Broad interest in developing new hemostatic technologies arises from unmet needs in mitigating uncontrolled hemorrhage in emergency, surgical, and battlefield settings. Although a variety of hemostats, sealants, and adhesives are available, development of ideal hemostatic compositions that offer a range of remarkable properties including capability to effectively and immediately manage bleeding, excellent mechanical properties, biocompatibility, biodegradability, antibacterial effect, and strong tissue adhesion properties, under wet and dynamic conditions, still remains a challenge. Benefiting from tunable mechanical properties, high porosity, biocompatibility, injectability and ease of handling, polymeric hydrogels with outstanding hemostatic properties have been receiving increasing attention over the past several years. In this review, after shedding light on hemostasis and wound healing processes, the most recent progresses in hydrogel systems engineered from natural and synthetic polymers for hemostatic applications are discussed based on a comprehensive literature review. Most studies described used in vivo models with accessible and compressible wounds to assess the hemostatic performance of hydrogels. The challenges that need to be tackled to accelerate the translation of these novel hemostatic hydrogel systems to clinical practice are emphasized and future directions for research in the field are presented.
The synthesis of Janus nanosheets using κ-carrageenan (κ-Ca) as a green template endows a greener and more straightforward method compared to traditional approaches of using wax template. We hypothesize that the hydrogen bonding interaction between κ-Ca and graphene oxide (GO) allows partial masking of GO's single facet, paving the way for the asymmetric modification of the exposed surface. GO is first encapsulated within the porous hydrogel matrix formed by κ-Ca to isolate one of the facets. The exposed surface was then selectively hydrophobized to produce an amphiphilic asymmetrically modified graphene oxide (AMGO). The properties of AMGO synthesized under different κ-Ca/GO ratios were studied. The κ-Ca/GO interactions and the properties of GO and AMGO were investigated and characterized. AMGO was successfully produced with a yield of 90.37 % under optimized synthesis conditions. The separation of κ-Ca and AMGO was conducted without organic solvents, and the κ-Ca could be subsequently recovered. Furthermore, the porous hydrogel matrix formed by κ-Ca and GO exhibited excellent shape-retaining properties with high thermal tolerance of up to 50 °C. Given these benefits, this newly developed method endows sustainability and open the possibility of formulating more flexible material synthesis protocols.
The present article evaluates the composition and synthesis of hydrogel beads. Hydrogels, owing to their known biocompatibility, are widely used in drug delivery as a host (or drug carrier). Hydrogels, owing to their physical, chemical and biological properties, are popular in many aspects. Hydrogels are crosslinked-hydrophilic polymers and commercialized/synthesized in both natural and synthetic forms. These polymers are compatible with human tissues, therefore can be potentially used for biomedical treatments. Hydrogels in drug delivery offer several points of interest such as sustainability, and sensitivity without any side-effects as compared to traditional methods in this field. Drugs can encapsulate and release continuously into the targets when hydrogels are activated/modified magnetically or by fluorescent materials. It is crucial to develop new crosslinked polymers in terms of "biocompatibility" and "biodegradability" for novel drug delivery platforms. In the event that the accomplishments of the past can be used into the longer terms, it is exceedingly likely that hydrogels with a wide cluster of alluring properties can be synthesized. The current review, offers an updated summary of latest developments in the nanomedicines field as well as nanobased drug delivery systems over broad study of the discovery/ application of nanomaterials in improving both the efficacy of drugs and targeted delivery of them. The challenges/opportunities of nanomedicine in drug delivery also discussed. SCOPE OF THE RESEARCH: Although several reviews have been published in the field of hydrogels, however many of them have just centralized on the general overviews in terms of "synthesis" and "properties". The utilization of hydrogels and hydrogel-based composites in vital applications have been achieved a great interest. In this review, our aim is to recap of the key points in the field of hydrogels such as; a) hydrogel nanocomposites, b) magnetic beads, c) biomedical applications, and d) drug delivery. In the same vein, these outlines will be expanded with emphasizing on the boon of magnetic beads and recent developments in this area.
