Widely distributable and retainable in-situ gelling material for treating myocardial infarction.

Intramyocardial hydrogel injection is a promising therapy to prevent negative remodeling following myocardial infarction (MI). In this study, we report a mechanism for in-situ gel formation without external stimulation, resulting in an injectable and tissue-retainable hydrogel for MI treatment, and investigate its therapeutic outcomes. A liquid-like polymeric solution comprising poly(3-acrylamidophenylboronic acid-co-acrylamide) (BAAm), polyvinyl alcohol (PVA), and sorbitol (S) increases the viscous modulus by reducing the pre-added sorbitol concentration is developed. This solution achieves a sol-gel transition in-vitro in heart tissue by spontaneously diffusing the sorbitol. After intramyocardial injection, the BAAm/PVA/S with lower initial viscous modulus widely spreads in the myocardium and gelate compared to a viscoelastic alginate (ALG) hydrogel and is retained longer than the BAAm/S solution. Serial echocardiogram analyses prove that injecting the BAAm/PVA/S into the hearts of subacute MI rats significantly increases the fraction shortening and ejection shortening and attenuates the expansion of systolic LV diameter for up to 21 d after injection compared to the saline injection as a control, but the ALG injection does not. In addition, histological evaluation shows that only the BAAm/PVA/S decreases the infarct size and increases the wall thickness 21 d after injection. The BAAm/PVA/S intramyocardial injection is better at restraining systolic ventricular dilatation and cardiac failure in the rat MI model than in the control groups. Our findings highlight an effective injectable hydrogel therapy for MI by optimizing injectability-dependent distribution and retention of injected material. STATEMENT OF SIGNIFICANCE: In-situ gelling material is a promising strategy for intramyocardial hydrogel injection therapy for myocardial infarction (MI). Since the sol-gel transition of reported materials is driven by external stimulation such as temperature, pH, or ultraviolet, their application in vivo remains challenging. In this study, we first reported a synthetic in-situ gelling material (BAAm/PVA/S) whose gelation is stimulated by spontaneously reducing pre-added sorbitol after contacting the heart tissue. The BAAm/PVA/S solution spreads evenly, and is retained for at least 21 d in the heart tissue. Our study demonstrated that intramyocardial injection of the BAAm/PVA/S with more extensive distribution and longer retention had better effects on preventing LV dilation and improving cardiac function after MI than that of viscoelastic ALG and saline solution. We expect that these findings provide fundamental information for the optimum design of injectable biomaterials for treating MI.

SpaceOAR hydrogel distribution and early complications in patients undergoing radiation therapy for prostate cancer.

OBJECTIVES: Hydrogel spacers aim to separate the rectum from the prostate during radiation therapy for patients with prostate cancer to decrease the radiation dose and thus toxicity to the rectum. The aim of this study was to evaluate the distribution of the hydrogel spacer between the rectum and the prostate, to assess for hydrogel rectal wall infiltration and to assess for immediate complications. METHODS: Retrospective study of 160 patients who had undergone hydrogel spacer placement. Distribution of the hydrogel was assessed on MRI. MRI images were reviewed for rectal wall injection or other malplacement of gel. Early post-procedure complications were recorded. RESULTS: 117 (73.1%) patients had a symmetrical distribution of the hydrogel spacer. The mean anteroposterior rectoprostatic separation was 10.2 ± 3.7 mm (range 0-27 mm). Seven (4.3%) patient had minimal rectal wall infiltration and one (0.6%) patient had moderate infiltration. One (0.6%) patient had an intraprostatic injection of hydrogel. Two (1.3%) patients required treatment in the emergency department: one for urinary retention and one for pain. CONCLUSIONS: Transperineal hydrogel placement separates the prostate from the rectum with a symmetrical distribution in the majority of cases prior to radiation therapy with a low rate of rectal wall injection and immediate complications. ADVANCES IN KNOWLEDGE: SpaceOAR hydrogel can be safely injected into radiation naive patients with low- or intermediate-risk organ-confined prostate cancer. The spacer separates the prostate from the rectum with a symmetrical distribution in the majority of cases prior to radiation therapy.

