Unloaded Hydrogels Research Articles

Synergistic Antibacterial Action of Norfloxacin-Encapsulated G4 Hydrogels: The Role of Boronic Acid and Cyclodextrin

In this present study, we developed and characterized a series of supramolecular G4 hydrogels by integrating β-cyclodextrin (β-CD) and boronic acid linkers into a supramolecular matrix to enhance antibacterial activity against Staphylococcus aureus (S. aureus). We systematically investigated how varying the number of free boronic acid moieties (ranging from two to six), along with guanosine and β-CD content, influences both the structural integrity and antimicrobial efficacy of these materials. Comprehensive characterization using FTIR, circular dichroism, X-ray diffraction, SEM, AFM, and rheological measurements confirmed successful synthesis and revealed that higher boronic acid content correlated with a stronger, more organized network. The most effective hydrogel displayed an inhibition zone of 25 mm in disk diffusion assays, and was further explored as a drug delivery platform, with the aim to exploit the capacity of the free β-CD cavity of the hydrogels to incorporate hydrophobic drugs. Norfloxacin (Nfx), a poorly water-soluble antibiotic, was successfully encapsulated within the hydrogel matrix through the inclusion of complex formation with β-CD, improving its solubility and enabling sustained, targeted release. The Nfx-loaded hydrogel expanded the inhibition zone to 49 mm and completely eradicated S. aureus cells within 24 h, outperforming both the unloaded hydrogel and free Nfx. These results highlight the synergistic effect of boronic acid moieties and controlled drug release, underlining the potential of these hydrogels as versatile platforms for localized antimicrobial therapy, such as in wound dressings or implant coatings. Nevertheless, further in vivo studies and long-term stability assessments are needed to fully establish clinical relevance, safety, and scalability before these systems can be translated into routine healthcare applications.

3D-Printed Hydrogels as Photothermal Actuators.

Thermoresponsive hydrogels were 3D-printed with embedded gold nanorods (GNRs), which enable shape change through photothermal heating. GNRs were functionalized with bovine serum albumin and mixed with a photosensitizer and poly(N-isopropylacrylamide) (PNIPAAm) macromer, forming an ink for 3D printing by direct ink writing. A macromer-based approach was chosen to provide good microstructural homogeneity and optical transparency of the unloaded hydrogel in its swollen state. The ink was printed into an acetylated gelatin hydrogel support matrix to prevent the spreading of the low-viscosity ink and provide mechanical stability during printing and concurrent photocrosslinking. Acetylated gelatin hydrogel was introduced because it allows for melting and removal of the support structure below the transition temperature of the crosslinked PNIPAAm structure. Convective and photothermal heating were compared, which both triggered the phase transition of PNIPAAm and induced reversible shrinkage of the hydrogel-GNR composite for a range of GNR loadings. During reswelling after photothermal heating, some structures formed an internally buckled state, where minor mechanical agitation recovered the unbuckled structure. The BSA-GNRs did not leach out of the structure during multiple cycles of shrinkage and reswelling. This work demonstrates the promise of 3D-printed, photoresponsive structures as hydrogel actuators.

Cellulose fibres enhance the function of hemostatic composite medical sealants.

Tissue adhesives and sealants offer promising alternatives to traditional wound closure methods, but the existing trade-off between biocompatibility and strength is still a challenge. The current study explores the potential of a gelatin-alginate-based hydrogel, cross-linked with a carbodiimide, and loaded with two functional fillers, the hemostatic agent kaolin and cellulose fibres, to improve the hydrogel's mechanical strength and hemostatic properties for use as a sealant. The effect of the formulation parameters on the mechanical and physical properties was studied, as well as the biocompatibility and microstructure. The incorporation of the two functional fillers resulted in a dual micro-composite structure, with uniform dispersion of both fillers within the hydrogel, and excellent adhesion between the fillers and the hydrogel matrix. This enabled to strongly increase the sealing ability and the tensile strength and modulus of the hydrogel. The fibres' contribution to the enhanced mechanical properties is more dominant than that of kaolin. A combined synergistic effect of both fillers resulted in enhanced sealing ability (247%), tensile strength (400%), and Young's modulus (437%), compared to the unloaded hydrogel formulation. While the incorporation of kaolin almost did not affect the physical properties of the hydrogel, the incorporation of the fibres strongly increased the viscosity and decreased the gelation time and swelling degree. The cytotoxicity tests indicated that all studied formulations exhibited high cell viability. Hence, the studied new dual micro-composite hydrogels may be suitable for medical sealing applications, especially when it is needed to get a high sealing effect within a short time. The desired hemostatic effect is obtained due to kaolin incorporation without affecting the physical properties of the sealant. Understanding the effects of the formulation parameters on the hydrogel's properties enables the fitting of optimal formulations for various medical sealing applications.

