Ultrathin and Highly Tough Hydrogel Films for Multifunctional Strain Sensors.

With good flexibility and biocompatibility, hydrogel-based sensors have been widely used in human motion detection, artificial intelligence, human-machine interface, and other fields. Previous research on hydrogel-based sensors has focused on improving the mechanical properties and signal transmission sensitivity. With the development of human smart devices, there is an increasing demand for hydrogel sensor comfort and more application functions, such as ultrathin structures and recognition functions for contact surfaces, which are realized with higher requirements for the thickness, flexibility, friction resistance, and biocompatibility of hydrogels. Inspired by the ultrathin and flexible characteristics of human organ biofilms, we constructed conductive hydrogel films by using the flim-casting and glycerol-H2O secondary hydration methods. This ultrathin structure enables the hydrogel films to have a high elongation at break of 523.3%, a stress of 3.5 MPa, and a good friction resistance. Combined with the excellent sensing properties (gauge factor = 2.1 and a response time of 200 ms), the hydrogel film-based sensor can not only record human motion signals but also recognize the surface texture and roughness of objects, such as glass, brushes, wood, and sandpaper with mesh sizes of 80, 50, and 24, accurately. In addition, this hydrogel film has a series of excellent properties such as UV shielding, antiswelling ability, and good biocompatibility. This research provides a novel way for the development of emerging soft-material smart devices, such as hydrogel-based electronic skin and soft robots.

Development and evaluation of pH-sensitive biodegradable ternary blended hydrogel films (chitosan/guar gum/PVP) for drug delivery application.

pH responsive hydrogels have gained much attraction in biomedical fields. We have formulated ternary hydrogel films as a new carrier of drug. Polyelectrolyte complex of chitosan/guar gum/polyvinyl pyrrolidone cross-linked via sodium tripolyphosphate was developed by solution casting method. Fourier transform infrared spectroscopy, scanning electron microscopy and thermogravimetric analysis were conducted to examine the interactions between the polymeric chains, surface morphology and thermal stability, respectively. The swelling tests resulted that the swelling was reduced with the increase in the concentration of crosslinker due to the more entangled arrangement and less availability of pores in hydrogels. Ciprofloxacin hydrochloride was used as a model drug and its release in simulated gastric fluid, simulated intestinal fluid and phosphate buffer saline solution was studied. pH responsive behaviour of the hydrogels have subjected these hydrogels for drug release applications.

Photo-Crosslinked Gelatin-Based Hydrogel Films to Support Wound Healing.

Gelatin is used widely in the biomedical field, among other for wound healing. Given its upper critical solution temperature, crosslinking is required. To this end, gelatin is chemically modified with different photo-crosslinkable moieties with low (32-34%) and high (63-65%) degree of substitution (DS): gelatin-methacrylamide (gel-MA) and gelatin-acrylamide (gel-AA) and gelatin-pentenamide (gel-PE). Next to the more researched gel-MA, it is especially interesting and novel to compare with other gelatin-derived compounds for the application of wound healing. An additional comparison is made with commercial dressings. The DS is directly proportional to the mechanical characteristics and inversely proportional to the swelling capacity. Gel-PE shows weaker mechanical properties (G' < 15 kPa) than gel-AA and gel-MA (G' < 39 and 45 kPa, respectively). All derivatives are predominantly elastic (recovery indices of 89-94%). Gel-AA and gel-MA show excellent biocompatibility, whereas gel-PE shows a significantly lower initial biocompatibility, evolving positively toward day 7. Overall, gel-MA shows to have the most potential to be applied as wound dressing. Future blending with gel-AA to improve the curing kinetics can lead to dressings able to compete with current commercial dressings.

Stretchable and Conductive Composite Structural Color Hydrogel Films as Bionic Electronic Skins.