Impact of hydrogel peri-rectal spacer insertion on seminal vesicles intrafraction motion during 1.5 T-MRI-guided adaptive stereotactic body radiotherapy for localized prostate cancer.

OBJECTIVES: MR-guided daily-adaptive radiotherapy is improving the accuracy in the planning and delivery phases of the treatment. Rectal hydrogel-spacer may help in mitigating organ motion, but few data are currently available. METHODS: We aimed to assess any potential impact of the device on seminal vesicles motion by measuring translational and rotational shifts between the pre- and post-treatment MRI scans of a total of 50 fractions in the first 10 patients who underwent MR-guided prostate SBRT (35 Gy/5 fx). Of them, five patients received the hydrogel-spacer. The comparative analysis was performed using the Mann-Whitney U-test. RESULTS: Median rotational shifts were: in anteroposterior 0° (range, 0.097°/0.112°; SD = 0.05°) vs 0° (-0.162/0.04°; SD = 0.07°) in the no-spacer subgroup (p = 0.36); lateral shifts were 0° (-0.1°/0.54°; SD = 0.28°) vs -0.85° in the no-spacer cohort (-1.56°/0.124°; SD = 0.054°; p = 0.22). Cranio-caudal shifts were 0° (-0.121°/0.029°; SD = 0.06°) in the spacer-cohort vs 0° (-0.066°/0.087°; SD = 0.69°; p = 0.53). Median translational shifts were: in anteroposterior 0.9 mm (-0.014 mm/0.031 mm; SD = 0.036 mm) in the spacer-group vs 0.030 mm (-0.14 mm/0.03 mm; SD = 0.032 mm; p = 0.8); latero-lateral shifts were -0.042 mm (-0.047 mm/0.07 mm; SD = 0.054 mm), vs -0.023 mm (-0.027 mm/-0.01 mm; SD = 0.023 mm) in the no-spacer group (p = 0.94). In cranio-caudal, statistically significant shifts were reported: 0.082 mm (0.06 mm/0.15 mm; SD = 0.04 mm) vs 0.06 mm (-0.06/0.08 mm; SD = 0.09 mm) in the no-spacer cohort (p = 0.031). CONCLUSIONS: A favorable impact of the hydrogel-spacer on seminal vesicles motion was observed only in cranio-caudal translational shifts, although being not clinically significant. Further studies are required to fully investigate the potential contribution of this device on vesicles motion. ADVANCES IN KNOWLEDGE: MR-guided daily adaptive radiotherapy may represent a game changer for prostate stereotactic body radiotherapy, given the possibility to better visualize soft-tissues anatomy and to daily recalculate the treatment plan based on real-time conditions. The use of devices like rectal ballon or rectal gel spacers has gained interest in the last years for the possibility to better spare the rectum during prostate radiotherapy. This is one of the first experiences exploring the role of rectal spacer on seminal vesicles intrafraction motion during MR-guided SBRT for prostate cancer.

Hidrogeles de polimerizacion in situ para la regeneracion de cartilago articular / In-situ hydrogel polymerization for articular cartilage regeneration

Una significativa cantidad de adultos jóvenes activos sufre lesiones condrales focales. Estas lesiones, si no se tratan, pueden progresar hacia la artrosis, que es una de las principales enfermedades musculoesqueléticas debilitantes y de gran carga económica que afectan a toda sociedad. Pese a los tratamientos quirúrgicos disponibles para la reparación de defectos condrales focales sintomáticos que mejoran la calidad de vida a mediano plazo, hay un mayor riesgo de progresión hacia la artrosis prematura. Los tratamientos biológicos (células madre, bioingeniería tisular) han avanzado a grandes pasos en los últimos años. La bioingeniería es un área que ha progresado en la regeneración de cartílago articular y que potencialmente podría progresar en el terreno de tratamientos articulares, promoviendo la regeneración y evitando la degeneración. Las células madre y los hidrogeles pueden proveer un tejido símil biológico de comportamiento dinámico-funcional equivalente que induce la regeneración tisular al ser degradado y reemplazado gradualmente. El abordaje consiste en colocar un hidrogel precursor o un biomaterial tridimensional impreso dentro del defecto condral por ocupar para inducir la regeneración. Esta revisión se focaliza en el uso actual y futuro de hidrogeles y bioimpresión tridimensional para la regeneración de cartílago articular en el tratamiento de lesiones condrales focales y proporciona datos preliminares de dos estudios piloto en animales. Nivel de Evidencia: V

