Soft Gel Research Articles

Contactless Rheology of Soft Gels Over a Broad Frequency Range

We report contactless measurements of the viscoelastic rheological properties of soft gels. The experiments are performed using a colloidal-probe atomic force microscope in a liquid environment and in dynamic mode. The mechanical response is measured as a function of the liquid gap thickness for different oscillation frequencies. Our measurements reveal an elastohydrodynamic coupling between the flow induced by the probe oscillation and the viscoelastic deformation of the gels. The data are quantitatively described by a viscoelastic lubrication model. The frequency-dependent storage and loss moduli of the polydimethylsiloxane gels are extracted from fits of the data to the model and are in good agreement with the Chasset-Thirion law. Our results demonstrate that contactless colloidal-probe methods are powerful tools that can be used for probing soft interfaces finely over a wide range of frequencies.

Chronic spinal cord injury repair by NT3-chitosan only occurs after clearance of the lesion scar

Spinal cord injury (SCI) is a severe damage usually leading to limb dysesthesia, motor dysfunction, and other physiological disability. We have previously shown that NT3-chitosan could trigger an acute SCI repairment in rats and non-human primates. Due to the negative effect of inhibitory molecules in glial scar on axonal regeneration, however, the role of NT3-chitosan in the treatment of chronic SCI remains unclear. Compared with the fresh wound of acute SCI, how to handle the lesion core and glial scars is a major issue related to chronic-SCI repair. Here we report, in a chronic complete SCI rat model, establishment of magnetic resonance-diffusion tensor imaging (MR-DTI) methods to monitor spatial and temporal changes of the lesion area, which matched well with anatomical analyses. Clearance of the lesion core via suction of cystic tissues and trimming of solid scar tissues before introducing NT3-chitosan using either a rigid tubular scaffold or a soft gel form led to robust neural regeneration, which interconnected the severed ascending and descending axons and accompanied with electrophysiological and motor functional recovery. In contrast, cystic tissue extraction without scar trimming followed by NT3-chitosan injection, resulted in little, if any regeneration. Taken together, after lesion core clearance, NT3-chitosan can be used to enable chronic-SCI repair and MR-DTI-based mapping of lesion area and monitoring of ongoing regeneration can potentially be implemented in clinical studies for subacute/chronic-SCI repair.

Pharmacokinetics and Clinical Implications of Two Non-Tablet Oral Formulations of L-Thyroxine in Patients with Hypothyroidism.

Background: Increased knowledge of the pharmacokinetic characteristics of orally administered levothyroxine (L-T4) has improved individualization of dosing regimens. However, up to 40–45% of patients, depending on the leading cause of hypothyroidism, are still over- or, more often, undertreated. Unintentional non-adherence to L-T4 replacement therapy includes all situations of unintended drug–drug and drug–food interactions as well as fasting conditions that are not necessarily respected by patients. Results: In this specific context, the overall information concerning those factors with the potential to affect L-T4 absorption refers only to tablet formulation. Indeed, this is the reason why new non-tablet formulations of L-T4 were introduced some years ago. In this regard, the current literature review was designed to summarize pharmacokinetic, drug and food interactions and clinical data focusing on two new oral L-T4 formulations, i.e., liquid and soft-gel capsule in healthy volunteers and patients with primary hypothyroidism. The non-tablet L-T4 soft-gel capsules and solution have proven bioequivalence with the usual L-T4 tablet Princeps and generic formulations. Clinical studies have suggested higher performance of non-tablet formulations than tablet in those patients with suboptimal adherence. The impact of gastrointestinal conditions and variation of gastric pH was lower with either soft gel/solution than with tablets. In addition, the extent of drug–drug and drug–food interactions remains low and of uncertain clinical relevance. Conclusions: Pending further studies allowing one to extend the use of soft-gel/solution preparations in unselected patients, non-tablet L-T4 formulations should be considered as a first-line choice, especially in those patients with moderate-to-high potential of suboptimal tablet performance.