Electronic skins have received increasing attention in biomedical areas. Current efforts about electronic skins are focused on the development of multifunctional materials to improve their performance. Here, the authors propose a novel natural-synthetic polymers composite structural color hydrogel film with high stretchability, flexibility, conductivity, and superior self-reporting ability to construct ideal multiple-signal bionic electronic skins. The composite hydrogel film is prepared by using the mixture of polyacrylamide (PAM), silk fibroin (SF), poly(3,4-ethylenedioxythiophene):poly (4-styrene sulfonate) (PEDOT:PSS, PP), and graphene oxide (GO) to replicate colloidal crystal templates and construct inverse opal scaffolds, followed by subsequent acid treatment. Due to these specific structures and components, the resultant film is imparted with vivid structural color and high conductivity while retaining the composite hydrogel's original stretchability and flexibility. The authors demonstrate that the composite hydrogel film has obvious color variation and electromechanical properties during the stretching and bending process, which could thus be utilized as a multi-signal response electronic skin to realize real-time color sensing and electrical response during human motions. These features indicate that the proposed composite structural color hydrogel film can widen the practical value of bionic electronic skins.

Innovative Eco-Friendly Hydrogel Film for Berberine Delivery in Skin Applications.

Hydrogel formulations (masks or patches, without tissue support) represent the new frontier for customizable skin beauty and health. The employment of these materials is becoming popular in wound dressing, to speed up the healing process while protecting the affected area, as well as to provide a moisturizing reservoir, control the inflammatory process and the onset of bacterial development. Most of these hydrogels are acrylic-based at present, not biodegradable and potentially toxic, due to acrylic monomers residues. In this work, we selected a new class of cellulose-derived and biodegradable hydrogel films to incorporate and convey an active compound for dermatological issues. Films were obtained from a combination of different polysaccharides and clays, and berberine hydrochloride, a polyphenolic molecule showing anti-inflammatory, immunomodulatory, antibacterial and antioxidant properties, was chosen and then embedded in the hydrogel films. These innovative hydrogel-based systems were characterized in terms of water uptake profile, in vitro cytocompatibility and skin permeation kinetics by Franz diffusion cell. Berberine permeation fitted well to Korsmeyer-Peppas kinetic model and achieved a release higher than 100 µg/cm2 within 24 h. The latter study, exploiting a reliable skin model membrane, together with the biological assessment, gained insights into the most promising formulation for future investigations.

Thermo-/pH-responsive preservative delivery based on TEMPO cellulose nanofiber/cationic copolymer hydrogel film in fruit packaging.

Hydrogels have great potential in food packaging. However, stimuli-responsive preservative delivery-based hydrogels for emerging active packaging have not yet been explored. Herein, Unprecedented pH/temperature-responsive hydrogel films for emerging active climacteric fruit packaging were developed based on TEMPO-oxidized nanofibrillated cellulose (TOCNFs) from wheat straw with food-grade cationic-modified poly(N-isopropyl acrylamide-co-acrylamide) (CPNIPAM-AM). TOCNF incorporation into CPNIPAM-AM revealed desirable enhancement of characterization, antimicrobial properties, and pH/thermal-responsive behaviour. In-vitro delivery and release mechanism studies with natamycin revealed the fastest release rates in preferred low pH media, up to 32.1 times higher than that under neutral conditions via anomalous diffusion. Applying a thermal stimulus increased natamycin release rates, providing 1.5-21% gradual-additional pulses by Fickian diffusion. The final hydrogel film showed efficient decay control in response to stimuli of the climacteric fruit environment with safe, recyclable, and feasible application demonstrating the significant potential to be used as an alternative-sustainable material for stimuli-triggered preservative delivery in climacteric fruit packaging.

PEG-crosslinked-chitosan hydrogel films for in situ delivery of Opuntia ficus-indica extract.

In the present study, chitosan-based wound dressings loaded with the extract of Opuntia ficus-indica (OPU) were prepared. OPU is known for its capability to accelerate skin injury repair. Chitosan (Ch) was crosslinked with a low molecular weight diepoxy-poly(ethylene glycol) (diePEG), and hydrogel films with different Ch/PEG composition and OPU content were prepared by casting. The occurrence of crosslinking reaction was confirmed by FTIR spectroscopy. FTIR and DSC analysis suggested that ionic interactions occur between chitosan and OPU. Tensile tests evidenced that the crosslinking caused a decrease of Young's modulus, which approaches the value of the human skin modulus. Swelling characteristics, water vapor transmission rate, and release kinetics demonstrated that these films are adequate for the proposed application. Finally, a scratch test on a keratinocytes monolayer showed that the rate of cell migration in the presence of OPU-loaded samples is about 3-fold higher compared to unloaded films, confirming the repairing activity of OPU.