In vivo evaluation of a Nano-enabled therapeutic vitreous substitute for the precise delivery of triamcinolone to the posterior segment of the eye

This study focused on the design of a thermoresponsive, nano-enabled vitreous substitute for the treatment of retinal diseases. Synthesis of a hydrogel composed of hyaluronic acid and a poloxamer blend was undertaken. Poly(D,L-lactide-co-glycolide) acid nanoparticles encapsulating triamcinolone acetonide (TA) were synthesised with a spherical morphology and mean diameter of ~ 153 nm. Hydrogel fabrication and nanoparticle loading within the hydrogel was confirmed via physicochemical analysis. Gelation studies indicated that hydrogels formed in nine minutes and 10 min for the unloaded and nanoparticle-loaded hydrogels, respectively. The hydrogels displayed in situ gel formation properties, and rheometric viscoelastic studies indicated the unloaded and loaded hydrogels to have modulus values similar to those of the natural vitreous at 37 °C. Administration of the hydrogels was possible via 26G needles allowing for clinical application and drug release of triamcinolone acetonide from the nanoparticle-loaded hydrogel, which provided sustained in vitro drug release over nine weeks. The hydrogels displayed minimal swelling, reaching equilibrium swelling within 12 h for the unloaded hydrogel, and eight hours for the nanoparticle-loaded hydrogel. Biodegradation in simulated vitreous humour with lysozyme showed < 20% degradation within nine weeks. Biocompatibility of both unloaded and loaded hydrogels was shown with mouse fibroblast and human retinal pigment epithelium cell lines. Lastly, a pilot in vivo study in a New Zealand White rabbit model displayed minimal toxicity with precise, localised drug release behaviour, and ocular TA levels maintained within the therapeutic window for the 28-day investigation period, which supports the potential applicability of the unloaded and nanoparticle-loaded hydrogels as vitreous substitutes that function as drug delivery systems following vitrectomy surgery.Graphical Fig. aSchematic representation of the nano-enabled therapeutic vitreous substitute synthesis process. This figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license

Evaluation of the Effect of an Intraperitoneal Cytostatic-Loaded Supramolecular Hydrogel on Intestinal Anastomotic Healing in an Animal Model.

The prognosis of colorectal cancer patients with peritoneal metastases is very poor. Intraperitoneal drug delivery systems, like supramolecular hydrogels, are being developed to improve local delivery and intraperitoneal residence time of a cytostatic such as mitomycin C (MMC). In this study, we evaluate the effect of intraperitoneal hydrogel administration on anastomotic healing. Forty-two healthy Wistar rats received a colonic end-to-end anastomosis, after which 6 animals received an intraperitoneal injection with saline, 18 with unloaded hydrogel and 18 with MMC-loaded hydrogel. After 7 days, animals were euthanized, and the anastomotic adhesion and leakage score were measured as primary outcome. Secondary outcomes were bursting pressure, histological anastomosis evaluation and body weight changes. Twenty-two rats completed the follow-up period (saline: n = 6, unloaded hydrogel: n = 10, MMC-loaded hydrogel: n = 6) and were included in the analysis. A trend towards significance was found for anastomotic leakage score between the rats receiving saline and unloaded hydrogel after multiple-comparison correction (p = 0.020, α = 0.0167). No significant differences were found for all other outcomes. The main reason for drop-out in this study was intestinal blood loss. Although the preliminary results suggest that MMC-loaded or unloaded hydrogel does not influence anastomotic healing, the intestinal blood loss observed in a considerable number of animals receiving unloaded and MMC-loaded hydrogel implies that the injection of the hydrogel under the studied conditions is not safe in the current rodent model and warrants further optimalisation of the hydrogel.

