This research aims to compare the ability of smart hydrogel in removing the methylene blue prepared by using two different radiation methods. The extracted pectin from the dragon fruit peel (Hylocereus polyrhizus) was used with acrylic acid (AA) to produce a polymerized hydrogel through gamma and microwave radiation. The optimum hydrogel swelling capacity was obtained by varying the dose of radiation, pectin to AA ratio and pH used. From the array of samples, the ideal hydrogel was obtained at pH 8 with a ratio of 2:3 (pectin: AA) using 10 kGy and 400 W radiated gamma and microwave respectively. The performance of both hydrogels namely as Pc/AA(G) (gamma) and Pc/AA(Mw) (microwave) were investigated using methylene blue (MB) adsorption studies. In this study, three variables were manipulated, pH and MB concentration and hydrogel mass in order to find the optimum condition for the adsorption. Results showed that 20 mg of Pc/AA(G) performed the highest MB removal which was about 45% of 20 mg/L MB at pH 8. While 30 mg of Pc/AA(Mw) able to remove up to 35% of 20 mg/L MB at the same pH condition. To describe the adsorption mechanism, both kinetic models pseudo-first-order, pseudo-second-order were employed. The results from kinetic data showed that it fitted the pseudo-first-order as compared to pseudo-second-order model equation. This study provides alternative of green, facile and affective biomaterial for dye absorbents that readily available.
Stimuli-responsive bacterial cellulose-g-poly(acrylic acid) hydrogels were investigated for their potential use as an oral delivery system for proteins. These hydrogels were synthesized using electron beam irradiation without any cross-linking agents, thereby eliminating any potential toxic effects associated with cross-linkers. Bovine serum albumin (BSA), a model protein drug, was loaded into the hydrogels, and the release profile in simulated gastrointestinal fluids was investigated. Cumulative release of less than 10% in simulated gastric fluid (SGF) demonstrated the potential of these hydrogels to protect BSA from the acidic environment of the stomach. Subsequent conformational stability analyses of released BSA by SDS-PAGE, circular dichroism, and an esterase activity assay indicated that the structural integrity and bioactivity of BSA was maintained and preserved by the hydrogels. Furthermore, an increase in BSA penetration across intestinal mucosa tissue was observed in an ex vivo penetration experiment. Our fabricated hydrogels exhibited excellent cytocompatibility and showed no sign of toxicity, indicating the safety of these hydrogels for in vivo applications.
The development of hydrogel films as wound healing dressings is of a great interest owing to their biological tissue-like nature. Polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogels loaded with asiaticoside, a standardized rich fraction of Centella asiatica, were successfully developed using the freeze-thaw method. Response surface methodology with Box-Behnken experimental design was employed to optimize the hydrogels. The hydrogels were characterized and optimized by gel fraction, swelling behavior, water vapor transmission rate and mechanical strength. The formulation with 8% PVA, 5% PEG 400 and five consecutive freeze-thaw cycles was selected as the optimized formulation and was further characterized by its drug release, rheological study, morphology, cytotoxicity and microbial studies. The optimized formulation showed more than 90% drug release at 12 hours. The rheological properties exhibited that the formulation has viscoelastic behavior and remains stable upon storage. Cell culture studies confirmed the biocompatible nature of the optimized hydrogel formulation. In the microbial limit tests, the optimized hydrogel showed no microbial growth. The developed optimized PVA/PEG hydrogel using freeze-thaw method was swellable, elastic, safe, and it can be considered as a promising new wound dressing formulation.
Biofilms comprise bacteria attached to wound surfaces and are major contributors to non-healing wounds. It was found that the increased resistance of biofilms to antibiotics allows wound infections to persist chronically in spite of antibiotic therapy. In this study, the reduced form of graphene oxide (rGO) was explored as plausible antibiofilm agents. The rGO was synthesized via reducing the functional groups of GO. Then, rGO were characterized using zetasizer, X-ray photoelectron spectroscopy, UV-Vis spectroscopy and FESEM. The rGO were then formulated into sodium carboxymethyl cellulose (NaCMC) hydrogels to form rGO hydrogel and tested for antibiofilm activities in vitro using XTT test, and in vivo biofilm formation assay using nematodes C. elegans. Reduced GO hydrogel was successfully formed by reducing the functional groups of GO, and a reduction of up to 95% of functional groups was confirmed with X-ray photoelectron spectroscopy analysis. XTT tests confirmed that rGO hydrogels reduced biofilm formation by S. aureus (81-84%) and P. aeruginosa (50-62%). Fluorescence intensity also confirmed that rGO hydrogel can inhibit biofilm bacteria in C. elegans experiments. This study implied that rGO hydrogel is an effective antibiofilm agent for infected wounds.
