Aminopoly(carboxylic acid)-Functionalized PolyHIPE Beads toward Eliminating Trace Heavy Metal Ions from Water.

Many advanced materials are designed for the removal of heavy metal ions from water. However, materials for eliminating trace heavy metal ions from wastewater to meet drinking water standards remain a major challenge. Herein, epoxy group-functionalized open-cellular beads are synthesized by UV polymerization of a water-in-oil-in-water system. The epoxy groups are further transformed into diethylenetriaminepentaacetic acid (DTPA) with hexamethylene diamine as a bridging agent. The resulting material (DTPA@polyHIPE beads) can eliminate trace Cu(II), Cr(III), Pb(II), Fe(III), or Cd(II) from water. When 0.15 g of DTPA@polyHIPE beads are used to adsorb metal ions of 20 mg in 100 mL of water, the residue concentrations of Cu(II), Cr(III), Pb(II), Fe(III), and Cd(II) are reduced to 0.08, 0.06, 0.02, 0.09, and 0.07 mg/L, respectively. The adsorption efficiencies of the beads for these ions are all higher than 99.55%. The adsorbent is durable and exhibits good recyclability by retaining an adsorption capacity of ≥91% after 5 cycles. The negative values of ΔG in the adsorption process indicate that the adsorption is feasible and spontaneous. The chemical adsorption follows the Freundlich adsorption model, indicating a multilayer heterogeneous adsorption. The DTPA@polyHIPE beads have a great potential application in dealing with trace heavy metal ion polluted water.

Salvianolic Acid B Inhibits Oxidative Stress in Glomerular Mesangial Cells Alleviating Diabetic Nephropathy by Regulating SIRT3/FOXO1 Signaling.

INTRODUCTION: Oxidative stress is pivotal in advancing diabetic nephropathy (DN). Salvianolic acid B (SAB), derived from Radix Salviae miltiorrhizae, exhibits renoprotective effects. However, the mechanisms underlying its action in DN are not fully elucidated. This study explores SAB's protective effect on DN, focusing on its antioxidative properties in glomerular mesangial cells. METHODS: The renoprotective effects of various SAB dosages on DN rats were assessed by evaluating kidney tissue pathological alterations through hematoxylin and eosin, periodic acid-Schiff, Masson, TUNEL staining, and kidney function through biochemical detection. Cell counting kit-8 and lactate dehydrogenase cytotoxicity assays were utilized to evaluate the viability of high glucose (HG)-induced HBZY-1 cells treated with various SAB dosages. Oxidative stress and inflammation levels were measured using enzyme-linked immunosorbent assay kits. The Sirtuin 3 (SIRT3)/Forkhead box transcription factor O1 (FOXO1) pathway was examined through Western blot and immunohistochemistry. RESULTS: SAB mitigated kidney histopathological alterations and function and cell apoptosis in DN rats at various dosages. It enhanced the activity of glutathione peroxidase and superoxide dismutase while decreasing reactive oxygen species and malondialdehyde levels both in vivo and in vitro. SAB also suppressed the levels of pro-inflammatory cytokines (IL-1ß, IL-6, MCP-1, and TNF-α) and the expression of collagen IV and fibronectin in HG-induced HBZY-1 cells. Furthermore, SAB activated the SIRT3/FOXO1 signaling pathway. CONCLUSION: Our findings suggest that SAB may alleviate oxidative stress in DN both in vivo and in vitro, potentially through the activation of the SIRT3/FOXO1-mediated signaling pathway. This study provides initial insights into the possible antioxidative and renoprotective effects of SAB, indicating its potential utility as a therapeutic agent for DN.

Highly efficient and recyclable monolithic bioreactor for interfacial enzyme catalysis.

