TFOS Lifestyle: Impact of contact lenses on the ocular surface.

Several lifestyle choices made by contact lens wearers can have adverse consequences on ocular health. These include being non-adherent to contact lens care, sleeping in lenses, ill-advised purchasing options, not seeing an eyecare professional for regular aftercare visits, wearing lenses when feeling unwell, wearing lenses too soon after various forms of ophthalmic surgery, and wearing lenses when engaged in risky behaviors (e.g., when using tobacco, alcohol or recreational drugs). Those with a pre-existing compromised ocular surface may find that contact lens wear exacerbates ocular disease morbidity. Conversely, contact lenses may have various therapeutic benefits. The coronavirus disease-2019 (COVID-19) pandemic impinged upon the lifestyle of contact lens wearers, introducing challenges such as mask-associated dry eye, contact lens discomfort with increased use of digital devices, inadvertent exposure to hand sanitizers, and reduced use of lenses. Wearing contact lenses in challenging environments, such as in the presence of dust and noxious chemicals, or where there is the possibility of ocular trauma (e.g., sport or working with tools) can be problematic, although in some instances lenses can be protective. Contact lenses can be worn for sport, theatre, at high altitude, driving at night, in the military and in space, and special considerations are required when prescribing in such situations to ensure successful outcomes. A systematic review and meta-analysis, incorporated within the review, identified that the influence of lifestyle factors on soft contact lens dropout remains poorly understood, and is an area in need of further research. Overall, this report investigated lifestyle-related choices made by clinicians and contact lens wearers and discovered that when appropriate lifestyle choices are made, contact lens wear can enhance the quality of life of wearers.

Mucoadhesive thermogel platform for treating anterior ocular conditions.

A platform mucoadhesive and thermogelling eyedrop was developed for application to the inferior fornix for the treatment of various anterior segment ocular conditions. The poly(n-isopropylacrylamide) polymers (pNIPAAm), containing a disulfide bridging monomer, were crosslinked with chitosan to yield a modifiable, mucoadhesive, and natively degradable thermogelling system. Three different conjugates were studied including a small molecule for treating dry eye, an adhesion peptide for modeling delivery of peptides/proteins to the anterior eye, and a material property modifier to create gels with different rheologic characteristics. Based on the conjugate used, different material properties such as solution viscosity and lower critical solution temperature (LCST) were produced. In addition to releasing the conjugates through disulfide bridging with ocular mucin, the thermogels were shown to deliver atropine, with 70%-90% being released over 24-h, depending on the formulation studied. The results illustrate that these materials can deliver multiple therapeutic payloads at one time and release them through various mechanisms. Finally, the safety and tolerability of the thermogels was demonstrated both in vitro and in vivo. The gels were instilled into the inferior fornix of rabbits and were shown to not produce any adverse effects over 4 days. These materials were demonstrated to be highly tunable, creating a platform that could be easily modified to deliver various therapeutic agents to treat a multitude of ocular diseases and have the potential to be an alternative to conventional eyedrops.

Thermo-responsive and mucoadhesive gels for the treatment of cystinosis.

Mucoadhesive thermogels were developed by crosslinking poly(n-isopropylacrylamide) based polymers with chitosan and incorporating disulfide bridges, capable of releasing cysteamine upon interaction with mucin, for the treatment of cystinosis. Through crosslinking with chitosan and incorporating varying concentrations of the disulfide monomer into the polymer backbone, the extent of how mucoadhesive the developed thermogels were could be controlled. Through disulfide bridging with mucin, the thermogels released 6 to 10 µg of the conjugate model 2-mercaptopyridine over five days. Utilizing chitosan as the crosslinker, the developed thermogels were shown to degrade to a statistically higher extent following incubation with lysozyme, the highest concentration tear enzyme, by gravimetric and rheologic analysis. The developed thermogels were extensively tested in vivo utilizing a rat model in which materials were applied directly to the corneal surface and a rabbit model in which thermogels were applied to the inferior fornix. With the developed models, there was no adverse reactions or visual discomfort incurred following application of the thermogels. It has been demonstrated that the thermogels produced can be applied to the inferior fornix and release the stable conjugated payload over several days. The developed thermogel was designed to improve upon the current clinical treatment options for ocular cystinosis which are acidic topical formulations that require reapplication multiple times a day.

