June 17, 2021

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Self-Assembling Biomaterials

Self-Assembling Biomaterials
Author : Helena S. Azevedo,Riccardo M. P. da Silva
Publisher : Woodhead Publishing Limited
Release Date : 2018-04
Category : Technology & Engineering
Total pages :810
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Self-assembling biomaterials: molecular design, characterization and application in biology and medicine provides a comprehensive coverage on an emerging area of biomaterials science, spanning from conceptual designs to advanced characterization tools and applications of self-assembling biomaterials, and compiling the recent developments in the field. Molecular self-assembly, the autonomous organization of molecules, is ubiquitous in living organisms and intrinsic to biological structures and function. Not surprisingly, the exciting field of engineering artificial self-assembling biomaterials often finds inspiration in Biology. More important, materials that self-assemble speak the language of life and can be designed to seamlessly integrate with the biological environment, offering unique engineering opportunities in bionanotechnology. The book is divided in five parts, comprising design of molecular building blocks for self-assembly; exclusive features of self-assembling biomaterials; specific methods and techniques to predict, investigate and characterize self-assembly and formed assemblies; different approaches for controlling self-assembly across multiple length scales and the nano/micro/macroscopic properties of biomaterials; diverse range of applications in biomedicine, including drug delivery, theranostics, cell culture and tissue regeneration. Written by researchers working in self-assembling biomaterials, it addresses a specific need within the Biomaterials scientific community. Explores both theoretical and practical aspects of self-assembly in biomaterials Includes a dedicated section on characterization techniques, specific for self-assembling biomaterials Examines the use of dynamic self-assembling biomaterials

Engineering New Self-assembling Biomaterials Based on Beta-sheet-forming Peptides

Engineering New Self-assembling Biomaterials Based on Beta-sheet-forming Peptides
Author : Joel Henderson Collier
Publisher : Unknown
Release Date : 2003
Category :
Total pages :129
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This thesis deals with the development of novel strategies for self-assembling biomaterials based on short beta-sheet fibril-forming peptides. These materials are potentially useful for a variety of biomedical applications, including tissue engineering and controlled drug release, and several aspects of these materials have been explored in this thesis in an effort to improve their clinical utility. First, a strategy for rapidly and uniformly triggering peptide self-assembly was developed. Stimulus-sensitive liposomes were utilized to sequester salts and release them in response to stimuli such as warming to body temperature or exposure to near infra-red light. Triggered salt release in turn initiated rapid self-assembly of extravesicular peptide and the transformation of the peptide/liposome suspension from a solution to a hydrogel. We show that peptide self-assembly can be rapidly, uniformly, and specifically triggered, with the storage modulus increasing three orders of magnitude upon triggering. This rapid triggering strategy is potentially useful for injectable biomaterial applications. In the second research thrust, a self-assembling peptide was developed that also possessed enzymatic activity for the cross-linking enzyme tissue transglutaminase. We then utilized tissue transglutaminase to conjugate cell-interactive peptides to the self-assembled structure and investigated cell attachment to these functionalized scaffolds. Such a strategy is potentially useful for designing biospecific self-assembling scaffolds for tissue engineering or wound healing. In the final research focus, to modulate the nanostructure of the self-assembled fibrillar structures, we developed a series of self-assembling polyethylene glycol-conjugated peptides. We found that polyethylene glycol conjugation significantly altered fibril morphology, including width, length, and degree of lateral aggregation. As previous beta-sheet fibrillar self-assembled materials have shown particular intransigence to such modification of the fibrillar structure, this strategy may be a useful route for tailoring the physical properties of these materials. As a whole, the strategies developed in this thesis address previous shortcomings of beta-sheet peptide-based self-assembling materials in an effort to bring them closer to clinical application.