HYPOTHESIS: Biocatalysts are key to the realization of all bioconversions in nature. However, the difficulty of combining the biocatalyst and other chemicals in one system limits their application in artificial reaction systems. Although some effort, such as Pickering interfacial catalysis and enzyme-immobilized microchannel reactors, have addressed this challenge an effective method to combine chemical substrates and biocatalysts in a highly efficient and re-usable monolith system is still to be developed. EXPERIMENTS: A repeated batch-type biphasic interfacial biocatalysis microreactor was developed using enzyme-loaded polymersomes in the void surface of porous monoliths. Polymersomes, loaded with Candida antarctica Lipase B (CALB), are fabricated by self-assembly of the copolymer PEO-b-P(St-co-TMI) and used to stabilize oil-in-water (o/w) Pickering emulsions as a template to prepare monoliths. By adding monomer and Tween 85 to the continuous phase, controllable open-cell monoliths are prepared to inlay CALB-loaded polymersomes in the pore walls. FINDINGS: The microreactor is proven to be highly effective and recyclable when a substrate flows through it, which offers superior benefits of absolute separation to a pure product and no enzyme loss. The relative enzyme activity is constantly maintained above 93% in 15 cycles. The enzyme is constantly present in the microenvironment of the PBS buffer ensuring its immunity to inactivation and facilitating its recycling.

Hierarchical Emulsion-Templated Monoliths (polyHIPEs) as Scaffolds for Covalent Immobilization of P. acidilactici.

The immobilized cell fermentation technique (IMCF) has gained immense popularity in recent years due to its capacity to enhance metabolic efficiency, cell stability, and product separation during fermentation. Porous carriers used as cell immobilization facilitate mass transfer and isolate the cells from an adverse external environment, thus accelerating cell growth and metabolism. However, creating a cell-immobilized porous carrier that guarantees both mechanical strength and cell stability remains challenging. Herein, templated by water-in-oil (w/o) high internal phase emulsions (HIPE), we established a tunable open-cell polymeric P(St-co-GMA) monolith as a scaffold for the efficient immobilization of Pediococcus acidilactici (P. acidilactici). The porous framework's mechanical property was substantially improved by incorporating the styrene monomer and cross-linker divinylbenzene (DVB) in the HIPE's external phase, while the epoxy groups on glycidyl methacrylate (GMA) supply anchoring sites for P. acidilactici, securing the immobilization to the inner wall surface of the void. For the fermentation of immobilized P. acidilactici, the polyHIPEs permit efficient mass transfer, which increases along with increased interconnectivity of the monolith, resulting in higher L-lactic acid yield compared to that of suspended cells with an increase of 17%. The relative L-lactic acid production is constantly maintained above 92.9% of their initial relative production after 10 cycles, exhibiting both its great cycling stability and the durability of the material structure. Furthermore, the procedure during recycle batch also simplifies downstream separation operations.

Fabrication of Macroporous Polymers via Water-in-Water Emulsion-Templating Technique.

Emulsion-templated porous polymers have attracted broad attention due to their great application prospects in many fields. However, scaling up the emulsion-templated technique from the lab to industrial production remains a great challenge, especially for systems involving an oil-in-water (o/w) emulsion template that is used normally for preparing hydrophilic porous polymers. These systems require large amounts of organic solvents to be the internal phase (i.e., major phase) of the emulsion templates, which causes a significant environmental impact and cost. Herein, a water-in-water (w/w) emulsion-templated technique is presented to prepare porous hydrophilic polymers. The w/w emulsion is prepared by mixing a PEG aqueous solution and a dextran aqueous solution with cellulose nanocrystals (CNCs) as a stabilizer. With varying the mass ratio of dextran/PEG in the range of 1/2 to 8/1, a series of dextran-rich-phase-in-PEG-rich-phase (dextran/PEG) emulsions are obtained. Subsequently, monomers, such as acrylamide, acrylic acid, and/or 2-acrylamido-2-methylpropanesulfonic acid, are introduced to the emulsions to fabricate porous hydrophilic polymers. These polymers have an open-cell structure like those of o/w emulsion-templated polymers. The system developed herein is an environmentally friendly, low cost, and universal emulsion-templated method toward porous hydrophilic polymers, which avoids the defects caused by the presence of large amounts of organic solvents in an o/w emulsion-templating method and can be moved from the lab to industrial-scale production.

Fabrication of Hierarchical Macroporous ZIF-8 Monoliths Using High Internal Phase Pickering Emulsion Templates.