A significant number of young active adults are affected by focal chondral lesions. These lesions, if left untreated, will progress to osteoarthritis (OA). OA is one of the main debilitating musculoskeletal diseases and leads to a high economic and social burden. Despite surgical cartilage repair for focal chondral lesions, which improve patient-reported outcomes at short- and mid-term, there is a risk of early OA progression. Biological treatments (i.e., stem-cell therapy, bioengineering) have made great progress in the last years. Tissue engineering is an evolving field for articular cartilage repair which could potentially be used for the treatment of focal chondral lesions, promoting regeneration and preventing joint surface degeneration. Stem cells and hydrogels may provide a functional, dynamic and biologically equivalent tissue that promotes tissue regeneration while being gradually degraded and replaced. The standard approach to tissue engineering consists in delivering cells within a hydrogel or a three-dimensional printed biomaterial scaffold into the chondral lesion to induce regeneration. This review focuses on the current and future use of hydrogels and tissue scaffold bioprinting for the treatment of focal chondral lesions, and provides preliminary data from two pilot animal studies. Level of Evidence: V

Progel Use is Not Associated with Decreased Incidence of Postoperative Air Leak after Nonanatomic Lung Surgery.

CONTEXT: Progel Pleural Air Leak Sealant (CR Bard, Warwick, RI) is a US Food and Drug Administration-approved hydrogel designed for application to surgical staple lines to prevent air leak after lung surgery. This product has demonstrated efficacy in reducing intraoperative air leaks compared with standard air leak closure methods. However, the impact on chest tube duration and length of hospital stay has not been reported. OBJECTIVE: To evaluate the effect on rates of postoperative air leak, chest tube duration, and hospital stay in surgical patients with and without use of Progel. DESIGN: Retrospective study of 176 patients aged 18 to 80 years who underwent video-assisted thoracoscopic wedge resections between 2014 and 2016. Eighty-four (48%) cases using Progel were included, as well as a representative sample of non-Progel cases (n = 92; 52%). MAIN OUTCOME MEASURE: Presence of postoperative lung air leak. RESULTS: No difference existed between the Progel and non-Progel groups in the rate of postoperative air leak (20/84, 23.81% Progel; 16/92, 17.39% non-Progel; p = 0.33). The length of time patients had a chest tube was similar (23.5 vs 23 hours, p = 0.721), as was percentage of patients with a less than 2-day hospitalization (77.17% non-Progel vs 82.14% Progel, p = 0.414). CONCLUSION: Our results suggest that Progel, used routinely in patients undergoing nonanatomic lung resection, does not have a significant impact on postoperative air leak, chest tube duration, or length of hospital stay. Further studies are warranted to evaluate the utility of Progel in reducing postoperative complications after thoracoscopic wedge resection in those treated for air leak or in the reduction of postoperative air leak in high-risk patients.

A Novel Recombinant Human Collagen-based Flowable Matrix for Chronic Lower Limb Wound Management: First Results of a Clinical Trial.

