Browsing by Subject "Hydrogels"

Now showing 1 - 15 of 15

Open Access
Boronic acid conjugated peptide amphiphile systems for controlled drug release
(2017-08) Kara, Hatice Kübra
Targeted cancer drug delivery is still under investigation and scientists have been focusing on major differences between healthy and cancer tissue to develop novel effective therapies. The cancer microenvironment has different physiological properties than the healthy tissues, for instance, it has more acidic pH, and much of the attention has been given to developing stimuli responsive agents for targeted drug delivery applications. Boronic acid is one of the most well-known stimuli responsive molecule which can form reversible covalent bonds with vicinal diols such as saccharide or catechol, that achieves targeted cancer drug release in a pH dependent manner. At neutral pH, the bond formation is triggered; however, these bonds become weaker at slightly acidic environment. Boronic acid conjugated polymers have been frequently preferred for doxorubicin encapsulation, which is a widely used chemotherapeutic drug utilized to treat several cancer types. In this study, boronic acid and DOPA conjugated peptide amphiphiles were used as a biocompatible and biodegradable alternative to polymeric systems. Peptide amphiphiles self assemble to form peptide nanofibers via noncovalent interactions, such as hydrogen bonding, hydrophobic interactions, van der Waals forces and electrostatic interactions, where boronic acid/DOPA units remain on the exterior part of the nanofibers. In addition to noncovalent interactions, at physiological pH, boronic acid and DOPA moieties on the peptide surface form reversible covalent complexes, resulting in improved hydrogel strength, self-healing capacity and entrapment of doxorubicin inside the 3D-network. On the other hand, under acidic conditions, these interactions weaken and doxorubicin release is accelerated at tumor site. Reversible covalent interaction, secondary structure, morphological, mechanical, release profile analysis were performed on the system. Results showed that this system exhibits promising features that can be used for therapeutic applications.
Embargo
Capturing the dynamic scaffold properties of hybrid GelMA based microgels toward tissue engineering and organ-on-chips
(2024-09) Çınar, Aslı Gizem
Microgels 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.
Open Access
Cucurbit [7] uril-threaded fluorene-thiophene-based conjugated polyrotaxanes
(Royal Society of Chemistry, 2016) Idris, M.; Bazzar, M.; Guzelturk, B.; Demir, Hilmi Volkan; Tuncel, D.
Here we investigate the effect of cucurbit[7]uril (CB7) on the thermal and optical properties of fluorene-thiophene based conjugated polyelectrolytes. For this purpose, poly(9,9′-bis(6′′-(N,N,N-trimethylammonium)hexyl)fluorene-alt-co-thiophenelene) P1 and poly(9,9′-bis(6′′-(N,N,N-trimethylammonium)propyl)fluorene-alt-co-thiophenelene) P2 and their CB7-based polyrotaxane counterparts, P1CB7 and P2CB7, are synthesized by threading the part of the conjugated backbone of these polymers with CB7 during their synthesis. Threading efficiency in the P1CB7 containing hexyl pendant of as high as 50% is achieved, but in the case of P2, with the propyl pendant, only around 15% is achieved. We observed significant changes in the optical properties of both P1CB7 and P2CB7 with respect to their polymers P1 and P2. Fluorescent quantum yields of P1 and P2 which are 0.11 and 0.35 have increased to 0.46 and 0.55 for P1CB7 (>4 fold) and P2CB7, respectively. Moreover, polyrotaxanes compared to their polymers exhibit longer fluorescence lifetimes in the solution and the solid state thanks to the suppressed overall nonradiative recombination via encapsulation of the conjugated polymer backbone. Thermal analysis also indicates that polyrotaxanes have higher thermal stabilities than their polymer counterparts. In order to demonstrate the applicability of the synthesized materials, we also fabricated proof-of-concept light emitting diodes from P1 and its CB7-based polyrotaxane counterpart P1CB7. The CB7-integrating polymer showed lower turn-on voltages with high electroluminescence colour purity due to balanced charge injection in P1CB7 as compared to the P1 polymer.
Open Access
Cucurbituril-based supramolecular engineered nanostructured materials
(Royal Society of Chemistry, 2014-11-03) Gürbüz, S.; Idris, M.; Tuncel, D.
Cucurbituril (CB) is a unique macrocycle with a rigid symmetrical structure, which is composed of two identical hydrophilic portals decorated with partially negatively charged carbonyl groups and a hydrophobic cavity. A number of different nanostructured materials, including nanoparticles, nanocomposites, vesicles and rods, have been prepared by taking advantage of the varying cavity size of the CB homologues, their ability to accommodate more than one guest in their cavities, their rigid symmetrical structures, as well as the water solubility of CB7. These nanostructures could find a wide range of potential applications in the areas of self-healing materials, nanomedicine, plasmonics, and nanocatalysis. Here, we review the recent progresses in the synthesis, properties and application of CB-based supramolecular engineered nanostructures, which are either constructed through CB-assisted self-assembly or from post-functionalized-CB homologues.
Open Access
Examination of fabrication conditions of acrylate-based hydrogel formulations for doxorubicin release and efficacy test for hepatocellular carcinoma cell
(Taylor and Francis., 2014) Bayramoglu, G.; Gozen, Damla; Ersoy, G.; Ozalp, V. C.; Akcali, K. C.; Arica, M. Y.
The objective of the present study was to develop 2-hydroxypropyl methacrylate-co-polyethylene methacrylate [p(HPMA-co-PEG-MEMA)] hydrogels that are able to efficiently entrap doxorubicin for the application of loco-regional control of the cancer disease. Systemic chemotherapy provides low clinical benefit while localized chemotherapy might provide a therapeutic advantage. In this study, effects of hydrogel properties such as PEG chains length, cross-linking density, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. In addition, the characterization of the hydrogel formulations was conducted with swelling experiments, permeability tests, Fourier transform infrared, SEM, and contact angle studies. In these drug-hydrogel systems, doxorubicin contains amine group that can be expected a strong Lewis acid-base interaction between drug and polar groups of PEG chains, thus the drug was released in a timely fashion with an electrostatic interaction mechanism. It was observed that doxorubicin release from the hydrogel formulations decreased when the density of cross-linking, and drug/polymer ratio were increased while an increase in the PEG chains length of the macro-monomer (i.e. PEG-MEMA) in the hydrogel system was associated with an increase in water content and doxorubicin release. The biocompatibility of the hydrogel formulations has been investigated using two measures: cytotoxicity test (using lactate dehydrogenase assay) and major serum proteins adsorption studies. Antitumor activity of the released doxorubicin was assessed using a human SNU398 human hepatocellular carcinoma cell line. It was observed that doxorubicin released from all of our hydrogel formulations which remained biologically active and had the capability to kill the tested cancer cells.
Open Access
Extracellular matrix mimetic peptide scaffolds for neural stem cell culture and differentiation
(Humana Press, 2014) Mammadov, Busra; Güler, Mustafa O.; Tekinay, Ayşe B.
Self-assembled peptide nanofibers form three-dimensional networks that are quite similar to fibrous extracellular matrix (ECM) in their physical structure. By incorporating short peptide sequences derived from ECM proteins, these nanofibers provide bioactive platforms for cell culture studies. This protocol provides information about preparation and characterization of self-assembled peptide nanofiber scaffolds, culturing of neural stem cells (NSCs) on these scaffolds, and analysis of cell behavior. As cell behavior analyses, viability and proliferation of NSCs as well as investigation of differentiation by immunocytochemistry, qRT-PCR, western blot, and morphological analysis on ECM mimetic peptide nanofiber scaffolds are described.
Open Access
Heparin mimetic peptide nanofiber gel promotes regeneration of full thickness burn injury
(Elsevier Ltd, 2017) Yergoz, F.; Hastar, N.; Cimenci, C. E.; Ozkan, A. D.; Güler, Mustafa O.; Tekinay, A. B.; Tekinay, T.; Güler, Mustafa O.
Burn injuries are one of the most common types of trauma worldwide, and their unique physiology requires the development of specialized therapeutic materials for their treatment. Here, we report the use of synthetic, functional and biodegradable peptide nanofiber gels for the improved healing of burn wounds to alleviate the progressive loss of tissue function at the post-burn wound site. These bioactive nanofiber gels form scaffolds that recapitulate the structure and function of the native extracellular matrix through signaling peptide epitopes, which can trigger angiogenesis through their affinity to basic growth factors. In this study, the angiogenesis-promoting properties of the bioactive scaffolds were utilized for the treatment of a thermal burn model. Following the excision of necrotic tissue, bioactive gels and control solutions were applied topically onto the wound area. The wound healing process was evaluated at 7, 14 and 21 days following injury through histological observations, immunostaining and marker RNA/protein analysis. Bioactive peptide nanofiber-treated burn wounds formed well-organized and collagen-rich granulation tissue layers, produced a greater density of newly formed blood vessels, and exhibited increased re-epithelialization and skin appendage development with minimal crust formation, while non-bioactive peptide nanofibers and the commercial wound dressing 3M™ Tegaderm™ did not exhibit significant efficiency over sucrose controls. Overall, the heparin-mimetic peptide nanofiber gels increased the rate of repair of burn injuries and can be used as an effective means of facilitating wound healing.
Open Access
Highly luminescent CB[7]-based conjugated polyrotaxanes embedded into crystalline matrices
(Wiley-VCH Verlag, 2017) Erdem, T.; Idris, M.; Demir, Hilmi Volkan; Tuncel, D.
π-Conjugated polymers suffer from low quantum yields (QYs) due to chain–chain interactions. Furthermore, their emission in solid films is significantly quenched due to aggregation leading further decrease in QY. These are the two main issues of these materials hampering their widespread use in optoelectronic devices. To address these issues, here the backbone of poly(9,9′-bis(6″-(N,N,N-trimethylammonium)hexyl)fluorene-alt-co-thiophenelene) is isolated by threading with cucurbit[7]uril (CB7). Subsequently, the conjugated polyrotaxanes are incorporated into organic crystalline matrices to obtain highly efficient color-converting solids suitable for solid-state lighting. Upon threading the polymer backbone with CB7s, although the QY of the resulting polyrotaxane in solution state increases, the quenching problem in their solid state is not completely tackled. To solve this problem, these conjugated polyrotaxanes are embedded into various crystalline matrices and their remarkably high QYs (>50%) in the solution are successfully maintained in the solid state. To demonstrate the suitability of these aforementioned materials for solid-state lighting, a proof-of-concept light-emitting diode is constructed by employing their powders as color converters.
Open Access
In situ synthesis of biomolecule encapsulated gold-cross-linked poly(ethylene glycol) nanocomposite as biosensing platform: A model study
(Elsevier BV, 2010) Odaci, D.; Kahveci, M.U.; Sahkulubey, E.L.; Ozdemir, C.; Uyar, Tamer; Timur, S.; Yagci Y.
In situ synthesis of poly(ethylene glycol) (PEG) hydrogels containing gold nanoparticles(AuNPs) and glucose oxidase (GOx) enzyme by photo-induced electron transfer process was reported here and applied in electrochemical glucose biosensing as the model system. Newly designed bionanocomposite matrix by simple one-step fabrication offered a good contact between the active site of the enzyme and AuNPs inside the network that caused the promotion in the electron transfer properties that was evidenced by cyclic voltammetryas well as higher amperometric biosensing responses in comparing with response signals obtained from the matrix without AuNPs. As well as some parameters important in the optimization studies such as optimum pH, enzyme loading and AuNP amount, the analytical characteristics of the biosensor (AuNP/GOx) were examined by the monitoring of chronoamperometric response due to the oxygen consumption through the enzymatic reaction at − 0.7 V under optimized conditions at sodium acetate buffer (50 mM, pH 4.0) and the linear graph was obtained in the range of 0.1–1.0 mM glucose. The detection limit (LOD) of the biosensor was calculated as 0.06 mM by using the signal to noise ratio of 3. Moreover, the presence of AuNPs was visualized by TEM. Finally, the biosensor was applied for glucose analysis for some beverages and obtained data were compared with HPLC as the reference method to test the possible matrix effect due to the nature of the samples.
Open Access
One-dimensional peptide nanostructure templated growth of iron phosphate nanostructures for lithium-ion battery cathodes
(American Chemical Society, 2016-06) Susapto, H. H.; Kudu, O. U.; Garifullin, R.; Yllmaz, E.; Güler, Mustafa O.
Template-directed synthesis of nanomaterials can provide benefits such as small crystalline size, high surface area, large surface-to-volume ratio, and structural stability. These properties are important for shorter distance in ion/electron movement and better electrode surface/electrolyte contact for energy storage applications. Here nanostructured FePO4 cathode materials were synthesized by using peptide nanostructures as a template inspired by biomineralization process. The amorphous, high surface area FePO4 nanostructures were utilized as a cathode for lithium-ion batteries. Discharge capacity of 155 mAh/g was achieved at C/20 current rate. The superior properties of biotemplated and nanostructured amorphous FePO4 are shown compared to template-free crystalline FePO4.
Open Access
One-Step Fabrication of Biocompatible Multifaceted Nanocomposite Gels and Nanolayers
(American Chemical Society, 2017) Topuz, F.; Bartneck, M.; Pan, Y.; Tacke, F.
Nanocomposite gels are a fascinating class of polymeric materials with an integrative assembly of organic molecules and organic/inorganic nanoparticles, offering a unique hybrid network with synergistic properties. The mechanical properties of such networks are similar to those of natural tissues, which make them ideal biomaterial candidates for tissue engineering applications. Existing nanocomposite gel systems, however, lack many desirable gel properties, and their suitability for surface coatings is often limited. To address this issue, this article aims at generating multifunctional nanocomposite gels that are injectable with an appropriate time window, functional with bicyclononynes (BCN), biocompatible and slowly degradable, and possess high mechanical strength. Further, the in situ network-forming property of the proposed system allows the fabrication of ultrathin nanocomposite coatings in the submicrometer range with tunable wettability and roughness. Multifunctional nanocomposite gels were fabricated under cytocompatible conditions (pH 7.4 and T = 37 °C) using laponite clays, isocyanate (NCO)-terminated sP(EO-stat-PO) macromers, and clickable BCN. Several characterization techniques were employed to elucidate the structure-property relationships of the gels. Even though the NCO-sP(EO-stat-PO) macromers could form a hydrogel network in situ on contact with water, the incorporation of laponite led to significant improvement of the mechanical properties. BCN motifs with carbamate links were used for a metal-free click ligation with azide-functional molecules, and the subsequent gradual release of the tethered molecules through the hydrolysis of carbamate bonds was shown. The biocompatibility of the hydrogels was examined through murine macrophages, showing that the material composition strongly affects cell behavior.
Open Access
Peptide nanofiber scaffolds for multipotent stromal cell culturing
(Humana Press Inc., 2013) Üstün, Seher; Kocabey, Samet; Güler, Mustafa O.; Tekinay, Ayse B.
Self-assembled peptide nanofibers are versatile materials providing suitable platforms for regenerative medicine applications. This chapter describes the use of peptide nanofibers as extracellular matrix mimetic scaffolds for two-dimensional (2D) and three-dimensional (3D) multipotent stromal cell culture systems and procedures for in vitro experiments using these scaffolds. Preparation of 2D and 3D peptide nanofiber scaffolds and cell culturing procedures are presented as part of in vitro experiments including cell adhesion, viability, and spreading analysis. Analysis of cellular differentiation on peptide nanofiber scaffolds is described through immunocytochemistry, qRT-PCR, and other biochemical experiments towards osteogenic and chondrogenic lineage. © Springer Science+Business Media New York 2013.
Open Access
Poly (hydroxyethyl methacrylate-glycidyl methacrylate) films modified with different functional groups: In vitro interactions with platelets and rat stem cells
(Elsevier, 2013) Bayramoglu, G.; Bitirim, V.; Tunali, Y.; Arica, M. Y.; Akcali, K. C.
Copolymerization of 2-hydroxyethylmethacrylate (HEMA) with glycidylmethacrylate (GMA) in the presence of α-α′- azoisobisbutyronitrile (AIBN) resulted in the formation of hydrogel films carrying reactive epoxy groups. Thirteen kinds of different molecules with pendant NH2 group were used for modifications of the p(HEMA-GMA) films. The NH2 group served as anchor binding site for immobilization of functional groups on the hydrogel film via direct epoxy ring opening reaction. The modified hydrogel films were characterized by FTIR, and contact angle studies. In addition, mechanical properties of the hydrogel films were studied, and modified hydrogel films showed improved mechanical properties compared with the non-modified film, but they are less elastic than the non-modified film. The biological activities of these films such as platelet adhesion, red blood cells hemolysis, and swelling behavior were studied. The effect of modified hydrogel films, including NH2, (using different aliphatic CH2 chain lengths) CH3, SO3H, aromatic groups with substituted OH and COOH groups, and amino acids were also investigated on the adhesion, morphology and survival of rat mesenchymal stem cells (MSCs). The MTT colorimetric assay reveals that the p(HEMA-GMA)-GA-AB, p(HEMA-GMA)-GA-Phe, p(HEMA-GMA)-GA-Trp, p(HEMA-GMA)-GA-Glu formulations have an excellent biocompatibility to promote the cell adhesion and growth. We anticipate that the fabricated p(HEMA-GMA) based hydrogel films with controllable surface chemistry and good stable swelling ratio may find extensive applications in future development of tissue engineering scaffold materials, and in various biotechnological areas. © 2012 Elsevier B.V.
Open Access
Preparation and characterization of poly(hydroxyethyl methacrylate-co-poly(ethyleneglycol-methacrylate)/hydroxypropyl-chitosan) hydrogel films: Adhesion of rat mesenchymal stem cells
(Hangug Gobunja Haghoi, 2010-12-02) Bayramoglu, G.; Akcalı, K. C.; Gultekin, S.; Bengu, E.; Arica, M. Y.
This study examined the effects of the surface properties of the materials, such as the hydroxyl, methyl and amino groups, on rat bone marrow derived Mesenchymal Stem Cell (MSC) seeding. A series of hydrogels were prepared in film form using 2-hydroxyethyl methacrylate (pHEMA), poly(ethyleneglycol) methacrylate (PEG-MA), and/or hydroxypropyl-chitosan (HPC). The physicochemical properties of these hydrogel films, such as water content, functional groups, contact angle, surface energy and thermal properties were affected by the composition of the materials. The ability of the MSCs to form colonies, as well as their viability on these materials were also analyzed. The water content of the hydrogel films increased with increasing PEG-MA and HPC ratio in the hydrogel. Contact angle measurements of the surface of the hydrogel films demonstrated that all the materials gave rise to a significantly hydrophilic surface compared to pure pHEMA. The blood protein interactions and platelet adhesion were reduced significantly on the surface of the materials upon the incorporation of PEG-MA compared to the control pure pHEMA and vice versa for HPC. The ability of the MSCs to adhere and form colonies on these materials was also analyzed. The results showed that these materials are suitable candidates to isolate and expand MSCs.
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.