The shaping of metal-organic frameworks (MOFs), referring to the integration of small sub-millimeter MOF crystals into bulk samples of desired size and shape, is an important step in the practical use of this class of porous material in many applications. Herein, we demonstrate for the first time the fabrication of hierarchical 3D MOF monoliths in situ within an MOF particle-stabilized high internal phase emulsion (HIPE). In this approach, a subfamily MOF (ZIF-8) is selected as the sole Pickering emulsion stabilizer for an oil-in-water (O/W) HIPE. With 2-methylimidazole and zinc nitrate in the continuous phase, ZIF-8 is formed in the emulsion to "bond" the ZIF-8 particles fabricating a ZIF-8 monolith without the addition of a polymer or polymerization of monomers. Freeze-drying of the HIPE produces a 3D ZIF-8 monolith. The monolith is packed into a chromatography column to test its catalytic performance as a flow-through catalyst in the Knoevenagel reaction. The monolith catalyst exhibits very high catalytic efficiency. Almost all the reaction mixture transforms to product within 2 min. Besides, the 3D ZIF-8 monolith showed excellent performance as an oil absorbent in oil-water separation. It achieved an absorption equilibrium of oil in less than 5 s, much faster than traditional high oil absorption materials.

A novel decision tree model based on chromosome imbalances in cell-free DNA and CA-125 in the differential diagnosis of ovarian cancer.

OBJECTIVE: CA-125 is widely used as biomarker of ovarian cancer. However, CA-125 suffers low accuracy. We developed a hybrid analytical model, the Ovarian Cancer Decision Tree (OCDT), employing a two-layer decision tree, which considers genetic alteration information from cell-free DNA along with CA-125 value to distinguish malignant tumors from benign tumors. METHODS: We consider major copy number alterations at whole chromosome and chromosome-arm level as the main feature of our detection model. Fifty-eight patients diagnosed with malignant tumors, 66 with borderline tumors, and 10 with benign tumors were enrolled. RESULTS: Genetic analysis revealed significant arm-level imbalances in most malignant tumors, especially in high-grade serous cancers in which 12 chromosome arms with significant aneuploidy (P<0.01) were identified, including 7 arms with significant gains and 5 with significant losses. The area under receiver operating characteristic curve (AUC) was 0.8985 for copy number variations analysis, compared to 0.8751 of CA125. The OCDT was generated with a cancerous score (CScore) threshold of 5.18 for the first level, and a CA-125 value of 103.1 for the second level. Our most optimized OCDT model achieved an AUC of 0.975. CONCLUSIONS: The results suggested that genetic variations extracted from cfDNA can be combined with CA-125, and together improved the differential diagnosis of malignant from benign ovarian tumors. The model would aid in the pre-operative assessment of women with adnexal masses. Future clinical trials need to be conducted to further evaluate the value of CScore in clinical settings and search for the optimal threshold for malignancy detection.

Ultralight Aerogels with Hierarchical Porous Structures Prepared from Cellulose Nanocrystal Stabilized Pickering High Internal Phase Emulsions.

Cellulose nanocrystal (CNC)-based aerogels with extremely low density and hierarchical porous structure were constructed via a facile Pickering-emulsion-templated strategy. In this method, aminated CNCs (CNC-NH2) were synthesized to stabilize o/w Pickering high internal phase emulsions (Pickering HIPEs). Amino groups were introduced to CNCs to decrease the net surface charges of CNCs, enhance their aggregation, and therefore achieve Pickering HIPEs stabilized by the particles of ultralow content (∼0.1 wt %). A series of CNC aerogels was then obtained by freeze drying these emulsions. The resulting aerogels were ultralight with a density that reached ca. 0.5 mg/cm3 (an order of magnitude lower than that previously reported for CNC aerogels) and an ultrahigh porosity (up to 99.969%). Contributed to the extremely low density, the thermal conductivity of the aerogels was around 0.021 W/(m·K) which is lower than that of air (0.024 W/(m·K)). This novel strategy could be applied to other materials, such as graphene and carbon nanotubes, to prepare ultralight aerogels with controllable porous structures and unique properties.

Tuning the thermoreversible temperature domain of PTMC-based networks with thermosensitive links concentration.

In this work, thermoreversible poly(trimethylene carbonate) (PTMC) based networks with different crosslinking densities were obtained by Diels-Alder (DA) reaction between furan-functionalized PTMC precursors and a bismaleimide. Furan-grafted PTMC with various functionalities determined by 1H-NMR analyses were prepared from telechelic PTMC oligomer, glycerol, 4,4'-methylenebis(cyclohexyl isocyanate) (H12MDI) and furfuryl alcohol. The formation of network structures by DA reaction between furan and maleimide groups were proved by Fourier-transform infrared spectroscopy (FT-IR). Although both exo and endo DA adduct forms exist, the thermally more stable exo form dominates. The thermoreversibility of networks was evidenced by FT-IR, solubility, differential scanning calorimetry (DSC) and rheology experiments at different temperatures. By increasing furan functionality or node concentration, denser and stiffer networks could be formed with higher Young's modulus and true stress at break in tensile tests, as well as higher crossover temperature, which indicates a nominal transition from elastic behavior to viscous state. The disruption of networks was found to occur in high temperature ranges from 130 to 160 °C, depending on their crosslinking density.