Acceleration of wound healing By PVA-PEG-MgO nanocomposite hydrogel with human epidermal growth factor

This study focuses on development of a nanocomposite hydrogel for wound healing purposes. Poly-vinyl alcohol and poly-ethylene glycol-4000 were used to fabricate the hydrogel, physically crosslinking through freeze-thaw method, and magnesium oxide nanoparticles were incoprorated onto them. Notably, the integration of these nanoparticles induced significant changes in the hydrogel's properties, leading to marked improvements in its swelling ratio, water content, and tensile strength. This, in conjunction with their intrinsic moisture retention ability and enhanced antibacterial efficacy, makes these hydrogel nanocomposites as highly promising candidates for wound healing applications. Also, the minimal leaching of nanoparticles from these films reduced the risk of metal accumulation on wounds. To evaluate their performance in wound contraction, assessments were conducted using a live Wister rat model. It was observed that both bare and unloaded hydrogels promoted cell proliferation, and addition of human epidermal growth factor exponentially accelerated the process.The hydrogel films demonstrated biocompatibility and stimulated cell growth. Various parameters, including wound size contraction, angiogenesis, and reconstruction of the damaged epithelial layer, were examined using microscopic methods to assess the rate of wound healing.

Development and assessment of carboxymethyl tamarind kernel gum-based pH-responsive hydrogel for release of diclofenac sodium

The current research work focuses on the fabrication of carboxymethyl tamarind kernel gum/polyvinylpyrrolidone/polyacrylamide (CMTKG/PVP/PAM) based hydrogel and its loading was done with diclofenac sodium drug (DS) to obtain smart pH-responsive hydrogels. In addition, the effect of concentration of cross-linker- N, N′-methylene bis(acrylamide) (MBA), biopolymer (CMTKG), as well as initiator- potassium persulphate (KPS) on the swelling behavior of smart hydrogel was also analyzed. The synthesized hydrogels were characterized using Scanning Electron Microscopy (SEM), Powder X-ray Diffraction (PXRD), Thermogravimetry Analysis (TGA), and Attenuated Total Reflection-Fourier Transform Infrared spectroscopy (ATR-FTIR). ATR-FTIR confirms the successful formation of hydrogels, while PXRD and SEM indicate the amorphous and porous nature of the polymeric network. The TGA results indicate higher thermal stability for DS-loaded hydrogel than unloaded hydrogel. However, sol–gel analysis shows a rise in gel fraction, with increased concentrations of CMTKG, MBA, and KPS. The swelling ratio as well as the release of DS were found to be higher under slightly alkaline conditions. The result of drug loading and release indicates that PVP increases drug loading (%) and release (%). The drug release behavior of DS-loaded hydrogel follows the Fickian mechanism of diffusion with the Korsmeyer-Peppas model as the best-fitted one. The synthesized DS-loaded CMTKG/PVP/PAM hydrogels could be a promising substitute for prolonged delivery of sparingly soluble DS in pH 7.4.

Treating colorectal peritoneal metastases with an injectable cytostatic loaded supramolecular hydrogel in a rodent animal model

Patients with peritoneal metastases (PM) of colorectal cancer have a very poor outcome. Intraperitoneal delivery of chemotherapy is the preferred route for PM treatment. The main limitation of the treatment options is the short residence time of the cytostatic, with subsequent short exposure of the cancer cells. To address this, a supramolecular hydrogel has been developed that allows both local and slow release of its encapsulated drug, mitomycin C (MMC) or cholesterol-conjugated MMC (cMMC), respectively. This experimental study investigates if drug delivery using this hydrogel improves the therapeutic efficacy against PM. PM was induced in WAG/Rij rats (n = 72) by intraperitoneally injecting syngeneic colon carcinoma cells (CC531) expressing luciferase. After seven days, animals received a single intraperitoneal injection with saline (n = 8), unloaded hydrogel (n = 12), free MMC (n = 13), free cMMC (n = 13), MMC-loaded hydrogel (n = 13), or cMMC-loaded hydrogel (n = 13). Primary outcome was overall survival with a maximum follow-up of 120 days. Intraperitoneal tumor development was non-invasive monitored via bioluminescence imaging. Sixty-one rats successfully underwent all study procedures and were included to assess therapeutic efficacy. After 120 days, the overall survival in the MMC-loaded hydrogel and free MMC group was 78% and 38%, respectively. A trend toward significance was found when comparing the survival curves of the MMC-loaded hydrogel and free MMC (p = 0.087). No survival benefit was found for the cMMC-loaded hydrogel compared to free cMMC. Treating PM with our MMC-loaded hydrogel, exhibiting prolonged MMC exposure, seems effective in improving survival compared to treatment with free MMC.

Antibacterial effects of in situ zinc oxide nanoparticles generated inside the poly (acrylamide-co-hydroxyethylmethacrylate) nanocomposite

The present work reports the antibacterial activity against Pseudomonas aeruginosa of a nanocomposite made of zinc oxide nanoparticles dispersed in a poly(acrylamide-co-hydroxyethylmethacrylate) matrix (PAAm-Hema-ZnONPs). The in situ synthesis of ZnONPs inside of the PAAm-Hema crosslinked network is described. Moreover, the physicochemical properties of the PAAm-Hema-ZnONPs nanocomposite are analyzed. The results confirm that the PAAm-Hema hydrogel provides an excellent scaffold to generate ZnONPs. The presence of ZnONPs inside the hydrogel was confirmed by UV–visible (band at 320 nm), by Infrared spectroscopy (peak at 470 cm−1), SEM, and TEM images. The presence of NPs in PAAm-Hema diminish the swelling percentage by 70%, and the Young modulus by 33.7%, compared with pristine hydrogel. The 75% of ZnONPs are released from the nanocomposite after 48 h of spontaneous diffusion, allowing the use of the nanocomposite as an antibacterial agent. In vitro, the agar diffusion test presents an inhibition halo against P. aeruginosa bacteria 50% higher than the unloaded hydrogel. Also, the PAAm-Hema-ZnONPs live/dead test shows 54% of dead cells more than the hydrogel. These results suggest that the easy, one-step way generated composites can be used in biomedical applications as antimicrobial agents.

A 3D hydrogel loaded with exosomes derived from bone marrow stem cells promotes cartilage repair in rats by modulating immunological microenvironment

To assess the efficacy of GelMA hydrogel loaded with bone marrow stem cell-derived exosomes for repairing injured rat knee articular cartilage. The supernatant of cultured bone marrow stem cells was subjected to ultracentrifugation separate and extract the exosomes, which were characterized by transmission electron microscopy, particle size analysis and Western blotting of the surface markers. The changes in rheology and electron microscopic features of GelMA hydrogel were examined after loading the exosomes. We assessed exosome release from the hydrogel was detected by BCA protein detection method, and labeled the exosomes with PKH26 red fluorescent dye to observe their phagocytosis by RAW264.7 cells. The effects of the exosomes alone, unloaded hydrogel, and exosome-loaded hydrogel on the polarization of RAW264.7 cells were detected by q-PCR and immunofluorescence assay. We further tested the effect of the exosome-loaded hydrogel on cartilage repair in a Transwell co-culture cell model of RAW264.7 cells and chondrocytes in a rat model of knee cartilage injury using q-PCR and immunofluorescence assay and HE and Masson staining. GelMA hydrogel loaded with exosomes significantly promoted M2-type polarization of RAW264.7 cells (P < 0.05). In the Transwell co-culture model, the exosome-loaded GelMA hydrogel significantly promoted the repair of injured chondrocytes by regulating RAW264.7 cell transformation from M1 to M2 (P < 0.05). HE and Masson staining showed that the exosome-loaded hydrogel obviously promoted cartilage repair in the rat models damage. GelMA hydrogel loaded with bone marrow stem cell-derived exosomes can significantly promote the repair of cartilage damage in rats by improving the immune microenvironment.

Well-Defined Polyethylene Glycol Microscale Hydrogel Blocks Containing Gold Nanorods for Dual Photothermal and Chemotherapeutic Therapy.

Local drug delivery offers a means of achieving a high concentration of therapeutic agents directly at the tumor site, whilst minimizing systemic toxicity. For heterogenous cancers such as glioblastoma, multimodal therapeutic approaches hold promise for better efficacy. Herein, we aimed to create a well-defined and reproducible drug delivery system that also incorporates gold nanorods for photothermal therapy. Solvent-assisted micromolding was used to create uniform sacrificial templates in which microscale hydrogels were formed with and without gold nanorods throughout their structure. The microscale hydrogels could be loaded with doxorubicin, releasing it over a period of one week, causing toxicity to glioma cells. Since these microscale hydrogels were designed for direct intratumoral injection, therefore bypassing the blood–brain barrier, the highly potent breast cancer therapeutic doxorubicin was repurposed for use in this study. By contrast, the unloaded hydrogels were well tolerated, without decreasing cell viability. Irradiation with near-infrared light caused heating of the hydrogels, showing that if concentrated at an injection site, these hydrogels maybe able to cause anticancer activity through two separate mechanisms.