Delivery of Cells to the Cornea Using Synthetic Biomaterials.

ABSTRACT: The cornea is subject to a myriad of ocular conditions often attributed to cell loss or cell dysfunction. Owing to the superficial positioning of tissues composing the anterior segment of the eye, particularly the cornea, regenerative medicine in this region is aided by accessibility as compared with the invasive delivery methods required to reach deep ocular tissues. As such, cell therapies employing the use of carrier substrates have been widely explored. This review covers recent advances made in the delivery of stem cells, corneal epithelial cells, and corneal endothelial cells. Particular focus is placed on the most popular forms of synthetic scaffolds currently being examined: contact lenses, electrospun substrates, polymeric films, and hydrogels.

Phenylboronic acid modified hydrogel materials and their potential for use in contact lens based drug delivery.

The use of hydrogel-based contact lens materials holds promise for ophthalmic drug delivery by increasing drug residence time, improving drug bioavailability, reducing administration frequency, and enhancing special site targeting. Issues such as ease of manufacturing, lens comfort and appropriate release kinetics must be considered. Furthermore, the high water content of hydrogel materials can result in rapid and poorly controlled release kinetics. Herein, we modified common hydrogels used in contact lens manufacturing with phenylboronic acid (PBA). PBA addresses these material design issues since boronate esters are easily formed when boron acid and diols interact, opening up a pathway for simple modification of the model lens materials with saccharide based wetting agents. The wetting agents have the potential to improve lens comfort. Furthermore, the hydrophobicity of PBA and the presence of diols can be useful to help control drug release kinetics. In this work, polymerizable 3-(acrylamido)phenylboronic acid (APBA) was synthesized and incorporated into various hydrogels used in contact lens applications, including poly(2-hydroxyethylmethacrylate) (PHEMA), polyvinylpyrrolidone (PVP) and poly(N,N-dimethyl acrylamide) (PDMA) using UV induced free radical polymerization. The APBA structure and its incorporation into the hydrogel materials were confirmed by NMR and FTIR. The materials were shown to interact with and bind wetting agents such as hyaluronan (HA) and hydroxypropyl guar (HPG) by simple soaking in an aqueous solution. The equilibrium water content of the modified materials was characterized, demonstrating that most materials are still in the appropriate range after the introduction of the hydrophobic PBA. The release of three model ophthalmic drugs with varying hydrophilicity, atropine, atropine sulfate and dexamethasone, was examined. The presence of PBA in the materials was found to promote sustained drug release due to its hydrophobic nature. The results suggest that the modification of the materials with PBA was able to not only provide a mucoadhesive property that enhanced wetting agent interactions with the materials, but had the potential to alter drug release. Thus, the modification of contact lens materials with mucoadhesive functionality may be useful in the design of hydrogel contact lenses for ophthalmic drug release and wetting agent binding.

A Radiolabeling Method for Precise Quantification of Polymers.

