Browsing by Subject "Biomaterials"
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Item Open Access Applications of biomaterials in cancer diagnosis and treatment(2013) Gözen, DamlaCancer remains to be a major burden of disease worldwide, despite the significant increase in the number of studies that focus on the development of novel diagnostic and treatment strategies. Recently, important part of these studies use biomaterials and their biomedical applications have been investigated extensively, due to their biocompatibility. Among these biomaterials two of them, carbon nanotubes (CNT) and polymer hydrogels have gained great importance due to their unique physical and chemical properties. The current study proposes new approaches that take advantage of these two biomaterials which could be used in the treatment and diagnosis of hepatocellular carcinoma (HCC). We first proposed the usage of CNTs as novel diagnostic tools for the determination of the aggressiveness of HCC. Two cell lines with different epithelial-to-mesenchymal (EMT) status, HUH7 and Snu182 were used and their attachment features on patterned CNT surfaces were compared. Our SEM images and MTT results revealed that the cells with epithelial phenotype (HUH7) attach and proliferate more on CNTs than the cells with mesenchymal phenotype (Snu182) which makes these surfaces promising diagnostic tools to differentiate HCC according to their aggressiveness. Secondly, polymer hydrogels with Dox release were suggested to be promising therapeutics to cure HCC. Our cell viability and cytotoxicity tests showed the inhibition of the proliferation of HCC line, SNU398 in the presence of drug-releasing hydrogels. This suggests the usage of hydrogels as drug delivery vehicles to have enhanced therapeutic efficacies in the HCC therapies.Item Open Access Atomic force microscopy for the investigation of molecular and cellular behavior(Elsevier, 2016-10) Ozkan A.D.; Topal, A. E.; Dana, A.; Güler, Mustafa O.; Tekinay, A. B.The present review details the methods used for the measurement of cells and their exudates using atomic force microscopy (AFM) and outlines the general conclusions drawn by the mechanical characterization of biological materials through this method. AFM is a material characterization technique that can be operated in liquid conditions, allowing its use for the investigation of the mechanical properties of biological materials in their native environments. AFM has been used for the mechanical investigation of proteins, nucleic acids, biofilms, secretions, membrane bilayers, tissues and bacterial or eukaryotic cells; however, comparison between studies is difficult due to variances between tip sizes and morphologies, sample fixation and immobilization strategies, conditions of measurement and the mechanical parameters used for the quantification of biomaterial response. Although standard protocols for the AFM investigation of biological materials are limited and minor differences in measurement conditions may create large discrepancies, the method is nonetheless highly effective for comparatively evaluating the mechanical integrity of biomaterials and can be used for the real-time acquisition of elasticity data following the introduction of a chemical or mechanical stimulus. While it is currently of limited diagnostic value, the technique is also useful for basic research in cancer biology and the characterization of disease progression and wound healing processes.Item Open Access Atomic force microscopy: Methods and applications(Elsevier, 2017) Baykara, Mehmet Z.; Schwarz, U. D.; Lindon, J.; Tranter, G. E.; Koppenaal, D.This chapter provides an overview of atomic force microscopy, covering the fundamental aspects of the associated instrumentation and methodology as well as representative results from the literature highlighting a variety of application areas. In particular, atomic-resolution imaging and spectroscopy capabilities are emphasized, in addition to applications in biology, nanotribology and catalysis research. Finally, an outlook on emerging aspects and future prospects of atomic force microscopy is provided.Item Open Access Bioinspired materials for regenerative medicine and drug delivery applications(2016-10) Hamsici, SerenThe structural organization and functional capabilities of natural materials have inspired many technological and scientific developments. Biological systems are under constant pressure for innovation due to the constraints imposed by natural selection, which has allowed various organisms to surmount engineering challenges in ways that can scarcely be matched by modern science. Biomimetics or bioinspiration is a field that focuses on the adaptation of engineering principles observed in biological models to fabricate materials capable of circumventing longstanding problems in fields such as energy and medicine. This transition from biological systems has facilitated the design of effective materials, structures or processes within the range of nature’s adaptations and strategies. In the first study of this thesis, I describe the development of a bioactive scaffold composed of adamantyl-conjugated, laminin-derived bioactive IKVAV peptide molecules enmeshed in electrospun