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.
The osteoprotegerin (OPG) system plays a critical role in bone remodelling by regulating osteoclast formation and activity. The study aimed to determine the physicochemical properties and biocompatibility of a newly formulated OPG-chitosan gel. The OPG-chitosan gel was formulated using human OPG protein and water-soluble chitosan. The physicochemical properties were determined using Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Gel morphology was determined using scanning electron microscopy (SEM) and then it was subjected to a protein release assay and biodegradability test. An in vitro cytotoxicity test on normal human periodontal ligament (NHPL) fibroblasts and normal human (NH) osteoblasts was carried out using the AlamarBlue assay. In vivo evaluation in a rabbit model involved creating critical-sized defects in calvarial bone, filling with the OPG-chitosan gel and sacrificing at 12 weeks. In vitro results demonstrated that the 25 kDa OPG-chitosan gel had the highest rate of protein release and achieved 90% degradation in 28 days. At 12 weeks, the defects filled with 25 kDa OPG-chitosan gel showed significant (p
This study conducted on the structure of modified acrylamide-based hydrogel by synthesizing the nano composites. The hydrogels employed in this study were provided through a combination of acrylamide monomers, sodium carboxymethyl cellulose (NaCMC) and magnesium oxide (MgO) nanoparticles by crosslinking polymerization. N,N,N',N'-tetramethylethylenediamine and ammonium persulfate as the initiator was applied in the structure of the polymer. Findings of the study considered the nano composites consisting of MgO have the highest swelling ratio compared to pure Aam hydrogels. Thus, MgO is an appropriate nanoparticle to be used in the nano composites. Response surface methodology (RSM) based on a central composite design (CCD Design) was applied to optimize the preparation variables of a hydrogel consisted of MgO, NaCMC. With the swelling ratio for acrylamide-based hydrogel as the response, the effects of two variables, i.e. MgO and NaCMC were investigated. The effects of pH, temperature, MgO, and NaCMC on the drug release were investigated using the CCD design. The predicted appropriate drug release conditions for the hydrogel at the highest rate of temperature (37.50 °C) and pH: 4.10, is at its highest value, while the lower drug release is at temperature 38 °C and pH 3.50. With the desired value of MgO (0.01 g) and amount of NaCMC (0.1 g).
A new approach to design multifunctional chitosan based nanohydrogel with enhanced glucose sensitivity, stability, drug loading and release profile are reported. Two approaches were followed for functionalization of chitosan based nanohydrogel with 3-APBA via EDC and 3-APTES. The effective functionalization, structure and morphology of Chitosan based IPN respectively were confirmed by FTIR, SEM and AFM. At physiological conditions, the glucose-induced volume phase transition and release profile of the model drug Alizarin Red with 1,2-diol structure (comparative to insulin as a drug as well as a dye for bio separation) were studied at various glucose concentrations, pH and ionic strengths. The results suggested a new concept for diabetes treatment and diols sensitivity in view of their potential hi-tech applications in self-regulated on-off response to the treatment (drug delivery and bio separation concurrently).
Gelatin hydrogels are attractive for wound applications owing to their well-defined structural, physical, and chemical properties as well as good cell adhesion and biocompatibility. This study aimed to develop gelatin hydrogels incorporated with bio-nanosilver functionalized with lactoferrin (Ag-LTF) as a dual-antimicrobial action dressing, to be used in treating infected wounds. The hydrogels were cross-linked using genipin prior to loading with Ag-LTF and characterized for their physical and swelling properties, rheology, polymer and actives interactions, and in vitro release of the actives. The hydrogel's anti-biofilm and antibacterial performances against S. aureus and P. aeruginosa as well as their cytotoxicity effects were assessed in vitro, including primary wound healing gene expression of human dermal fibroblasts (HDFs). The formulated hydrogels showed adequate release of AgNPs and LTF, with promising antimicrobial effects against both bacterial strains. The Ag-LTF-loaded hydrogel did not significantly interfere with the normal cellular functions as no alteration was detected for cell viability, migration rate, and expression of the target genes, suggesting the nontoxicity of Ag-LTF as well as the hydrogels. In conclusion, Ag-LTF-loaded genipin-cross-linked gelatin hydrogel was successfully synthesized as a new approach for fighting biofilms in infected wounds, which may be applied to accelerate healing of chronic wounds.
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.