Curable benzoxazine/siloxane hybrid networks from renewable phenolics and glycerol

Siloxane bearing benzoxazines from renewable phenolics such as vanillin and coumarin were prepared and reacted with glycerol by silyl ether exchange reactions to yield processable, soft, and curable bio-hybrid gels. Moreover, these benzoxazine-based gels were cured below 200 °C favored by the catalytic effect of hydroxyl groups present on glycerol moieties to yield bio-hybrid polybenzoxazines. All the synthesized intermediates, gels, and ultimate networks were characterized by 1H, 13C NMR, FTIR, and UV–Vis analyses. The curing behavior and thermal stabilities of the monomers, glycerol-based gels and related polybenzoxazines were investigated by differential scanning calorimeter (DSC) and thermogravimetric analysis (TGA). Moreover, the activation energies of polymerization of benzoxazine monomers were determined by DSC using the Kissinger and Ozawa methods.

Soft Movable Polymer Gel for Controlling Water Coning of Horizontal Well in Offshore Heavy Oil Cold Production.

Horizontal well water coning in offshore fields is one of the most common causes of rapid declines in crude oil production and, even more critical, can lead to oil well shut down. The offshore Y oil field with a water cut of 94.7% urgently needs horizontal well water control. However, it is a challenge for polymer gels to meet the requirements of low-temperature (55 °C) gelation and mobility to control water in a wider range. This paper introduced a novel polymer gel cross-linked by hydrolyzed polyacrylamide and chromium acetate and phenolic resin for water coning control of a horizontal well. The detailed gelant formula and treatment method of water coning control for a horizontal well in an offshore field was established. The optimized gelant formula was 0.30~0.45% HPAM + 0.30~0.5% phenolic resin + 0.10~0.15% chromium acetate, with corresponding gelation time of 26~34 h at 55 °C. The results showed that this gel has a compact network structure and excellent creep property, and it can play an efficient water control role in the microscopic model. The thus-optimized gelants were successively injected with injection volumes of 500.0 m3. The displacement fluid was used to displace gelants into the lost zone away from the oil zone. Then, the formed gel can be worked as the chemical packer in the oil–water interface to control water coning after shutting in for 4 days of gelation. The oil-field monitoring data indicated that the oil rate increased from 9.2 m3/d to 20.0 m3/d, the average water cut decreased to 60~70% after treatment, and the cumulative oil production could obtain 1.035 × 104 t instead of 3.9 × 103 t.

Nutrient Strength and Dissolution Test Results of Nationally Representative Prescription Prenatal Multivitamin/Mineral (RxP MVM) Supplements

ObjectivesUS pregnant women are at risk of dietary deficiencies of iron, folate, calcium and vitamin D and take Rx or non-Rx MVM supplements to optimize their nutritional status. The efficacy of a MVM is determined not only by its ingredient content but also by the ability of tablets and capsules to properly disintegrate and release nutrients. The goals of this Dietary Supplement Ingredient Database study were to measure micronutrients in RxP MVMs and to assess dosage form adherence to the United States Pharmacopeial (USP) dissolution standards.MethodsMultiple lots of 24 RxP MVMs, representing 61% of the market were tested by commercial laboratories. We compared the content with Recommended Dietary Allowances (RDAs) and Upper Tolerable Intake Levels (ULs). The MVMs were tested for folic acid, iron, riboflavin, and retinol dissolution. To pass, at least 75% of the labeled amount must be released in 1 hour.ResultsThe means of daily intakes provided by most RxP MVMs were below 20% RDAs for calcium and magnesium, at about half of the RDA for iodine, at or slightly above RDAs for iron and copper, and almost twice the RDA for zinc. The mean amounts of daily intakes of vitamins A, C, D, E, niacin, and thiamin provided by most MVMs were 70–160%RDAs, although some products contained thiamin, vitamins C or D at 170–240% of RDAs. All MVMs provided amounts of folic acid exceeding the RDA (mean %RDA ± SD; 334 ± 49). Average measured contents of vitamins and minerals exceeded labeled amounts, including those labeled with amounts above ULs. However, none of the 15 tablet and 4 soft gel products passed dissolution testing for all ingredients required by USP. None of 7 products passed the test for retinol. Only 55% of 11 MVMs in tablets with fast releasing iron sources passed dissolution tests for iron, folic acid and riboflavin. For at least one of those three ingredients, 80–93% of 12–15 tablets passed dissolution, and only 1 of 4 soft gels passed the test with pepsin added to the testing media.ConclusionsAlthough RxP MVMs contained several micronutrients significantly exceeding RDAs that might help to close nutrient gaps, the sample of nationally representative RxP MVMs failed to meet all USP standards for ingredient dissolution. This is a concern for pregnant women because nutrients in failed products might not be available for absorption and utilization.Funding SourcesNIH ODS and the USDA.