BACKGROUND: Chronic ulcers pose a significant health concern and economic burden. Numerous products, including animal-derived collagen products, have been designed to provide the injured site with a biocompatible structural matrix that promotes tissue regeneration. Yet, animal-derived collagens can evoke immune responses, bear risk of disease transmission, and fail to closely mimic the function of native collagen. OBJECTIVE: This study aims to assess the safety and performance of a novel flowable wound matrix, formulated from tobacco plant-purified fibrillated recombinant human type I collagen (rhCollagen), in patients with chronic lower limb ulcers. MATERIALS AND METHODS: This single-arm, open-label, multicenter trial took place at 5 treatment centers. Wounds were photographed and preliminary surgical debridement was performed prior to rhCollagen application. Patients received a single application of rhCollagen to the wound bed, followed by weekly assessments of the wound. RESULTS: Twenty patients (mean age, 63 years), presenting with a chronic ulcer of neuropathic (45%), posttraumatic (35%), postoperative (10%), and venous (10%) origin, underwent rhCollagen treatment. Initial wound area ranged between 0.2 cm3 to 9.2 cm3. At 4-weeks posttreatment, median wound area reduction was 94%. Fifteen ulcers exhibited ≥ 70% wound closure, 9 of which achieved complete closure. Only 1 participant suffered a local self-resolving wound infection. No significant device-related adverse events were reported throughout the study. CONCLUSIONS: A single, easy-to-use rhCollagen flowable gel application for chronic lower limb ulcers may promote wound closure with minimal adverse events.

Formulation development and characterization of cefazolin nanoparticles-loaded cross-linked films of sodium alginate and pectin as wound dressings.

The present study focuses on the preparation of nanoparticles-loaded ionic cross-linked films for the topical delivery of cefazolin. The aim of the study was to prepare a dosage form which can provide local effect of cefazolin along with sustained delivery at the site of application. Cefazolin was loaded into chitosan nanoparticles to mask the burst release of the drug and they were optimized based on particle size, PDI, % EE and zeta potential. Finally, the prepared nanoparticles were loaded into the films comprising of sodium alginate and pectin which were then subjected to cross-linking via calcium chloride to improve the mechanical strength of the hydrogel films upon exposure to wound fluid. The films were assessed for physical and mechanical properties, swelling behavior, water transmission rate, mucoadhesion, FTIR, DSC, percent inhibition assay and in vitro release profile. Optimized formulation with Cefazolin nanoparticles in the size range of 227 nm and 0.5% CL films showed significantly better results (p < 0.05) as compared to the films with increased cross-linker concentration. Therefore, 0.5% CL films were considered more suitable for the treatment of infections when applied as wound dressing.

Injectable Maltodextrin-Based Micelle/Hydrogel Composites for Simvastatin-Controlled Release.

Injectable hydrogels have shown great potential in bone tissue engineering. Simvastatin (SIM), a common hypolipidemic drug, has been suggested as a potential agent to promote bone regeneration. However, due to its hydrophobic nature, the compatibility between SIM and hydrogels is rather poor, thereby greatly affecting the drug release behavior, the mechanical properties, and dimensional stability of the hydrogels. Herein, we presented a novel design to entrap SIM in an injectable maltodextrin-based micelle/hydrogel composite system. Maltodextrin-based micelles were prepared to solubilize and encapsulate SIM. The SIM-loaded aldehyde-modified micelles were anchored to the hydrogel network and served as a cross-linker to realize improved mechanical strength of hydrogel, controlled release, and osteogenic capability of SIM. In all, this study demonstrated a strategy to incorporate drug loaded carriers into hydrogels for drug delivery and tissue engineering applications.

Alginate hydrogel beads as a carrier of low density lipoprotein/pectin nanogels for potential oral delivery applications.

Alginate hydrogel beads have been extensively investigated as drug delivery systems due to promising gastric environment stability. In the present study, alginate hydrogel beads were prepared with Ca2+ or Fe3+ to serve as the loading vehicles for egg yolk low density lipoprotein (LDL)/pectin nanogels. Scanning electron microscope was carried out to confirm the successful incorporation of nanogels into the beads. The FT-IR spectra and swelling ratio analyses proved that incorporation of nanogels did not affect the physicochemical properties of the hydrogel beads. The developed hydrogel beads exhibited pH dependent release of curcumin pre-encapsulated in nanogels, with significant retention of curcumin in gastric condition compared to curcumin encapsulated in nanogels or alginate beads alone. Hydrogel beads prepared with low viscous alginate and Ca2+ showed limited swelling property and more sustained release of curcumin in simulated gastrointestinal conditions, compared to the beads prepared with high viscous alginate and Fe3+. Gradual dissociation of nanogels from the beads during incubation in simulated intestinal fluid was studied with transmission electron microscope. Our study demonstrated the promising potential of alginate beads as a carrier to protect LDL-based nanogels from destabilization in gastric condition, thus expanding their applications as oral delivery system.