Polysaccharides are excellent candidates for drug delivery applications as they are available in abundance from natural sources. Polysaccharides such as starch, cellulose, lignin, chitosan, alginate, and tragacanth gum are used to make hydrogels beads. Hydrogels beads are three-dimensional, cross-linked networks of hydrophilic polymers formed in spherical shape and sized in the range of 0.5-1.0 mm of diameter. Beads are formed by various cross-linking methods such as chemical and irradiation methods. Natural polymer-based hydrogels are biocompatible and biodegradable and have inherently low immunogenicity, which makes them suitable for physiological drug delivery approaches. The cross-linked polysaccharide-based hydrogels are environment-sensitive polymers that can potentially be used for the development of "smart" delivery systems, which are capable of control release of the encapsulated drug at a targeted colon site. This topic focuses on various aspects of fabricating and optimizing the cross-linking of polysaccharides, either by a single polysaccharide or mixtures and also natural-synthetic hybrids to produce polymer-based hydrogel vehicles for colon-targeted drug delivery.
The gastroretentive dosage form of famotidine was modified using tamarind seed powders to prolong the gastric retention time. Tamarind seeds were used in two different forms having different swelling and gelling properties: with husk (TSP) or without husk (TKP). TKP (TKP1 to TKP 6) and TSP (TSP1 to TSP 6) series were prepared using tamarind powder:xanthan in the ratios of 5:0, 4:1, 3:2, 2:3, 1:4, 0:5, respectively. The matrix tablets were prepared by the wet granulation method and evaluated for pharmacopoeial requirements. TKP2 was the optimum formulation as it had a short floating lag time (FLT<30 s) and more than 98.5% drug release in 12 h. The dissolution data were fitted to popular mathematical models to assess the mechanism of drug release, and the optimum formulation showed a predominant first order release and diffusion mechanism. It was concluded that the TKP2 prepared using tamarind kernel powder:xanthan (4:1) was the optimum formulation with shortest floating lag time and more than 90% release in the determined period of time.
Research was aimed on microemulsion-based hydrogel for voriconazole. Oleic acid and isopropyl myristate as lipid phases; tween 20: tween 80 as surfactants and PEG600 as cosurfactant were selected to formulate voriconazole microemulsions. The promising microemulsions in terms of zeta potential, pH, viscosity, and drug release were selected and developed into hydrogels using carbopol 934. Resulting microemulsion-based hydrogel (MBH) of voriconazole were evaluated for in vitro diffusion and ex vivo permeation. Antifungal potentials of MBH were assessed against selected fungal strains. Optimal MBH formulations, O6 and O8 had displayed their antifungal potentials with enlarged zone of inhibition against selected fungal strains.
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.
Nanocellulose reinforced chitosan hydrogel was synthesized using chemical crosslinking method for the delivery of curcumin which is a poorly water-soluble drug. Curcumin extracted from the dried rhizomes of Curcuma longa was incorporated to the hydrogel via in situ loading method. A nonionic surfactant (Tween 20) was incorporated into the hydrogel to improve the solubility of curcumin. After the gas foaming process, hydrogel showed large interconnected pore structures. The release studies in gastric medium showed that the cumulative release of curcumin increased from 0.21% ± 0.02% to 54.85% ± 0.77% with the increasing of Tween 20 concentration from 0% to 30% (w/v) after 7.5 h. However, the entrapment efficiency percentage decreased with the addition of Tween 20. The gas foamed hydrogel showed higher initial burst release within the first 120 min compared to hydrogel formed at atmospheric condition. The solubility of curcumin would increase to 3.014 ± 0.041 mg/mL when the Tween 20 concentration increased to 3.2% (w/v) in simulated gastric medium. UV-visible spectra revealed that the drug retained its chemical activity after in vitro release. From these findings, it is believed that the nonionic surfactant incorporated chitosan/nanocellulose hydrogel can provide a platform to overcome current problems associated with curcumin delivery.
This work reports the modification of freeze/thaw poly(vinyl alcohol) hydrogel using citric acid as the bioactive molecule for hydroxyapatite formation in simulated body fluid. Inclusion of 1.3 mM citric acid into the poly(vinyl alcohol) hydrogel showed that the mechanical strength, crystalline phase, functional groups and swelling ability were still intact. Adding citric acid at higher concentrations (1.8 and 2.3 mM), however, resulted in physically poor hydrogels. Presence of 1.3 mM of citric acid showed the growth of porous hydroxyapatite crystals on the poly(vinyl alcohol) surface just after one day of immersion in simulated body fluid. Meanwhile, a fully covered apatite layer on the poly(vinyl alcohol) surface plus the evidence of apatite forming within the hydrogel were observed after soaking for seven days. Gel strength of the soaked poly(vinyl alcohol)/citric acid-1.3 mM hydrogel revealed that the load resistance was enhanced compared to that of the neat poly(vinyl alcohol) hydrogel. This facile method of inducing rapid growth of hydroxyapatite on the hydrogel surface as well as within the hydrogel network can be useful for guided bone regenerative materials.