Hydrogel is the most emblematic soft material which possesses significantly tunable and programmable characteristics. Polymer hydrogels possess significant advantages including, biocompatible, simple, reliable and low cost. Therefore, research on the development of hydrogel for biomedical applications has been grown intensely. However, hydrogel development is challenging and required significant effort before the application at an industrial scale. Therefore, the current work focused on evaluating recent trends and issues with hydrogel development for biomedical applications. In addition, the hydrogel's development methodology, physicochemical properties, and biomedical applications are evaluated and benchmarked against the reported literature. Later, biomedical applications of the nano-cellulose-based hydrogel are considered and critically discussed. Based on a detailed review, it has been found that the surface energy, intermolecular interactions, and interactions of hydrogel adhesion forces are major challenges that contribute to the development of hydrogel. In addition, compared to other hydrogels, nanocellulose hydrogels demonstrated higher potential for drug delivery, 3D cell culture, diagnostics, tissue engineering, tissue therapies and gene therapies. Overall, nanocellulose hydrogel has the potential for commercialization for different biomedical applications.
Over the last decade, numerous investigations have attempted to clarify the intricacies of tumor development to propose effective approaches for cancer treatment. Thanks to the unique properties of hydrogels, researchers have made significant progress in tumor model reconstruction, tumor diagnosis, and associated therapies. Notably, hydrogel-based systems can be adjusted to respond to cancer-specific hallmarks and/or external stimuli. These well-known drug reservoirs can be used as smart carriers for multiple cargos, including both naked and nanoparticle-encapsulated chemotherapeutics, genes, and radioisotopes. Recent works have attempted to specialize hydrogels for cancer research; we comprehensively review this topic for the first time, synthesizing past results and defining paths for future work.
Given their highly porous nature and excellent water retention, hydrogel-based biomaterials can mimic critical properties of the native cellular environment. However, their potential to emulate the electromechanical milieu of native tissues or conform well with the curved topology of human organs needs to be further explored to address a broad range of physiological demands of the body. In this regard, the incorporation of nanomaterials within hydrogels has shown great promise, as a simple one-step approach, to generate multifunctional scaffolds with previously unattainable biological, mechanical, and electrical properties. Here, recent advances in the fabrication and application of nanocomposite hydrogels in tissue engineering applications are described, with specific attention toward skeletal and electroactive tissues, such as cardiac, nerve, bone, cartilage, and skeletal muscle. Additionally, some potential uses of nanoreinforced hydrogels within the emerging disciplines of cyborganics, bionics, and soft biorobotics are highlighted.
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.
Cellulose is a natural homopolymer, composed of β-1,4- anhydro-d-glucopyranose units. Unlike plant cellulose, bacterial cellulose (BC), obtained from species belonging to the genera of Acetobacter, Rhizobium, Agrobacterium, and Sarcina through various cultivation methods and techniques, is produced in its pure form. BC is produced in the form of gel-like, never dry sheet with tremendous mechanical properties. Containing up to 99% of water, BC hydrogel is considered biocompatible thus finding robust applications in the health industry. Moreover, BC three-dimensional structure closely resembles the extracellular matrix (ECM) of living tissue. In this review, we focus on the porous BC morphology particularly suited to host oxygen and nutrients thus providing conducive environment for cell growth and proliferation. The remarkable BC porous morphology makes this biological material a promising templet for the generation of 3D tissue culture and possibly for tissue-engineered scaffolds.
The aim of present research aims to fabricate a system of enteric coating of hydrogel beads with pH-sensitive polymer, which shows solubility at pH > 7, and explore their potential to target the colon for drug delivery. Hydrogel beads were fabricated through the extrusion-dripping technique followed by ion gelation crosslinking. Moreover, freeze-thaw cycle was implemented for crosslinking of polyvinyl alcohol (PVA)/Ca-alginate blend beads. The oil-in-oil solvent evaporation method was adopted for the Eudragit coating of hydrogel beads using different coat: core ratios (4:1 or 8:1). Coated and uncoated hydrogel beads were evaluated by in vitro physicochemical properties, swelling and drug release behaviours, and in vivo pharmacokinetics, swelling, and toxicity evaluation. Diclofenac sodium was loaded as an experimental drug. Drug entrapment efficiency for the PVA/Ca-alginate beads was calculated as 98%, and for Ca-alginate beads, it came out to a maximum of 74%. Drug release study at various pH suggested that, unlike uncoated hydrogel beads, the coated beads delay the release of diclofenac sodium in low pH of the gastric and intestinal environment, thus targeting the colon for the drug release. It was concluded that Eudragit S-100-coated hydrogel beads could serve as a more promising and reliable way to target the colon for drug delivery.Graphical abstract.
Caffeine is therapeutically effective for treating apnea, cellulite formation, and pain management. It also exhibits neuroprotective and antioxidant activities in different models of Parkinson's disease and Alzheimer's disease. However, caffeine administration in a minimally invasive and sustainable manner through the transdermal route is challenging owing to its hydrophilic nature. Therefore, this study demonstrated a transdermal delivery approach for caffeine by utilizing hydrogel microneedle (MN) as a permeation enhancer. The influence of formulation parameters such as molecular weight (MW) of PMVE/MA (polymethyl vinyl ether/maleic anhydride) copolymer and sodium bicarbonate (NaHCO3) concentration on the swelling kinetics and mechanical integrity of the hydrogel MNs was investigated. In addition, the effect of different MN application methods and needle densities of hydrogel MN on the skin insertion efficiency and penetration depth was also evaluated. The swelling degree at equilibrium percentage (% Seq) recorded for hydrogels fabricated with Gantrez S-97 (MW = 1,500,000 Da) was significantly higher than formulation with Gantrez AN-139 (MW = 1,080,000 Da). Increasing the concentration of NaHCO3 also significantly increased the % Seq. Moreover, a 100% penetration was recorded for both the applicator and combination of applicator and thumb pressure compared with only 11% for thumb pressure alone. The average diameter of micropores created by the applicator method was 62.94 μm, which was significantly lower than the combination of both applicator and thumb pressure MN application (100.53 μm). Based on histological imaging, the penetration depth of hydrogel MN increased as the MN density per array decreased. The hydrogel MN with the optimized formulation and skin insertion parameters was tested for caffeine delivery in an in vitro Franz diffusion cell setup. Approximately 2.9 mg of caffeine was delivered within 24 h, and the drug release profile was best fitted to the Korsmeyer-Peppas model, displaying Super Case II kinetics. In conclusion, a combination of thumb and impact application methods and reduced needle density improved the skin penetration efficiency of hydrogel MNs. The results also show that hydrogel MNs fabricated from 3% w/w NaHCO3 and high MW of copolymer exhibit optimum physical and swelling properties for enhanced transdermal delivery.
The current study sought to create graphene oxide-based superstructures for gastrointestinal drug delivery. Graphene oxide has a large surface area that can be used to load anti-cancer drugs via non-covalent methods such as surface adsorption and hydrogen bonding. To enhance the bio-applicability of graphene oxide, nano-hybrids were synthesized by encapsulating the graphene oxide into calcium alginate hydrogel beads through the dripping-extrusion technique. These newly developed bio-nanocomposite hybrid hydrogel beads were evaluated in structural analysis, swelling study, drug release parameters, haemolytic assay, and antibacterial activity. Doxorubicin served as a model drug. The drug entrapment efficiency was determined by UV-spectroscopy analysis and was found to be high at ⁓89% in graphene oxide hybrid hydrogel beads. These fabricated hydrogel beads ensure the drug release from a hybrid polymeric matrix in a more controlled and sustained pattern avoiding the problems associated with a non-hybrid polymeric system. The drug release study of 12 h shows about 83% release at pH 6.8. In vitro drug release kinetics proved that drug release was a Fickian mechanism. The cytotoxic effect of graphene oxide hybrid alginate beads was also determined by evaluating the morphology of bacterial cells and red blood cells after incubation. Additionally, it was determined that the sequential encapsulation of graphene oxide in alginate hydrogel beads hides its uneven edges and lessens the graphene oxide's negative impacts. Also, the antibacterial study and biocompatibility of fabricated hydrogel beads made them potential candidates for gastrointestinal delivery.
Supramolecular hydrogels, formed by noncovalent crosslinking of polymeric chains in water, constitute an interesting class of materials that can be developed specifically for drug delivery and biomedical applications. The biocompatibility, stimuli responsiveness to various external factors, and powerful functionalization capacity of these polymeric networks make them attractive candidates for novel advanced dosage form design.
This paper focuses on the micro- and nano-topological organization of a hydrogel, constituted by a mixture of bacterial cellulose and acrylic acid, and intended for biomedical applications. The presence of acrylic acid promotes the formation of two interpenetrated continuous phases: the primary "pores phase" (PP) containing only water and the secondary "polymeric network phase" (PNP) constituted by the polymeric network swollen by the water. Low field Nuclear Magnetic Resonance (LF NMR), rheology, Scanning Electron Microscopy (SEM) and release tests were used to determine the characteristics of the two phases. In particular, we found that this system is a strong hydrogel constituted by 81% (v/v) of PP phase the remaining part being occupied by the PNP phase. Pores diameters span in the range 10-100 μm, the majority of them (85%) falling in the range 30-90 μm. The high PP phase tortuosity indicates that big pores are not directly connected to each other, but their connection is realized by a series of interconnected small pores that rend the drug path tortuous. The PNP is characterized by a polymer volume fraction around 0.73 while mesh size is around 3 nm. The theoretical interpretation of the experimental data coming from the techniques panel adopted, yielded to the micro- and nano-organization of our hydrogel.
This article aims to review the literature concerning the choice of selectivity for hydrogels based on classification, application and processing. Super porous hydrogels (SPHs) and superabsorbent polymers (SAPs) represent an innovative category of recent generation highlighted as an ideal mould system for the study of solution-dependent phenomena. Hydrogels, also termed as smart and/or hungry networks, are currently subject of considerable scientific research due to their potential in hi-tech applications in the biomedical, pharmaceutical, biotechnology, bioseparation, biosensor, agriculture, oil recovery and cosmetics fields. Smart hydrogels display a significant physiochemical change in response to small changes in the surroundings. However, such changes are reversible; therefore, the hydrogels are capable of returning to its initial state after a reaction as soon as the trigger is removed.
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.
Dissolved oil palm empty fruit bunch (EFB) cellulose in NaOH/urea solvent was mixed with sodium carboxymethylcellulose (NaCMC) to form a green regenerated superabsorbent hydrogel. The effect of concentration of epichlorohydrin (ECH) as the crosslinker on the formation, physical, and chemical properties of hydrogel was studied. Rapid formation and higher gel content of hydrogel were observed at 10% concentration of ECH. The superabsorbent hydrogel was successfully fabricated in this study with the swelling ability >100,000%. Hydrogel with higher concentration of ECH showed opposite trend by having higher superabsorbent property than that of lower concentration. The covalent bond of COC was observed with Attenuated total reflectance fourier transform infrared (ATR-FT-IR) spectroscopy to confirm the occurrence of crosslinking. The physical and chemical properties of hydrogel were affected by swelling phenomenon. Hydrogel with higher degree of swelling exhibited lower moisture retention and higher transparency. Moreover, the weight of the superabsorbent hydrogel increased with the decrement of pH value of external media (distilled water). This study provided substantial information on the effect of different percentage of ECH as crosslinker on hydrogel basic properties. Furthermore, this study affords correlation of many essential driving forces that affected hydrogel superabsorbent property.
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.
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.
Chemically crosslinked hydrogel magnetorheological (MR) plastomer (MRP) embedded with carbonyl iron particles (CIPs) exhibits excellent magnetic performance (MR effect) in the presence of external stimuli especially magnetic field. However, oxidation and desiccation in hydrogel MRP due to a large amount of water content as a dispersing phase would limit its usage for long-term applications, especially in industrial engineering. In this study, different solvents such as dimethyl sulfoxide (DMSO) are also used to prepare polyvinyl alcohol (PVA) hydrogel MRP. Thus, to understand the dynamic viscoelastic properties of hydrogel MRP, three different samples with different solvents: water, DMSO, and their binary mixtures (DMSO/water) were prepared and systematically carried out using the oscillatory shear. The outcomes demonstrate that the PVA hydrogel MRP prepared from precursor gel with water shows the highest MR effect of 15,544% among the PVA hydrogel MRPs. However, the samples exhibit less stability and tend to oxidise after a month. Meanwhile, the samples with binary mixtures (DMSO/water) show an acceptable MR effect of 11,024% with good stability and no CIPs oxidation. Otherwise, the sample with DMSO has the lowest MR effect of 7049% and less stable compared to the binary solvent samples. This confirms that the utilisation of DMSO as a new solvent affects the rheological properties and stability of the samples.
Honey is one of the oldest substances used in wound management. Efficacy of Gelam honey in wound healing was evaluated in this paper. Sprague-Dawley rats were randomly divided into four groups of 24 rats each (untreated group, saline group, Intrasite Gel group, and Gelam honey group) with 2 cm by 2 cm full thickness, excisional wound created on neck area. Wounds were dressed topically according to groups. Rats were sacrificed on days 1, 5, 10, and 15 of treatments. Wounds were then processed for macroscopic and histological observations. Gelam-honey-dressed wounds healed earlier (day 13) than untreated and saline treated groups, as did wounds treated with Intrasite Gel. Honey-treated wounds exhibited less scab and only thin scar formations. Histological features demonstrated positive effects of Gelam honey on the wounds. This paper showed that Gelam honey dressing on excisional wound accelerated the process of wound healing.