Browsing by Subject "Bone regeneration"

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Open Access
Bioactive peptide nanofibers for bone tissue regeneration
(2017-06) Tansık, Gülistan
Replacement and repair of bone tissue that is lost due to fractures, tumor resection, degenerative diseases and infections still remain major clinical challenges. Autografting, allografting and xenografting are the current strategies for the treatment of bone defects. However, these strategies cause problems such as immunological response and disease transmission in clinical applications. To overcome these limitations, regeneration of new bone can be induced by the use of synthetic bioactive materials. One of the most promising strategies is to develop synthetic scaffolds mimicking the functional components of the extracellular matrix (ECM). Biomineralization is mineralization carried out by living organisms. Glycosaminoglycans have crucial roles in biomineralization and enhance the functions of growth factors involved in biomineralization. Success in bone regeneration studies requires a thorough understanding of the necessary conditions for triggering biomineralization during the bone tissue formation process. In this study, the effect of bioactive and biocompatible peptide nanofibers on osteogenic differentiation, biomineralization and bone tissue regeneration are investigated under in vitro and in vivo conditions. In the first chapter, bone tissue composition, the clinical need for bone regeneration and general principles in bone tissue engineering are discussed. Bone tissue regeneration strategies are also highlighted in this part, with emphasis on peptide amphiphiles and self-assembly behavior. In the second chapter, a fully synthetic, extracellular matrix-mimetic peptide nanofiber system is described for enhancing the biomineralization and regeneration of bone tissue. This nanostructural environment forms artificial intracellular networks and supports biomineralization by providing cell-material and protein-material interactions. In the third chapter, effect of osteoinductive peptide nanofibers on osteogenic differentiation of rat mesenchymal stem cells (MSCs) were investigated. In the fourth chapter, the natural biomineralization process in bone tissue was mimicked on peptide nanofibers and the effect of this system on the osteogenic differentiation of osteoblast-like cells was investigated. In the fifth chapter, a dentin-mimetic peptide amphiphile (SpDSp-PA) molecule that is capable of emulating the structure and function of dentin phosphoprotein was designed and its capacity to support the deposition of hydroxyapatite and survival and biomineralization of osteoblast-like cells was evaluated.
Open Access
Chemical and topographical modification of PHBV surface to promote osteoblast alignment and confinement
(John Wiley & Sons, Inc., 2008) Kenar, H.; Kocabas, A.; Aydınlı, Atilla; Hasirci, V.
Proper cell attachment and distribution, and thus stronger association in vivo between a bone implant and native tissue will improve the success of the implant. In this study, the aim was to achieve promotion of attachment and uniform distribution of rat mesenchymal stem cell-derived osteoblasts by introducing chemical and topographical cues on poly(3-hydroxybutyrate-co-3- hydroxyvalerate) (PHBV) film surfaces. As the chemical cues, either alkaline phosphatase was covalently immobilized on the film surface to induce deposition of calcium phosphate minerals or fibrinogen was adsorbed to improve cell adhesion. Microgrooves and micropits were introduced on the film surface by negative replication of micropatterned Si wafers. Both chemical cues improved cell attachment and even distribution on the PHBV films, but Fb was more effective especially when combined with the micropatterns. Cell alignment (<10° deviation angle) parallel to chemically modified microgrooves (1, 3, or 8 μm groove width) and on 10 μm-thick Fb lines printed on the unpatterned films was achieved. The cells on unpatterned and 5 μm-deep micropitted films were distributed and oriented randomly. Results of this study proved that microtopographies on PHBV can improve osseointegration when combined with chemical cues, and that microgrooves and cell adhesive protein lines on PHBV can guide selective osteoblast adhesion and alignment.
Open Access
A glycosaminoglycan mimetic peptide nanofiber gel as an osteoinductive scaffold
(Royal Society of Chemistry, 2016) Tansik, G.; Kilic, E.; Beter, M.; Demiralp, B.; K.Sendur, G.; Can, N.; Ozkan, H.; Ergul, E.; Güler, Mustafa O.; Tekinay, A. B.
Biomineralization of the extracellular matrix (ECM) plays a crucial role in bone formation. Functional and structural biomimetic native bone ECM components can therefore be used to change the fate of stem cells and induce bone regeneration and mineralization. Glycosaminoglycan (GAG) mimetic peptide nanofibers can interact with several growth factors. These nanostructures are capable of enhancing the osteogenic activity and mineral deposition of osteoblastic cells, which is indicative of their potential application in bone tissue regeneration. In this study, we investigated the potential of GAG-mimetic peptide nanofibers to promote the osteogenic differentiation of rat mesenchymal stem cells (rMSCs) in vitro and enhance the bone regeneration and biomineralization process in vivo in a rabbit tibial bone defect model. Alkaline phosphatase (ALP) activity and Alizarin red staining results suggested that osteogenic differentiation is enhanced when rMSCs are cultured on GAG-mimetic peptide nanofibers. Moreover, osteogenic marker genes were shown to be upregulated in the presence of the peptide nanofiber system. Histological and micro-computed tomography (Micro-CT) observations of regenerated bone defects in rabbit tibia bone also suggested that the injection of a GAG-mimetic nanofiber gel supports cortical bone deposition by enhancing the secretion of an inorganic mineral matrix. The volume of the repaired cortical bone was higher in GAG-PA gel injected animals. The overall results indicate that GAG-mimetic peptide nanofibers can be utilized effectively as a new bioactive platform for bone regeneration. © 2016 The Royal Society of Chemistry.