This study aimed to develop a dual action, namely anti-inflammatory and antimicrobial, nanogels (NG) for the treatment of periodontitis using triclosan (TCS) and flurbiprofen (FLB). Triclosan, an antimicrobial drug, was prepared as nanoparticles (NPs) using poly-ε-caprolactone (PCL), while flurbiprofen, an anti-inflammatory drug, was directly loaded in a chitosan (CS) based hydrogel. The entwinement of both NPs and hydrogel loaded systems resulted in the NG. The characterisation data confirmed that the developed formulation consists of nanosized spherical structures and displays pH-dependent swelling/erosion and temperature-responsiveness. Besides, the NG exhibited adequate bioadhesiveness using the chicken pouch model and displayed antibacterial activity through the agar plate method. An in-vivo study of the NG on experimental periodontitis (EP) rats confirmed the dual antibacterial and anti-inflammatory effects which revealed an excellent therapeutic outcome. In conclusion, a dual action NG was successfully developed and proved to have superior therapeutic effects in comparison to physical mixtures of the individual drugs.
Starch-based hydrogels are promising smart materials for biomedical and pharmaceutical applications, which offer exciting perspectives in biophysical research at molecular level. This work was intended to develop, characterize and explore the properties of hydrogel from starch extracted from new source, Dioscorea hispida Dennst. Starch-mediated hydrogels were successfully synthesized via free radical polymerization method with varying concentrations of acrylic acid (AA),N,N'-methylenebisacrylamide (MBA) and sodium hydroxide (NaOH) in aqueous system. The grafting reaction between starch and AA was examined by observing the decline in intensity peak of hydrogel FTIR spectrum at 3291cm-1 and peak around 1600-1680cm-1, indicating the stretching of hydroxyl group (OH) and stretching of carbon-carbon double bond (CC) respectively. The effects of cross-linker, monomer and NaOH concentration on swelling ratio and gel content in different medium and conditions were also evaluated. The thermal stability and structural morphology of as-synthesized hydrogels were studied by thermogravimetry analysis (TGA) and scanning electron microscopy (SEM). In-vitro cytotoxicity study using small intestine cell line (FHS-74 Int) revealed that the as-formulated eco-friendly-hydrogel was free from any harmful material and safe to use for future product development.
Novel pH sensitive N-succinyl chitosan-g-poly (acrylic acid) hydrogels were synthesized through free radical mechanism. Rheometer was used to observe the mechanical strength of the hydrogels. In vitro degradation was conducted in SIF (pH 7.4). The effect of concentration of monomers, initiator, and crosslinking agent and pH and ionic strength of NaCl, CaCl2, and AlCl3 on swelling of the hydrogels was observed. The results showed that equilibrium swelling ratio was highly influenced by concentration of monomers, initiator, and crosslinking agent concentration, and pH and salt solutions of NaCl, CaCl2, and AlCl3. The swelling kinetics revealed that swelling followed non-Fickian anomalous transport. Furthermore, theophylline loading (DL %) and encapsulation efficiency (EE %) of the hydrogels was in the range of 15.5 ± 0.15-22.8 ± 0.06% and 62 ± 0.15-91 ± 0.26%, respectively. The release of theophylline in physiological mediums was strongly influenced by the pH. The theophylline release was in the range of 51 ± 0.20-92 ± 0.12% in SIF and 7.4 ± 0.02-14.9 ± 0.03% in SGF (pH 1.2), respectively. The release data fitted well to Korsmeyer-Peppas model. The chemical activity of the theophylline suggested that drug maintained its chemical activity after release in vitro. The results suggest that synthesized hydrogels are excellent drug carriers.
There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug delivery carriers.
Soft tissue defects like hernia and post-surgical fistula formation can be resolved with modern biomaterials in the form of meshes without post-operative complications. In the present study hand knitted silk meshes were surface coated with regenerated silk fibroin hydrogel and pure natural extracts. Two phytochemicals (Licorice extract (LE) and Bearberry extract (BE)) and the two honeybee products (royal jelly (RJ) and honey (HE)) were incorporated separately to induce antibacterial, anti-inflammatory, and wound healing ability to the silk hydrogel coated knitted silk meshes. Meshes were dip coated with a blend of 4 % silk hydrogel (w/v) and 5 % extracts. Dried modified meshes were characterized using SEM, DMA, GC-MS and FTIR. Antimicrobial testing, in-vitro cytotoxicity, in-vitro wound healing and Q-RT-PCR were also performed. SEM analysis concluded that presence of coating reduced the pore size up to 47.7 % whereas, fiber diameter was increased up to 17.9 % as compared to the control. The presence of coating on the mesh improved the mechanical strength/Young's modulus by 1602.8 %, UTS by 451.7 % and reduced the % strain by 51.12 %. Sustained release of extracts from MHRJ (62.9 % up to 72 h) confirmed that it can induce antibacterial activity against surgical infections. Cytocompatibility testing and gene expression results suggest that out of four variables MHRJ presented best cell viability, % wound closure and expression of wound healing marker genes. In-vivo analyses in rat hernia model were carried out using only MHRJ variant, which also confirmed the non- toxic nature and wound healing characteristics of the modified mesh. The improved cell proliferation and activated wound healing in vitro and in vivo suggested that MHRJ could be a valuable candidate to promote cell infiltration and activate soft tissue and hernia repair as a biomedical implant.
Tissue engineering focuses on developing biological substitutes to restore, maintain or improve tissue functions. The three main components of its application are scaffold, cell and growthstimulating signals. Scaffolds composed of biomaterials mainly function as the structural support for ex vivo cells to attach and proliferate. They also provide physical, mechanical and biochemical cues for the differentiation of cells before transferring to the in vivo site. Collagen has been long used in various clinical applications, including drug delivery. The wide usage of collagen in the clinical field can be attributed to its abundance in nature, biocompatibility, low antigenicity and biodegradability. In addition, the high tensile strength and fibril-forming ability of collagen enable its fabrication into various forms, such as sheet/membrane, sponge, hydrogel, beads, nanofibre and nanoparticle, and as a coating material. The wide option of fabrication technology together with the excellent biological and physicochemical characteristics of collagen has stimulated the use of collagen scaffolds in various tissue engineering applications. This review describes the fabrication methods used to produce various forms of scaffolds used in tissue engineering applications.
Biomaterials provide novel platforms to deliver stem cell and growth factor therapies for central nervous system (CNS) repair. The majority of these approaches have focused on the promotion of neural progenitor cells and neurogenesis. However, it is now increasingly recognized that glial responses are critical for recovery in the entire neurovascular unit. In this study, we investigated the cellular effects of epidermal growth factor (EGF) containing hydrogels on primary astrocyte cultures. Both EGF alone and EGF-hydrogel equally promoted astrocyte proliferation, but EGF-hydrogels further enhanced astrocyte activation, as evidenced by a significantly elevated Glial fibrillary acidic protein (GFAP) gene expression. Thereafter, conditioned media from astrocytes activated by EGF-hydrogel protected neurons against injury and promoted synaptic plasticity after oxygen-glucose deprivation. Taken together, these findings suggest that EGF-hydrogels can shift astrocytes into neuro-supportive phenotypes. Consistent with this idea, quantitative-polymerase chain reaction (qPCR) demonstrated that EGF-hydrogels shifted astrocytes in part by downregulating potentially negative A1-like genes (Fbln5 and Rt1-S3) and upregulating potentially beneficial A2-like genes (Clcf1, Tgm1, and Ptgs2). Further studies are warranted to explore the idea of using biomaterials to modify astrocyte behavior and thus indirectly augment neuroprotection and neuroplasticity in the context of stem cell and growth factor therapies for the CNS. Stem Cells Translational Medicine 2019;8:1242&1248.
Device applications of shape memory polymers demand diverse shape changing geometries, which are currently limited to non-omnidirectional movement. This restriction originates from traditional thermomechanical programming methods such as uniaxial, biaxial stretching, bending, or compression. A solvent-modulated programming method is reported to achieve an omnidirectional shape memory behavior. The method utilizes freeze drying of hydrogels of polyethylene glycol networks with a melting transition temperature around 50 °C in their dry state. Such a process creates temporarily fixed macroporosity, which collapses upon heating, leading to significant omnidirectional shrinkage. These shrunken materials can swell in water to form hydrogels again and the omnidirectional programming and recovery can be repeated. The fixity ratio (R f ) and recovery ratio (R r ) can be maintained at 90% and 98% respectively upon shape memory multicycling. The maximum linear recoverable strain, as limited by the maximum swelling, is ≈90%. Amongst various application potentials, one can envision the fabrication of multiphase composites by taking advantages of the omnidirectional shrinkage from a porous polymer to a denser structure.
The development of oral vaccine formulation is crucial to facilitate an effective mass immunization program for various vaccine-preventable diseases. In this work, the efficacy of hepatitis B antigen delivered by bacterial nanocellulose/poly(acrylic acid) composite hydrogel microparticles (MPs) as oral vaccine carriers was assessed to induce both local and systemic immunity. Optimal pH-responsive swelling, mucoadhesiveness, protein drug loading, and drug permeability were characterized by MPs formulated with minimal irradiation doses and acrylic acid concentration. The composite hydrogel materials of bacterial nanocellulose and poly(acrylic acid) showed significantly greater antigen release in simulated intestinal fluid while ensuring the integrity of antigen. In in vivo study, mice orally vaccinated with antigen-loaded hydrogel MPs showed enhanced vaccine immunogenicity with significantly higher secretion of mucosal immunoglobulin A, compared to intramuscular vaccinated control. The splenocytes from the same group demonstrated lymphoproliferation and significant increased secretion of interleukin-2 cytokines upon stimulation with hepatitis B antigen. Expression of CD69 in CD4+ T lymphocytes and CD19+ B lymphocytes in splenocytes from mice orally vaccinated with antigen-loaded hydrogel MPs was comparable to that of the intramuscular vaccinated control, indicating early activation of lymphocytes elicited by our oral vaccine formulation in just two doses. These results demonstrated the potential of antigen-loaded hydrogel MPs as an oral vaccination method for hepatitis B.
Establishing cultures of human embryonic (ES) and induced pluripotent (iPS) stem cells in xeno-free conditions is essential for producing clinical-grade cells. Development of cell culture biomaterials for human ES and iPS cells is critical for this purpose. We designed several structures of oligopeptide-grafted poly (vinyl alcohol-co-itaconic acid) hydrogels with optimal elasticity, and prepared them in formations of single chain, single chain with joint segment, dual chain with joint segment, and branched-type chain. Oligopeptide sequences were selected from integrin- and glycosaminoglycan-binding domains of the extracellular matrix. The hydrogels grafted with vitronectin-derived oligopeptides having a joint segment or a dual chain, which has a storage modulus of 25 kPa, supported the long-term culture of human ES and iPS cells for over 10 passages. The dual chain and/or joint segment with cell adhesion molecules on the hydrogels facilitated the proliferation and pluripotency of human ES and iPS cells.
Paper-based devices have been broadly used for the point-of-care detection of dengue viral nucleic acids due to their simplicity, cost-effectiveness, and readily observable colorimetric readout. However, their moderate sensitivity and functionality have limited their applications. Despite the above-mentioned advantages, paper substrates are lacking in their ability to control fluid flow, in contrast to the flow control enabled by polymer substrates (e.g., agarose) with readily tunable pore size and porosity. Herein, taking the benefits from both materials, the authors propose a strategy to create a hybrid substrate by incorporating agarose into the test strip to achieve flow control for optimal biomolecule interactions. As compared to the unmodified test strip, this strategy allows sensitive detection of targets with an approximately tenfold signal improvement. Additionally, the authors showcase the potential of functionality improvement by creating multiple test zones for semi-quantification of targets, suggesting that the number of visible test zones is directly proportional to the target concentration. The authors further demonstrate the potential of their proposed strategy for clinical assessment by applying it to their prototype sample-to-result test strip to sensitively and semi-quantitatively detect dengue viral RNA from the clinical blood samples. This proposed strategy holds significant promise for detecting various targets for diverse future applications.
Mesenchymal stems cells (MSCs) are currently the focus of numerous therapeutic approaches in tissue engineering/repair because of their wide multi-lineage potential and their ability to modulate the immune system response following transplantation. Culturing these cells, while maintaining their multipotency in vitro, currently relies on biological substrates such as gelatin, collagen and fibronectin. In addition, harvesting cells from these substrates requires enzymatic or chemical treatment, a process that will remove a multitude of cellular surface proteins, clearly an undesirable process if cells are to be used therapeutically. Herein, we applied a high-throughput 'hydrogel microarray' screening approach to identify thermo-modulatable substrates which can support hES-MP and ADMSC growth, permit gentle reagent free passaging, whilst maintaining multi-lineage potential. In summary, the hydrogel substrate identified, poly(AEtMA-Cl-co-DEAA) cross-linked with MBA, permitted MSCs to be maintained over 10 passages (each time via thermo-modulation), with the cells retaining expression of MSC associated markers and lineage potency. This chemically defined system allowed the passaging and maintenance of cellular phenotype of this clinically important cell type, in the absence of harsh passaging and the need for biological substrates.
Although anionic polyelectrolyte hydrogel beads offer attractive adsorption of cationic dyes, phosphate adsorption is limited by electrostatic interactions. In this work, carboxymethyl cellulose (CMC)/sodium alginate (SA) hydrogel beads were modified with calcium carbonate (CaCO3) and/or bentonite (Be). The compatibility between CaCO3 and Be was proven by the homogeneous surface, as shown in the scanning electron microscopic images. Fourier-transform infrared and X-ray diffraction spectra further confirmed the existence of inorganic filler in the hydrogel beads. Although CMC/SA/Be/CaCO3 hydrogel beads attained the highest methylene blue and phosphate adsorption capacities (142.15 MB mg/g, 90.31 P mg/g), phosphate adsorption was significantly improved once CaCO3 nanoparticles were incorporated into CMC/SA/CaCO3 hydrogel beads. The kinetics of MB adsorption by CMC/SA hydrogel beads with or without inorganic fillers could be described by the pseudo-second-order model under chemical interactions. The phosphate adsorption by CMC/SA/Be/CaCO3 hydrogel beads could be explained by the Elovich model due to heterogeneous properties. The incorporation of Be and CaCO3 also improved the phosphate adsorption through chemical interaction since Langmuir isotherm fitted the phosphate adsorption by CMC/SA/Be/CaCO3 hydrogel beads. Unlike MB adsorption, the reusability of these hydrogel beads in phosphate adsorption reduced slightly after 5 cycles.
Here, a stable derivative of cellulose, called cellulose carbamate (CC), was produced from Kenaf (Hibiscus cannabinus) core pulp (KCP) and urea with the aid of a hydrothermal method. Further investigation was carried out for the amount of nitrogen yielded in CC as different urea concentrations were applied to react with cellulose. The effect of nitrogen concentration of CC on its solubility in a urea-alkaline system was also studied. Regenerated cellulose products (hydrogels and aerogels) were fabricated through the rapid dissolution of CC in a urea-alkaline system. The morphology of the regenerated cellulose products was viewed under Field emission scanning electron microscope (FESEM). The transformation of allomorphs in regenerated cellulose products was examined by X-ray diffraction (XRD). The transparency of regenerated cellulose products was determined by Ultraviolet-visible (UV-Vis) spectrophotometer. The degree of swelling (DS) of regenerated cellulose products was also evaluated. This investigation provides a simple and efficient procedure of CC determination which is useful in producing regenerated CC products.
Inflammation is a key challenge in the treatment of chronic diseases. Spurred by topical advancement in polymer chemistry and drug delivery, hydrogels that release a drug in temporal, spatial and dosage controlled fashion have been trendy. This research focused on the fabrication of hydrogels with controlled drug release properties to control inflammation. Chitosan and polyvinyl pyrrolidone were used as base polymers and crosslinked with epichlorohydrin to form hydrogel films by solution casting technique. Prepared hydrogels were analyzed by swelling analysis in deionized water, buffer and electrolyte solutions and gel fraction. Functional groups confirmation and development of new covalent and hydrogen bonds, thermal stability (28.49%) and crystallinity were evaluated by FTIR, TGA and WAXRD, respectively. Rheological properties including gel strength and yield stress, elasticity (2309 MPa), porosity (75%) and hydrophilicity (73°) of prepared hydrogels were also evaluated. In vitro studies confirmed that prepared hydrogels have good biodegradability, excellent antimicrobial property and admirable cytotoxicity. Drug release profile (87.56% in 130 min) along with the drug encapsulation efficiency (84%) of prepared hydrogels was also studied. These results paved the path towards the development of hydrogels that can release the drugs with desired temporal patterns.