Gels For Use Research Articles

Intermolecular interactions and gel properties of composite agglomerative networks based on oppositely charged polymers: Effects of pH and ionic strength

The effects of pH and ionic strength on the intermolecular interactions and gel properties—textural and mechanical properties, water holding capacity, and color— of kidney-bean-protein-isolate–sodium-alginate (KPI-SA) composite gels were investigated. According to the zeta potentials of KPI, SA, and KPI-SA in the pH range of 2.0–7.0, pH values of 3.0, 4.0, 5.0, and 7.0 were selected as the experimental conditions. Protein solubility and ATR-FTIR analysis results indicated that the forces for the formation of KPI-SA gels were different under different conditions. Specifically, under neutral conditions (pH 7.0), hydrogen bonding was the most significant force, but when the pH (5.0) approached the isoelectric point (pI), hydrophobic interactions became dominant. Furthermore, as the pH (4.0, 3.0) became lower than the pI, electrostatic association became the main force. With an increase in Ca2+ concentration (20–80 mg/mL), the hydrophobic interactions were gradually enhanced while the electrostatic association was first enhanced and then weakened. When the pH decreased or the ionic strength increased, the KPI-SA gel network gradually formed a uniform and dense honeycomb structure, and the gel texture and mechanical and water-holding properties improved accordingly. The obtained results suggest that moderate acidification and increased ionic strength are promising conditions to produce composite gels for use in the food industry and other fields.

The Impact of Over-The-Counter Lactic Acid Containing Vaginal Gels on the Integrity and Inflammatory State of the Vaginal Epithelium in vitro.

The vaginal microbiome influences a wide range of health outcomes in women, where a microbiome dominated by Lactobacillus spp. is considered optimal and associated with reduced risk of pre-term birth and acquisition of sexually transmitted infections including HIV. Conversely, replacement of lactobacilli by non-optimal bacteria leads to the development of bacterial vaginosis, which is associated with increased risk of these outcomes. Lactobacilli produce the metabolite lactic acid (LA) which is a potent antibacterial and antiviral agent. The potential therapeutic benefits of LA have prompted the development of numerous over-the-counter LA-containing gels for use in the vagina, although a comprehensive analysis of the impact of these formulations on the cervicovaginal epithelium and pro-inflammatory cytokine/chemokine responses, has not been assessed. Here, we evaluated the properties of 11 over-the-counter gels, including 9 containing LA, marketed for use in the vagina. Ten of the 11 gels had an osmolality greater than vaginal fluid from women with Lactobacillus-dominated microbiota (370 ± 40 mOsmol/kg in women with Nugent score 0–3), with six gels that were hyperosmolal >2,000 mOsmol/kg. Using a reconstructed primary cell model of the vaginal epithelium, we found hyperosmolal gels had a detrimental impact on epithelial barrier integrity, resulting in substantial cellular toxicity (<10% viability as compared to untreated cells) and reduced epithelial barrier integrity [≈30% of untreated cells, assessed by transepithelial electrical resistance (TEER)]. Treatment of vaginal tissues with most of the gels elicited the production of pro-inflammatory factors including IL-1α (8 of 11) and IL-1β (10 of 11) which are associated with heightened risk of HIV acquisition in vivo. The majority of the OTC gels elicited moderate tissue damage as determined by histology. The detrimental effects of these gels on the human vaginal epithelium in vitro may predict compromised epithelial barrier integrity and genital inflammation in vivo, which has implications for sexual and reproductive health. This study highlights the importance of evaluating the impact of intravaginal products on the integrity and inflammatory status of the mucosal epithelium to avoid unfavorable off target effects.