Radiolabeling a protein, molecule, or polymer can provide accurate and precise quantification in biochemistry, biomaterials, pharmacology, and drug delivery research. Herein, we describe a method to 125I label two different polymers for precise quantification in different applications. The surfaces of model contact lenses were modified with phenylboronic acid to bind and release the natural polymer, hyaluronic acid (HA); HA uptake and release were quantified by radiolabeling. In the second example, the in vivo distribution of a mucoadhesive micelle composed of the block copolymer of poly(lactide)-b-poly(methacrylic acid-co-acrylamidophenylboronic acid) was investigated. The presence of phenyl boronic acid groups (PBA), which bind to mucosal surfaces, was proposed to improve the retention of the micelle. 125I labeling of polymers was examined for quantification of microgram amounts of HA present on a contact lens or to evaluate the enhanced retention of PBA micelles on mucosal surfaces in vivo. The introduction of phenol groups onto the polymers allowed for the labeling. HA was modified with phenol groups through a coupling reaction of its carboxylic acid with hydroxybenzylamine. Phenol functional block copolymer micelles with and without PBA were synthesized by including N-(4-hydroxyphenethyl)acrylamide during polymerization. The phenol groups of HA and the block copolymers were labeled with 125I using a modified ICl labeling method. 125I labeling enabled quantification of HA loading and release including the effect of varying amounts of PBA on the contact lens surfaces. Micelles made from 125I-labeled block copolymers with and without PBA were administered intranasally to Brown Norway rats. The animals were sacrificed either immediately after or 4 h after their last nasal instillation, and the nasopharyngeal tissues were removed and quantified. Radioactivity measurements demonstrated that the presence of the PBA mucosal binding groups led to approximately four times higher retention. The HA and block copolymer 125I labeling presented in this article demonstrates the utility of the method for quantification and tracking of microgram quantities of polymers in diverse applications.

Thermo-sensitivity and erosion of chitosan crosslinked poly[N-isopropylacrylamide-co-(acrylic acid)-co-(methyl methacrylate)] hydrogels for application to the inferior fornix.

Thermo-gels based on chitosan crosslinked poly(N-isopropylacrylamide) were developed as alternatives to conventional eye drops for the sustained release of ketotifen fumarate in the treatment of allergic conjunctivitis. The thermo-gelling properties of the base polymer were altered prior to crosslinking with chitosan by incorporation of the hydrophilic and hydrophobic comonomers acrylic acid and methyl methacrylate respectively. Varying amounts of chitosan were incorporated by ionic interaction to produce polyelectrolyte complexes or by carbodiimide chemistry to produce covalently crosslinked networks. The lower critical solution temperature of all the chitosan crosslinked thermo-gels produced was below the surface temperature of the eye. All the chitosan crosslinked thermo-gels were found to have greater than 80% equilibrium water contents following gelation. The method and amount of chitosan incorporation allowed for tailor-ability of material rheologic properties, with full degradation occurring over a one-to-four-day period, and tailorable rates of release of 40-60% of the loaded allergy medication ketotifen fumarate. The chitosan crosslinked thermo-gels were demonstrated to be nontoxic both in vitro and in vivo. It was demonstrated that the synthesized materials could be applied to the inferior fornix of eye, sustaining a multiple day release of ketotifen fumarate, as an alternative to conventional eyedrops. STATEMENT OF SIGNIFICANCE: Topical eyedrops are the main treatment modality for anterior ocular conditions. However, due to the natural clearance mechanisms of the eye, topical eyedrops are well established to be largely ineffective as a method of drug delivery. Herein, we investigate a method of altering thermo-gel properties of an n-isopropylacrylamide based polymer to enable the incorporation of greater amounts of chitosan by different methods of crosslinking. By controlling the synthesis parameters, final material properties can be tailored to impart ideal spreading, retention on the eye, and the rate of degradation and drug release over several days. This work also focuses on studying the rheological properties of the chitosan crosslinked thermo-gels which has not been investigated previously.

Deletion of transcription factor AP-2ß from the developing murine trabecular meshwork region leads to progressive glaucomatous changes.