Sampling Plan for a Study of Cranberry Dietary Supplements (DS) for the Dietary Supplement Ingredient Database (DSID)

ObjectivesThe intake of cranberry juice or supplements has been found in several, but not all, clinical studies to reduce the recurrence of urinary tract infections (UTIs). Several studies indicate that cranberry proanthocyanidins (PACs) may have a role in UTI prevention due to their ability to inhibit bacterial adhesion. For cranberry DS products on the US market, the relationship between PAC content and the cranberry source (e.g., powder, juice, extract) used in formulations is largely unknown. Therefore, a sampling plan was developed to identify and purchase DS for PAC testing as part of the Dietary Supplement Ingredient Database project. This will include popular cranberry DS, those used in clinical trials, and products with a variety of label claims and source ingredients. MethodsDS usage data from the National Health and Nutrition Examination Survey and retail sales data were used to identify the most popular cranberry DS in the natural health (NH), mass market (MM), and direct distribution sales channels. Other sources of information were the Dietary Supplement Label Database and web-based DS sellers. Three DS label categories were identified: those with a trademarked cranberry ingredient, those without a trademarked cranberry ingredient, and those with a numeric PAC claim. Some products may fall into two categories. Most products chosen for the study had cranberry as the primary ingredient by weight. Popular products with D-mannose and vitamin C were also included. ResultsIn the first phase of this study, we purchased 41 DSs (18 MM, 11 NH, and 12 direct). Our sample included caplets, capsules, soft gels, tablets, and liquid DSs. Cranberry source materials for the DSs included extracts, concentrates, powder, juice, and whole fruit. Fifteen (15) supplements had trademarked cranberry ingredients and 9 had a specific voluntary claim for PAC content. ConclusionsIn 2020, cranberries were the 6th ranked herbal ingredient sold in the US, according to the Nutrition Business Journal. The range of PAC content in the diverse cranberry DSs on the market is currently not known, since there is no requirement for this information on labels. This study will answer questions about the PAC content in a variety of DSs and whether multiple laboratories testing using the dimethylaminocinnamaldehyde (DMAC) method will yield similar results. Funding SourcesNIH ODS and the USDA.

A Questionnaire Survey of German Thyroidologists on the Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: The THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) Collaborative

To identify the attitudes of German thyroid specialists towards the clinical treatment of hypothyroidism using thyroid hormones (TH). All members of the thyroid section of the German Endocrine Society (DGE) were e-mailed an invitation to participate in a web-based survey about substitution with TH. Out of 206 members of the DGE's thyroid section, 163 (79.1%) responses were received and included in the analysis. Of responding members, 98.6% used levothyroxine (LT4) as the treatment of choice, and 45.4% also prescribed combination therapy with liothyronine (LT4+LT3) in their clinical practice (p<0.001). LT4+LT3 combination was favored in patients with persistent hypothyroidism symptoms despite biochemical euthyroidism on LT4 treatment (p<0.001). Of all respondents, 26.4% never indicated TH therapy for euthyroid patients (p<0.001), while the remainder would consider THs for one or more indications (62.9% for euthyroid infertile women with high anti-thyroid antibody levels (p<0.001), 7.1% in patients with severe hypercholesterolemia, as complementary treatment (p=0.007), and 57.1% in patients with simple goiter (p<0.001)). In conditions that could interfere with LT4 absorption, most respondents still preferred tablets and did not expect a significant difference when switching from one LT4 formulation to another. For German thyroid specialists, LT4 is the treatment of choice for hypothyroidism. Combination therapy with LT4+LT3 was considered for patients with persistent symptoms. Even in conditions that could affect bioavailability, German thyroid specialists prefer LT4 tablets rather than other LT4 formulations, such as liquid or soft-gel capsules. The widespread use of thyroid hormone for non-hypothyroid conditions is not consistent with current evidence and needs further study.

