Browsing by Subject "Hyaluronic acid"
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Item Open Access Bioactive glycopeptide nanofibers for tissue regeneration applications(Bilkent University, 2016-05) Çalışkan, Özüm Şehnaz.Natural extracellular matrix (ECM) is rich in glycopeptides and glycosaminoglycans, which function in controlling cellular processes. In this thesis, glycopeptide molecules that mimic natural glycopeptides and glycosaminoglycans were designed and synthesized and it was demonstrated that they induce directed differentiation of mesenchymal stem cells into chondrogenic and adipogenic lineages. In the first part of the study, hyaluronic acid (HA)-mimicking glycopeptide amphiphile molecules were synthesized to induce chondrogenic differentiation of mesenchymal stem cells (MSC). HA is the most abundant glycosaminoglycan (GAG) found in hyaline cartilage ECM. Peptide amphiphiles were synthesized by solid phase peptide synthesis method and used to form self-assembled bioactive glycopeptide nanofibers which mimic fibrous morphology of the ECM. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and circular dichroism (CD) were used for morphology and secondary structure analyses of the obtained nanofibers. It was demonstrated that glycopeptide amphiphiles create fibrous structure formed by nanofibers. Morphological changes, GAG production (Safranin-O staining and DMMB analysis), and chondrogenic gene marker expressions (qRT-PCR) of MSCs cultured on HA-mimetic nanofibers were analyzed. It was shown that HA-mimetic glycopeptide nanofibers induce early differentiation of MSCs into hyaline like chondrocytes. In the second part of the study, it was demonstrated that minor changes on glycopeptide backbone can create specific glycopeptides which induce differentiation of MSCs into brown adipocytes. Brown fat adipocytes do not store chemical energy as fat but dissipates it as heat and so they have emerged as promising anti-obesity agents. Lipid droplet accumulation (Oil Red-O staining) and adipogenic gene marker expression analyses (qRT-PCR) showed that the new glycopeptide nanofiber scaffold is a specific inducer of differentiation of MSCs into brown fat adipocytes.Item Open Access Investigating physical properties of hybrid hyaluronic acid and collagen compositions of GelMA microgels toward tissue engineering and organ-on-chip applications(American Chemical Society, 2023-10-13) Çınar, Aslı Gizem; Munir, IqraMicrogels are promising tools in biomedical sciences to be utilized as 3D cell culture scaffolds and cell-delivery or drug-delivery vehicles. Carrying the desired properties of hydrogels, they can be fabricated from various materials in different shapes and sizes. Additionally, due to their increased surface-to-volume ratio, they provide fast nutrient, waste, and species transport with altered solute–material interactions. Despite their micrometer size and the differentiated behaviors that come with these properties, the characterization methods utilized so far to investigate their physical and morphological properties are majorly carried out on their bulk versions, resulting in inaccurate estimates and somewhat missed information. Here, in this work, swelling, degradation, and morphological examination assays curated for microgels are proposed to reflect the actual behavior of microgels. Accordingly, gelatin methacryloyl, complemented with hyaluronic acid methacrylate and collagen to set an example of different types of polymer networks, was fabricated into microgels using a droplet microfluidic platform with in situ photopolymerization. An easy washing and drying process is proposed as a substitution for the harsh conditions of lyophilization for morphological analysis, resulting in a much more accurate picture of the porous structures. Swelling and enzymatic degradation assays, usually done by immersing a bulk hydrogel in a medium for an extended period, are substituted with swelling and degrading individual microgels in a custom-made platform that enables real-time, statistically significant data acquisition. Results showed that, due to their small size, swelling occurs in a matter of minutes, with different temporal profiles depending on the medium and microgel compositions, and enzymatic degradation takes place in a couple of hours with varying behaviors, changing due to the polymers, enzyme type, and concentration. Overall, this work highlights the necessity and importance of characterizing microgels in their respective sizes, hopefully advancing their utilization in microphysiological systems and biomedical applications.Item Open Access Protective therapeutic effects of peptide nanofiber and hyaluronic acid hybrid membrane in in vivo osteoarthritis model(Acta Materialia Inc, 2018) Arslan, Elif; Ekiz, Melis Sardan; Cimenci, Cagla Eren; Can, N.; Gemci, M. H.; Ozkan, H.; Güler, Mustafa O.; Tekinay, Ayse B.Osteoarthritis (OA) is a condition where tissue function is lost through a combination of secondary inflammation and deterioration in articular cartilage. One of the most common causes of OA is age-related tissue impairment because of wear and tear due to mechanical erosion. Hyaluronic