Uncovering Design Principles of Intermediate Filaments, a Self-Assembling Biomaterial: Lessons in Nanoscale Materials Design

Uncovering Design Principles of Intermediate Filaments, a Self-Assembling Biomaterial: Lessons in Nanoscale Materials Design
Author : Anonim
Publisher : Unknown
Release Date : 2007
Category :
Total pages :18
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Our broad long-term objective is to create novel biomaterials that advance the technical capabilities of the U.S. Army. In the short term, we seek to design self-assembling biomaterials that are adaptable in their structure and function. To do so, we must understand the molecular physicochemical aspects of biomaterials design, and we use three different systems to study this issue: 1) intermediate filaments, a class of protein with a broad range of structural roles from the nanometer to macroscale, as a model system; (2) self-assembled virus-based nanostructures, and (3) adiponectin, an adipocyteproduced hormone that serves as a soluble model system of higher order collagen. Such proteins may be harnessed for military purposes (eg. protective self-healing materials or nanoscale scaffolds) if one had a better understanding of how molecular structure determines material properties. In this final progress report, we summarize our studies on these systems.

Engineering Modular Self-assembling Biomaterials for Multifunctionality

Engineering Modular Self-assembling Biomaterials for Multifunctionality
Author : Jangwook Philip Jung
Publisher : Unknown
Release Date : 2010
Category :
Total pages :232
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The objective of this thesis was to design self-assembling biomaterials whose physical and biological properties can be systematically adjusted to modulate cell growth and differentiation. The intended applications of these biomaterials include defined 3D cell culture scaffolds as well as coatings for existing prosthetics. The complex and dynamic nature of extracellular matrices necessitates the precise integration and adjustment of multiple physical, chemical, and biological features within engineered biomaterials, but this has been challenging for previous scaffolds owing to the fact that these features tend not to be adjustable independently. Instead, these properties tend to be conflated and entangled, limiting the ability to systematically engineer scaffolds with multiple components. As a step towards addressing this issue, this thesis describes the development of a modular self-assembling biomaterial system capable of incorporating multiple physical or biological functions into precisely defined biomaterials without affecting other material properties. Three families of different biological and physical functionalities were designed, synthesized, and investigated: those that modulate matrix mechanics, those that mediate cell-matrix binding, and those that can release soluble effector molecules. All materials were based on a short, synthetic, self-assembling peptide sequence, Q11, which formed self-supporting hydrogels in physiological conditions. To independently modulate matrix mechanics, Q11 derivatives were developed possessing chemoselective functional groups that could be polymerized via native chemical ligation. This method produced significantly stiffened gels, which also significantly enhanced endothelial cell proliferation in an independent manner. To develop modular self-assembling ligand-bearing peptides, endothelial cell-interactive ligands, RGDS, REDV, IKVAV, and YIGSR amino acid sequences were added to the N-terminus of Q11 (X-Q11). The incorporation of X-Q11 into hydrogels was quantitative and did not significantly alter stiffness when different ligands were included in the hydrogels. The ligands were physically presented on the surface of fibrils, retained their biological activities, and interacted with cell surface receptors to modulate endothelial cell behaviors. To develop Q11 derivatives capable of releasing soluble effectors, Q11 peptides were synthesized containing a nitric oxide (NO) donor compound. The conjugation efficiency was about 88%, and fibril morphologies were not significantly altered by the NO donor compound, allowing quantitative incorporation of this peptide into Q11 hydrogels. The last stage of the project employed a statistical method, design of experiments, to capitalize upon the modularity of the developed co-assembling matrices, with the purpose of maximizing the growth of endothelial cells on the materials. Through several rounds of multifactorial experimentation, an optimal formulation of multiple peptides was determined, resulting in endothelial cell attachment and proliferation comparable to the native matrix protein, fibronectin. Such a calculation of an optimal formulation would be prohibitively costly, both in terms of time and materials, for conventional biomaterials not constructed in a modular fashion. These results suggested that modular Q11-based self-assembling systems enable facile manipulation of multiple factors, allowing the efficient targeting of a desired response, in this case endothelial cell growth. This approach should allow for the systematic design of biomaterials for a wide range of applications, without relying on ad hoc strategies.

