Browsing by Subject "Mineralization"
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Item Open Access Biomimetic self-assembled peptide nanofibers for bone regeneration(Bilkent University, 2012) Kocabey, SametSelf-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.Item Unknown Glycosaminoglycan mimetric peptide nanofibers promote mineralization by osteogenic cells(Elsevier, 2013) Kocabey, Samet; Ceylan, Hakan; Tekinay, Ayse B.; Güler, Mustafa O.Bone tissue regeneration is accomplished by concerted regulation of protein-based extracellular matrix components, glycosaminoglycans (GAGs) and inductive growth factors. GAGs constitute a significant portion of the extracellular matrix and have a significant impact on regulating cellular behavior, either directly or through encapsulation and presentation of growth factors to the cells. In this study we utilized a supramolecular peptide nanofiber system that can emulate both the nanofibrous architecture of collagenous extracellular matrix and the major chemical composition found on GAGs. GAGs and collagen mimetic peptide nanofibers were designed and synthesized with sulfonate and carboxylate groups on the peptide scaffold. The GAG mimetic peptide nanofibers interact with bone morphogenetic protein-2 (BMP-2), which is a critical growth factor for osteogenic activity. The GAG mimicking ability of the peptide nanofibers and their interaction with BMP-2 promoted osteogenic activity and mineralization by osteoblastic cells. Alkaline phosphatase activity, Alizarin red staining and energy dispersive X-ray analysis spectroscopy indicated the efficacy of the peptide nanofibers in inducing mineralization. The multifunctional and bioactive microenvironment presented here provides osteoblastic cells with osteogenic stimuli similar to those observed in native bone tissue.Item Open Access Molecular analysis of enginereed nanomaterials in biomedical and regenerative medicine applications(Bilkent University, 2019-04) Gündüz, NurayMolecular mechanisms are inspiration source for effective nanomaterial synthesis through minimalist bottom-up approaches. Mimicking functional biophysicochemical properties of biomacromolecules can give new insights for design and synthesis of nanomaterials used in biomedical and regenerative medicine applications. In this thesis, rationally-designed nanomaterials and their biomedical applications as oral ketone delivery and biomineralization and long-term potential toxicities were investigated. In the first chapter, basic concepts of nanomaterial design, synthesis, characterization, and nano-bio interface were explained. In the second chapter, a novel long-term nanoparticle accumulation model was developed to understand active regulation of nanoparticle uptake, nanoparticle accumulation behavior and the impact of long-term exposure on cellular machineries (e.g. ER stress). In the third chapter, the role of ketone body betahydroxybutryrate (βOHB) generated by a metabolic enzyme, hydroxymethylglutaryl CoA synthase 2 (HMGCS2), on intestinal stem cell maintenance and regeneration after radiation injury was investigated. Consequences of βOHB depletion in intestine were rectified by oral delivery of PLGA-encapsulated and oligomer forms of βOHB. The last chapter, acidic epitopes of enamel proteins (e.g. amelogenin) were integrated into self-assembling peptides to remineralize eroded enamel. Overall these studies show potential of natureinspired engineered nanomaterials in vast range of biomedical and regenerative medicine applications.Item Open Access Nanomaterials for bone tissue regeneration and orthopedic implants(John Wiley & Sons, 2016-03-11) Gülseren, Gülcihan; Ceylan, Hakan; Tekinay, Ayşe B.; Güler, Mustafa O.; Güler, Mustafa O.; Güler, Ayşe B.Hierarchical organization and specialized composition of bone extracellular matrix (ECM) control the cellular processes including proliferation, migration, and differentiation for continuous modulation and maintenance of structure. For bone tissue regeneration, peptideor polymer‐based biomaterials have offered a framework to design interactive molecules displaying bone composite properties to mimic living bone tissue. This chapter reviews the structure and properties of peptide‐ and polymer‐based soft grafts for bone tissue regeneration, with a summary of upcoming goals and challenges in the future of these versatile materials. It basically covers types and applications of soft bone grafts, directed bone regeneration from biocompatible and bioactive biomaterials, and nanocomposite scaffolds for bone tissue regeneration. Bone regeneration studies have been primarily focused on polymers and synthetic proteins. The chapter describes some of the significant contribcutions to the field of bone regeneration with self‐assembled peptide structures.