BSA/Silver Nanoparticle-Loaded Hydrogel Film for Local Photothermal Treatment of Skin Cancer.

PURPOSE: To develop a hydrogel film containing bovine serum albumin (BSA)-coated silver nanoparticles (BSA/AgNP) and evaluate its applicability for topical photothermal treatment (PTT) of skin cancer. METHODS: BSA/AgNP-loaded hydrogel films were prepared and their swelling, bioadhesive, mechanical, and photothermal properties were characterized in vitro and in vivo. RESULTS: The synthesized BSA/AgNP exhibited a narrow size distribution with good size stability and, notably, possessed great photothermal activity that could stably maintain through repetitive laser irradiation. The BSA/AgNP-loaded hydrogel films showed favorable swelling, bioadhesive, tensile, and photothermal properties. Based on these results, when tested the anti-cancer effects in B16F10 s.c. tumor-bearing mice, the PTT with the topical treatment of BSA/AgNP-loaded hydrogel films could significantly inhibit the tumor growth by a single treatment with no apparent toxicity. CONCLUSIONS: Overall, the results of this study demonstrated that the BSA/AgNP-loaded hydrogel films may serve as an effective but safe topical PTT agent for the treatment of skin cancer.

High-mechanical strength carboxymethyl chitosan-based hydrogel film for antibacterial wound dressing.

Hydrogels, being highly biocompatible and adaptable with biological tissues, have shown great usability in biomedical applications. In this research, a novel hydrogel film developed from carboxymethyl chitosan (CMCS) loaded with waterborne polyurethane-gelatin hydrolysate was synthesized via aqueous emulsion copolymerization. The synthesized hydrogel film was characterized using mechanical strength tests, FTIR, XPS, SEM, AFM, and various other analysis technologies. The results demonstrated that the hydrogel film exhibited good thermal stability, swelling behavior, as well as controllable biodegradability. Specifically, when the CMCS content was loaded at 6 %, the maximum tensile strength and elongation at the break of the hydrogel film were reached 31.69 MPa and 447.187, respectively. The disk diffusion tests indicated that the hydrogel film presented significant antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). These results indicate that hydrogel films with high mechanical strength and high antibacterial activity could be used for wound dressing applications.

Hydroxypropyl methylcellulose-copper nanoparticle and its nanocomposite hydrogel films for antibacterial application.

Currently, special emphasis is being given to the design and fabrication of antibacterial nanocomposite hydrogels for wound dressing applications. Herein, we report the synthesis and characterization of hydroxypropyl methylcellulose (HPMC) reinforced with HPMC capped copper nanoparticles (HCu NPs) based nanocomposite hydrogel films (NHFs). Spherical nanostructures of HCu NPs (∼40 nm) were achieved by facile precipitation technique using ascorbic acid as a nucleating agent and subsequently made their NHFs via solution casting method. Spectral, thermal and structural characteristics of the developed materials were carried out. Antibacterial activity of the resultant NHFs showed the MIC and MBC values of 350 and 1400 µg/mL for S. aureus, and 500 and 2000 µg/mL for E. coli, respectively. These results conveyed that the HCu NPs incorporated HPMC NHFs can be used effectively in antibacterial applications.

In vitro and in vivo evaluation of gellan gum hydrogel films: Assessing the co impact of therapeutic oils and ofloxacin on wound healing.

Herein, we report co-encapsulation of ofloxacin with tea tree or lavender oil in gellan gum based hydrogel films by solvent casting ionotropic gelation method as wound dressing. Prepared films were transparent, flexible, and displayed antioxidant activity with superior antibacterial response against common inhabitants of wound i.e. gram positive and negative bacteria. Solid-state characterization of optimized formulation (OL3 and OT3) revealed successful incorporation of drug and oils in hydrogel structure without any noticeable interaction. In vitro release studies showed an initial burst release but remaining portion released in controlled manner over 48 h from the films and furthermore, presence of oils did not affected the ofloxacin release. Optimized formulation containing ofloxacin and 25% w/w lavender/tea tree oil showed 98% wound contraction in rats after ten days of treatment. Histological images displayed completely healed epidermis. Taken together, our prepared hydrogel films demonstrated favorable features with appreciable antibacterial, wound healing activity and could be useful for the treatment of full thickness wounds.

Fabrication, Physical Characterizations, and In Vitro, In Vivo Evaluation of Ginger Extract-Loaded Gelatin/Poly(Vinyl Alcohol) Hydrogel Films Against Burn Wound Healing in Animal Model.

Crude ginger has been used to treat wounds since ancient times till nowadays. The present study aimed at designing and characterizing topical hydrogel films loaded with ginger extract for wound healing in animal model. The hydrogel films were prepared using PVA and gelatin. The prepared films were evaluated for FTIR analysis, surface morphology, pH, swelling behavior, in vitro release, and % drug content. The wound-healing activity of the extract-loaded hydrogel films was compared with commercially available Silver Sulfadiazine® cream. The drug was compatible with the selected polymers and indicated the suitability of the selected polymers for preparation of topical hydrogel films. The SEM images clearly indicated porous structure of the prepared hydrogel films. Slight changes were observed in pH, ranging from 4.98 ± 0.079 in the beginning of the study to 4.9 ± 0.58 in the end. The swelling percentage after 8 h was 257.7%. The films released 78.7 ± 1.7% of the drug in 250 min. The percent drug content was 97.78 ± 5% which did not change significantly during the storage period. The hydrogel films showed similar wound-healing activity as compared to the commercial product (p > 0.05; ANOVA), while greater wound-healing activity as compared to the control group (p < 0.05; ANOVA) evidenced by intensive collagen formation in histopathological analysis.

Synthesis of chemically cross-linked hydrogel films based on basil seed (Ocimum basilicum L.) mucilage for wound dressing drug delivery applications.

The present study aims toward the preparation of pH-sensitive hydrogel films based on basil seed mucilage (OBM) biopolymer as a novel drug delivery system for wound dressing. Various contents of polyvinyl alcohol (PVA), glutaraldehyde (GA) as cross-linker, and glycerol as a plasticizer were incorporated to have an optimal combination of softness and resilience. OBM hydrogel films characterized by FT-IR, thermogravimetric analysis (TGA), morphological analysis by scanning electron microscope (SEM) and their physical properties were discussed on the reportage of the results of several tests: rheology, mechanical tests (stress at maximum load and Young's modulus), O2 permeability and water vapor permeability, gel fraction, water retention capacity and swelling degree measurements. The best results for this work were Mu-Gly2, which has the acceptable swelling degree and gel fraction leading to functional water retention capacity, as well as the selected formulations, which were non-toxic and biocompatible according to the result of cytotoxicity test. The optimized formulations of films were used for loading of Tetracycline hydrochloride (TH) as a model drug, and the release studies showed better results at pH = 8.5 and pH = 7.4 rather than acidic pH.

Physical and biological properties of alginate/carbon nanofibers hydrogel films.

Alginates are renewable materials with excellent biocompatibility and cost-effectiveness in comparison with other biodegradable polymers. However, these hydrogels have poor mechanical properties that restrict their applications in biomedical fields such as skin tissue engineering. In this regard, the study follows an enhanced engineering route to produce alginate-based films reinforced with different amounts (0, 0.1, 0.5, 1 and 2% w/w) of carbon nanofibers (CNFs) and characterize their physical and biological properties. The results of this study showed that these composites possess similar biological properties to neat alginate hydrogels. Thus, none of the synthesized composite materials were cytotoxic and no cell adhesion was observed on the films. Water sorption at the body temperature did not suffer strong changes with the incorporation of CNFs into the alginate matrix. The dynamic mechanical and tensile/compressive properties of calcium alginate significantly improved with the addition of even a very low amount of CNFs. Thus, the tensile and compression modulus of the calcium alginate films in the dry and hydrated state increases up to three and six times, respectively, with the addition of 2% w/w CNFs. In addition, the composites reinforced with the lowest CNFs content have the advantage of possessing more transparency and lower production costs.

A lectin with anti-microbial and anti proliferative activities from Lantana camara, a medicinal plant.

BACKGROUND: Lectins are known to possess interesting biological properties such as anti microbial, nematicidal, anti tumor and anti viral activities. Lantana camara from verbenaceae family is a medicinal plant known for possessing anti oxidant and anticancer activities. Since anticancer activity is reported in plant lectins, leaves of Lantana camara was used to check the presence of lectin. METHODS AND RESULTS: Here we report the purification, characterization and biological properties of a lectin from Lantana camara (LCL) leaves. LCL was purified by ion exchange chromatography on CM-cellulose column followed by affinity chromatography on mucin coupled Sepharose 4B column and gel filtration chromatography on Superdex G75 column. LCL is a glycoprotein with 10% of the carbohydrate and is blood group non specific. SDS-PAGE analysis of affinity purified LCL showed two proteins with apparent molecular weight of 14.49 kDa and 17.4 kDa which were subsequently separated by Gel filtration chromatography on Superdex G75 column. Hapten inhibition studies of LCL revealed its highest affinity for Chitin, Milibiose, α-D-Methyl galactopyranoside and glycoproteins like mucin, asialomucin. LCL showed strong binding to human colon adenocarcinoma HT29 cells with MFI of 242 which was effectively blocked by 68.1 and 62.5% by both mucin and milibiose. LCL showed dose and time dependent growth inhibitory effects on HT29 cells with IC50 of 3.75  µg/ml at 48 h. LCL has potent antibacterial and anti fungal activity. CONCLUSION: LCL can be explored for its clinical potential.

Cellulose based nanocomposite hydrogel films consisting of sodium carboxymethylcellulose-grapefruit seed extract nanoparticles for potential wound healing applications.

The impact of grapefruit seed extract (GFSE) as an antibacterial agent on citric acid (CA) crosslinked sodium carboxymethylcellulose (NaCMC)/hydroxypropylmethylcellulose (HPMC) hydrogel films has been studied by incorporating different quantities of GFSE. The prepared films were examined for their physical, thermal, mechanical and antibacterial properties. It was observed that crystallinity and initial decomposition temperature of hydrogel films decreased with GFSE concentration. Furthermore, the swelling degree and tensile strength of hydrogel films were found to be 257.29 ± 5.08%-162.06 ± 1.78% and 11.61 ± 0.27-2.21 ± 0.94 MPa for increasing GFSE concentration varying from 0.25% - 1.5% (v/v). The presence of nanoparticles in the films was observed by FESEM and FETEM analysis. It was confirmed that the formation of nanoparticles (micelles) is due to the addition of NaCMC and GFSE, probably glycerides, which is one of the main components in GFSE. The hydrogel films have demonstrated excellent antimicrobial activity and elongation at break (%). Moreover, zeta potential of nanoparticles was recorded to be -55.26 mV ascertaining their stability in water that contributed to a higher antimicrobial activity against gram negative bacteria. All these outcomes prove the nanocomposite films to be a potential substitute for hydrogels loaded with synthetic drugs in wound healing and other biological applications.

Sprayed in-situ synthesis of polyvinyl alcohol/chitosan loaded silver nanocomposite hydrogel for improved antibacterial effects.

To overcome the practical limitations of hydrogel preparations, applications and strength-based problems, the present study utilizes the use of sprayers for preparing polyvinyl alcohol/chitosan (PVA/CH) hydrogels. The particle size, morphology, stability, release studies and antibacterial activity of silver nanoparticles (AgNPs) had been studied. The particle size of AgNPs was found to be in the range of 4.59-10 nm (75 °C) with a polydispersity index (PDI) of 0.84. The morphological images exhibited inter-connecting porous structure with pore size in submicron's (<1 µm). Major infra-red spectral peaks of PVA (2946.67 cm-1; stretching of CH, 1142.72 cm-1; CO stretching) and CH (3287.49 cm-1; OH stretching, 2917.48 cm-1; CH stretching) maintain their place in PVA/CH and PVA/CH/Ag hydrogels. In addition, X-ray diffraction (XRD) pattern showed peaks with 2θ values at 38.08°, 44.29° and 64.50° corresponding to the crystal planes of (1 1 1), (2 0 0) and (2 2 0), respectively, allocated to face-centered cubic crystalline structure of AgNPs. The drug release and antibacterial studies showed a maximum release of 91.83% from hydrogels and a concentration dependent zone of inhibition (ZOI) for >24 h, respectively. Thus, the newly developed sprayed hydrogels could turn out to be a suitable dressing material for wound healing applications.

A feasible biocompatible hydrogel film embedding Periplaneta americana extract for acute wound healing.

The wound healing effects of pharmaceutic preparations of Periplaneta americana, Kangfuxin liquid, have been widely utilized in clinics. However, its wound repair efficacy is limited due to short retention capability on cutaneous wound location. Herein, Periplaneta americana extract (PAE), which showed pro-fibrogenic and pro-angiogeneic effects, was embedded into hydrogel film (PAE/Film) by solution cast method by blending polyvinyl alcohol, hydroxypropyl chitosan and carbomer at the weight ratio of 78/6/3, with glycerol as plasticizer. PAE/Film exhibited smooth, flexible, and excellent swelling ability (WVTR of 2464 ±â€¯31.5 g/m2/day), characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry, meting the condition of ideal wound dressing. The superior wound healing capacity of PAE/Film was demonstrated that it significantly accelerated wound healing process in vivo in both full-thickness skin defect and scald wounded models. Compared to saline, blank vehicle (drug-free) and free PAE group, PAE/Film could accelerate wound healed, promote re-epithelialization and collagen deposition by means of TGF-ß/Smad signal pathway activation. Taken together, this novel hydrogel film-loading PAE would be a useful pharmaceutic candidate for acute cutaneous wound health care.

Sacran Hydrogel Film Containing Keratinocyte Growth Factor Accelerates Wound Healing by Stimulating Fibroblast Migration and Re-epithelization.

Regenerative therapy with keratinocyte growth factor (KGF) is a novel therapeutic approach for treatment of chronic wounds. However, KGF cannot be used directly to the wound site due to its physicochemical instability. In previous study, sacran, a natural megamolecular polysaccharide, showed potential properties as a biomaterial for hydrogel film in wound healing. In this study, we fabricated sacran hydrogel film containing KGF (Sac/KGF-HF) and evaluated the effects of Sac/KGF-HF on fibroblasts migration and re-epithelialization process. We successfully prepared a homogenous and -amorphous Sac/KGF-HF by a casting method. In addition, Sac/KGF-HF had a high swelling ratio and flexibility. Sac/KGF-HF promoted a migration process of NIH3T3 cells and improved wound healing ability in mice with a percentage of wound closure reaching 90.4% at 9 d. Interestingly, the addition of KGF in Sac-HF considerably increased the number of epithelial cells compared to control, which is important in the re-epithelialization process. It could be concluded that KGF in Sac-HF has the potential for promoting Sac-HF abilities in wound healing process.

Development of film-forming gel containing nanoparticles for transdermal drug delivery.

Despite several studies on film-forming systems with the advantages of both the film and the hydrogel, there are still no effective systems for fast film formation with a high level of control over permeability. In this study, a film-forming system for the delivery of nanomedicine, termed a film-forming nanogel (FFN), was produced and investigated for the first time to meet this need. The objective of this research was to study a new generation of film-forming hydrogels (FFHs) loaded with curcumin nanoparticles (CUR-GNPs) for transdermal applications. FFHs were prepared by employing zein and HPMC 4000 as film-forming polymers. Meanwhile, CUR-GNPs were obtained by sonoprecipitation. The film-forming time, particle characteristics and FFN drug release profile were assessed. The optimized FFH had a smooth surface and a fast drying time of 6 min and 4.5 min in vitro and ex vivo, respectively. Additionally, high, sustained drug permeation from the FFN was observed after 24 h. The FFH containing CUR-GNPs showed potential for application in transdermal drug delivery with a fast film-forming time, uniform particle dispersion and high, sustained drug permeation.