Testing of some cosmetic and hygiene products of the CHOICE campany in patients with chronic dermatoses using skin application tests

Objective — using skin application samples to test for allergenicity of some cosmetic and hygienic environmentally friendly products of the CHOICE campany in patients with chronic recurrent dermatosis — eczema, atopic dermatitis and psoriasis.&#x0D; Materials and methods. With the help of skin application tests, some cosmetic and hygiene products of the CHOICE (Ukraine) company were tested in 36 patients with the most common chronic recurrent dermatosis — eczema, atopic dermatitis and psoriasis. The test products were applied to dry skin, free from rashes and topical medications, under a medical patch. Samples were counted on the 2nd, as well as on the 4th—5th and 7th—8th days after application.&#x0D; Results and discussion. No skin reactions were recorded in patients with psoriasis who participated in the study. The phenomena of contact dermatitis were observed in contact with only one type of tested product, namely, «Gentle Phytomousse» of the «Seaweed» line for washing all skin types. This type of product was allergenic for 1 out of 6 patients with true eczema and 4 out of 9 patients with atopic dermatitis. Other types of products did not cause any phenomena of contact dermatitis at all in the observed patients.&#x0D; Conclusions. Four of the five CHOICE (Ukraine) products tested by skin application trials, namely: ECO liquid soap, Green max.; egg shampoo for dry and damaged hair line Intensive Moisturizer, White mandarin; Soft and velvety skin hand and body milk, White mandarin; Soft and velvety skin shower gel, White mandarin can be used in patients with eczema, atopic dermatitis and psoriasis without prior allergy testing. Gentle Phytomousse for washing all skin types of the Seaweed line can cause contact dermatitis in patients with true eczema and atopic dermatitis.

Material characterization and simulation for soft gels subjected to impulsive loading

For impact and blast experiments of traumatic brain injury (TBI), soft gel materials are used as surrogates to imitate the mechanical responses of brain tissue. To properly model a viscoelastic gel brain in a surrogate head using a finite element (FE) model, material parameters such as the shear moduli and relaxation time at high strain rates are required. However, such information is scarce in the literature and its applicability for a range of dynamic conditions is unclear. We used an integrated experiment and simulation approach to efficiently determine mechanical properties of soft gels at finite strains, as well as over a wide range of strain rates. A novel impact experiment using a gel block was developed to capture the high strain rate behavior by maximizing the inherent shear wave motion at different impact conditions. A corresponding computational model was used to simulate the gel dynamics of the impact. Parametric simulations utilizing optimization and correlation analyses were used to calibrate multiple material parameters in the nonlinear viscoelastic model to the experimental data. The optimal parameters for gels, including Sylgards 184, 3–6636, and 527, were found. We ascertained the initial shear stiffening effect in gels at high strain rate loadings experimentally and incorporated this effect in the simulation. We have verified the integrated approach by comparing the material properties of the gels with analytical results based on shear wave propagation. This study provides a new approach to calibrate the material behavior of soft gels under high strain rate loading conditions.

Signaling Downstream of Focal Adhesions Regulates Stiffness-Dependent Differences in the TGF-β1-Mediated Myofibroblast Differentiation of Corneal Keratocytes.

Following injury and refractive surgery, corneal wound healing can initiate a protracted fibrotic response that interferes with ocular function. This fibrosis is related, in part, to the myofibroblast differentiation of corneal keratocytes in response to transforming growth factor beta 1 (TGF-β1). Previous studies have shown that changes in the mechanical properties of the extracellular matrix (ECM) can regulate this process, but the mechanotransductive pathways that govern stiffness-dependent changes in keratocyte differentiation remain unclear. Here, we used a polyacrylamide (PA) gel system to investigate how mechanosensing via focal adhesions (FAs) regulates the stiffness-dependent myofibroblast differentiation of primary corneal keratocytes treated with TGF-β1. Soft (1 kPa) and stiff (10 kPa) PA substrata were fabricated on glass coverslips, plated with corneal keratocytes, and cultured in defined serum free media with or without exogenous TGF-β1. In some experiments, an inhibitor of focal adhesion kinase (FAK) activation was also added to the media. Cells were fixed and stained for F-actin, as well as markers for myofibroblast differentiation (α-SMA), actomyosin contractility phosphorylated myosin light chain (pMLC), focal adhesions (vinculin), or Smad activity (pSmad3). We also used traction force microscopy (TFM) to quantify cellular traction stresses. Treatment with TGF-β1 elicited stiffness-dependent differences in the number, size, and subcellular distribution of FAs, but not in the nuclear localization of pSmad3. On stiff substrata, cells exhibited large FAs distributed throughout the entire cell body, while on soft gels, the FAs were smaller, fewer in number, and localized primarily to the distal tips of thin cellular extensions. Larger and increased numbers of FAs correlated with elevated traction stresses, increased levels of α-SMA immunofluorescence, and more prominent and broadly distributed pMLC staining. Inhibition of FAK disrupted stiffness-dependent differences in keratocyte contractility, FA patterning, and myofibroblast differentiation in the presence of TGF-β1. Taken together, these data suggest that signaling downstream of FAs has important implications for the stiffness-dependent myofibroblast differentiation of corneal keratocytes.

A comparative study of dietary fiber content, In vitro starch digestibility and cooking quality characteristics of pigmented and non–pigmented traditional and improved rice (Oryza sativa L.)

Thirty-two traditional and newly improved pigmented and non-pigmented rice varieties were evaluated for their eating and cooking quality and dietary fiber (DF) content. Seasonal variability of DF content, in–vitro starch digestion rate (DR) and expected glycemic index (eGI) were evaluated using selected representative samples. Rice varieties were categorized either high or intermediate amylose content but with hard, medium or soft gel consistency. Average insoluble dietary fiber (IDF) and soluble dietary fiber (SDF) content ranged between 1.13–6.76% and 0.03–1.00%, respectively. Pigmented rice reported significantly higher IDF content compared to non–pigmented rice and also showed a significant statistical correlation (r > 0.56, P < 0.01) between IDF and pigmentation. There was no seasonal variation observed in rice DF content between two cropping seasons. Pigmented rice varieties showed significantly lower (P < 0.05) starch digestibility and glycemic index values (DR:58.8–66.5; eGI:71.9–76.2) than non–pigmented rice (DR:69.1–71.5; eGI:77.6–79.0). Pigmented rice showed significantly higher negative correlation (r > -0.68, P < 0.01) with DR.

Organic solvent vapor/thermal responsive binary gels with tunable transparency and mechanical strength

In this work, we illustrate the fabrication of binary gels via self-sorting assembly between β-cyclodextrin and the second gelators, which show significant transparency changes responsive to the solvent vapor and temperature. The mixing of β-cyclodextrin and clay minerals in the mixture of dimethylformamide and water produced opaque gels. After exposed to specific solvent environments, the light transmittance of opaque gels was greatly enhanced ascribed to the host-guest complexation between β-cyclodextrin and organic solvent vapors. Toluene, xylene, tetrahydrofuran, dioxane and pyridine aroused gel fiber to bulky crystal transformation, which also slightly enhanced the mechanical strength of the binary gels. In addition, the gelator could be expanded to organic gelator like folic acid. This work offers a feasible way to fabricate soft gel composites that show transparency changes responsive to solvent vapors.

Echinacea angustifolia and Echinacea purpurea Supplementation Combined with Vaginal Hyaluronic Acid to Boost the Remission of Cervical Low-Grade Squamous Intraepithelial Lesions (L-SILs): A Randomized Controlled Trial.

Background and Objectives: Echinacea angustifolia and purpurea have known immunomodulatory effects which boost viral clearance, including HPV infection. However, evidence regarding the improvement due to Echinacea-based supplements of cervical HPV-related pathologies is still lacking. The aim of this study is to evaluate the efficacy of Echinacea supplementation on the remission of cervical low-grade squamous intraepithelial lesions (L-SIL). Materials and Methods: A single-blind 1:1:1 parallel randomized controlled trial was conducted at the Colposcopy Unit of a tertiary care referral center. Reproductive-aged women were allocated either to (a) an oral supplement based on Echinacea extracts plus vaginal hyaluronic acid-based soft gel capsules, (b) the Echinacea supplement alone, or (c) vaginal hyaluronic acid-based soft gel capsules alone for 3 months. The primary outcome was the regression of cervical intraepithelial neoplasia (CIN)-1 for each treatment arm at 3, 6 and 12 months after the diagnosis. Secondary outcomes included changes in the epithelialization, pap smear, colposcopic parameters, histological reports, and vaginal health indexes (VHI) in the study groups. Results: 153 women (52 for arm A, 50 for arm B and 51 for arm C) completed the follow-up and were included in the analysis. There were no significant differences in both primary and secondary outcomes for the three groups after 3 months. At the 6-month follow-up, the number of persistent CIN-1 diagnoses was significantly lower in arm A (15/51), rather than in arm B (23/48, p = 0.03) and C (27/49, p = 0.03). Similarly, the same effect was seen after 12 months for treatment A (5/51) relative to B (15/48, p = 0.03) and C (14/48, p = 0.03). Colposcopic, histological and vaginal parameters were all significantly improved at 6 and 12 months for arm A relative to B and C, while no beneficial effects were seen after 3 months. Conclusions: Echinacea extracts supplementation in women with L-SIL/CIN-1 significantly boosts HPV lesion clearance, reducing the overall amount of diagnosis, histological, colposcopic and vaginal parameters after 6 and 12 months. However, a limited sample size reduces the quality of evaluated evidence, emphasizing the need for additional studies to validate these findings.

A Flexible, Transparent, Ultralow Detection Limit Capacitive Pressure Sensor

AbstractThe capacitive pressure sensor (CPS) with low detection limit and high sensitivity is crucial for the future development of electronic skins. Although introducing surface microstructures on dielectric layer may improve the sensitivity of CPS in some extent, it leads to a limited pressure‐response range due to the poor structural compressibility. Moreover, such microstructures deteriorate the transparency and flexibility of the final sensor and require costly microfabrication methods. Herein, a low‐cost high performance pressure sensor is developed by integrating the high permittivity and soft dielectric gel with the mechanically comparable ionic conductor. The device shows an unprecedented detection limit of 0.2 Pa, a high sensitivity of 4.2 kPa−1 in the low‐pressure regime of &lt;1.2 kPa, and a fast response time of 13 ms. This ultralow detection limit allows for the efficient and accurate detection of weak pressure signals from acoustic waves to pulse and air‐flow, exhibiting promising application potentials in voice recognition, screening of cardiovascular diseases, and diagnosis of gas leakage. Furthermore, the combination of ionic conductor and dielectric gel also endows the capacitive pressure sensor with remarkable transparency, mechanical stability, and durability even under extreme environments. This study proposes a novel perspective for development of flexible and transparent electronic skins.

Spatial-temporal mapping of the intra-gastric pepsin concentration and proteolysis in pigs fed egg white gels

While there is a consensus that food structure affects food digestion, the underlying mechanisms remain poorly understood. A previous experiment in pigs fed egg white gels of same composition but different structures evidenced such effect on food gastric disintegration. In this study, we detailed the consequences on intra-gastric pH, pepsin concentration and proteolysis by sampling throughout the stomach over 6 h digestion. Subsequent amino acid absorption was investigated as well by blood sampling. While acidification was almost homogeneous after 6 h digestion regardless of the gel, pepsin distribution never became uniform. Pepsin started to accumulate in the pylorus/antrum region before concentrating in the body stomach beyond 4 h, time from which proteolysis really started. Interestingly, the more acidic and soft gel resulted in a soon (60 min) increase in proteolysis, an earlier and more intense peak of plasmatic amino acids, and a final pepsin concentration three times higher than with the other gels.

Gelatin-Based Colloidal Versus Monolithic Gels to Regulate Macrophage-Mediated Inflammatory Response.