Effects of Hydrogel With Enriched Sodium Alginate in Wounds of Diabetic Patients.

Objective of this study was to evaluate the efficacy of the autolytic debridement promoted by hydrogel with sodium alginate enriched with fatty acids and vitamins A and E in the healing of foot wounds in diabetic patients. A clinical study was conducted at an outpatient clinic of medical specialties. The sample comprised 8 patients supervised for a 3-month period, from April to July 2017, by means of a clinical history, photographic record, planimetry, and classification of the wound severity by the Pressure Ulcer Scale for Healing (PUSH) system. Of the 8 patients supervised, 1 dropped out and 7 were followed up for 12 weeks. Only 2 had complete wound healing, but all presented a reduction of the lesion area of approximately 22.2% and PUSH score of 9.8 to 6.6. This study found that hydrogel showed good results for the treatment of diabetic feet, reducing the area and overall PUSH score of the wounds.

Engineering Dendritic-Cell-Based Vaccines and PD-1 Blockade in Self-Assembled Peptide Nanofibrous Hydrogel to Amplify Antitumor T-Cell Immunity.

Dendritic cells (DCs) are increasingly used in cancer vaccines due to their ability to regulate T-cell immunity. Major limitations associated with the present DC adoptive transfer immunotherapy are low cell viability and transient duration of transplanted DCs at the vaccination site and the lack of recruitment of host DCs, leading to unsatisfactory T-cell immune response. Here, we developed a novel vaccine nodule comprising a simple physical mixture of the peptide nanofibrous hydrogel, anti-PD-1 antibodies, DCs, and tumor antigens. Upon subcutaneous injection, the vaccine nodule maintained the viability and biological function including the antigen uptake and maturation of encapsulated DCs and simultaneously recruited a number of host DCs and promoted the drainage of activated DCs to lymph nodes, resulting in enhanced proliferation of antigen-specific splenocytes and provoking potent cellular immune responses. Compared with adoptive transfer of DCs and subcutaneous administration of antigen vaccine, such a vaccine nodule shows superior antitumor immunotherapy efficiency in both prophylactic and therapeutic tumor models including delayed tumor growth and prolonged mice survival due to effective stimulation of antitumor T-cell immunity and increased infiltration of activated CD8+ effector T-cells in the tumor. Our findings provide a simple and robust vaccination strategy for DC-based vaccines and also a unique vaccine product for stimulating and enhancing T-cell immunity, holding great promise for immunotherapy against cancer and infectious diseases.

Dual-responsive IPN hydrogel based on sugarcane bagasse cellulose as drug carrier.

In this work, the stepwise synthesis of interpenetrating polymer network (IPN) strategy was developed in an attempt to fabricate novel hydrogels consisting of sugarcane bagasse cellulose (SBC), carboxymethylcellulose (CMC) and poly (N-isopropylacrylamide) (PNIPAm) as a dual-responsive drug carrier. The pretreated and dissolved SBC was pre-crosslinked using epichlorohydrin in the presence of CMC, followed by in-situ free-radical polymerization of NIPAm in the presence of N,N'-Methylene-bis(acrylamide) as a crosslinking agent. The carboxyl groups in CMC and PNIPAm chains rendered the resulting hydrogel pH and thermal responsive. The results from scanning electron microscopy, infrared spectroscopy, thermogravimetric analysis and mechanical property testing demonstrated the successful formation of the IPN with proper structure and mechanical strength. The swelling experiments at different temperatures and pH showed the dual-sensibility of the hydrogels. Moreover, bovine serum albumin (BSA) was used as a model drug and loaded in the hydrogel; and the drug release behavior was revealed in phosphate buffer solution (PBS) and simulated gastric fluid (SGF). The results indicated that the dual-responsive IPN hydrogel is of great potential for the controlled release of drug.

Controlled Delivery of a Focal Adhesion Kinase Inhibitor Results in Accelerated Wound Closure with Decreased Scar Formation.