cyclodextrin nanofiber (CDNFs). Accordingly, host-guest interactions between adamantyl groups on peptide termini and cyclodextrin molecules on electrospun nanofiber surfaces were utilized to produce a composite material for the treatment of neurodegenerative disorders. Electrospun CDNFs provided a 3-dimensional environment conductive for the growth of PC12 cells and expressed functionalized bioactive epitopes on their surfaces to enhance the differentiation of neural progenitors. In addition, CDNFs further supported neural growth through their highly aligned mesh structure. Neural bIII tubulin and synaptophysin I gene expression levels significantly increased when PC12 cells were cultured on aligned and IKVAV-functionalized CDNFs. Neurite extension of PC12 cells also increased significantly when cultured on aligned and IKVAVfunctionalized CDNFs when compared to random and unfunctionalized electrospun CDNFs. As such, these nanofibers are able to effectively induce the neural differentiation of PC-12 cells through the physical and biochemical signals provided by their structure and bioactive sequence. The second part of the present thesis focuses on the local delivery of gemcitabine, a cytotoxic cancer drug that is rapidly degraded in plasma and cannot be encapsulated in conventional delivery vesicles due to its highly hydrophobic nature. In order to overcome these limitations, gemcitabine was coupled with Fmoc-Gly and integrated into a peptide-based nanocarier system in order to control drug concentration within the therapeutic range and minimize the adverse effects. Two oppositely-charged amyloid inspired peptides (Fmoc-AIPs) were chosen as drug carrier systems. These molecules self assemble into nanofiber structures at physiological conditions through non-covalent interactions. Overall, the present thesis demonstrates the significance of peptide-based materials for the purpose of designing functional bioinspired/biomimetic materials for various cellular applications such as tissue engineering and drug delivery. The complexity of nature necessitates the design of biomaterials that can mimic the cellular microenvironment for the treatment of diseases, and further insight into natural processes will no doubt enhance our ability to overcome the engineering challenges presented by modern medicine.Item Embargo Capturing the dynamic scaffold properties of hybrid GelMA based microgels toward tissue engineering and organ-on-chips(2024-09) Çınar, Aslı GizemMicrogels have emerged as versatile materials in tissue engineering, drug delivery, and organ-on-chip (OoC) platforms due to their small scale, uniformity, and customizable properties. Their adaptability as injectable materials and dynamic scaffolds makes them promising candidates for a wide range of biomedical applications. However, traditional methods for characterizing their physical and mechanical behaviors, designed for bulk hydrogels, do not capture the unique properties of microgels, which differ significantly in terms of size and surface-to-volume ratio. This work explores the physical properties of Gelatin Methacryloyl (GelMA)-based Collagen and Hyaluronic Acid Methacrylate (HAMA) hybrid microgels produced via droplet microfluidics, employing novel assays tailored specifically to their micro-scale. Real-time observation of their swelling and degradation properties is carried out using a custom-made platform enabling the tracking of individual microgels, and electron microscopy provides insights into their internal structures, revealing previously unobserved behaviors. We have shown the interpenetrating network formation when GelMA and Collagen are used; and copolymer formation when GelMA and HAMA are used. Under the effect of Collagenase and Hyaluronidase, the individual microgels showed different degradation mechanisms, which have proven to be affected by crosslink densities, enzyme-substrate specificity, enzyme saturation, and properties of the individual network components. The work is extended by focusing more on the temporal profiling of GelMA and HAMA hybrid microgels' behaviors under enzymatic degradation, examining how volume, mechanical properties, and surface features evolve over time, simulating the dynamic conditions encountered in vivo during especially tissue engineering applications. We found that instead of carrying out separate assays to understand the changes, a more holistic approach to evaluating the aforementioned properties gives a more thorough discussion. This approach revealed that changing the ratios of GelMA against HAMA affects the crosslink densities, network formation, and ultimately degrative behaviors. We have observed, for the first time in droplet microfluidics, that a certain combination of GelMA HAMA results in microgels with a network gradient, getting denser towards the center, while the other combinations only increased the crosslink densities without altering the porous homogeneity. Furthermore, the number of microgels exposed to the same concentration of enzyme is altered to emulate different injection volumes into similar tissues, or the enzyme concentration is altered to emulate injection into different tissues. These assays showed the sensitivity of degradation profiles against enzyme saturation and competition. Meanwhile, the stiffness and surface morphology changes of microgels during degradation are examined, revealing the importance of network homogeneity in presenting stable mechanical properties during degradation. Lastly, drug release from these scaffolds is modeled for prospective applications, and their relation to scaffold properties is evaluated. Overall, this thesis is poised to discover the peculiar behaviors of GelMA hybrid microgels produced with droplet microfluidics uncovering the importance of carrying out investigations true to the sample at hand and the conditions that will be imposed upon them during application.Item Open Access Design and application of peptide nanofibers for modulating angiogenesis(2016-06) Şentürk, BernaAngiogenesis is important in many diseases, such as diabetic wound healing, cancer and corneal neovascularization. Angiogenesis can be induced or inhibited by complex biological systems. Mimicking the complexity in natural systems requires smart supramolecular architectures with predictable properties and functions. Peptides are particularly attractive as molecular building blocks in the bottom-up fabrication of supramolecular structures based on self-assembly and have potential in many important applications in the fields of tissue engineering and regenerative medicine. Peptide-based biomaterials for angiogenesis are currently an intensely investigated topic in pathology and pharmacology related studies. Peptide-based biomaterials can be utilized for the treatment of angiogenesis-deficient complications by mimicking natural glycosaminoglycans. Diabetic ulcerations are largely caused by the lack of vascularization during the wound healing process, and angiogenesis-promoting peptide nanofibers are highly promising for the treatment of these injuries. In addition to the induction of angiogenesis, peptide-based systems can also be used to prevent it in locations where it is detrimental to health. In particular, peptide amphiphiles with anti-angiogenic properties may enable the treatment severe eye diseases, including corneal neovascularization. This thesis describes nature-inspired combinatorial methods for designing peptide nanostructures that display angiogenic and anti-angiogenic functional moieties. The importance of multivalent peptide-constructs for high affinity binding and efficiency will be highlighted. Furthermore, in vitro and in vivo efficiency of angiogenesis related therapeutic agents is reported. Another type of products that will be discussed is black silicon surface that inspired also from nature, utilized for anti-bacterial and unique topographical characteristic.Item Open Access Design and applications of self-assembled soft living materials using synthetic biology(Elsevier, 2022-01-01) Özkul, Gökçe; Yavuz, Merve; Hacıosmanoğlu, Nedim; Kırpat, Büşra Merve; Şeker, Urartu Özgür ŞafakIn nature, the cells are unique biofactories of various kinds of macroscale structures. These biofactories are as old as the earth. However, as technology developed and new areas of research fields developed these cellular biofactories became the center of attention. The motive was the question if we can engineer them according to the world’s needs. At that point, approaches and tools of synthetic biology came into the picture. After its development, people started to engineer biofactories and produce materials with new properties. One of those materials is classified as self-assembled soft living materials with their specific features and usage areas. To be more specific, biofilms are examples of self-assembled soft living materials due to their self-sustaining and self-assembling properties. They can be engineered starting from genetic circuits leading to creation of their building blocks and finally formation of complex biofilm systems. With the diversity in their engineering aspects, their application areas also vary. In this chapter, the design of biofilm structures from genetic circuits until the formation of complex biofilm structures and their various applications will be investigated.Item Open Access Design, synthesis and characterization of bioinspired nanomaterials for engineering and biomedicine(2014) Ceylan, HakanNature is an inspirational school for materials scientists. Natural selection process puts a massive pressure on biological organisms giving rise to effective strategies for fabricating materials, which generally outperform their man-made counterparts. Mimicking physical and chemical features of biological materials can greatly aid in overcoming existing design constraints of engineering and medicine. In this dissertation, a reductionist, bottom-up approach is demonstrated to recapitulate biological functionalities in fully-synthetic hybrid constructs. For material design, the potential of short, rationally-designed peptides for programmed organization into nanostructured materials is explored. The resulting nano-ordered materials exhibit multifunctional and adaptive properties, which can be tailored by the information within monomeric peptide sequences as well as the emerging properties upon their self-assembly. In light of these, design, synthesis and characterization of the prototypes of nanostructured functional materials are described in the context of regenerative medicine and biomineralization.Item Open Access Development and characterization of peptide nanofibers for cartilage regeneration(2015-09) Yaylacı, SeherArticular cartilage is a tissue that is continuously exposed to cyclical compressive stresses, but exhibits no capacity for self-healing following trauma. Cartilage has a dense extracellular matrix that is sparsely populated with cells, and the whole tissue lacks blood and lymphatic vessels, which complicates the cell infiltration response that ordinarily occurs during inflammation. In addition, the only cell type capable of synthesizing new cartilage matrix lies deeper in the tissue, near the bone boundary, and due to the dense extracellular matrix, chondrocytes cannot migrate to the defect site following injury. Consequently, cartilage tissue cannot effectively respond to treatment options. Treatment options exist for the short-term reduction of pain in smaller defects, but larger injuries necessitate tissue donation, and there is a severe shortage of articular cartilage that can be donated for autografting. Microfracture and autologous chondrocyte implantation are the current treatment options that use cellular therapy for the repair of cartilage. However, the cartilage tissue that forms in the course of these treatments is not the functional hyaline cartilage, but rather fibrous cartilage, which is mechanically weaker and degenerates over time. Tissue engineering studies using biodegradable scaffolds and autologous cells are gaining importance as effective long-term treatment options for the postinjury production of hyaline cartilage. Such scaffold systems are designed to be biodegradable and bioactive, which allows them to induce new tissue formation in shorter periods of time. In this dissertation, peptide nanofibers mimicking glycosaminoglycan molecules, which are important constituents of cartilage extracellular matrix, are designed and the effectiveness of these materials in terms of chondrocyte differentation are tested under in vitro conditions. As a follow-up study to in vitro experiments, the capacity of bioactive peptide nanofibers to support cartilage regeneration is evaluated in the rabbit osteochondral defect model. Structural and mechanical properties of newly deposited cartilage are highly dependent on the quality and quantity of its extracellular matrix, which also has a major impact on the integration of replacement cartilage into the surrounding healthy tissue. Signals provided by bioactive peptide nanofibers to cells at the defect site can strongly alter the quality of the newly synthesized extracellular matrix. Consequently, we designed glycosaminoglycanmimetic peptide nanofibers that closely imitate the structure of the native cartilage extracellular matrix and demonstrated that these nanofiber networks are able to induce the synthesis of collagen II and aggrecan molecules, which are the main constituents of cartilage tissue, during chondrogenic differentiation.Item Open Access Force and time-dependent self-assembly, disruption and recovery of supramolecular peptide amphiphile nanofibers(Institute of Physics Publishing, 2018) Dikecoglu, F. B.; Topal, A. E.; Ozkan A.D.; Tekin, E. D.; Tekinay, A. B.; Güler, Mustafa O.; Dana, A.Biological feedback mechanisms exert precise control over the initiation and termination of molecular self-assembly in response to environmental stimuli, while minimizing the formation and propagation of defects through self-repair processes. Peptide amphiphile (PA) molecules can self-assemble at physiological conditions to form supramolecular nanostructures that structurally and functionally resemble the nanofibrous proteins of the extracellular matrix, and their ability to reconfigure themselves in response to external stimuli is crucial for the design of intelligent biomaterials systems. Here, we investigated real-time self-assembly, deformation, and recovery of PA nanofibers in aqueous solution by using a force-stabilizing double-pass scanning atomic force microscopy imaging method to disrupt the self-assembled peptide nanofibers in a force-dependent manner. We demonstrate that nanofiber damage occurs at tip-sample interaction forces exceeding 1 nN, and the damaged fibers subsequently recover when the tip pressure is reduced. Nanofiber ends occasionally fail to reconnect following breakage and continue to grow as two individual nanofibers. Energy minimization calculations of nanofibers with increasing cross-sectional ellipticity (corresponding to varying levels of tip-induced fiber deformation) support our observations, with high-ellipticity nanofibers exhibiting lower stability compared to their non-deformed counterparts. Consequently, tip-mediated mechanical forces can provide an effective means of altering nanofiber integrity and visualizing the self-recovery of PA assemblies.Item Open Access Functional bacterial amyloid nanomaterials(2016-09) Önür, TuğçeMis-folded or unfolded proteins tend to aggregate and aggregated structures are called as amyloids. Amyloid formation contributes to some human diseases and resulting in death in some cases. On the other hand, functional amyloids are found in nature and they are highly ordered assembled structures and they function in cellular events. Some bacteria, fungi or yeast species synthesize these kind of functional amyloids. For example, curli proteins of Escherichia coli play a role in initial attachments for biofilm formation and contribute to stiffness of the biofilm matrix. CsgA is the major subunit while CsgB is the minor subunits which nucleates CsgA polymerization. They are capable of attachment to the abiotic or biotic surfaces. Both of them share some characteristics with non-functional amyloids. For instance, their structures are dominated by ß sheets so they have a rigid amyloid core domain that enables to resist stress factors such as proteases and detergent treatment or pH. Their stable structures and adhesive properties make them useful in materials science. Moreover, high yield could be obtained easily by using molecular biology techniques such as cloning and protein purification so they are highly cost-effective materials. In this study, CsgA and CsgB fibers were proposed as new type of functional biomaterials to do so fiber formations of CsgA and CsgB were analyzed in detail. csgA and csgB genes were cloned into expression vectors. Their ß sheet rich structures were validated with CD analysis and binding capability to Thioflavin T dye were assayed which is the general property of amyloids. Self-seeding and cross-seeding strategies were applied to analyze fiber formation and quartz crystal microbalance with dissipation (QCM-D) was used. Gold coated sensors were deposited with freshly purified proteins and polymerized. Then, sensor surfaces were monitored with SEM and AFM. With self-seeding strategies long and branched fibers were obtained from CsgA proteins while sphere like structures were formed by CsgB proteins. Also, it was concluded from the cross-seeding experiments, the order of protein addition determines the final assembled structures. Furthermore, fluorescent properties of CsgA and CsgB were analyzed in detail for the first time. Finally, binding affinity of the purified proteins to different materials (gold, silica and hydroxyapatite) were determined by using QCM-D.Item Open Access Investigation of the effects of bioactive peptide nanofibers on acute muscle injury regeneration(2016-10) Eren Çimenci, ÇağlaSkeletal muscle constitutes a large part of the human body. It is a hierarchically organized heterogeneous tissue and is composed of muscle fiber bundles, muscle fibers, myofibrils and myofilaments. Since muscle cells are terminally differentiated, they have limited capacity to renew themselves. Only new cells can fuse with muscle fibers and increase the size and volume of skeletal muscle. Myosatellite cells or satellite cells are small, mononuclear progenitor cells with virtually no cytoplasm. They are located in between the sarcolemma and basement membrane of terminally-differentiated muscle fibers. Satellite cells are precursors to skeletal muscle cells, and are able to give rise to satellite cells or differentiated skeletal muscle cells. They are normally found in silent state in adult muscle, but act as a reserve cell population that is able to proliferate in response to injury and give rise to regenerated muscle and to more satellite cells. Formation of the new muscular tissue is called myogenesis. During this event, satellite cells differentiate into myoblasts, and then myoblasts fuse with each other in order to form myofibers. There are many genes that regulate the myogenesis process and each of them is activated in a different step of myogenesis. Increased or decreased levels of gene expression determine the differentiation capacity. Peptide nanofibers are supramolecular structures formed via self-assembly and they are promising molecules in regenerative medicine and tissue engineering. Peptide-based molecules for tissue regeneration is a widely studied area and currently used in the treatment-investigation of many different tissues such as bone, cartilage, skin and nerve. Since laminin is one of the most abundant proteins found in the basal membrane of the skeletal muscle; in this thesis, we designed and synthesized a laminin-mimetic bioactive (LM/E-PA) molecule functionalized with bioactive groups for mimicking laminin activities and capable of accelerating satellite cell activation. Our research group had previously shown that LM/E-PA containing nanofibers can support muscle differentiation in vitro. In this thesis, the clinical relevance was demonstrated further by assessing laminin-mimetic bioactive scaffold in acute muscle injury in an in vivo rat model. Our findings revealed that this scaffold system significantly promotes satellite cell activation in skeletal muscle and accelerates regeneration following acute muscle injury. In addition, our findings show that the regeneration capacity of the skeletal muscle was increased and consequently regeneration time was reduced. This study is one of the first examples of molecular level and tissue level regeneration of skeletal muscle by using bioactive peptide nanofibers following acute muscle injury, and shows that laminin mimetic nanofiber system is a promising material for development of new therapeutic curatives for acute skeletal