Unlike conventional monolithic hydrogels with covalent cross-linkage that are typically elastic, colloidal gels assembled by reversibly assembled particles as building blocks have shown fascinating viscoelastic properties. They follow a gel-sol transition upon yielding and recover to the initial state upon the release of the shear force (so-called shear-thinning and self-healing behavior); this makes them an ideal candidate as injectable and moldable biomaterials for tissue regeneration. The immune response provoked by the implantation of the colloidal gels with special viscoelastic and structural features is critical for the successful integration of the implants with the host tissues, which, however, remains little explored. Since macrophages are known as the primary immune cells in determining the inflammatory response against the implants, we herein investigated in vitro macrophage polarization and in vivo inflammatory response induced by gelatin-based colloidal gels as compared to monolithic gels. Specifically, self-healing colloidal gels composed of pure gelatin nanoparticles, or methacrylate gelatin (GelMA) nanoparticles to allow secondary covalent cross-linkage were compared with GelMA bulk hydrogels. We demonstrated that hydrogel's elasticity plays a more dominant role rather than the structural feature in determining in vitro macrophage polarization evidenced by the stiffer gels inducing pro-inflammation M2 macrophage phenotype as compared to soft gels. However, subcutaneous implantation revealed a significantly alleviated immune response characterized by less fibrous capsule formation for the colloidal gels as compared to bulk gels of similar matrix elasticity. We speculated this can be related to the improved permeability of the colloidal gels for cell penetration, thereby leading to less fibrosis. In general, this study provided in-depth insight into the biophysical regulator of hydrogel materials on macrophage behavior and related inflammatory response, which can further direct future implant design and predict biomaterial-host interactions for immunotherapy and regenerative medicine. Impact statement Macrophages response to implanted biomaterials is a highly regulated process that influences device functionality and clinical outcome. Nowadays, the viscoelastic properties of colloidal versus monolithic hydrogels on macrophage phenotype in vitro and the host inflammatory response are not known. Our study found that colloidal hydrogels composed of nanoparticles of gelatin and methacrylate gelatin (GelMA) led to more anti-inflammatory polarization especially on soft colloidal gel (5.9 KPa) compared to bulk GelMA hydrogels. It suggested that macrophage response can be mechanically regulated by the viscoelastic signals of the hydrogels, which could be a promising strategy for the future design and application of novel biomaterials.

Self-assembly of N-, C- and N-/C-terminated Val-and Phe-amino acid side chains of naphthalene

The fundamental component of a protein is the polypeptide chain comprised of a sequence of condensed monomeric amino acid residues, twenty of which are deemed essential to the production of protein synthesis in the human body. In this study, the N-, C- and N-/C-naphthyl substituted hydrophobic amino acid sidechains, Val-and Phe, are two of the most common, and here, were synthesized and studied for their propensity to self-assemble in vitro. This study characterized bioconjugates in solution (FT-IR and 1H NMR), as well as in their solid states (single-crystal X-ray diffraction, FT-IR, powder X-ray diffraction). To initiate self-assembly, these bioconjugates were either subjected to heat/cool variations or sonication, and the aggregates produced were further characterized by SEM. All soft gels consisted of extensive fibrillar networks of similar morphology and their formation was highly dependent on the bioconjugate, the organic solvent used and stimuli present. Interestingly, the 2-NAP-Val-OMe (1), 2-NAP-Phe-OMe (2) and Boc-Val-1-NAP (3) bioconjugates did not undergo gelation. The Boc-Phe-1-NAP (4) formed opaque soft gels in multiple non-polar solvents when stimulated by heating/cooling but not by sonication. Further, both disubstituted bioconjugates, 2-NAP-Val-1-NAP (5) and 2-NAP-Phe-1-NAP (6), also underwent gelation. The bioconjugate 6 formed opaque gels in polar protic solvents after heat/cool or sonication. A soft transparent gel was formed only by compound 5 in benzene following the heating/cooling treatment, which was then doped with quantum dots and the highly fluorescent organogel was characterized by fluorescence spectroscopy and microscopy. Morphological investigations proved that these bioconjugates could assemble themselves into an ordered structures such as a fiber or crystal. FTIR and 1H NMR studies indicated that hydrogen bonding, π-π stacking, and van der Waals forces played key roles in the formation of a gel.

Grain Properties of Indigenous Rice Cultivars from Khagrachari District of Bangladesh

A study was conducted in the Agronomy Laboratory of Agrotechnology Discipline, Khulna University, Khulna, Bangladesh to find out the variations in grain characters of fifteen local rice cultivars collected from Khagrachari district, Bangladesh. Significant variations were observed in all of the investigated parameter. The highest and lowest length of grain was recorded in the cultivar Chonchonbini (7.1 mm) and Mashlajira (4.12 mm), respectively. Grain width of Badia (2.78 mm) was the highest and the lowest width was recorded in Mashlajira (2.13 mm). Grain thickness varied from 1.6 mm to 1.94 mm. The highest L/W ratio (3.11) was observed in Curi. Most of the variety showed medium grain shape. The highest alkali spreading score was found in Moisanguribini (6). All of the varieties showed soft gel consistency. Variation in grain characters observed among the local rice cultivars in the present study and these characters may be used as valuable resources for future breeding programs. South Asian J. Agric., 8(1&amp;2): 51-56

P231 Targeting the Rho/MRTF-A pathway inhibits growth factor and cytokine release but enhances efferocytosis in scleroderma macrophages

Abstract Background/Aims In the systemic sclerosis (SSc) microenvironment, accumulation of extracellular matrix (ECM) components induces changes in the matrix's mechanical properties, which triggers Rho/MRTFF-A activation and the downstream signalling cascades, inducing the expression of fibrotic and inflammatory genes in fibroblasts. However, macrophages also play a key role in tissue homeostasis and wound repair. It is possible that these cells are also influenced by ECM stiffness and therefore we investigated the effects of altering substrate stiffness and tested the effects of an inhibitor of the mechano-sensing Rho/MRTF-A pathway on the activation state of SSc macrophages. Methods SSc and healthy control macrophages (both n = 4 donors) were derived by culture of blood monocytes in the presence of M-CSF (4ng/ml) for 7 days. Soft substrates (4kPa) or stiff ECM substrates (50kPa) were used to model the effect of soft healthy skin tissue and stiff fibrotic SSc skin (Softwell, Matrigen, polymer gels, collagen I coated). Morphology, gene expression (qPCR for CD86 for M1-like, CD206 for M2-like, MerTK for efferocytosis), Multiplex assay, labelled E. Coli uptake assay and Rho/MRTF/SRF pathway inhibition (small molecule CCG-257081) were used to assess the polarisation and activation state of these cells. Results Morphology and CD86 did not vary with matrix stiffness, but CD206 expression was significantly lower in stiff compared to soft gels (Mean+/- SEM; soft 38.2+/- 4.2 vs stiff 16.2+/-3.7 relative expression, p value 0.0167). CCG-257081 strongly inhibited secretion of cytokines, growth factors and chemokines. Factors present at &amp;gt; 50 pg/ml suppressed by CCG-257081 include TNFα, GM-CSF, IL-1RA, IP-10, RANTES, MIP-1α, MIP-1β, MCP-1, MCP-3, PDGF-BB (all p &amp;lt; 0.05). SSc macrophages secreted at high levels on soft, and were attenuated by culture on stiff, whereas healthy control macrophages showed the opposite trend inducing more secretion on stiff, inhibited by CCG-257081. Although polarisation markers CD206 and CD86 did not alter with the CCG-257081 treatment, there was a significant increase in MerTK with treatment (p &amp;lt; 0.0001). Endocytosis was moderately yet significantly suppressed by the CCG treatment (basal endocytosis 80.2+/- 4.0 vs CCG-257081 treated 62+/-2.5; % endocytosis; p &amp;lt; 0.01), whereas cell viability was not significantly altered. Conclusion Although differences are observed amongst patients, this data indicates that stiffness of the matrices, as used in this study, did not greatly alter the morphology or polarisation of the macrophages. However, transfer to stiff matrices enhanced the secretion of certain cytokines by control macrophages. Strong effects were seen with the Rho/MRTF-A inhibitor, which appeared to block the secretion of multiple factors, including inflammatory cytokines, pro-fibrotic factors, as well as regulatory factors and to strongly induce MerTK, a marker of efferocytosis. One possibility is that the inhibitor converts these cells from secretory to resolving phenotype. Based on these findings, CCG-257081 has promising effects against activated macrophages, which could be utilised in inflammatory fibrotic diseases. Disclosure S. Lopez Garces: None. B. Ahmed Abdi: None. C. MacFadyen: None. R. Smillie: None. L. Nagib: None. S. Ghani: None. S. Shah: None. D. Abraham: None. C. Denton: None. R.J. Stratton: None.