Formation of scars after wounding or trauma represents a significant health care burden costing the economy billions of dollars every year. Activation of focal adhesion kinase (FAK) has been shown to play a pivotal role in transducing mechanical signals to elicit fibrotic responses and scar formation during wound repair. We have previously shown that inhibition of FAK using local injections of a small molecule FAK inhibitor (FAKI) can attenuate scar development in a hypertrophic scar model. Clinical translation of FAKI therapy has been challenging, however, because of the lack of an effective drug delivery system for extensive burn injuries, blast injuries, and large excisional injuries. To address this issue, we have developed a pullulan collagen-based hydrogel to deliver FAKI to excisional and burn wounds in mice. Specifically, two distinct drug-laden hydrogels were developed for rapid or sustained release of FAKI for treatment of burn wounds and excisional wounds, respectively. Controlled delivery of FAKI via pullulan collagen hydrogels accelerated wound healing and reduced collagen deposition and activation of scar-forming myofibroblasts in both wound healing models. Our study highlights a biomaterial-based drug delivery approach for wound and scar management that has significant translational implications.

Cellulose hydrogel with tunable shape and mechanical properties: From rigid cylinder to soft scaffold.

Cellulose hydrogel from aqueous solution of lithium bromide demonstrated excellent tunability of mechanical property and shape. A series of compression tests showed that cellulose hydrogel covered a wide range of mechanical property, where the compressive Young's modulus was controllable from 30 kPa to 1.3 MPa by changing the initial concentration of cellulose solution. Meanwhile, the diameter of the building block of gel, namely nano-fibrous cellulose, was constant at 15-20 nm irrelevant of the initial concentration of cellulose solution. Moreover, thanks to the biocompatibility of cellulose, the cultivation of cartilage tissue was successful in the micro-porous sponge-like cellulose hydrogel prepared by salt-leaching process. These findings show that this environmentally-benign versatile gel offers a new substrate for the biomaterial-based nanomaterial in biomedical applications.

Hydrogel Contact Lens Water Content is Dependent on Tearfilm pH.

Introduction: Based on clinical inferences, investigators theorized in situ soft lens hydration was linked to the precorneal tearfilm pH. Methods: Forty-one myopic subjects at Fort Rucker, AL, USA were fitted with one of two types of extended-wear soft contact lenses, and were followed quarterly for a period of 33 mo. The anterior soft contact lens surface pH was measured in situ, while the in vitro lens water content was measured immediately after lens removal, using a hand-held refractometer on one lens, and a gravimetric means of hydration measurement on the other lens. Results: The in situ pH increased logarithmically across extended wearing time, reaching an asymptote at approximately 5 d' wearing time at a pH of 7.45 ± 0.03. Lens water content was shown to similarly decrease at an inversely logarithmic rate, leveling off at 4-5 d' extended wearing time. Both means of hydration assessment correlated well with each other across days' extended wearing time (R = 0.98; p < 0.0001). Discussion: A log-log dual conversion yielded significantly different linear slopes (p < 0.001), based on a multifactorial analysis of both lens types, by the pH, and by their water content. The differing ionic status of each material accentuated their varied polar attraction characteristics. Two soft lenses, identical in all patient-based parameters, could provide differing oxygen availability, as well as differing physical fits in patients of identical physical characteristics, as a result of their unique tearfilm pH differences. Conclusion: The in situ hydrogel lens water content is directly dependent on the precorneal tearfilm pH.

Macromolecule-Network Electrostatics Controlling Delivery of the Biotherapeutic Cell Modulator TIMP-2.