Glaucoma is one of the leading causes of irreversible blindness and can result from abnormalities in anterior segment structures required for aqueous humor outflow, including the trabecular meshwork (TM) and Schlemm's canal (SC). Transcription factors such as AP-2ß play critical roles in anterior segment development. Here, we show that the Mgp-Cre knock-in (Mgp-Cre.KI) mouse can be used to target the embryonic periocular mesenchyme giving rise to the TM and SC. Fate mapping of male and female mice indicates that AP-2ß loss causes a decrease in iridocorneal angle cells derived from Mgp-Cre.KI-expressing populations compared to controls. Moreover, histological analyses revealed peripheral iridocorneal adhesions in AP-2ß mutants that were accompanied by a decrease in expression of TM and SC markers, as observed using immunohistochemistry. In addition, rebound tonometry showed significantly higher intraocular pressure (IOP) that was correlated with a progressive significant loss of retinal ganglion cells, reduced retinal thickness, and reduced retinal function, as measured using an electroretinogram, in AP-2ß mutants compared with controls, reflecting pathology described in late-stage glaucoma patients. Importantly, elevated IOP in AP-2ß mutants was significantly reduced by treatment with latanoprost, a prostaglandin analog that increases unconventional outflow. These findings demonstrate that AP-2ß is critical for TM and SC development, and that these mutant mice can serve as a model for understanding and treating progressive human primary angle-closure glaucoma.

Ocular drug delivery to the anterior segment using nanocarriers: A mucoadhesive/mucopenetrative perspective.

There is a growing demand for effective treatments for ocular conditions that improve patient compliance and reduce side-effects. While methods such as implants and injections have proven effective, topical administration remains the method of choice for the delivery of therapeutics to the anterior segment of the eye. However, topical administration suffers from multiple drawbacks including low bioavailability of the target therapeutic, systemic toxicity, and the requirement for high therapeutic doses due to the effective clearance mechanisms that exist in the eye. Nanoparticles that have tunable mucoadhesion and/or mucopenetration offer outstanding potential to overcome the anatomical and physiological barriers present to improve ocular bioavailability, reduce toxicity, and increase ocular retention, among other benefits. The current review highlights recent advances in the field of developing nanocarriers with tunable mucoadhesion and mucopenetration for drug delivery to the eye.

Polymer-free corticosteroid dimer implants for controlled and sustained drug delivery.

Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients. These implants undergo surface erosion, achieving tightly controlled and reproducible drug release kinetics in vitro. As an example, when used as ocular implants in rats, a dexamethasone dimer implant is shown to effectively inhibit inflammation induced by lipopolysaccharide. In a rabbit model, dexamethasone dimer intravitreal implants demonstrate predictable pharmacokinetics and significantly extend drug release duration and efficacy (>6 months) compared to a leading commercial polymeric dexamethasone-releasing implant.

Property modelling of lysozyme-crosslinker-alginate complexes using latent variable methods.

Statistical methods were used to provide insight into a polymer complex system composed of lysozyme and alginate to quantify the effects of such parameters as pH, and ionic composition of the mixing solution on the properties of the complexes including composition, particle diameter, and zeta potential. Various crosslinkers (calcium, barium, iron[III], and bovine serum albumin), were used with lysozyme for complex formation to investigate the effect of crosslinker charge density on protein release kinetics, modelled using ktn . Multivariate statistical analysis showed that the kinetic parameters associated with the release were, not surprisingly highly dependent on the ionic strength of the release media, with higher ionic strength leading to faster release. The release parameter k was also shown to depend on the protein properties (size, ionic strength) while n was slightly, but not statistically dependent on the charge density of the crosslinker demonstrating that the nature of the crosslinker had minimal impact on drug release. The multivariate statistical has the potential to be used for optimization of the complexes and prediction of physical properties and degradation rates.

Fast Thermoresponsive Poly(oligoethylene glycol methacrylate) (POEGMA)-Based Nanostructured Hydrogels for Reversible Tuning of Cell Interactions.