EMBR-31. DEVELOPMENT OF INJECTABLE POLYSACCHARIDE HYDROGEL TO ENHANCE DRUG PENETRATION IN PEDIATRIC BRAIN TUMORS

Improving unacceptable low response rates and reducing acute and long-term morbidities remain significant challenges in pediatric neuro-oncology. Chemotherapy is an effective primary or adjuvant treatment for pediatric disease, but current administration approaches hinder the pharmacological activity exerted by chemotherapy treatments. Barriers in the route of drug administration and in the tumor microenvironment limit anticancer drugs from penetrating tissue efficiently and reaching all cancer cells. Strategies have been proposed to overcome these barriers with hope of leading to sustained and elongated drug exposure in solid tumors. However, few methods have been explored to design drug delivery systems to circumvent these barriers with potential to enhance drug penetration and reduce adverse systemic side effects in treating pediatric brain tumors. In this study, we validate an injectable polysaccharide hydrogel capable of releasing drugs locally at tumor site, sustaining drug concentration, and eliciting tumor response. We synthesized a hydrogel with dimethyl sulfoxide (DMSO) incorporating amylopectin, a polysaccharide found in starch, loaded with doxorubicin. We determined the structure of doxorubicin is not altered when released from the hydrogel through characterization of drug-loaded and unloaded hydrogels, suggesting drug is encapsulated in the hydrogel network and is able to maintain structure to induce mechanism of action. We tested sustained release of drug and therapeutic efficacy in vitro with DAOY, a medulloblastoma cell line. Our approach demonstrates that local drug delivery presents potential to enhance drug penetration in pediatric brain tumors by sustaining drug concentration at tumor site for an extended period of time. Local drug delivery systems have been investigated for decades but few have been investigated for treatment of pediatric brain tumors. For researchers, physicians, and clinicians, this research can lead to a greater effort to improve current outcomes of conventional drug treatment and provide an opportunity to address current challenges in pediatric oncology.

Tratamiento de la Neumonía Asociada a la Ventilación Mecánica: cofactor de mortalidad en pacientes COVID-19 positivos

La infección por Sars-CoV-2 produce diversos cuadros clínicos, que incluyen la infección asintomática, enfermedad leve del tracto respiratorio superior y neumonía viral grave con insuficiencia respiratoria e incluso la muerte. La necesidad de internación de los pacientes más comprometidos introduce una complicación adicional, que es el riesgo de adquirir una infección intrahospitalaria. Entre éstas, la neumonía asociada a la ventilación mecánica (NAV) es una de las más frecuentes en las Unidades de Cuidados Intensivos (UCI) y actualmente es una complicación en el cuadro clínico de pacientes COVID-19 positivos que necesitan asistencia de respiración mecánica. La prevención de la NAV es crucial para eliminar este cofactor de morbimortalidad, así como disminuir los costos asociados a la atención de salud (tiempo de internación, antibióticos, elementos descartables, etc.).&#x0D; La NAV ocurre en pacientes que son ventilados por un tubo endotraqueal o por traqueotomía, como respuesta del huésped a la invasión bacteriana. Los pacientes con ventilación mecánica están inconscientes y no hay eliminación de las secreciones en la orofaringe, generando un aumento de la flora oral normal. Los microorganismos colonizadores pasan a lo largo del tubo traqueal formando biofilms en la parte interna y externa del mismo particularmente en la región cercana al bulbo. Finalmente, estos microorganismos son capaces de alcanzar las vías aéreas distales superando la respuesta inmune del huésped y generando neumonía. La propuesta de este trabajo consiste en modificar la superficie de los tubos endotraqueales con agentes antimicrobianos que inhiban la adhesión y proliferación bacteriana actuando como coadyuvantes de los antibióticos administrados por vía sistémica.&#x0D; El objetivo general de este trabajo es contribuir a la prevención de la NAV por medio de la funcionalización de las superficies interna y externa del tubo endotraqueal empleado en la ventilación mecánica. La modificación se realiza mediante el depósito de una delgada película de hidrogeles biocompatibles y biodegradables cargados con agentes antimicrobianos convencionales (antibióticos) y no convencionales (nanopartículas de plata, AgNPs) para combatir la formación de los biofilms bacterianos que generan la NAV. Los hidrogeles proporcionan control espacial y temporal sobre la liberación de los agentes terapéuticos debido a su degradabilidad controlable y capacidad para proteger a los medicamentos lábiles, permitiendo, además, alcanzar concentraciones locales superiores a las obtenidas por administración sistémica. Para alcanzar los objetivos, se ha optimizado la síntesis de un hidrogel en base a polietilenglicol capaz de adherirse fuertemente a la superficie de cloruro de polivinilo del tubo endotraqueal. Se logró recubrir la superficie del tubo con el hidrogel, comprobándose una buena estabilidad mecánica tanto para el hidrogel deshidratado como para el mismo hidratado. Se analizaron diferentes rutas de incorporación de los agentes antimicrobianos, encontrándose que la más adecuada es el agregado de éstos al polímero precursor del hidrogel. Los hidrogeles modificados con AgNPs presentan características de adhesión y estabilidad similares a las de los hidrogeles sin modificar. Al momento de escribir este trabajo se están llevando cabo los experimentos tendientes a determinar la capacidad antimicrobiana de las superficies modificadas.

In vitro study of versatile drug formulations based on α-cyclodextrin and polyethylene glycol using colloidal tectonics

In response to the environmental problems, we propose herein to use a common base of formulation leading to a set of galenic systems such as ethanol-free hydrogels, surfactant-free and silica-free Pickering emulsions and microcapsules. All of the systems are developed from the self-assembly of α-cyclodextrin (α-CD) and polyethylene glycol (PEG) using the colloidal tectonics approach. Firstly, α-CD and PEG were mixed to obtain stable hydrogels loaded with antifungal drugs in the form of complexes with 2-hydroxypropyl-β-CD to increase the drugs solubility in the gels. Secondly, oil-in-water Pickering emulsions were prepared from the unloaded hydrogels by adding paraffin oil containing antifungals in their native forms. Thirdly, these emulsions were dried to obtain loaded microcapsules. The different systems were characterized by means of physicochemical measurements (microscopy, pH, rheology and stability) and anti-pathogen activities. Their properties are close to those of commercially available ones but superior for their stability, with even a clear enhancement of the anti-pathogen activity (up to 1.6). All formulations reduce the potential drawbacks of the commonly used excipients and are in line with the current trend of simplifying formulas in terms of ingredients.

Prophylaxis of implant-related infections by local release of vancomycin from a hydrogel in rabbits.

Local prophylaxis with antibiotic-loaded bone cement is a successful method to prevent post-operative infections in patients receiving orthopaedic implants. No comparable method is available for uncemented implants. Therefore, a hydrogel consisting of hyaluronic and polylactic acids was evaluated in a rabbit model for delivery of antimicrobial agents to prevent post-operative infections. In a pilot study, the suitability of the in vivo model was assessed by testing the hydrogel as carrier material for antimicrobial agents.In the main study, the antimicrobial-agent-loaded hydrogel was evaluated for infection prophylaxis. Rabbits received a titanium rod intramedullary in the tibia after contamination with Staphylococcus aureus. The rods were coated with unloaded hydrogel (Gel), hydrogel loaded with 2 % (Van2) or 5 % vancomycin (Van5), bioactive glass (BAG) or N-acetyl-L-cysteine (NAC). To analyse the infection severity after 28 d, histopathological, bacteriological, micro-computed tomographic and haematological analyses were performed. In the pilot study, the Van5 group had less infection (0/6 infected) as compared to the Gel group (5/5, p = 0.000) and the in vivo model was deemed suitable. In the main study, in the Van2 and Van5 groups, the number of infected animals was lower [1/6 (p = 0.006) and 2/6 (p = 0.044) infected, respectively]. In contrast, BAG and NAC groups showed no infection reduction (5/6 both groups, p = 0.997). The hydrogel can be used as a local carrier of vancomycin for prophylaxis of implant-related infections.The present study showed promising results for local delivery of antibacterial agents by hydrogel to prevent implant-related infections.

Preparation of a thermoresponsive maize seed coating agent using polymer hydrogel for chilling resistance and anti-counterfeiting

Sweet-waxy corn is susceptible to chilling injury, and vulnerable to be counterfeited. This study developed a kind of newly thermoresponsive coating material with dual efficacies of intelligent chilling-resistant and anti-counterfeiting for maize seed. The coating material was named as PRBSA, which was made of salicylic acid (SA) and rhodamine B (RB) co-loaded poly (N-isopropylacrylamide-co-butylmethacrylate) hydrogel. The surface morphology of PRBSA was compact than its interior, where it was uneven and irregularly distributed pore structure. Below the lower critical solution temperature (LCST), PRBSA was water-soluble and hydrophilic, loaded SA and RB could release sharply from PRBSA, whereas above this LCST, PRBSA formed an insoluble and hydrophobic aggregate, the release rate of SA and RB was obviously decreased. Meanwhile, PRBSA showed a better thermal stability than unloaded hydrogel. In addition, seeds were coated with PRBSA, and its seedling quality and fluorescence labeling under chilling stress were determined. These results showed that compared with the CK (basic coating agent), PRBSA treatment significantly enhanced seed germination percentage by 17.8% and vigor index by 53.1% under chilling stress. The seedling shoot height and dry weight were also significantly improved, which might closely related with the lowest malondialdehyde and relative electrical conductivity level, and the highest maximal quantum yield of PSII (Fv/Fm). Moreover, the surface of PRBSA coated seeds showed bright red fluorescence under the excitation green light of 546 nm. When responding to low temperatures, its fluorescence intensity exhibited a sharp decline, showing a temperature-sensitive release of RB. Therefore, PRBSA was considered as a novel seed coating with intelligent chilling-resistant and anti-counterfeiting function.

Long-term effects and potential limits of intratympanic dexamethasone-loaded hydrogels combined with dexamethasone-eluting cochlear electrodes in a low-insertion trauma Guinea pig model

Cochlear implantation has become the most effective hearing restoration method and is one of the great advances in modern medicine. Early implants have been continuously developed into more efficient devices, and electro-acoustic stimulation is increasingly expanding the indication criteria for cochlear implants to patients with more residual hearing. Therefore, protecting the cochlear structures and maintaining its intrinsic capacities like residual hearing has become more important than ever before.In the present study, we aimed to assess the long-term protective effects of a dexamethasone-eluting electrode combined with the preoperative intratympanic application of a dexamethasone-loaded thermoreversible hydrogel in a cochlear implant guinea pig model. 40 normal-hearing animals were equally randomized into a control group receiving an unloaded hydrogel and a non-eluting electrode, a group receiving a dexamethasone-loaded hydrogel and a non-eluting electrode, a group receiving an unloaded hydrogel and a dexamethasone-eluting electrode and a group receiving both a dexamethasone-loaded hydrogel and a dexamethasone-eluting electrode. Residual hearing and impedances were investigated during a period of 120 days. Tissue response and histological changes of cochlear structures were analyzed at the end of the experiments.Treatment with dexamethasone did not show a significant protective effect on residual hearing independent of treatment group. Although the majority of the cochleae didn’t exhibit any signs of electrode insertion trauma, a small degree of tissue response could be observed in all animals without a significant difference between the groups. Foreign body giant cells and osteogenesis were significantly associated with tissue response. Hair cells, synapsin-1-positive cells and spiral ganglion cells were preserved in all study groups. Cochlear implantation using a dexamethasone-eluting electrode alone and in combination with a dexamethasone-loaded hydrogel significantly protected auditory nerve fibers on day 120. Post-implantation impedances were equal across study groups and remained stable over the duration of the experiment.In this study we were able to show that use of a dexamethasone-eluting electrode alone and in combination with preoperative application of dexamethasone-loaded hydrogel significantly protects auditory nerve fibers. Furthermore, we have shown that a cochlear implantation-associated hearing threshold shift and tissue response may not be completely prevented by the sole application of dexamethasone.

Hyperosmolar potassium inhibits myofibroblast conversion and reduces scar tissue formation.

Scar formation is a natural result of almost all wound healing in adult mammals. Unfortunately, scarring disrupts normal tissue function and can cause significant physical and psychological distress. In addition to improving surgical techniques to limit scar formation, several therapies are under development towards the same goal. Many of these treatments aim to disrupt transforming growth factor β1 (TGFβ1) signaling, as this is a critical control point for fibroblast differentiation into myofibroblasts; a contractile cell that organizes synthesized collagen fibrils into scar tissue. The present study aimed to examine the role of hyperosmolar potassium gluconate (KGluc) on fibroblast function in skin repair. KGluc was first determined to negatively regulate fibroblast proliferation, metabolism, and migration in a dose-dependent manner in vitro. Increasing concentrations of KGluc also inhibited differentiation into myofibroblasts, suggesting that local KGluc treatment might reduce fibrosis. KGluc delivery was confirmed via loading into collagen hydrogels and used to treat a full thickness skin wound in mice. KGluc qualitatively slowed initial closure of the wounds and resulted in tissue that more closely resembled mature, healthy skin (epidermal thickness and dermal-epidermal morphology) when compared to unloaded collagen hydrogels. KGluc treatment significantly reduced the number of myofibroblasts within the dermis while upregulated blood vessel density with respect to unloaded hydrogels, likely a result of disruption of TGFβ1 signaling. Taken together, these data demonstrate the effectiveness of KGluc treatment on skin wound healing and suggest that this may be an efficient treatment to limit scar formation.