Ordered Surface Nanostructures Self-Assembled from Rod-Coil Block Copolymers on Microspheres.

An ordered surface nanostructure endows materials advanced functions. However, fabricating ordered surface-patterned particles via the polymer self-assembly approach is a challenge. Here we report that poly(γ-benzyl-l-glutamate)-block-poly(ethylene glycol) rod-coil block copolymers are able to form uniform-surface micelles on polystyrene microspheres through a solution self-assembly approach. The size of the surface micelles can be varied by the molecular weight of the block copolymers. These surface micelles are arranged in a manner consistent with the Euler theorem. Most of the micelles are six-fold coordinated, and the number difference between the five-fold and the seven-fold coordination is 12. Simulations on model systems qualitatively reproduced the experimental findings and provided direct observations for the surface-patterned particles, including the polymer chain packing manner in surface micelles at the molecular level and the array feature of the surface micelles through 2D projections of the surface patterns.

Production of High Internal Phase Emulsion with a Miniature Twin Screw Extruder.

Emulsions are traditionally prepared by batched emulsifying an oil phase and aqueous phase with a magnetic/mechanical stirrer, homogenizer, or ultrasonic machine, etc. Herein, high internal phase emulsions (HIPEs) produced with a miniature twin screw extruder were first investigated. Adding an oil phase (the mixture of styrene, divinylbenzene, and span 80) and aqueous phase to the inlet of a miniature twin screw extruder, a series of white and viscous HIPEs were obtained at the outlet of the extruder. With the screw rotation speed and the surfactant content varied respectively in the ranges of 50-200 rpm and 5-20%, a series of HIPEs having uniform droplet size were produced. Polymerizing these HIPEs caused a series of polymerized HIPES, which have a well-defined open-cell structure. The method developed herein shows that it is possible to prepare emulsions with oil and water by twin screw extrusion. Also, it may also cause a continuous preparation of HIPEs when the miniature twin screw extruder was replaced by an industrial extruder.

Preparation of Macroporous Polymers from Microcapsule-Stabilized Pickering High Internal Phase Emulsions.

The ability to make stable water-in-oil (W/O) Pickering high internal phase emulsions (HIPEs) is demonstrated using microcapsules as a stabilizer. The microcapsules are prepared with glycidyl methacrylate (GMA) and poly(melamine-formaldehyde) (PMF) as core and wall materials, respectively. Using these GMA-loaded PMF-walled microcapsules as a sole stabilizer of water-in-styrene/divinylbenzene HIPE, the polymerization of this HIPE causes a closed-cell porous polymer. While with the addition of a certain amount of the nonionic surfactant Span80 to the microcapsule-stabilized HIPEs, a series of open-cell porous materials are obtained. The morphologies of the porous materials are tunable with changing the microcapsules content and/or surfactant amount in the HIPE templates. When Raft polymerization is introduced to cure these HIPEs, owing to both the self-healing agent GMA within the microcapsules and the residue of the chain-transfer agent from Raft polymerization of HIPEs, the resulting porous polymers are proved to be self-repairable. This work suggests a new type of Pickering HIPE and provides a novel idea for preparing self-healing porous materials.

Pickering emulsion-templated polymers: insights into the relationship between surfactant and interconnecting pores.

Pickering high internal phase emulsions (HIPEs) using micron-size polymeric particles as stabilizer were developed. By adding a small amount of surfactant to the Pickering HIPEs, macroporous polymers with a well-define open-cell structure were synthesized with these HIPEs as templates. Owing to the micron-size of the particles, the particle locations could be observed directly by laser scanning confocal microscopy. It was found that the excess and attached particles aggregated and formed thick particle layers around the droplets when the HIPE was stabilized solely by particles. These thick particle layers were extremely stable, and did not easily rupture during or after polymerization, which caused the resulting polymers to have a closed-cell structure. When a small amount of surfactant was added, it was found that the surfactant disaggregated the particles, leaving them well-dispersed in the continuous phase. Moreover, the surfactant tended to occupy the oil-water interface at the contact point of adjacent droplets, where the interconnecting pores were hence likely to be formed after consolidation of the continuous phase. This observation confirmed experimentally the mechanism of interconnecting pore formation in Pickering-HIPE-templated porous polymers proposed theoretically in previous works.