Reactive electrospinning is demonstrated as a viable method to create fast-responsive and degradable macroporous thermoresponsive hydrogels based on poly(oligoethylene glycol methacrylate) (POEGMA). Hydrazide- and aldehyde-functionalized POEGMA precursor polymers were coelectrospun to create hydrazone cross-linked nanostructured hydrogels in a single processing step that avoids the need for porogens, phase separation-driving additives, or scaffold postprocessing. The resulting nanostructured hydrogels can respond reversibly and repeatedly to changes in external temperature within seconds, in contrast to the minutes-to-hours response time observed with bulk hydrogels. Furthermore, nearly quantitative cell delamination can be achieved within 2 min of incubation at 4 °C, resulting in the recovery of as many or more (as well as more proliferatively active) cells from the substrate relative to the conventional trypsinization protocol. The combined macroporosity, nanoscale feature size, and interfacial switching potential of these nanostructured hydrogels thus offer promise for manipulating cell-hydrogel interactions as well as other applications in which rapid responses to external stimuli are desirable.

Investigating the Synergistic Interactions of Surface Immobilized and Free Natural Ocular Lubricants for Contact Lens Applications: A Comparative Study between Hyaluronic Acid and Proteoglycan 4 (Lubricin).

The main reasons for the discontinuation of contact lens wear are ocular dryness and discomfort. Proteoglycan 4 (PRG4), a mucinous glycoprotein, and hyaluronic acid (HA), a nonsulfated linear glycosaminoglycan, are naturally present in the eye and contribute to ocular hydration and lubrication. This study aimed to investigate the impact of the structure of the recombinant human PRG4 (rhPRG4)/HA complex on contact lens properties, when one agent is grafted and the counterpart is physisorbed on the surface of model conventional or silicone contact lens materials. Investigation of the wettability, water retention, antifouling, and boundary lubricant properties of the prepared hydrogels showed that the rhPRG4/HA interactions varied with the rhPRG/HA configuration on the hydrogel surface as well as the composition of the underlying substrate used. The rhPRG4-physisorbed/HA-grafted sample was characterized by better antifouling and boundary lubricant properties on the model conventional hydrogels, while the HA-physisorbed/rhPRG4-grafted sample exhibited improved surface wettability, antifouling, and water-retentive properties on the model silicone hydrogels. The results of this study contribute to the design of biomimetic contact lens surfaces that work synergistically with ocular fluid-phase biological agents to enhance compatibility between the contact lens and the ocular environment, alleviating dry eye symptoms and improving comfort.

New soluble angiopoietin analog of Hepta-ANG1 prevents pathological vascular leakage.

Vascular leak is a key driver of organ injury in diseases, and strategies that reduce enhanced permeability and vascular inflammation are promising therapeutic targets. Activation of the angiopoietin-1 (ANG1)-Tie2 tyrosine kinase signaling pathway is an important regulator of vascular quiescence. Here we describe the design and construction of a new soluble ANG1 mimetic that is a potent activator of endothelial Tie2 in vitro and in vivo. Using a chimeric fusion strategy, we replaced the extracellular matrix (ECM) binding and oligomerization domain of ANG1 with a heptameric scaffold derived from the C-terminus of serum complement protein C4-binding protein α. We refer to this new fusion protein biologic as Hepta-ANG1, which forms a stable heptamer and induces Tie2 phosphorylation in cultured cells, and in the lung following intravenous injection of mice. Injection of Hepta-ANG1 ameliorates vascular endothelial growth factor- and lipopolysaccharide-induced vascular leakage, in keeping with the known functions of Angpt1-Tie2 in maintaining quiescent vascular stability. The new Hepta-ANG1 fusion is easy to produce and displays remarkable stability with high multimericity that can potently activate Tie2. It could be a new candidate ANG1 mimetic therapy for treatments of inflammatory vascular leak, such as acute respiratory distress syndrome and sepsis.

Block copolymer synthesis using free-radical polymerization and thiol-maleimide 'click' conjugation.

A method of making block copolymers utilizing free-radical polymerization and subsequent polymer conjugation is described. A disulphide functional radical initiator was used to polymerize methacrylic acid and 3-acrylamidophenylboronic acid. After purification, the disulphide bond of the end group was cleaved, revealing a thiol group which was used for subsequent conjugation to a polylactide containing the complementary maleimide functional group. The method is versatile and can be applied to the synthesis of various block copolymers without requiring the use of controlled/living radical polymerization methods.

PEG-containing siloxane materials by metal-free click-chemistry for ocular drug delivery applications.

Metal-free click-chemistry can be used to create silicone hydrogels for ocular drug delivery applications, imparting the benefits of silicones without catalyst contamination. Previous work has demonstrated the capacity for these materials to significantly reduce protein adsorption. Building upon this success, the current work examines and optimizes different materials in terms of their protein adsorption and drug release capabilities. Specifically, incorporating lower molecular weight poly-ethylene glycol (PEG) is better able to reduce protein adsorption. However, with higher molecular weight PEG, the materials exhibit excellent water content and better drug release profiles. The lower molecular weight PEG is also able to deliver the drug over a period in excess of four months, with the amount of crosslinking having the greatest impact on the amount of drug release. Overall, these materials show great promise for ocular applications.

Antifouling silicone hydrogel contact lenses via densely grafted phosphorylcholine polymers.

Silicone hydrogel contact lenses (CLs) permit increased oxygen permeability through their incorporation of siloxane functional groups. However, contact lens biofouling can be problematic with these materials; surface modification to increase lens compatibility is necessary for acceptable properties. This work focuses on the creation of an antifouling CL surface through a novel grafting method. A polymer incorporating 2-methacryloyloxyethyl phosphorylcholine (MPC), well known for its antifouling and biomimetic properties, was grafted to the model lens surfaces using surface-initiated atom transfer radical polymerization (SI-ATRP). The SI-ATRP modification generated a unique double-grafted polymeric architecture designed to resist protein adsorption through the presence of a surrounding hydration layer due to the PC groups and steric repulsion due to the density of the grafted chains. The polymer was grafted from model silicone hydrogel CL using a four-step SI-ATRP process. Attenuated total reflectance-Fourier transform infrared spectroscopy and XPS were used to confirm the surface chemical composition at each step of the synthesis. Both the surface wettability and equilibrium water content of the materials increased significantly upon polyMPC modification. The surface water contact angle was as low as 16.04 ± 2.37° for polyMPC-50 surfaces; complete wetting (∼0°) was observed for polyMPC-100 surfaces. A decrease in the protein adsorption by as much as 83% (p < 0.000 36) for lysozyme and 73% (p < 0.0076) for bovine serum albumin was observed, with no significant difference between different polyMPC chain lengths. The data demonstrate the potential of this novel modification process for the creation of extremely wettable and superior antifouling surfaces, useful for silicone hydrogel CL surfaces.

Mucoadhesive Nanoparticles for Drug Delivery to the Anterior Eye.

While the use of topical drops for the delivery of drugs to the anterior of the eye is well accepted, it is far from efficient with as little as 5% of the drug instilled on the eye actually reaching the target tissue. The ability to prolong the residence time on the eye is desirable. Based on the acceptability of 2-hydroxyethyl methacrylate based polymers in contact lens applications, the current work focuses on the development of a poly(2-hydroxyethyl methacrylate (HEMA)) nanoparticle system. The particles were modified to allow for degradation and to permit mucoadhesion. Size and morphological analysis of the final polymer products showed that nano-sized, spherical particles were produced. FTIR spectra demonstrated that the nanoparticles comprised poly(HEMA) and that 3-(acrylamido)phenylboronic acid (3AAPBA), as a mucoadhesive, was successfully incorporated. Degradation of nanoparticles containing N,N'-bis(acryloyl)cystamine (BAC) after incubation with DL-dithiothreitol (DTT) was confirmed by a decrease in turbidity and through transmission electron microscopy (TEM). Nanoparticle mucoadhesion was shown through an in-vitro zeta potential analysis.