Hydrogel implants for transscleral drug delivery for retinoblastoma treatment.

Retinoblastoma (Rb) is the most common primary malignant intraocular tumor in children which develops from the retinal stem cells. Systemic chemotherapy is the typical therapeutic treatment and though most children survive Rb, they often lose their vision, or the eye needs to be enucleated. Regarding to the pure availability of the target tumor by systemic chemotherapy, the local anticancer drug administration would be advantageous to increase the local drug concentration and minimize adverse side effects of chemotherapy. The present paper describes a new hydrogel implant enabled to deliver therapeutically active doses of low molecular weight hydrophilic antitumor drugs topotecan and vincristine. The hydrogel implant is proposed as bi-layered with an inner hydrophilic layer from 2-hydroxyethyl methacrylate (HEMA) serving as a reservoir of the chemotherapeutic agent and an outer hydrophobic layer from 2-ethoxyethyl methacrylate (EOEMA) acting as a barrier to protect the surrounding vascularized tissue against cytotoxicity of the delivered chemotherapeutics. The experiments with enucleated pig eyes demonstrated the ability of tested drugs to diffuse through sclera and reach the vitreous humor. HEMA-based hydrogels were examined in terms of sorption, release and transport properties, showing the possibility of adjusting the loading capacity and diffusion of the drugs by the degree of crosslinking. The EOEMA-based gels proved to be an inert for drug sorption and diffusion. A chorioallantoic membrane assay demonstrated excellent biocompatibility of unloaded hydrogels, and in vitro experiments confirmed significant cytotoxicity of drug-loaded hydrogels against a Rb cell line; 2 days for those topotecan-loaded and a minimum of 6 days for vincristine-loaded hydrogels. The bi-layered hydrogel implant can be considered promising for local administration of active agents to eye-globe for the treatment of Rb and also other ocular disorders.

Growth factor release and enhanced encapsulated periodontal stem cells viability by freeze-dried platelet concentrate loaded thermo-sensitive hydrogel for periodontal regeneration

Periodontium regeneration is a highly challenging process as it requires the regeneration of three different tissues simultaneously. The aim of this study was to develop a composite material that can be easily applied and can sufficiently deliver essential growth factors and progenitor cells for periodontal tissue regeneration.Freeze-dried platelet concentrate (FDPC) was prepared and incorporated in a thermo-sensitive chitosan/β-glycerol phosphate (β-GP) hydrogel at concentrations of 5, 10, or 15 mg/ml. The viscosity of the hydrogels was investigated as the temperature rises from 25 °C to 37 °C and the release kinetics of transforming growth factor (TGF-β1), platelet-derived growth factor (PDGF-BB) and insulin-like growth factor (IGF-1) were investigated at four time points (1 h, 1 day, 1 week, 2 weeks). Periodontal ligament stem cells (PDLSCs) were isolated from human third molars and encapsulated in the different hydrogel groups. Their viability was investigated after 7 days in culture in comparison to standard culture conditions and non FDPC-loaded hydrogel.Results showed that loading FDPC in the hydrogel lowered the initial viscosity in comparison to the unloaded control group and did not affect the sol-gel transition in any group. All FDPC-loaded hydrogel groups exhibited sustained release of TGF-β1 and PDGF-BB for two weeks with significant difference between the different concentrations. The loading of 10 and 15 mg/ml of FDPC in the hydrogel increased the PDLSCs viability significantly compared to the unloaded hydrogel and was comparable to the standard culture conditions.Accordingly, it may be concluded that loading FDPC in a chitosan/β-GP hydrogel can offer enhanced injectability, a sustained release of growth factors and increased viability of encapsulated stem cells which can be beneficial in periodontium tissue regeneration.