Self-assembling Biomaterials

Self-assembling Biomaterials
Author : Helena S. Azevedo,Ricardo M. P. da Silva
Publisher : Woodhead Publishing
Release Date : 2018-04-17
Category : Technology & Engineering
Total pages :612
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Self-assembling biomaterials: molecular design, characterization and application in biology and medicine provides a comprehensive coverage on an emerging area of biomaterials science, spanning from conceptual designs to advanced characterization tools and applications of self-assembling biomaterials, and compiling the recent developments in the field. Molecular self-assembly, the autonomous organization of molecules, is ubiquitous in living organisms and intrinsic to biological structures and function. Not surprisingly, the exciting field of engineering artificial self-assembling biomaterials often finds inspiration in Biology. More important, materials that self-assemble speak the language of life and can be designed to seamlessly integrate with the biological environment, offering unique engineering opportunities in bionanotechnology. The book is divided in five parts, comprising design of molecular building blocks for self-assembly; exclusive features of self-assembling biomaterials; specific methods and techniques to predict, investigate and characterize self-assembly and formed assemblies; different approaches for controlling self-assembly across multiple length scales and the nano/micro/macroscopic properties of biomaterials; diverse range of applications in biomedicine, including drug delivery, theranostics, cell culture and tissue regeneration. Written by researchers working in self-assembling biomaterials, it addresses a specific need within the Biomaterials scientific community. Explores both theoretical and practical aspects of self-assembly in biomaterials Includes a dedicated section on characterization techniques, specific for self-assembling biomaterials Examines the use of dynamic self-assembling biomaterials

Fabrication and Self Assembly of Nanobiomaterials

Fabrication and Self Assembly of Nanobiomaterials
Author : Alexandru Grumezescu
Publisher : William Andrew
Release Date : 2016-01-11
Category :
Total pages :520
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Fabrication and Self Assembly of Nanobiomaterials: Applications of Nanobiomaterials introduces the reader to the most recent findings regarding current biomaterials used in nanotechnology, starting with their synthesis, characterization, and current, and future, potential use. Respected authors from around the world offer a comprehensive look at how nanobiomaterials are made, enabling findings from research to be applied in the wider field. This book contains results of current research to reach those who wish to use this knowledge in an applied setting. The book is a collection of titles that bring together many of the novel applications these materials have in biology, also discussing the advantages and disadvantages of each application and the perspectives of the technologies based on these findings. At the moment, there is no other comparable book series covering all the subjects approached in this set of titles. Provides an updated and highly structured reference material for students, researchers, and practitioners working in the bio- medical, biotechnological, and engineering fields Presents a valuable resource of recent scientific progress, along with the most known applications of nanomaterials in the biomedical field Includes novel opportunities and ideas for developing or improving technologies in fabrication and self-assembly

Design of Self-assembling Nucleo-peptide Hydrogels for Molecular Self-assembly Study and Functional Biomaterials Development

Design of Self-assembling Nucleo-peptide Hydrogels for Molecular Self-assembly Study and Functional Biomaterials Development
Author : Kiheon Baek
Publisher : Unknown
Release Date : 2019
Category :
Total pages :236
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Self-assembling peptide-based biomaterials are promising for use in biomedical applications due to their inherent extracellular matrix-like structure, comparable nanofiber dimensions and responsiveness to cells and proteins. Among them, short peptides and their derivatives have been studied because of their ease of synthesis and bottom-up design for controlling fibrillar supra-structure. In this dissertation, nucleo-tripeptides which can self-assemble into a hydrogel form were designed based on considerations of their gelation conditions and applications to functional cell scaffolds and controlled drug release. From the result of Fmoc modified short depsipeptides study, showing functional potential but cytotoxicity upon degradation, nucleobases were evaluated as a replacement for the Fmoc group. A small library, composed of 16 nucleo-tripeptides, was constructed in order to control the self-assembly conditions and to identify a molecule which can form a hydrogel under physiologic conditions. The resulting supra-structures were analyzed experimentally and computationally. We found that nucleo-tripeptides can self-assemble into nano-fibers which then lead to hydrogel formation under physiologic pH. Self-assembled nano-fibers have DNA-like structures, exhibiting nucleobase stacking and Watson-Crick-like interactions. By using these DNA-like structures as well as the self-healing capability of the nucleo-tripeptide hydrogel, applications as functional cell scaffolds and controlled drug release were studied. The self-assembled nucleo-tripeptide hydrogel can be functionalized via mixing with a second molecule having a complementary nucleobase via Watson-Crick interactions. A molecule possessing arginine-glycine-aspartic acid (RGD), interacting with integrin located on the surface of cells, and a nucleobase was incorporated into the self-assembled nucleo-tripeptide hydrogel. This incorporation resulted in improved viability and cell attachment during 3D culture of fibroblasts. Nucleobase stacking structures were applied to the sequestration and controlled release of the doxorubicin, a cancer drug which exerts its action by intercalated DNA. The self-assembled nucleo-tripeptide hydrogel was able to load doxorubicin effectively through its DNA-like interactions, and in vitro and in vivo studies showed that controlled release of doxorubicin can inhibit tumor growth over a long-term period