Nanostructured degradable macroporous hydrogel scaffolds with controllable internal morphologies via reactive electrospinning.

Creating micro/nanostructured hydrogels with tunable morphologies under cell-friendly processing conditions would enable rational engineering of hydrogel scaffolds for targeted biomedical applications. Herein, an all-aqueous single-step reactive electrospinning method is applied to prepare hydrogel networks with controlled morphologies on both the nanoscale and the microscale. Hydrazide and aldehyde-functionalized poly(oligo ethylene glycol methacrylate) (POEGMA) are co-spun from a double barrel syringe together with poly(ethylene oxide) (PEO) as an electrospinning aid. By varying the concentrations and molecular weights of PEO and/or POEGMA, various morphologies from pure fibers to beaded fibers to bead network morphologies with tunable bead sizes can be fabricated, all of which remain monolithically stable in water due to the dynamic covalent crosslinks formed within the gel structure. The rates and magnitudes of swelling, degradation, and mechanics of the resulting scaffolds can be tuned by independently controlling gel morphologies on the nanoscale (i.e. crosslink density within the gel) and the microscale (i.e. the network structure formed), with an atypical independence of swelling relative to the mechanics and degradation rate observed. Furthermore, the internal morphology of the networks is demonstrated to systematically alter both the cell responses within the scaffolds and the rate of protein release from the scaffolds, with small fibers showing optimal cell proliferation, bead networks exhibiting the slowest protein release kinetics and very high maintained cell viabilities post-electrospinning, and beaded fibers showing intermediate properties. STATEMENT OF SIGNIFICANCE: Controlling the internal structure of hydrogels is critical to successfully applying hydrogels in biomedical applications such as tissue engineering or cell/drug delivery. However, current techniques to fabricate hydrogel scaffolds typically require additives or gelation processes that are poorly compatible with cells and/or require multi-step processes. In this paper, we describe the fabrication of hydrogel scaffolds with tunable feature sizes (from nanometer to micrometer scale) and structures (from all fibers to bead/fiber mixtures to a new "bead network" morphology) using a reactive electrospinning strategy leveraging dynamic hydrazone crosslinking. We show single-step cell/protein loading and systematic control over cell proliferation and protein release kinetics by systematically manipulating the scaffold morphologies and feature sizes, allowing facile customization of scaffold properties for targeted applications.

Altering the release of tobramycin by incorporating poly(ethylene glycol) into model silicone hydrogel contact lens materials.

Delivery of drugs from contact lens materials is attractive for a number of reasons. However, the controlled delivery of hydrophilic drugs can be difficult to achieve due to the burst release of drug that is associated with materials of high water content, such as hydrogels. Silicone hydrogels have significant potential for drug delivery due to their increased hydrophobicity and the tortuous nature of the pores, overcoming some of the limitations associated with conventional hydrogel materials. The aim of this study was to examine the potential of model poly(ethylene glycol) (PEG) containing silicone hydrogels for delivery of hydrophilic aminoglycoside antibiotics. It was hypothesized that PEG, a polymer that has seen extensive use in biomedical applications, will provide in addition to hydrophilicity and protein repulsion, a mechanism for controlling the delivery of this hydrophilic antibiotic. PEG was combined with the macromer TRIS to create the model silicone hydrogel materials. The optical and physical properties of the novel TRIS-co-PEG silicone hydrogels exhibited excellent transparency, appropriate refractive index and high transmittance indicating minimal phase separation. Desirable properties such as wettability and protein repulsion were maintained across a wide range of formulations. The water content was found to be highly correlated with the ethylene oxide content. Drug release could be influenced through PEG content and was found to fit Higuchi-like kinetics. Overall, the study demonstrates that incorporation of PEG into a model silicone hydrogel could be used to control the release of a hydrophilic compound. Data suggests this is related to the unique structure and properties of PEG, which alter the types of water found in each formulation and the water content.