Empirical Estimation of Ethanol-Methylcellulose based Green Gel Propellant Viscosity at Varying Temperature

The rheological behavior of the Ethanol based green gels for use in propulsion systems at temperature range of 100C – 500C is investigated by employing a novel empirical model developed. The study is conducted at various shear rates. Empirically predicted results were observed to be in good agreement with experimental data at higher shear rates for both pure and energized gel system (&gt;100 s-1). Considering the results, the present empirical model is deemed suitable for those Non Newtonian shear thinning fluids which obey Power law.

Newly developed acrylate injection resin gels for structural sealing and active corrosion protection of embedded steel reinforcement

AbstractThe corrosion potential of waterproofing acrylate injection resins is relevant when these materials are used in reinforced concrete structures. Sika Technology AG has developed a new generation of acrylate resin gels for use as injection material to seal cracks, repair honeycombed areas, and fill voids in concrete structures. This new material shows promising results in electrochemical laboratory tests for the provision of corrosion protection to the embedded reinforcement. These electrochemical analyses have been carried out at Sika Technology AG and in the Institute for Building Research (ibac) at RWTH Aachen University. The results of this investigation and the corresponding conclusions for their use in building, construction, and refurbishment works are presented below.

Are teething gels safe or even necessary for our children? A review of the safety, efficacy and use of topical lidocaine teething gels.

Lidocaine-based teething gels have been widely available in Australia for decades in both commercial preparations and those compounded by pharmacies. However, many case reports have highlighted potential risks and toxicity associated with lidocaine-based teething gels when used in infants and young children, including seizures, respiratory arrest and death. The Australian and New Zealand Society of Paediatric Dentistry and the American Academy of Paediatrics do not recommend topical agents for teething, and the US Food and Drug Administration does not recommend topical lidocaine for this purpose due to concerns of toxicity. Literature supporting the efficacy of lidocaine for teething is scant and difficult to interpret due to the flawed design of the trials conducted and varied formulations used. This opinion article aims to summarise the available literature showing the limited effectiveness and associated risks of topical lidocaine gels for use in teething. In light of these findings, the authors recommend that regulatory bodies such as the Australian Therapeutic Goods Administration review the efficacy and safety of this type of medicine and consider removing the indication for teething or limiting the age of use to older children.

Fabrication of Alternative Bolus for Cobalt-60 Teletherapy Using Two Locally Available Materials

Bolus is a tissue equivalent material which is use in radiation therapy in order to eliminate skin sparing effect of higher energy photon beams that always reduce the surface dose. There are several commercially bolus material such as Superflab, Aquaplast and gels for use but literature have shown that they are expensive and are not readily available in developing countries. This work presents the fabrication of an alternative bolus for Cobalt-60 Teletherapy using two locally available materials (Beeswax and Petroleum jelly). Beeswax was liquefied at a temperature of 60°C followed by the addition of Petroleum jelly at ratio 3:1 by weight for proper molding and flexibility. In order to determine the depth of maximum dose, Thermoluminescent Dosimeter (TLD) chips were inserted in between ten bolus materials of thickness 0.5 cm that were arranged in layers and placed on a solid water phantom. This was then irradiated with Cobalt-60 radiation source using field size ranging from 5 cm x 5 cm to 10 cm x 10 cm field size. For all the field size, maximum absorbed dose was found to be at 0.5 cm depth. This depth of maximum dose was compared to two tissue equivalent materials in use in radiation therapy: water and Superflab for Cobalt-60 Teletherapy and found to be in agreement. The percentage dose deviation when compared with water for 1 cm, 2 cm, 3 cm, 4 cm and 5 cm were less than 2%. The flexibility of the bolus material and the analysis of the absorbed dose measured have shown that the fabricated bolus material of thickness 0.5 cm can be used as an alternative bolus material for Cobalt-60 Teletherapy.

Conjugation of the T1 sequence from CCN1 to fibrin hydrogels for therapeutic vascularization.

Hydrogel matrices with angiogenic properties are much desirable for therapeutic vascularization strategies, namely to provide vascular supply to ischemic areas, transplanted cells, or bioengineered tissues. Here we report the pro-angiogenic effect of fibrin (Fb) functionalization with the T1 sequence from the angiogenic inducer CCN1, forseeing its use in the injured brain and spinal cord. Fibrin functionalization with 40 μM of T1 peptide effectively improved cellular sprouting of human brain microvascular endothelial cells (hCMEC/D3) in the absence of vascular endothelial growth factor (VEGF), without impacting the viscoelastic properties of Fb, cell viability, or proliferation. The pro-angiogenic effect of immobilized T1 was potentiated in the presence of VEGF and partially mediated through α6β1 integrin. The tethering of T1 also enhanced sprouting of human cord blood-derived outgrowth endothelial cells (OEC). Still, to elicit such effect, a higher input T1 concentration was required (60 μM), in line with the lower protein levels of α6 and β1 integrin subunits found in OEC comparing to hCMEC/D3, prior to embedment in Fb gel. Finally, the ability of T1-functionalized Fb in inducing cappilary invasion in vivo was assessed using the CAM assay, which evidenced a significant increase in the number of newly formed vessels at sites of implantation of T1-functionalized Fb, in the absence of soluble angiogenic factors. Overall these results demonstrate the potential of T1 peptide-presenting gels for use in therapeutic vascularization approaches. Considering T1 neurite-extension promoting capability and pro-angiogenic properties, T1-functionalized Fb hydrogels are particularly promising for application in the injured central nervous system.

Evaluation of Noncommercial Ultrasound Gels for Use in Resource-Limited Settings.

Ultrasound (US) is increasingly used in settings where commercial US gel is unavailable. This study evaluated noncommercial gel recipes compared to commercial gel. A search for US gel formulations revealed 6 recipes. Half-strength commercial gel and a modified glucomannan recipe were also tested. Nine gels, including commercial gel, were tested in Liberia and the United States. In each session, 2 physician sonologists evaluated 9 gels on 2 models, obtaining videos from the hepatorenal space with a curvilinear transducer, the cardiac parasternal long view with a phased array transducer, and the left basilic vein with a linear transducer. The sonologists and models, who were blinded to gel identity, made independent quantitative and qualitative gel evaluations comparing the test gel to commercial gel. Two physician sonologists who were blinded to the gel identities and a US operator reviewed the images and rated their quality. An analysis of variance in repeated measures was performed to test for differences in the overall score, real-time quality, and other characteristics. Post hoc pairwise comparisons to commercial gel were performed with a Tukey-Kramer adjustment. Inter- and intra-rater reliability was calculated for the image review. Commercial gel earned a perfect score. Compared to commercial gel, xanthine gum gel scored highest, followed by half-strength commercial gel. Hot concentrated glucomannan and cold glucomannan gel were found to be significantly worse than commercial gel. No significant difference was found between images based on the gel used on the image review. No significant difference in image quality was found between commercial and noncommercial gels on US image review.

Investigation of Temperature Dependence of Polymer Gels for Use with Scanning Magnetic Resonance Imaging

Polymer gels are three-dimensional dosimetric tools. The purpose of the present study was to investigate the temperature dependence of polymer gels during scanning Magnetic Resonance Imaging. Prepared gels were irradiated with a 6MV X-ray beam at intensities ranging from 0 to 20 Gy in order to investigate their dose-R2 and dose-R1 responses. Irradiated gels were evaluated from 1.5-T magnetic resonance R2 and R1 images for each 5°C change in temperature from 5°C to 41°C, and then the four-field box technique irradiation plan was used to deliver a total dose of 4 Gy using the same beam weight in each direction to the prepared gels. The profile of the dose map generated from the four-field irradiated gel data at 20°C was then compared with the planned data. The dose-R2 response curve was linear up to 20 Gy at 20°C, with a slope of 1.17 Gy-1&dot;s-1. The slopes of the fitted curves of the dose-R2 decreased as gel temperature increased. The slopes of the dose-R1 curves were more parallel than the slopes of the dose-R2 curves between 5 and 41°C. The difference in the full width of half maximum of the gel profile data obtained using the four-field box technique at 20°C and the planned data were below 5% on average. The dose map from the irradiated gels obtained using the dose-R2 curve was the same as that from the planned data under the same temperature conditions. Measurement of difference between various temperatures is significant with dose accuracy. It is suitable to evaluate the gel dosimeter under the thermal equilibrium condition, MRI room temperature from the point of view of the stability of the irradiated gels.

Self-Healable Gels for Use in Wearable Devices

Self-healing gels, which are able to restore their original shape/condition after damage, have recently attracted considerable interest. The present review provides an update on the current status of self-healing gels for use in soft self-healing devices, with the main focus on wearable devices. Following a brief introduction of conventional self-healing gels, this review summarizes the current strategies for synthesizing self-healing gels, comparing the properties of polymeric and small molecular self-healing gels. Some of the strengths and weaknesses of these two types of self-healing gels are clearly highlighted. Several typical instances to outline the emerging applications of self-healing gels with partially or fully self-healing devices/materials, including wearable sensors, supercapacitors, lithium batteries, and coatings, are provided. Finally, the current challenges and future perspectives regarding the further development of self-healing gels are also discussed.

Evaluation of microencapsulation of the UFV-AREG1 bacteriophage in alginate-Ca microcapsules using microfluidic devices

The indiscriminate use of antibiotics and the emergence of resistant microorganisms have become a major challenge for the food industry. The purpose of this work was to microencapsulate the bacteriophage UFV-AREG1 in a calcium alginate matrix using microfluidic devices and to study the viability and efficiency of retention. The microcapsules were added to gel of propylene glycol for use as an antimicrobial in the food industry. The technique showed the number of the phage encapsulation, yielding drops with an average 100–250μm of diameter, 82.1±2% retention efficiency and stability in the gel matrix for 21days. The gel added to the microencapsulated phage showed efficiency (not detectable on the surface) in reducing bacterial contamination on the surface at a similar level to antimicrobial chemicals (alcohol 70%). Therefore, it was possible to microencapsulate bacteriophages in alginate-Ca and apply the microcapsules in gels for use as sanitizers in the food industry.

Characterization of Water-Clear Polymeric Gels for Use as Radiotherapy Bolus

Our purpose was to investigate polymeric gels for use as a highly transparent radiotherapy bolus and determine the relevant physical and dosimetric properties. We first quantified tensile properties (maximum stress, strain, and Young modulus) for various polymeric gels, along with a commercial bolus product in order to illustrate the wide variety of potential materials. For a select polymeric gel with tensile properties similar to currently used radiotherapy bolus, we also evaluated mass and electron density, effective atomic number, optical transparency, and percent depth dose in clinical megavoltage photon and electron beams. For this polymeric gel, mass density was 872 ± 12 and 896 ± 13 g/cm3 when measured via weight/volume and computed tomography Hounsfield units, respectively. Electron density was 2.95 ± 0.04 ×1023 electrons/cm3. Adding fused silica (9% by weight) increases density to that of water. The ratio of the effective atomic number to that of water without and with added silica was 0.780 and 0.835 at 1 MeV, 0.767 and 0.826 at 6 MeV, and 0.746 and 0.809 at 20 MeV. Percent depth dose for 6 MV photons was within 2% of water within the first 2.5 cm and after scaling by the density coincided within 1% out to >7 cm. For 6 and 20 MeV electrons, after scaling for density D80% was within 1.3 and 1.5 mm of water, respectively. The high transparency and mechanical flexibility of polymeric gels indicate potential for use as a radiotherapy bolus; differences in density from water may be managed via either using “water equivalent thickness” or by incorporating fused silica into the material.

Biomimetic sulphated alginate hydrogels suppress IL-1β-induced inflammatory responses in human chondrocytes.

Loss of articular cartilage from ageing, injury or degenerative disease is commonly associated with inflammation, causing pain and accelerating degradation of the cartilage matrix. Sulphated glycosaminoglycans (GAGs) are involved in the regulation of immune responses in vivo, and analogous polysaccharides are currently being evaluated for tissue engineering matrices to form a biomimetic environment promoting tissue growth while suppressing inflammatory and catabolic activities. Here, we characterise physical properties of sulphated alginate (S-Alg) gels for use in cartilage engineering scaffolds, and study their anti-inflammatory effects on encapsulated chondrocytes stimulated with IL-1β. Sulphation resulted in decreased storage modulus and increased swelling of alginate gels, whereas mixing highly sulphated alginate with unmodified alginate resulted in improved mechanical properties compared to gels from pure S-Alg. S-Alg gels showed extensive anti-inflammatory and anti-catabolic effects on encapsulated chondrocytes induced by IL-1β. Cytokine-stimulated gene expression of pro-inflammatory markers IL-6, IL-8, COX-2 and aggrecanase ADAMTS-5 were significantly lower in the sulphated gels compared to unmodified alginate gels. Moreover, sulphation of the microenvironment suppressed the protein expression of COX-2 and NF-κB as well as the activation of NF-κB and p38-MAPK. The sulphated alginate matrices were found to interact with IL-1β, and proposed to inhibit inflammatory induction by sequestering cytokines from their receptors. This study shows promising potential for sulphated alginates in biomimetic tissue engineering scaffolds, by reducing cytokine-mediated inflammation and providing a protective microenvironment for encapsulated cells.

Emulsification properties of pea protein isolate using homogenization, microfluidization and ultrasonication

Pea protein isolate (PPI) is used in many food formulations, due to its low cost, commercial availability and excellent amino acid profile. The objective of this study was to determine the emulsification properties of PPI. Particle size of PPI powders showed neither temperature (25–65°C) nor time (up to 24h) increased solubilisation of powder particles during mixing. Heating PPI dispersions (10%, w/w, protein) from 45 to 90°C led to an increase in storage modulus (G′; Pa) at 71°C, indicating the onset of protein aggregation. Gel formation occurred at 79°C (G′>1Pa). Pea protein-stabilised emulsions made using homogenization (15MPa; 1 pass) or microfluidization (50MPa; 1 pass) resulted in the formation of cold-set gels, with gel strength increasing with increasing oil concentration and fluidic pressure. Droplet size and viscosity of pea protein-stabilised emulsions decreased and increased, respectively, with increasing ultrasonication time. Overall, ultrasonication (<50°C) can create a uniform droplet size emulsion, while, homogenization and microfluidization can produce cold-set gels for use in a wide-range of food applications.

Evaluation of the percutaneous absorption of chlorpromazine from PLO gels across porcine ear and human abdominal skin

ABSTRACTObjective: The overall objective of this work is to determine the percutaneous absorption of chlorpromazine hydrochloride from pluronic lecithin organogels (PLO gels) and verify the suitability of topically applied chlorpromazine hydrochloride PLO gels for use in hospice patients for relieving symptoms such as vomiting and nausea during the end stages of life.Methods: PLO gels of chlorpromazine hydrochloride were prepared using isopropyl palmitate (IPP) or ricinoleic acid (RA) as oil phase. In vitro percutaneous absorption of chlorpromazine hydrochloride was assessed through porcine ear and human abdominal skin. Further, the theoretical steady state plasma concentration (Css) of chlorpromazine was calculated from the flux values.Results: The pH, viscosity, and stability of both PLO gels prepared with IPP and RA were comparable. The thixotropic property of RA PLO gel was found to be better than that of IPP PLO gel. The permeation of chlorpromazine hydrochloride was higher from RA PLO gel than from IPP PLO gel and pure drug solution. Theoretical Css of chlorpromazine from pure drug solution, IPP PLO gel and RA PLO gel were found to be 1.05, 1.20, and 1.50 ng/ml, respectively. PLO gels only marginally increased the flux and theoretical Css of chlorpromazine.Conclusion: From this study, it is clearly evident that PLO gels fail to achieve required systemic levels of chlorpromazine following topical application. Chlorpromazine PLO gel may not be effective in treating nausea and vomiting for hospice patients with swallowing difficulties.

Development of diclofenac potassium gel from hydrophobically modified HPMC

An improved topical gel was developed which could allow fast release of drug and having appropriate organoleptic (texture) and rheological properties (viscosity). In vitro release of diclofenac potassium from hydrophobically modified hydroxypropyl methyl cellulose (hm-HPMC, 90L grade) based gels (F1, F2 and F3 at 1, 1.5 and 2 % (w/v) concentration, respectively) was compared with conventional hydrophilic hydroxypropyl methylcellulose (HPMC, 50 mPa s) based gels (F4 and F5 at 12 and 15 % (w/v) concentration, respectively). This study was performed in Franz diffusion cell using cellulose dialysis membrane. The hm-HPMC-based gels of higher viscosity release remarkable quantity of the drug in comparison to conventional hydrophilic HPMC-based gels of lower viscosity. So in the drug-release process polymer concentration is more important and a determinant factor compared to viscosity. Texture profile and viscosity of hm-HPMC-based gels were compared with a commercial gel and all the rheological data obtained from the experiments confirm the suitability of these hm-HPMC-based gels for use as a topical drug delivery system. In order to achieve percutaneous penetration of drug, permeation enhancers (n-octanol and propylene glycol) were added in hm-HPMC-based gels. Both enhancers have shown enhancement of drug penetration through rat skin. Propylene glycol at both lower concentration (2 %) and higher concentration (5 %) exhibited a greater increase in the permeation flux as well as more antinociceptive activity than formulations without enhancer or with n-octanol as enhancer.

Design of Tenofovir–UC781 Combination Microbicide Vaginal Gels

Tenofovir (TFV) is a proven microbicide when administered topically as a vaginal gel. To improve its efficacy, TFV was combined with the nonnucleoside reverse-transcriptase inhibitor UC781 in a vaginal gel. Mixture design of experiments theory was used to define a range of gel compositions with varying rheological properties and to assess in vitro drug release and tissue retention. Experiments and computations led to the specification of three different gels referred to as a spreading gel (SG), an intermediate spreading gel (ISG), and a bolus gel (BG). These three gels, all containing 1.0% TFV and 0.1% micronized UC781, were evaluated for in vitro release, in vitro tissue retention and safety, and in vivo pharmacokinetics in the rabbit. There were some differences in in vitro release rates of UC781 (the higher the gel viscosity, the slower the release rate) across gels, while release of TFV was independent of gel type. In an organotypic human vaginal-ectocervical (VEC) tissue model, the amounts of tissue-associated TFV and UC781 were several orders of magnitude higher than their in vitro half-maximal inhibitory concentration. There were no differences in VEC tissue concentrations of TFV or UC781 between the SG, ISG, and BG. All three gels were well tolerated in the VEC model as assessed by tissue viability, electrical resistance, histology, and cytokine (interleukin-8 and interleukin-1 beta) release. The local vaginal tissue concentrations in rabbits following a single dose or seven once-daily doses were variable and generally lower than those found in the VEC tissue model. The approach described herein provides a rational schema to design and evaluate vaginal gels for use as microbicides.

Gelation time, homogeneity, and rupture testing of alginate‐calcium carbonate‐hydrogen peroxide gels for use as wound dressings

The care of chronic wounds carries a heavy financial burden on the healthcare industry, with billons being spent annually on their treatment. This, coupled with a decreased quality of life for sufferers, has led to a real urgency in developing inexpensive wound dressings that promote wound healing. Alginate gels for application as wound dressings were formed by varying alginate (0%-6% w/v), calcium carbonate (0%-1% w/v), hydrogen peroxide (0%-3.75% v/v), and hyaluronic acid (0-1.25 mg/L) content. The aging effects on the physical properties of the gels over a 14-day period were also investigated. The results indicated that the concentration of calcium carbonate and hydrogen peroxide, as well as sample age, all had a significant effect on the rupture characteristics and gelation time of the gels. Increased calcium carbonate content caused an increase in rupture force and rupture energy values, whereas increased hydrogen peroxide content and sample age resulted in a decrease in rupture force and rupture energy measurements. Increased calcium carbonate and hydrogen peroxide content produced a decrease in the time required for gel formation. Statistical models were also produced to provide a means of estimating rupture characteristics and gelation times for gels containing other concentrations of these components.

Effect of alkalis on konjac glucomannan gels for use as potential gelling agents in restructured seafood products

Four dispersions of 3% glucomannan in water, deacetylated with 5% 0.6 N and 1 N KOH (lots L1 and L2) and 0.6 N and 1 N NaOH (lots L3 and L4) as gelling agents, were evaluated for use in raw restructured seafood products. Several properties (pH, moisture content, water binding capacity, cooking loss and lightness) together with puncture data (breaking force and breaking deformation) were determined after 1 and 10 days of chilled storage at 5 °C. All these data were analyzed together with different viscoelastic parameters obtained at small amplitude oscillatory strain (SAOS) after 1 day of chilled storage, showing that L1 and L4 samples were the most suitable gels for incorporation in raw restructured fish products. In both cases the highest stress ( σ max) and strain ( γ max) amplitude values were found in the linear viscoelastic (LVE) range; however, L1 showed both high strain amplitude and breaking deformation values. Moreover, creep and recovery (transient) data showed that L1 was the most time-stable gel with the highest elasticity and the lowest relaxation exponent ( n). L4 gel showed strong rigidity, i.e. the highest values of breaking force and storage moduli ( G′) and the highest n value, making it less gel-like. Both L1 and L4 gels became significantly less gel-like over 10 days of chilled storage due to the loss of gel strength ( S) and a noticeable increase of n. These chilled storage effects were more intense in L4 than in L1.

Flow-manipulated, crosslinked collagen gels for use as corneal equivalents

Our aim was to construct a mechanically stable and optically transparent collagen gel from an acidified atelocollagen solution which is suitable for use as a corneal stromal equivalent. Light transmission and mechanical testing were conducted on variously crosslinked constructs at different pH levels. Ultrastructural analysis was performed to assess directionality of the molecular arrangement produced by flow manipulation, as well as the amount of collagen fibrillogenesis which resulted from different pH and/or crosslinking conditions. Clinical and histological integration of the gels with living tissue was examined following implantation into rabbit corneal intra-stromal pockets. Transmission electron microscopy revealed the importance of the fine control of pH levels during gel formation and indicated that the stage at which collagen fibrillogenesis is halted within the constructs was critically dependent on the pH of the collagen solution. Transparency testing disclosed that high levels of collagen fibrillogenesis, as well as high levels of crosslinker concentration, detrimentally affected the transparency of the construct. As a result, a dual titration was required to achieve good light transmission through the gels. It was also evident that the amount of crosslinking required to gelate the collagen solution was reduced as the level of fibrillogenesis progressed. Thus, it was necessary to establish a balance between the solution pH and crosslinker concentration. Implantation of the collagen constructs into partial depth intra-stromal pockets in rabbits was followed up for 6 months, and demonstrated favourable biocompatibility. This showed that gels which had lower levels of both fibrillogenesis and crosslinking were degraded more readily by the host tissue. The collagen gels described here are mass-production friendly, and have promise as potential functional stromal equivalents for use in stromal grafting, or in constructing full thickness artificial corneas.