Class I hysterectomy in stage Ia2-Ib1 cervical cancer.

INTRODUCTION: During the last 3 decades, the standard treatment for stage Ia2-Ib1 cervical cancer has been Piver-Rutledge class II or III radical hysterectomy. However, this surgery is associated with a high rate of urologic morbidity. AIM: To determine the efficacy of class I radical hysterectomy compared with class III radical hysterectomy in terms of morbidity, overall survival, and patterns of relapse in patients with Ia2-Ib1 cervical cancer undergoing primary surgery. MATERIAL AND METHODS: A total of 101 patients with stage Ia2-Ib1 cervical cancer < 2 cm were randomized to class I and class III hysterectomy groups. Clinical, pathologic, and follow-up data were prospectively collected. Univariate analysis was carried out. Of the total patients, 45 were randomized to class I surgery and 56 to class III surgery. No significant differences were observed in terms of pathologic findings or adjuvant treatment (p > 0.05). The morbidity rates were higher after class III surgery. RESULTS: The difference in recurrence rate between the class I and class III groups was not statistically significant (p > 0.05). The 5-year overall survival rate was 93% and 91%, respectively (p > 0.05). There were no significant differences in terms of recurrence rate or overall survival among patients with stage Ia2-Ib1 cervical cancer < 2 cm who underwent class I or radical (class III) hysterectomy. Morbidity was proportional to the extent of radicality. CONCLUSIONS: These data confirm the need for reducing surgical radicality in the treatment of patients with early cervical cancer, by tailoring the extent of resection according to the extent of disease.

Synthesis of Emulsion-Templated Magnetic Porous Hydrogel Beads and Their Application for Catalyst of Fenton Reaction.

The pristine Fe3O4 nanoparticle (FeNP) is supposed to be a good catalyst of Fenton processes which have shown significant potential for water purification. Herein the magnetic macroporous hydrogel beads, having an open-cell structure, were synthesized by sedimentation polymerization of pristine FeNP stabilized oil-in-water high internal phase emulsions. The effects of the FeNP amount, internal phase fraction, and the costabilizer Tween85 concentration on the structure, such as interconnecting degree, void size, and its distribution of both the surface and inner of the beads, were investigated. With a methyl orange (MO) aqueous solution passing through a chromatography column that was filled with the FeNPs loaded hydrogel beads, the efficiency of these hydrogel beads as catalyst for Fenton reaction to decompose MO in water was tested. The MO was decomposed quickly at the first hour, followed by decomposed gradually in a further 5 h, and the decomposition rate of MO could be up to 99.6% at the end of the test. Moreover, MO decomposition rate remained over 98.2% in six batches which were run in the same beads filled column. The results showed that these FeNPs loaded porous hydrogel beads were reusable and highly efficient supporter for catalysis of Fenton reaction for decomposing organic pollutants in water.

Integrated analysis of HPV-mediated immune alterations in cervical cancer.

OBJECTIVE: Human papillomavirus (HPV) infection is the primary cause of cervical cancer. HPV-mediated immune alterations are known to play crucial roles in determining viral persistence and host cell transformation. We sought to thoroughly understand HPV-directed immune alterations in cervical cancer by exploring publically available datasets. METHODS: 130 HPV positive and 7 HPV negative cervical cancer cases from The Cancer Genome Atlas were compared for differences in gene expression levels and functional enrichment. Analyses for copy number variation (CNV) and genetic mutation were conducted for differentially expressed immune genes. Kaplan-Meier analysis was performed to assess survival and relapse differences across cases with or without alterations of the identified immune signature genes. RESULTS: Genes up-regulated in HPV positive cervical cancer were enriched for various gene ontology terms of immune processes (P=1.05E-14~1.00E-05). Integrated analysis of the differentially expressed immune genes identified 9 genes that displayed either CNV, genetic mutation and/or gene expression changes in at least 10% of the cases of HPV positive cervical cancer. Genomic amplification may cause elevated levels of these genes in some HPV positive cases. Finally, patients with alterations in at least one of the nine signature genes overall had earlier relapse compared to those without any alterations. The altered expression of either TFRC or MMP13 may indicate poor survival for a subset of cervical cancer patients (P=1.07E-07). CONCLUSIONS: We identified a novel immune gene signature for HPV positive cervical cancer that is potentially associated with early relapse of cervical cancer.