Dissolved oil palm empty fruit bunch cellulose (EFBC) and sodium carboxymethylcellulose (NaCMC) were chemically crosslinked with epichlorohydrin (ECH) to generate designated hydrogel. After swelling process in distilled water, the swollen hydrogel was frozen and freeze-dried to form cryogel. The swelling phenomenon of hydrogel during the absorption process gave substantial effects on thinning of crosslinked network wall, pore size and volume, steadiness of cryogel skeletal structure, and re-swelling of cryogel. The swelling effects on hydrogel were confirmed via microscopic study using variable pressure scanning electron microscope (VPSEM). From the retrieved VPSEM images, nano-thin crosslinked network wall of 24.31 ± 1.97 nm and interconnected pores were observed. As a result, the amount of water, the swelling degree, and the freeze-drying process indirectly affected the VPSEM images that indicated pore size and volume, formation of interconnected pores, and re-swelling of cryogel. This study determined the intertwined factors that affected both hydrogel and cryogel properties by investigating the swelling phenomenon and its ensuing effects.
As a natural raw material to replace synthetic chemicals, cellulose and its derivatives are the most popular choices in the pharmaceutical industry. For drug delivery applications, cellulose is usually used as a cellulose nanocrystal (CNC). CNC-based hydrogels are widely utilized for drug delivery because drug molecules can be encapsulated in their pore-like structures. This study aims to develop CNC hydrogels for the delivery of doripenem antibiotics. CNC was obtained from jackfruit peel extraction, and alginate was used as a network polymer to produce hydrogels. Ionotropic gelation was used in the synthesis of CNC-alginate hydrogel composites. The maximum adsorption of doripenem by CNC was 65.7 mg/g, while the maximum adsorption by CNC-alginate was 98.4 mg/g. One of the most challenging aspects of drug delivery is predicting drug release from a solid matrix using simple and complex mathematical equations. The sigmoidal equation could represent the doripenem release from CNC, while the Ritger-Peppas equation could describe the doripenem release from CNC-Alginate. The biocompatibility testing of CNC and CNC-alginate against a 7F2 cell line indicates that both materials were non-toxic.
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.
The tentative clinical application of human pluripotent stem cells (hPSCs), such as human embryonic stem cells and human induced pluripotent stem cells, is restricted by the possibility of xenogenic contamination resulting from the use of mouse embryonic fibroblasts (MEFs) as a feeder layer. Therefore, we investigated hPSC cultures on biomaterials with different elasticities that were grafted with different nanosegments. We prepared dishes coated with polyvinylalcohol-co-itaconic acid hydrogels grafted with an oligopeptide derived from vitronectin (KGGPQVTRGDVFTMP) with elasticities ranging from 10.3 to 30.4 kPa storage moduli by controlling the crosslinking time. The hPSCs cultured on the stiffest substrates (30.4 kPa) tended to differentiate after five days of culture, whereas the hPSCs cultured on the optimal elastic substrates (25 kPa) maintained their pluripotency for over 20 passages under xeno-free conditions. These results indicate that cell culture matrices with optimal elasticity can maintain the pluripotency of hPSCs in culture.
Magnetic nanocellulose alginate hydrogel beads are produced from the assembly of alginate and magnetic nanocellulose (m-CNCs) as a potential drug delivery system. The m-CNCs were synthesized from cellulose nanocrystals (CNCs) that were isolated from rice husks (RH) by co-precipitation method and were incorporated into alginate-based hydrogel beads with the aim of enhancing mechanical strength and regulating drug release behavior. Ibuprofen was chosen as a model drug. The prepared CNCs, m-CNCs and the alginate hydrogel beads were characterized by various physicochemical techniques such as Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM) and vibrating sample magnetometer studies (VSM). Besides the magnetic property, the presence of m-CNCs increased the integrity of the alginate hydrogel beads and the swelling percentage. The drug release study exhibited a controlled release profiles and based on the drug release data, the drug release mechanism was analyzed and discussed based on mathematical models such as Korsmeyer-Peppas and Peppas-Sahlin.
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.