Tissue inhibitor of metalloproteinase 2 (TIMP-2) is an endogenous 22 kDa proteinase inhibitor, demonstrating antitumorigenic, antimetastatic and antiangiogenic activities in vitro and in vivo. Recombinant TIMP-2 is currently undergoing preclinical testing in multiple, murine tumor models. Here we report the development of an inert, injectable peptide hydrogel matrix enabling encapsulation and sustained release of TIMP-2. We studied the TIMP-2 release profile from four ß-hairpin peptide gels of varying net electrostatic charge. A negatively charged peptide gel (designated AcVES3) enabling encapsulation of 4 mg/mL of TIMP-2, without effects on rheological properties, facilitated the slow sustained release (0.9%/d) of TIMP-2 over 28 d. Released TIMP-2 is structurally intact and maintains the ability to inhibit MMP activity, as well as suppress lung cancer cell proliferation in vitro. These findings suggest that the AcVES3 hydrogel will be useful as an injectable vehicle for systemic delivery of TIMP-2 in vivo for ongoing preclinical development.

Self-Assembly of Partially Alkylated Dextran- graft-poly[(2-dimethylamino)ethyl methacrylate] Copolymer Facilitating Hydrophobic/Hydrophilic Drug Delivery and Improving Conetwork Hydrogel Properties.

Key issues of injectable hydrogels are incapability of loading hydrophobic drugs due to insolubility of drugs in aqueous prepolymer solution as well as in hydrogel matrix, and high water swelling, which leads to poor mechanical and bioadhesive properties. Herein, we report that self-assembly of partially long-chain alkylated dextran- graft-poly[(2-dimethylamino)ethyl methacrylate] copolymer in aqueous solution could encapsulate pyrene, a hydrophobic probe, griseofulvin, a hydrophobic antifungal drug, and ornidazole, a hydrophilic antibiotic. Addition of activated chloride terminated poly(ethylene glycol) (PEG) into the guest molecules loaded copolymer solution produced an injectable dextran- graft-poly[(2-dimethylamino)ethyl methacrylate]-linked-PEG conetwork hydrogel. The alkylated hydrogels exhibited zero order release kinetics and were mechanically tough (50-54 kPa storage modulus) and bioadhesive (8-9 kPa). The roles of alkyl chains and dextran on the drug loading-release behavior, degradation behavior, gelation time, and the mechanical property of the hydrogels have been studied in details. Additionally, DNA hybrid composite hydrogel was formed owing to the cationic nature of the prepolymer solution and the hydrogel. Controlled alkylation of a prepolymer thus highlights the potential to induce and enhance the hydrogel property.

Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies.

Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydrogels were found to correlate with the mucoadhesive properties. The results confirmed the ability of nanoparticle-based hydrogels to affect viral attachment, impede penetration and cell-to-cell transmission, although profound differences in the activity evoked by tested preparations toward HSV-1 and HSV-2 were noted. In addition, these findings demonstrated the in vivo potential of tannic acid modified silver nanoparticle-based hydrogels for vaginal treatment of HSV-2 genital infection.

Design of psyllium-g-poly(acrylic acid-co-sodium acrylate)/cloisite 10A semi-IPN nanocomposite hydrogel and its mechanical, rheological and controlled drug release behaviour.

Soft biomaterials derived from polysaccharides are generally suffers from lack of mechanical robustness and instability. The naturally occurring highly abundance low cost polysaccharide has immense aspect as biomaterial after functionalization which can be designed as stretchable and rubber-like elastic with reversible ductility. A highly swellable, stretchable, low creep, non-cytotoxic nanocomposite hydrogel has been fabricated by simple one-pot Michael type covalent grafting of acrylic acid based copolymer onto psyllium biomacromolecular chian by free radical gelation technique. The fabricated hydrogel was rheologically tested which implies its viscoelastic and thixotropic like features. The porous morphology of the hydrogel was confirmed by scanning electron micrograph. The cryo-transmission electron micrograph shows the random dispersion of the nanoclay (cloisite 10A) tactoids in exfoliated as well intercalated forms. These random distributions of clay nanosheets also enhance the mechanical toughness and reversible ductility of the hydrogels which was also supported by the mechanical and loading-unloading cycle measurement. Nonetheless, the nanocomposite hydrogel was non-cytotoxic against human cell-line (human osteosarcoma) and shows good cell attachment of live cells in a 5-day 'live-dead' assay with almost negligible quantity of cell death. These attributes can promote this material as a soft biomaterial for controlled release device with mechanical robustness and rubber-like elasticity.