MOLECULAR SELF-ASSEMBLY FOR BIOMATERIALS DESIGN.

MOLECULAR SELF-ASSEMBLY FOR BIOMATERIALS DESIGN.
Author : Anonim
Publisher : Unknown
Release Date : 2019
Category :
Total pages :129
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Developing New Protein Self-assembling Strategies for Biomaterials Design and Synthesis

Developing New Protein Self-assembling Strategies for Biomaterials Design and Synthesis
Author : Xiaotian Liu
Publisher : Unknown
Release Date : 2019
Category :
Total pages :142
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Self-assembling Fibrous Biomaterials for Cell-biology Applications

Self-assembling Fibrous Biomaterials for Cell-biology Applications
Author : Anonim
Publisher : Unknown
Release Date : 2007
Category :
Total pages :326
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Micro and Nanofabrication Using Self-Assembled Biological Nanostructures

Micro and Nanofabrication Using Self-Assembled Biological Nanostructures
Author : Jaime Castillo-León,Winnie Svendsen
Publisher : William Andrew
Release Date : 2014-09-09
Category : Technology & Engineering
Total pages :126
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Self-assembled nanostructures based on peptides and proteins have been investigated and presented as biomaterials with an impressive potential for a broad range of applications such as microfabrication, biosensing platforms, drug delivery systems, bioelectronics and tissue reparation. Through self-assembly peptides can give rise to a range of well-defined nanostructures such as nanotubes, nanofibers, nanoparticles, nanotapes, gels and nanorods. However, there are challenges when trying to integrate these biological nanostructures in the development of sensing devices or drug-delivery systems – challenges such as controlling the size during synthesis, the stability in liquid environments and manipulation. In "Micro and Nanofabrication Using Self-assembled Biological Nanostructures" the options and challenges when using self-assembled peptide nanostructures in micro and nanofabrication are discussed. The publication covers different ways to manipulate, deposit and immobilize on specific locations these biological nanostructures in order to use them in the fabrication of new structures or as part of biosensing platforms. Examples where researchers used biological nanostructures for those types of applications are provided. Finally, future applications are discussed as well as parameters to accelerate and expand the use of these biological building blocks in nano- and micro-fabrication processes by taking advantage of their impressive properties such as low-cost and short synthesis time.

Self-Assembled, Peptide Based Biomaterials for Regenerative Medicine and Drug Delivery

Self-Assembled, Peptide Based Biomaterials for Regenerative Medicine and Drug Delivery
Author : Katie Anna Black
Publisher : Unknown
Release Date : 2014
Category :
Total pages :88
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A focus of the field of biomaterials is to use directed design to create new materials which replicate and enhance the intricate functions of the human body. Nature's own building blocks, peptides, are an ideal material to create self-assembling biomaterials as they are biodegradable, relatively easy to synthesize, and can be designed with a wide array of functions. In this dissertation, self-assembling peptide materials were optimized for two important medical applications: regenerative medicine and drug delivery. Peptide amphiphiles (PAs), peptides conjugated to fatty acid tails, can self-assemble into both spherical micelles and worm-like micelles. PA worm-like micelles are of particular interest for regenerative medicine applications for their ability to form viscoelastic hydrogels at high concentration. Here we created PA hydrogel systems with active formation and stabilization triggers that are amenable to in situ gelation. Two different methods of in situ gel formation in PA systems were investigated, shear force and pH. Shear-induced formation of worm-like micelles is demonstrated in the PA termed C16-W3K. Before shearing, C16-W3K PAs form spherical micelles in solution and exhibit little to no viscoelasticity. As the solution is subjected to simple shear flow with increasing shear rate, spherical micelles form elongated worm-like micelles up to microns in length. In the C16-W3K PA system, shear force induced the change not only of the micelle structure but also of the peptide secondary structure simultaneously. Worm-like micelle formation was also demonstrated using pH modulation, in the PA termed C16GSH, which was designed with a branched peptide headgroup of histidine and serine amino acids. At low pH, the histidine side chains are protonated and hydrogen bonding does not occur, creating weakly elastic hydrogels. At pH 7.4, above the pKa of the histidine imidazole group, cooperative hydrogen bonding occurs, stabilizing the self-assembled worm-like micelles and creating a strong viscoelastic hydrogel. This unique architecture of C16GSH makes it possible to create hydrogels spanning a wide range of stiffness (0.1-10 kPa). C16GSH were optimized in vitro and in vivo for the application of peripheral nerve regeneration. Peripheral nerve injury is a debilitating condition for which new bioengineering solutions are needed. One strategy to enhance regeneration inside nerve guide conduits is to fill the conduits with a hydrogel to mimic the native extracellular matrix found in peripheral nerves. C16GSH hydrogels were compared to a commercially available collagen gel, which has been previously investigated as a nerve guide filler gel. Schwann cells, a cell type important in the peripheral nerve regenerative cascade, were able to spread, proliferate and migrate better on C16GSH gels in vitro when compared to cells seeded on collagen gels. Moreover, C16GSH gels were implanted subcutaneously in a murine model and were found to be biocompatible, degrade over time, and support angiogenesis without causing inflammation or a foreign body immune response. Taken together, these results help optimize and instruct the development of a new synthetic, hydrogel as a luminal filler for conduit-mediated peripheral nerve repair. In the second half of this dissertation, peptide based complex coacervates were optimized for delivery of protein therapeutics. Complex coacervation is a liquid-liquid phase separation based on the electrostatic association of two oppositely charged polymers in aqueous solution. Coacervation results in micron sized droplets of a dense polymer-rich phase (coacervate) which is separate from the dilute polymer-poor solution phase (aqueous phase). Complex coacervates based on synthetic polypeptides have many desirable features for therapeutic protein delivery. They can be synthetically produced, can be made to be biocompatible and biodegradable, and their formation can be tuned by a wide array of parameters. In this dissertation, a method to encapsulate proteins by complex coacervation using polypeptides is explored. Protein encapsulation with a model protein system: bovine serum albumin (BSA) was demonstrated. Rheological properties were studied to determine the viscoelasticity which may have implications for cell internalization. It was demonstrated that there is tradeoff between loading efficiency and total loading. Therefore, depending on the application, high loading capacity, up to 1:3 molar ratio of protein to polypeptide, or 100% loading of the protein can be achieved, depending on the process and cost of the protein which is often high. Encapsulated BSA retained its secondary structure when encapsulated and was released under conditions of low pH due to disassembly of the coacervate. Lastly, protein loaded coacervates were shown to be non-toxic in a cell viability assay. Polypeptide complex coacervates show promise at encapsulating proteins for therapeutic delivery, but it is difficult to control their size and stability to due dynamic rearrangement and coalescence. To control the size and stability of polypeptide coacervates, the crosslinker EDC was used to create a peptide bond between the amino acid side groups of poly(L-lysine) (PLys) and poly(D/L-glutamic acid) (PGlu). By changing the ratio of PGlu to PLys colloidal stability was achieved without the need for an additional excipient. Surface charge of the particles was also controlled by this method. Final particle size was controlled by both molecular weight and concentration of the polypeptides. A span of particle diameter from to 272nm to 1.3 μm was achieved. Lastly, stability at low pH, where non-crosslinked coacervates disassemble, was demonstrated. A simple and tunable method to control particle size, such as the one presented here provides a possible solution to a major limitation in the field of drug delivery, control of particle size.

Structure and Interactions in Biomaterials Based on Membrane-biopolymer Self-assembly

Structure and Interactions in Biomaterials Based on Membrane-biopolymer Self-assembly
Author : Ilya Koltover
Publisher : Unknown
Release Date : 1998
Category :
Total pages :694
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Self-assembly of Peptide-polymer Conjugates for the Formation of Functional Biomaterials Via Molecular Dynamics Simulations

Self-assembly of Peptide-polymer Conjugates for the Formation of Functional Biomaterials Via Molecular Dynamics Simulations
Author : Iris Wing Yin Fu
Publisher : Unknown
Release Date : 2015
Category :
Total pages :255
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Peptide-polymer conjugates are versatile molecular building blocks that can self-assemble into well-defined nanostructures with customizable biofunctionality and tunable physical properties for a wide range of biomedical applications. In this dissertation, two structural analogues of peptide-polymer conjugates are discussed: peptide amphiphiles and block copolymers with the difference between their respective domains tailored for specific applications. Self-assembly process of these peptide-polymer conjugates into different nanostructure morphologies is examined via molecular dynamics simulations using our recently developed integrated simulation package, called BioModi (Biomolecular Multiscale Models at UC Irvine). This simulation package consists of coarse-grained models that mimic realistic molecules and molecular interactions of amino acids, nucleic acids, and polymers, yet are simplified enough to allow molecular simulation of large systems over long time scales. For peptide amphiphiles, emphasis is placed on achieving a fine balance between the two distinct hydrophobic and hydrophilic domains to attain a supramolecular architecture that can serve as a biomimetic hydrogel scaffold for tissue engineering. The role of different environmental factors (e.g. temperature, pH, solvent) on the self-assembly behavior of peptide amphiphiles is elucidated in detail. Our simulations show that under optimal conditions, spontaneously self-assembly results in the formation of cylindrical nanofibers that can switch into spherical micelles in response to a small pH range as similarly observed by in vitro experiments. Moreover, phase diagrams are constructed to identify morphological transitions, and unique self-assembly kinetic mechanisms are characterized. Chemical modification of the peptide amphiphile sequence is investigated and contrasting structural characteristics are observed to correlate with differences in mechanical behavior of the resulting gel. For block copolymers, the inherent design utilizes a cationic polypeptide conjugated to a synthetic polymer that promotes favorable electrostatic interactions with nucleic acid fragments upon the formation of a polyionic complex as an effective gene carrier. Efficient complexation of block polymers with siRNA is determined via molecular dynamics simulations to be a function of the length of the polymer and the charge density of the system. Implementation of our newly developed coarse-grained models, BioModi, and insight gained from our simulations will provide key parameters to advance computer-aided design and development of innovative smart biomaterials.

Peptides and Peptide-based Biomaterials and their Biomedical Applications

Peptides and Peptide-based Biomaterials and their Biomedical Applications
Author : Anwar Sunna,Andrew Care,Peter L. Bergquist
Publisher : Springer
Release Date : 2017-10-26
Category : Science
Total pages :300
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Solid-binding peptides have been used increasingly as molecular building blocks in nanobiotechnology as they can direct the assembly and functionalisation of a diverse range of materials and have the ability to regulate the synthesis of nanoparticles and complex nanostructures. Nanostructured materials such as β-sheet fibril-forming peptides and α-helical coiled coil systems have displayed many useful properties including stimulus-responsiveness, modularity and multi-functionality, providing potential technological applications in tissue engineering, antimicrobials, drug delivery and nanoscale electronics. The current situation with respect to self-assembling peptides and bioactive matrices for regenerative medicine are reviewed, as well as peptide-target modeling and an examination of future prospects for peptides in these areas.