Browsing by Subject "Peptide Nanofibers"

Now showing 1 - 5 of 5

Open Access
Bioactive porous peg-peptide composite hydrogels with tunable mechanical properties
(2014) Göktaş, Melis
Mimicking the instructive cues of native extracellular matrix (ECM) is fundamental to understand and control the processes regulating cell function and cell fate. Extensive research on the structure and biological complexity of ECM has shown that three types of critical information from the ECM have influence on cellular behaviour: (1) biophysical properties (elasticity, stiffness), (2) biochemical properties (bioactive peptide epitopes of ECM molecules), and (3) nanoarchitecture (nanofibrillar structure, porosity) of ECM. Recent efforts have therefore focused on the construction of ECM mimetic materials to modulate tissue specific cell functions. Advances in biomaterial platforms include artificial ECM mimics of peptide conjugated synthetic polymer hydrogels presenting bioactive ligands produced with covalent chemistry. These materials have already found application in tissue engineering, however, these biomaterial platforms represent oversimplified mimics of cellular microenvironment and lack the complexity and multifunctional aspects of native ECM. In this work, we developed a novel polyethylene glycol (PEG)-peptide nanofiber composite hydrogel system with independently tunable biochemical, mechanical and physical cues that does not require any chemical modification of polymer backbone to create synthetic ECM analogues. This approach allows noninteracting modification of multifactorial niche properties (i.e. bioactive ligands, stiffness, porosity), since no covalent conjugation method was used to modify PEG monomers for the incorporation of bioactivity and porosity. Combining the self-assembled peptide nanofibers with crosslinked polymer network simply by facile mixing followed by photo-polymerization resulted in the formation of porous hydrogel systems. Resulting porous network can be functionalized with desired bioactive signalling epitopes by simply altering the amino acid sequence of peptide amphiphile molecules. In addition, the mechanical properties of the composite system can be precisely controlled by changing the PEG concentration. Ultimately, multifunctional PEG-peptide composite scaffolds reported in this work, can fill a critical gap in the available biomaterials as versatile synthetic mimics of ECM with independently tunable properties. Such a system could provide a useful tool allowing the investigation of how complex niche cues interplay to influence cellular behaviour and tissue formation both in 2D and 3D platforms.
Open Access
Biomimetic self-assembled peptide nanofibers for bone regeneration
(2012) Kocabey, Samet
Self-assembled peptide nanofibers are exploited in regenerative medicine applications due to their versatile, biofunctional and extracellular-matrixresembling structures. These properties provide peptide nanofibers with osteoinductive and osteoconductive behaviors for bone regeneration applications through several approaches. In this thesis, two different approaches were discussed, which were developed to induce bone regeneration and mineralization including extracellular matrix mimicking peptide nanofibers based 2-D gel formation and surface functionalization of titanium implants. For this purpose, we designed glycosaminoglycan-mimetic peptide nanofibers inspired by chemical structure of glycosaminoglycans present in the bone extracellular matrix. We demonstrated that glycosaminoglycan-mimetic peptide nanofibers interact with BMP-2, a critical growth factor for osteogenic activity. Glycosaminoglycan-mimicking ability of the peptide nanofibers and their interaction with BMP-2 promoted osteogenic activity of and mineralization by osteoblastic cells. ALP activity, Alizarin Red Staining and EDAX spectroscopy indicated efficacy of the peptide nanofibers for inducing mineralization. We also developed a hybrid osteoconductive system for titanium biomedical implants inspired by mussel adhesion mechanism in order to overcome bone tissue integration problems. For this purpose, Dopa conjugated peptide nanofiber coating was used along with bioactive peptide sequences for osteogenic activity to enhance osseointegration of titanium surface. Dopamediated immobilization of osteogenic peptide nanofibers on titanium surfaces created an osteoconductive interface between osteoblast-like cells and inhibited adhesion and viability of soft tissue forming fibroblasts compared to the uncoated titanium substrate. In summary, osteoinductive and osteoconductive self-assembled peptide nanofibers were developed to promote osteogenic activity and mineralization of osteogenic cells. These bioactive nanofibers provide a potent platform in clinical applications of bone tissue engineering.
Open Access
Design and application of peptide nanofibers for modulating angiogenesis
(2016-06) Şentürk, Berna
Angiogenesis 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.
Open Access
Investigation of the effects of supramolecular structures of cationic peptides on antibacterial activity
(2017-05) Beter, Mustafa
Many organisms including mammalians use Antimicrobial Peptides (AMPs) which are also called Host Defense Peptides against microbial organisms. AMPs are among one of the ancient and successful strategies for both plant and animal kingdoms. Even though AMPs vary among closely related species and despite they have different sequences, many of the natural AMPs share similar properties. They are mostly short sequenced, structurally amphipathic and they carry overall net positive charge. Cationic AMPs target bacterial membranes because of the electrostatic attractions between positively charged peptides and negatively charged membranes. Due to the electrostatic attractions, cationic AMPs might work on membrane disruption by passing a certain threshold concentration for hydrophobic groups to penetrate into membrane. Noncovalent interactions and electrostatic interactions can create molecular attractions and may cause molecular self-assembly which is a common mechanism used by nature for several tasks. Self-assembling peptide amphiphiles are a group of molecules which can form nanofibrous structures and may contain bioactive epitopes depending on the target of the peptide amphiphile molecule. This thesis describes the presentation of antimicrobial sequences on supramolecular nanofibers which are formed by self-assembling peptides. The comparison of self-assembling peptides and single soluble peptides without self-assembling capacity, resulting significant improvement for peptide nanofiber systems for antimicrobial therapeutic purposes is reported.
Open Access
Small functional groups presented on peptide nanofibers for determining fate of rat mesenchymal stem cells
(2014) Yaşa, Öncay
Glycosaminoglycans (GAGs) are negatively-charged, unbranched polysaccharides that play important roles in various biological processes and are vital for the regeneration of damaged tissues. Like other natural extracellular matrix components, glycosaminoglycans and proteoglycans show considerable variation in local concentration and chemical composition depending on tissue type. They are found in various connective tissues, including bone, cartilage and fat, and display strong water-binding capacity due to their negative charges. Mechanical characters of GAGs are heavily influenced by the degree and pattern of sulfation, which may greatly alter their viscoelasticity and physiological functions. Variations in GAG sulfation patterns are created principally through extracellular matrix modeling. Due to their extracellular matrix-organizing abilities, glycosaminoglycans are promising biomacromolecules for the design of new bioactive materials for tissue engineering and tissue reconstruction applications. In this study, we functionalized peptide amphiphile molecules with carboxylate and sulfonate groups to develop nanofibrous networks displaying a range of chemical patterns, and evaluated the effect of the chemical groups over the differentiation fate of rat mesenchymal stem cells. We demonstrate that higher sulfonate-to-glucose ratios are associated with adipogenesis, while higher carboxylate-to-glucose ratios resulted in chondrogenic and osteogenic differentiation of the rat mesenchymal stem cells.