Macroporous polymers prepared via frozen UV polymerization of the emulsion-templates stabilized by a low amount of surfactant.

Macroporous polymers based on high internal phase emulsions (HIPEs) possess tunable porous structures and device shapes, and these characteristics make it possible for it to be applied in many fields. However, such materials also demonstrate undesirable properties, such as their brittleness and chalkiness, due to a great amount of surfactant required (5.0-50.0%, relative to the external phase) to realize the transformation from HIPEs to macroporous polymers (polyHIPEs). Herein, O/W HIPEs stabilized by a small amount (as low as 0.1 wt%, relative to the external phase) of commercial surfactant were prepared by magnetic stirring and subsequently homogenizing, and well-defined polyHIPEs were obtained through frozen UV polymerization of these HIPEs. In this process, the prepared HIPE was squeezed out by an injector and frozen at once, which effectively prevented the coalescence of internal phase. Then a 365 nm UV light was utilized to initiate the polymerization and the temperature was kept at -20 °C in order to avoid the melting of the frozen HIPE. After the polymerization, samples, having a typical polyHIPE structure, were obtained. Besides, the original monomer, surfactant and the oil (internal phase) were respectively replaced, and well-defined polyHIPEs could still be obtained. All the results suggested that frozen UV polymerization of HIPEs was an effective and universal approach to produce polyHIPEs with a low amount of surfactant.

Macroporous Polymers with Aligned Microporous Walls from Pickering High Internal Phase Emulsions.

A novel class of macroporous polymers, open macroporous polymers with aligned microporous void walls, were prepared by combining particle-stabilized high internal phase emulsion (Pickering HIPE) and unidirectional freezing technique. These Pickering HIPEs were prepared by utilizing poly(urethane urea)/(vinyl ester resin) nanoparticles as the sole stabilizer, and this nanoparticles also acted as building blocks for the resulting macroporous polymers. Moreover, the morphology and compression modulus of the resulting porous materials could be tuned easily. This means now Pickering-HIPE templated open-cell foams can be prepared, and this route was normally achieved with surfactant and/or chemical reaction involved.

Functionalization of Cellulose Nanocrystals with PEG-Metal-Chelating Block Copolymers via Controlled Conjugation in Aqueous Media.

Elongated nanoparticles have recently been shown to have distinct advantages over their spherical counterparts in drug delivery applications. Cellulose nanocrystals (CNCs) have rodlike shapes in nature and have demonstrated biocompatibility in a variety of mammalian cell lines. In this report, CNCs are put forward as a modular platform for the production of multifunctional rod-shaped nanoparticles for cancer imaging and therapy. For the first time, PEGylated metal-chelating polymers containing diethylenetriaminepentaacetic acid (DTPA) (i.e., mPEG-PGlu(DPTA)18-HyNic and PEG-PGlu(DPTA)25-HyNic) are conjugated to CNCs to enable the chelation of radionuclides for diagnostic and therapeutic applications. The entire conjugation is based on UV/vis-quantifiable bis-aryl hydrazone-bond formation, which allows direct quantification of the polymers grafted onto the CNCs. Moreover, it has been shown that the mean number of polymers grafted per CNC could be controlled. The CNCs are also fluorescently labeled with rhodamine and Alexa Fluor 488 by embedding the probes in the polymer corona. Preliminary evaluation in a human ovarian cancer cell line (HEYA8) demonstrated that these CNCs are nontoxic and their penetration properties can be readily assessed in multicellular tumor spheroids (MCTSs) by optical imaging. These findings provide support for biomedical applications of CNCs, and further in vitro and in vivo studies are warranted to evaluate their potential as imaging and therapeutic agents for cancer treatment.

Evaluation of nystatin containing chitosan hydrogels as potential dual action bio-active restorative materials: in vitro approach.

Healing is a specific biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into "dual action bioactive restorative materials", capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM), release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro.