The comparison of contribution of GO and rGO produced by green synthesis to the properties of CMC-based wound dressing material.

Herein, GO (graphene oxide) or rGO (reduced graphene oxide) which is produced by the green synthesis method using plant extract (Laurus nobilis) was incorporated into a polymeric structure consisting of carboxymethyl cellulose (CMC) and polyethylene glycol (PEG) to produce a wound dressing material with enhanced mechanical and electrical properties. The effect of GO and rGO on the wound dressing features of the produced materials was investigated and compared to each other. Conductivity tests demonstrated that rGO contributed more significantly to the electrical conductivity than GO. While rGO-CMC/PEG/CA reached 3.01 × 10-6 S.cm-1 as the conductivity value, that of GO-CMC/PEG/CA was determined as 0.85 × 10-6 S.cm-1. As for the mechanical tests, it was seen that rGO achieved the best results in terms of elastic modulus (588.62 N/mm2), tensile strength (94.95 MPa) and elongation at break (17.64 %) compared to GO reinforced and pure hydrogel. Curcumin and ascorbic acid were used for antibiotic-free wound treatment and their release kinetics were also modeled. The results showed that rGO reinforced hydrogel provided a more controlled release. All results assured that both the produced GO reinforced and especially rGO reinforced hydrogels could be utilized as modern wound dressing materials with suitable properties to achieve remarkable results for wound healing.

Gelatin microsphere-alginate hydrogel combined system for sustained and gastric targeted delivery of 5-fluorouracil.

In the current study, novel gelatin microspheres/methacrylated alginate hydrogel combined system (5-FU-GELms/Alg-MA) was developed for gastric targeted delivery of 5-fluorouracil as an anticancer agent. While water-in-oil emulsification method was used for the production of 5-FU-GELms, Alg-MA was synthesized through methacrylation reaction occurred by epoxide ring-opening mechanism. Then, 5-FU-GELms/Alg-MA hydrogel system was fabricated by the encapsulation of 5-FU-GELms into Alg-MA hydrogel network via UV-crosslinking. To evaluate applicability of fabricated 5-FU-GELms/Alg-MA as gastric targeted drug delivery vehicle, both swelling and in vitro drug release experiments were carried out at pH 1.2 medium resembling gastric fluid. Compared to drug release directly from 5-FU-GELms, 5-FU-GELms/Alg-MA hydrogel system showed more controlled and sustained drug release profile with lower amount of cumulative release starting from early stages, since hydrogel matrix created a barrier to the diffusion of 5-FU included in microspheres. Drug release kinetic results obtained by applying various kinetic models to release data showed that the mechanism of 5-FU release from 5-FU-GELms/Alg-MA hydrogel system is controlled by Fickian diffusion. All results revealed that 5-FU-GELms/Alg-MA hydrogel integrated system could be potentially utilized as gastric targeted drug carrier to enhance therapeutic efficacy and reduce systemic side effects in gastric cancer treatments for future studies.

Electro-stimulated drug release by methacrylated hyaluronic acid-based conductive hydrogel with enhanced mechanical properties.

Recently, the design of stimuli-responsive hydrogels for controlled drug delivery systems has been extensively investigated to meet therapeutic needs and optimize the release pattern of the drug. Being a natural polyelectrolyte, hyaluronic acid (HA) is excellent potential to generate new opportunities for electro-responsive drug carrier applications. In the current study, HA-based electroconductive hydrogel was developed as a novel smart drug carrier for anti-inflammatory drug release by the combination of in-situ and post polymerization mechanisms. HA was modified through methacrylation reaction to introduce photocrosslinkable groups into its structure and then reduced graphene oxide (rGO) was encapsulated into methacrylated HA (HA/MA) hydrogel by using the photopolymerization technique. In the post polymerization process, polyaniline (PANI) was incorporated/loaded into HA/MA-rGO polymeric network produced in previous step. The produced HA/MA-rGO-PANI hydrogel exhibited sufficient electrical conductivity providing the desirable electro-responsive ability for Ibuprofen (IBU) release. Furthermore, it has superior mechanical performance compared to pure (HA/MA) and rGO containing (HA/MA-rGO) hydrogels. IBU release from the hydrogel was successfully triggered by electrical stimulation and the cumulative drug release also enhanced by increasing of the applied voltage. These results highlighted that the novel HA/MA-rGO-PANI hydrogel could be a promising candidate for electrical-stimulated anti-inflammatory release systems in neural implant applications.

Production of ciprofloxacin loaded chitosan/gelatin/bone ash wound dressing with improved mechanical properties.

Polymeric films with enhanced mechanical performance were fabricated by incorporation of bone ash (BA) at various concentrations (0-25 v. %) into chitosan/gelatin (CTS/GEL) polymeric structure as a wound healing-dressing. The test results for mechanical performance of polymeric films proved that the encapsulation of BA into the polymeric films enhances the elastic modulus and tensile strength of polymeric films significantly. Oxygen permeability and water vapor transmission rate (WVTR) of films were also improved by BA reinforcement. Ciprofloxacin was chosen as the antibacterial model drug. The release of ciprofloxacin was provided in a more controlled manner at pH 7.4 owing to the incorporation of bone ash into the polymeric films. Also, drug loaded films showed great antibacterial activity against Escherichia coli and Bacillus subtilis bacteria. The results prove that ciprofloxacin loaded BA reinforced CTS/GEL composite films are potentially applicable in controlled drug delivery as wound dressings.

Modeling the drug release from reduced graphene oxide-reinforced hyaluronic acid/gelatin/poly(ethylene oxide) polymeric films.

Herein, electroconductive polymeric films consisting of hyaluronic acid (HyA), gelatin (Gel), poly(ethylene oxide) (PEO) reinforced by reduced graphene oxide (RGO) were used in drug release studies to investigate usability of the films as drug carrier in the future. Irbesartan (IRB) used for the treatment of cardiovascular diseases was loaded to the polymeric films and its release kinetic was investigated. Afterwards, the obtained controlled drug release data were simulated using different dynamic differential mathematical models such as 1st, 2nd, 3rd degree and Higuchi model. In addition, a novel approach considering the drug release rate to be inversely proportional to the drug release percentage was presented to reproduce the experimental drug release percentage results. Thus, the approach used in this work covers different aspects of drug release kinetics to assure that HyA/Gel/PEO films w/out RGO could be considered as a potential carrier for controlled drug delivery systems.

Electroconductive 3D polymeric network production by using polyaniline/chitosan-based hydrogel.

Herein, polyaniline/chitosan(PANI/CTS)-based electroconductive hydrogel was produced by photocrosslinked network in which CTS was used as a main component. Firstly, glycidyl methacrylate (GMA) was grafted on the CTS backbone to form CTS-g-GMA. Then, a three-dimensional polymeric network consisting of CTS-g-GMA and poly(ethylene glycol)diacrylate (PEGDA) was obtained by using photocrosslinking technique. At last, aniline monomer solution prepared by utilizing three different aniline concentrations (0.08, 0.16 and 0,32 M) was absorbed into (CTS-g-GMA)-PEGDA crosslinked structure to form [(CTS-g-GMA)-PEGDA]-PANI electroconductive semi interpenetrating network. FT-IR, XRD, SEM, TGA analyses and cytotoxicity test were performed for the produced samples. Conductivities of the hydrogels were determined by four-point probe technique. According to the conductivity measurements, among the PANI/CTS-based hydrogels, [(CTS-g-GMA)-PEGDA]-PANI(0.32 M) has the highest conductivity value (7437 × 10-3 S/cm). The obtained results showed that the fabricated electroconductive hydrogel (ECHs) in this study is a promising candidate owing to its advantages for biomedical applications especially biosensors in the future.

Oxygen-Generating Photocrosslinkable Hydrogel.

Providing sufficient amount of oxygen to the cells is a critical issue since the lack of adequate oxygen leads to cell death and tissue necrosis. Therefore, there is a vital need to design and fabricate oxygen-generating biomaterials to mitigate hypoxia-induced cell death in engineered tissues. Here, we report the fabrication of an oxygen-generating hydrogel by incorporating calcium peroxide (CPO) into the methacrylated gelatin (GelMA) structure using photocrosslinking process. A sustainable release of oxygen could be provided from CPO-GelMA hydrogel over a period of 5 days under hypoxic conditions (1% O2).

Development of pH-responsive chitosan-based hydrogel modified with bone ash for controlled release of amoxicillin.

In present study, bone ash-reinforced chitosan-based hydrogels were obtained by encapsulation of bone ash into the hydrogel structure which was fabricated by photopolymerization of chitosan-grafted-glycidyl methacrylate (CTS-g-GMA) and poly(ethylene glycol)diacrylate (PEGDA) under the UV light. Hydrogels were characterized by ATR-FTIR, SEM and XRD analyses. Mechanical performance of the hydrogels was determined by universal mechanical tester. Cytotoxicity tests for hydrogels were conducted with L929 cell lines to determine cellular compatibility. Swelling tests were carried out to investigate the water uptake capacity of hydrogels. Amoxicillin which could be used for treatment of gastric ulcer was selected as the model drug. The release of amoxicillin was provided at simulated gastric (pH: 1.2) and intestinal media (pH: 7.4) in efficient and controlled manner. All results visualized that the obtained pH-sensitive chitosan-based hydrogel with enhanced mechanical properties could be a potential candidate as a drug carrier for treatment of gastric ulcer in the future applications.

Oxygen-Generating Photo-Cross-Linkable Hydrogels Support Cardiac Progenitor Cell Survival by Reducing Hypoxia-Induced Necrosis.

Oxygen is essential to cell survival and tissue function. Not surprisingly, ischemia resulting from myocardial infarction induces cell death and tissue necrosis. Attempts to regenerate myocardial tissue with cell based therapies exacerbate the hypoxic stress by further increasing the metabolic burden. In consequence, implanted tissue engineered cardiac tissues suffer from hypoxia-induced cell death. Here, we report on the generation of oxygen-generating hydrogels composed of calcium peroxide (CPO) laden gelatin methacryloyl (GelMA). CPO-GelMA hydrogels released significant amounts of oxygen for over a period of 5 days under hypoxic conditions (1% O2). The released oxygen proved sufficient to relieve the metabolic stress of cardiac side population cells that were encapsulated within CPO-GelMA hydrogels. In particular, incorporation of CPO in GelMA hydrogels strongly enhanced cell viability as compared to GelMA-only hydrogels. Importantly, CPO-based oxygen generation reduced cell death by limiting hypoxia-induced necrosis. The current study demonstrates that CPO based oxygen-generating hydrogels could be used to transiently provide oxygen to cardiac cells under ischemic conditions. Therefore, oxygen generating materials such as CPO-GelMA can improve cell-based therapies aimed at treatment or regeneration of infarcted myocardial tissue.

Fabrication of a novel bone ash-reinforced gelatin/alginate/hyaluronic acid composite film for controlled drug delivery.

In this study, a novel pH-sensitive composite film with enhanced thermal and mechanical properties was prepared by the incorporation of bone ash at varying concentrations from 0 to 10v.% into gelatin/sodium alginate/hyaluronic acid (Gel/SA/HyA) polymeric structure for colon-specific drug delivery system. Films were characterized by FT-IR, SEM, and XRD analyses. Thermal and mechanical performances of films were determined by DSC, TGA and universal mechanical tester, respectively. Results proved that thermal stability and mechanical properties of bone ash-reinforced composite films improved significantly with respect to that of neat Gel/SA/HyA film. Cytotoxicity assay for composite films was carried out by using L929 cells. Water uptake capacity of films was determined by swelling test. Herein, release experiments of 5-Fluorouracil (5-FU) were performed in two different solutions (pH 2.1 and 7.4). The results assured that Gel/SA/HyA film containing BA could be considered as a potential biomaterial for controlled drug delivery systems.

Tri-layered elastomeric scaffolds for engineering heart valve leaflets.

Tissue engineered heart valves (TEHVs) that can grow and remodel have the potential to serve as permanent replacements of the current non-viable prosthetic valves particularly for pediatric patients. A major challenge in designing functional TEHVs is to mimic both structural and anisotropic mechanical characteristics of the native valve leaflets. To establish a more biomimetic model of TEHV, we fabricated tri-layered scaffolds by combining electrospinning and microfabrication techniques. These constructs were fabricated by assembling microfabricated poly(glycerol sebacate) (PGS) and fibrous PGS/poly(caprolactone) (PCL) electrospun sheets to develop elastic scaffolds with tunable anisotropic mechanical properties similar to the mechanical characteristics of the native heart valves. The engineered scaffolds supported the growth of valvular interstitial cells (VICs) and mesenchymal stem cells (MSCs) within the 3D structure and promoted the deposition of heart valve extracellular matrix (ECM). MSCs were also organized and aligned along the anisotropic axes of the engineered tri-layered scaffolds. In addition, the fabricated constructs opened and closed properly in an ex vivo model of porcine heart valve leaflet tissue replacement. The engineered tri-layered scaffolds have the potential for successful translation towards TEHV replacements.

Oxygen Releasing Biomaterials for Tissue Engineering.

Due to the increasing demand to generate thick and vascularized tissue engineered constructs, novel strategies are currently being developed. An emerging example is the generation of oxygen-releasing biomaterials to tackle mass transport and diffusion limitations within engineered tissue-like constructs. Biomaterials containing oxygen releasing molecules can be fabricated in various forms such as, hybrid thin films, microparticles, or three dimensional (3D) scaffolds. In this perspective, we will summarize various oxygen-releasing reagents and their potential applications in regenerative engineering. Moreover, we will review the main approaches to fabricate oxygen-releasing biomaterials for a range of tissue engineering applications.