide materials have been developed to accomplish certain functions such as the creation of specific secondary structures (a- or 310-helices, b-turns, b-sheets, coiled coils) or biocompatible surfaces with predetermined properties. They also play a key role in the generation of hybrid materials e.g. as peptide-inorganic biomineralized systems and peptide/polymer conjugates, producing smart materials for imaging, bioelectronics, biosensing and molecular recognition applications. Organized into four sections, the book covers the fundamentals of peptide materials, peptide nanostructures, peptide conjugates and hybrid nanomaterials, and applications with chapters including: Properties of peptide scaffolds in solution and on solid substrates Nanostructures, peptide assembly, and peptide nanostructure design Soft spherical structures obtained from amphiphilic peptides and peptide-polymer hybrids Functionalization of carbon nanotubes with peptides Adsorption of peptides on metal and oxide surfaces Peptide applications including tissue engineering, molecular switches, peptide drugs and drug delivery Peptide Materials: From Nanostructures to Applications gives a truly interdisciplinary review, and should appeal to graduate students and researchers in the fields of materials science, nanotechnology, biomedicine and engineering as well as researchers in biomaterials and bio-inspired smart materials.

Electrospun Nanofibers covers advances in the electrospinning process including characterization, testing and modeling of electrospun nanofibers, and electrospinning for particular fiber types and applications. Electrospun Nanofibers offers systematic and comprehensive coverage for academic researchers, industry professionals, and postgraduate students working in the field of fiber science. Electrospinning is the most commercially successful process for the production of nanofibers and rising demand is driving research and development in this field. Rapid progress is being made both in terms of the electrospinning process and in the production of nanofibers with superior chemical and physical properties. Electrospinning is becoming more efficient and more specialized in order to produce particular fiber types such as bicomponent and composite fibers, patterned and 3D nanofibers, carbon nanofibers and nanotubes, and nanofibers derived from chitosan. Provides systematic and comprehensive coverage of the manufacture, properties, and applications of nanofibers Covers recent developments in nanofibers materials including electrospinning of bicomponent, chitosan, carbon, and conductive fibers Brings together expertise from academia and industry to provide comprehensive, up-to-date information on nanofiber research and development Offers systematic and comprehensive coverage for academic researchers, industry professionals, and postgraduate students working in the field of fiber science

This book aims to present the different aspects of electrospinning for designing and fabricating high performing materials for sensors applied in gaseous and liquid environments. Since electrospinning is a versatile and inexpensive manufacturing technology, the book emphasizes the industrial applications perspective. The volume is an edited collection of the most recent and encouraging results concerning advanced nanostructured (bio) sensors. The feats achieved by these sensors range from high sensitivity to extreme operating conditions and satisfy a wide range of requirements. Most of the contributions in this book come from First International Workshop on Electrospinning for High Performance Sensing (EHPS2014) that was held in Rome in 2014, as part of the European COST Action MP1206 Electrospun Nanofibres for bio inspired composite materials and innovative industrial applications.

Synthesis of Polypeptides by Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydrides, by Jianjun Cheng and Timothy J. Deming.- Peptide Synthesis and Self-Assembly, by S. Maude, L. R. Tai, R. P. W. Davies, B. Liu, S. A. Harris, P. J. Kocienski and A. Aggeli.- Elastomeric Polypeptides, by Mark B. van Eldijk, Christopher L. McGann, Kristi L. Kiick andJan C. M. van Hest.- Self-Assembled Polypeptide and Polypeptide Hybrid Vesicles: From Synthesis to Application, by Uh-Joo Choe, Victor Z. Sun, James-Kevin Y. Tan and Daniel T. Kamei.- Peptide-Based and Polypeptide-Based Hydrogels for Drug Delivery and Tissue Engineering, by Aysegul Altunbas and Darrin J. Pochan.-

Peptide and protein therapeutics are highly effective for the treatment and management of numerous diseases. Despite this, their clinical potential is underutilized mainly due to drawbacks inherent to many native proteins such as poor stability, immunogenicity, and short pharmacokinetics. These issues cause a multitude of challenges in manufacturing, formulation, transportation, and administration. Ideally, peptide and protein therapeutics are shelf stable and are able to be administered in its native state through a minimally invasive method. My research focuses on 1) the exploration of different polymeric models in response to various stimuli to elucidate mechanisms behind certain drug delivery vehicles, 2) the sustained release of therapeutic peptide glucagon through a glucose-responsive hydrogel for the prevention of hypoglycemia, 3) the site-selective conjugation of a degradable, zwitterionic polymer to a model protein, and 4) the investigation of how polymer tacticity affects biological function through the conjugation of regio-and sequence-defined macromolecules to a model protein. Chapter 1 discusses three different strategies Stimuli-responsive nanoparticles, particularly those that respond to two different environmental cues, are useful materials in drug delivery. In chapter 2, the size-response of nanogels based on two different polymers, poly(N-isopropylacrylamide) p(NIPAM) and poly(oligo(ethylene glycol) methyl ether methacrylate) (PEGMA), to temperature and glucose concentration changes was investigated. The nanogels were prepared by precipitation polymerization, 114 nm and 169 nm for pNIPAM and PEGMA at 37 C, respectively, and characterized by proton nuclear magnetic resonance and infrared spectroscopies. Both nanogels underwent a volume phase transition in biologically relevant ranges upon heating. Incorporation of 2-aminophenylboronic acid enabled glucose-binding, resulting in a shift of the volume phase transition temperature (VPTT) of both nanogels as assessed by differential scanning calorimetry (DSC) and turbidity measurements. P(NIPAM) nanogel demonstrated a predictable decrease in size in response to both increase of temperature and glucose. PEGMA nanogel showed a predictable decrease in size to increasing temperature and but exhibited a surprising increase then decease in size to increasing concentrations of glucose.Glucagon is a peptide hormone used in the treatment of hypoglycemia. Unlike its counterpart insulin, glucagon has only started garnering interest in the past few decades. While recent advances have introduced user friendly formulations for glucagon administration, there remain no glucagon formulations on the market intended for combating nocturnal hypoglycemia. Chapter 3 details the sustained release of native glucagon using a glucose- and thermo-responsive hydrogel. RAFT polymerization was used to create PEG-b-p(NIPAM-co-2-APBA) polymers which were subsequently crosslinked using glucose. Polymer size, PEG length, boronic acid incorporation, and polymer wt % were varied to optimize hydrogel sensitivity to 1 mg/mL glucose at 37 0C, which correspond to normoglycemia. Glucagon release was tested over 48 hours in which the hydrogel released up to 80% of the payload, 40% more than its control. Rheological measurements demonstrate the shear-thinning property of the hydrogel. Finally, viscosity measurements in conjunction with injectability calculations show that the hydrogel can be formulated as an injectable. Chapter 4 describes the exploration of a degradable zwitterionic polymer as a PEG-alternative. Zwitterionic polymers have gained rising interest for their ability to stabilize proteins, increase circulation time, and retain bioactivity. While polyethylene glycol (PEG) still exists as the gold standard polymer used to mitigate challenges associated with native proteins, there are merits to investigating alternative polymers for this purpose. In this work, we report the site-selective conjugation of degradable zwitterionic poly(caprolactone-carboxybetaine) (pCLZ) to growth hormone receptor antagonist (GHA) B2036-alkyne and study bioactivity, pharmacokinetics, and immunogenicity. Azide-containing pCLZs of 5, 20, and 60 kDa are conjugated to GHA B2036-Alkyne via copper-catalyzed click reaction and their in vitro bioactivity is compared to PEGylated GHA B2036 5, 10, and 20 kDa, of matching hydrodynamic radii. The ability of pCLZs to elicit IgG and IgM antibody production was tested in vivo and no measurable antibody production was detected. Herein, we report that pCLZs demonstrate a high retention of bioactivity, as measured by half-maximal inhibitory concentrations in vitro, as well as low immunogenicity in vivo. Using 18F labeled PET/CT imaging, pharmacokinetics of our pCLZ conjugates show a significant increase in circulation time by 23 min compared to that of GHA B2036. Finally, in chapter five, a series of uniform, stereospecific protein-polymer conjugates were synthesized through copper-mediated click chemistry. Discrete, uniform polymers were provided by Wencong Wang from Prof. Jeremiah Johnson's lab at the Massachusetts Institute of Technology. The impact of molecular features of the conjugated polymers were evaluated through activity studies of growth hormone antagonist. Preliminary attempts at crystallizing the protein, polymer, and protein-polymer conjugates are demonstrated. Crystallization screening and crystallography model fitting was done largely with help from Genesis Falcon, Niko Vlahakis, and Dr. Michael Sawaya.