muscle injuries.Item Open Access Materials for articular cartilage regeneration(Bentham Science Publishers B.V., 2012) Tombuloglu, Ayşegül; Tekinay, Ayşe B.; Güler, Mustafa O.Many health problems remaining to be untreatable throughout the human history can be overcome by utilizing new biomedical materials. Healing cartilage defects is one of the problems causing significant health issue due to low regeneration capacity of the cartilage tissue. Scaffolds as three-dimensional functional networks provide promising tools for complete regeneration of the cartilage tissue. Diversity of materials and fabrication methods give rise to many forms of scaffolds including injectable and mechanically stable ones. Various approaches can be considered depending on the condition of cartilage defect. A scaffold should maintain tissue function within a short time, and should be easily applied in order to minimally harm the body. This review will cover several patents and other publications on materials for cartilage regeneration with an outlook on essential characteristics of materials and scaffolds.Item Open Access Protein-releasing conductive anodized alumina membranes for nerve-interface materials(Elsevier Ltd, 2016) Altuntas, S.; Buyukserin, F.; Haider, A.; Altinok, B.; Bıyıklı, Necmi; Aslim, B.Nanoporous anodized alumina membranes (AAMs) have numerous biomedical applications spanning from biosensors to controlled drug delivery and implant coatings. Although the use of AAM as an alternative bone implant surface has been successful, its potential as a neural implant coating remains unclear. Here, we introduce conductive and nerve growth factor-releasing AAM substrates that not only provide the native nanoporous morphology for cell adhesion, but also induce neural differentiation. We recently reported the fabrication of such conductive membranes by coating AAMs with a thin C layer. In this study, we investigated the influence of electrical stimulus, surface topography, and chemistry on cell adhesion, neurite extension, and density by using PC 12 pheochromocytoma cells in a custom-made glass microwell setup. The conductive AAMs showed enhanced neurite extension and generation with the electrical stimulus, but cell adhesion on these substrates was poorer compared to the naked AAMs. The latter nanoporous material presents chemical and topographical features for superior neuronal cell adhesion, but, more importantly, when loaded with nerve growth factor, it can provide neurite extension similar to an electrically stimulated CAAM counterpart.Item Open Access Self-assembled peptide based biomaterials for drug delivery and regenerative medicine(2016-06) Çinar, GöksuSelf-assembly is a nature inspired novel engineering tool to build functional new generation of adaptable and complex biomaterials with variety of chemical and physical properties based on recent discoveries at the interface of chemistry, biology and materials science. Within self-assembling building blocks, peptides consisting natural amino acids and possibilities to integrate other molecules via synthetic approaches are intriguing biomacromolecules to obtain dynamic architectures at both nano and bulk scales for biomedical applications. In this thesis, the development of novel biomaterials through molecular self-assembly of the biomimetic peptides, bioactive peptide amphiphiles and their composite architectures with polymeric system for biomedical applications were presented. In the first chapter, the concept of self-assembly, design principles of the self-assembling peptide based building blocks and advanced characterization techniques for these materials were discussed to provide general perspective on the field. The applications of peptide based biomaterials with an emphasis on the drug delivery and regenerative medicine purposes were also highlighted in this part. In the second chapter, amyloid inspired self-assembling peptides and their supramolecular assemblies were presented in the context of developing nature-inspired biocompatible and mechanically stable supramolecular peptide based biomaterials. In the third chapter, supramolecular PA nanofiber gels which can form supramolecular nanofibrous networks at physiological conditions and encapsulate chemotherapeutics with high efficacy were examined as controlled local drug delivery system at both in vitro and in vivo conditions. In the fourth chapter, the facile fabrication strategy to create a novel self-assembled peptide amphiphile (PA) nanofibers and PEG composite hydrogel system as synthetic ECM analogues was discussed. It was showed that the synergistic combination of different classes of materials provide us new opportunities to develop biomaterials with independently tunable biochemical, mechanical and physical properties.Item Open Access Tuning viscoelastic properties of supermolecular peptide gels via dynamic covalent crosslinking(Royal Society of Chemistry, 2015-12-19) Khalily, M. A.; Goktas, M.; Güler, Mustafa O.A dynamic covalent crosslinking approach is used to crosslink supramolecular peptide gels. This novel approach facilitates tuning viscoelastic properties of the gel and enhances mechanical stability (storage modulus exceeding 10(5) Pa) of the peptide gels.