acid-based viscoelastic supplements have been widely used for the treatment of knee injuries. However, the current formulations of hyaluronic acid are unable to provide efficient healing and recovery. Here, a nanofiber-hyaluronic acid membrane system that was prepared by using a quarter of the concentration of commercially available hyaluronic acid supplement, Hyalgan® was used for the treatment of an osteoarthritis model, and Synvisc® which is another commercially available hyaluronic acid containing viscoelastic supplement, was used as a control. The results show that this system provides efficient protection of arthritic cartilage tissue through the preservation of cartilage morphology with reduced osteophyte formation, protection of the subchondral region from deterioration, and maintenance of cartilage specific matrix proteins in vivo. In addition, the hybrid nanofiber membrane enabled chondrocyte encapsulation and provided a suitable culturing environment for stem cell growth in vitro. Overall, our results suggest that this hybrid nanofibrous scaffold provides a potential platform the treatment of OA. Statement of Significance: Osteoarthritis is a debilitating joint disease affecting millions of people worldwide. It occurs especially in knees due to aging, sport injuries or obesity. Although hyaluronic acid-based viscoelastic supplements are widely used, there is still no effective treatment method for osteoarthritis, which necessitates surgical operation as an only choice for severe cases. Therefore, there is an urgent need for efficient therapeutics. In this study, a nanofiber-HA membrane system was developed for the efficient protection of arthritic cartilage tissue from degeneration. This hybrid nanofiber system provided superior therapeutic activity at a relatively lower concentration of hyaluronic acid than Hyalgan® and Synvisc® gels, which are currently used in clinics. This work demonstrates for the first time that this hybrid nanofiber membrane scaffold can be utilized as a potential candidate for osteoarthritis treatment.Item Open Access Rose petal topography mimicked poly(dimethylsiloxane) substrates for enhanced corneal endothelial cell behavior(Elsevier, 2021-04-30) Öztürk-Öncel, M. Ö.; Erkoc-Biradli, F. Z.; Rasier, R.; Marçalı, Merve; Elbüken, Çağlar; Garipcan, B.Low proliferation capacity of corneal endothelial cells (CECs) and worldwide limitations in transplantable donor tissues reveal the critical need of a robust approach for in vitro CEC growth. However, preservation of CEC-specific phenotype with increased proliferation has been a great challenge. Here we offer a biomimetic cell substrate design, by optimizing mechanical, topographical and biochemical characteristics of materials with CEC microenvironment. We showed the surprising similarity between topographical features of white rose petals and corneal endothelium due to hexagonal cell shapes and physiologically relevant cell density (≈ 2000 cells/mm2). Polydimethylsiloxane (PDMS) substrates with replica of white rose petal topography and cornea-friendly Young's modulus (211.85 ± 74.9 kPa) were functionalized with two of the important corneal extracellular matrix (ECM) components, collagen IV (COL 4) and hyaluronic acid (HA). White rose petal patterned and COL 4 modified PDMS with optimized stiffness provided enhanced bovine CEC response with higher density monolayers and increased phenotypic marker expression. This biomimetic approach demonstrates a successful platform to improve in vitro cell substrate properties of PDMS for corneal applications, suggesting an alternative environment for CEC-based therapies, drug toxicity investigations, microfluidics and organ-on-chip applications.Item Open Access Supramolecular GAG-like self-assembled glycopeptide nanofibers Induce chondrogenesis and cartilage regeneration(American Chemical Society, 2016) Yaylaci, U. S.; Ekiz, M. S.; Arslan, E.; Can, N.; Kilic, E.; Ozkan, H.; Orujalipoor, I.; Ide, S.; Tekinay, A. B.; Güler, Mustafa O.Glycosaminoglycans (GAGs) and glycoproteins are vital components of the extracellular matrix, directing cell proliferation, differentiation, and migration and tissue homeostasis. Here, we demonstrate supramolecular GAG-like glycopeptide nanofibers mimicking bioactive functions of natural hyaluronic acid molecules. Self-assembly of the glycopeptide amphiphile molecules enable organization of glucose residues in close proximity on a nanoscale structure forming a supramolecular GAG-like system. Our in vitro culture results indicated that the glycopeptide nanofibers are recognized through CD44 receptors, and promote chondrogenic differentiation of mesenchymal stem cells. We analyzed the bioactivity of GAG-like glycopeptide nanofibers in chondrogenic differentiation and injury models because hyaluronic acid is a major component of articular cartilage. Capacity of glycopeptide nanofibers on in vivo cartilage regeneration was demonstrated in microfracture treated osteochondral defect healing. The glycopeptide nanofibers act as a cell-instructive synthetic counterpart of hyaluronic acid, and they can be used in stem cell-based cartilage regeneration therapies.