Mucoadhesive hyaluronic acid-based films for vaginal delivery of metronidazole.

Bacterial vaginosis is a prevalent women's health issue that affects millions of women worldwide every year; however, current treatments are often messy, inconvenient, and ineffective. Therefore, we developed a new hyaluronic acid-based film to deliver metronidazole that would be more effective, more convenient, and at a pH similar to that of the normal vaginal environment. Films were made by crosslinking modified hyaluronic acid to create a hydrogel, in which metronidazole or metronidazole benzoate and methylcellulose were incorporated, and the hydrogel was dried to a thin film.

Novel Cross-Linked Ocular Bandage Gel Improves Reepithelialization After Photorefractive Keratectomy: A Randomized, Masked Prospective Study.

To compare, in a masked manner, a novel cross-linked hyaluronic acid ocular bandage gel (OBG) versus standard-of-care bandage contact lens (BCL) plus artificial tears with respect to safety and effectiveness in healing epithelial defects created for photorefractive keratectomy (PRK). This was a randomized, reading center-masked, exploratory study. Forty-five patients (myopic without significant anisometropia) scheduled for bilateral PRK (9-mm epithelial defect) were randomized post-PRK to treatment with OBG 8 times daily for 3 days, followed by 4 times daily for 11 days (Group 1); OBG 4 times daily for 14 days (Group 2); or BCL and artificial tears (Control).

Correction: Effect of Carboxymethylation on the Rheological Properties of Hyaluronan.

[This corrects the article DOI: 10.1371/journal.pone.

Ability of a new crosslinked polymer ocular bandage gel to accelerate reepithelialization after photorefractive keratectomy.

Purpose: To evaluate the safety and performance of a crosslinked thiolated carboxymethyl hyaluronic acid liquid-gel (CMHA-S) ocular bandage gel in accelerating reepithelialization of corneal defects created for photorefractive keratectomy (PRK).

Setting: Three community-based clinical research sites.

Design: Prospective case series.

Ocular translational science: A review of development steps and paths.

Developing successful drug delivery methods is challenging for any tissue, and the eye is no exception. Translating initial concepts into advanced technologies treating diseases in preclinical models and finally into functional and marketable products for humans can be particularly daunting. While referring to specific ophthalmic companies and products, this review considers key exchanges that lead to successful translation.

Topical Cross-Linked HA-Based Hydrogel Accelerates Closure of Corneal Epithelial Defects and Repair of Stromal Ulceration in Companion Animals.

Purpose: The purpose of this study was to determine the safety of topical ocular administration of a cross-linked, modified hyaluronic acid (xCMHA-S) hydrogel, and its effectiveness in accelerating repair and closure of acute and nonhealing corneal ulcers in companion animals as a veterinary treatment and its utility as a model for therapy in human corneal ulceration.

Methods: Two concentrations of xCMHA-S (0.33% and 0.

Effect of Carboxymethylation on the Rheological Properties of Hyaluronan.

Chemical modifications made to hyaluronan to enable covalent crosslinking to form a hydrogel or to attach other molecules may alter the physical properties as well, which have physiological importance. Here we created carboxymethyl hyaluronan (CMHA) with varied degree of modification and investigated the effect on the viscosity of CMHA solutions. Viscosity decreased initially as modification increased, with a minimum viscosity for about 30-40% modification.

The Effects of a Crosslinked, Modified Hyaluronic Acid (xCMHA-S) Gel on Equine Tendon Healing.

Objective: To assess the effects of a crosslinked, modified hyaluronic acid (xCMHA-S) gel on equine tendon healing using an in vivo surgical model.

Study Design: In vivo experimental study.

Animals: Adult horses (n = 5).

Single-lumen and multi-lumen poly(ethylene glycol) nerve conduits fabricated by stereolithography for peripheral nerve regeneration in vivo.

Background: The use of nerve conduits to facilitate nerve regrowth after peripheral nerve injury is limited to defects less than 3 cm. The purpose of this study is to determine the capability of novel single and multi-lumen poly(ethylene glycol) (PEG) conduits manufactured by stereolithography to promote peripheral nerve regeneration.

Materials And Methods: Eight Sprague Dawley rats with sharp transection injuries of the sciatic nerve were randomly assigned to receive single-lumen or multi-lumen PEG conduits to bridge a 10-mm gap.

Ophthalmic Uses of a Thiol-Modified Hyaluronan-Based Hydrogel.

Hyaluronic acid (HA, or hyaluronan) is a ubiquitous naturally occurring polysaccharide that plays a role in virtually all tissues in vertebrate organisms. HA-based hydrogels have wound-healing properties, support cell delivery, and can deliver drugs locally. A few HA hydrogels can be customized for composition, physical form, and biomechanical properties.

Efficacy of a crosslinked hyaluronic acid-based hydrogel as a tear film supplement: a masked controlled study.

Keratoconjunctivitis sicca (KCS), or dry eye, is a significant medical problem in both humans and dogs. Treating KCS often requires the daily application of more than one type of eye drop in order to both stimulate tear prodcution and provide a tear supplement to increase hydration and lubrication. A previous study demonstrated the potential for a crosslinked hyaluronic acid-based hydrogel (xCMHA-S) to reduce the clinical signs associated with KCS in dogs while using a reduced dosing regimen of only twice-daily administration.

A Crosslinked HA-Based Hydrogel Ameliorates Dry Eye Symptoms in Dogs.

Keratoconjunctivitis sicca, commonly referred to as dry eye or KCS, can affect both humans and dogs. The standard of care in treating KCS typically includes daily administration of eye drops to either stimulate tear production or to hydrate and lubricate the corneal surface. Lubricating eye drops are often applied four to six times daily for the life of the patient.

Nasal continuous positive airway pressure: a multisite study of suctioning practices within NICUs.

Purpose: The purpose of this multisite study was to describe suctioning techniques of registered nurses (RNs) and respiratory therapists (RTs) caring for neonates requiring nasal continuous positive airway pressure (CPAP). The care practices investigated included suctioning frequency, assessment parameters, and techniques used to suction.

Subjects: A convenience sample of neonatal intensive care unit (NICU) RNs and practicing RTs at 8 Midwestern hospitals in the United States caring for neonates on nasal CPAP in a level II or III NICU were included.

Formulation Changes Affect Material Properties and Cell Behavior in HA-Based Hydrogels.

To develop and optimize new scaffold materials for tissue engineering applications, it is important to understand how changes to the scaffold affect the cells that will interact with that scaffold. In this study, we used a hyaluronic acid- (HA-) based hydrogel as a synthetic extracellular matrix, containing modified HA (CMHA-S), modified gelatin (Gtn-S), and a crosslinker (PEGda). By varying the concentrations of these components, we were able to change the gelation time, enzymatic degradation, and compressive modulus of the hydrogel.

Comparing predictive drug nephrotoxicity biomarkers in kidney 3-D primary organoid culture and immortalized cell lines.

The cellular microenvironment is recognized to play a key role in stabilizing cell differentiation states and phenotypes in culture. This study addresses the hypothesis that preservation of in vivo-like tissue architecture in vitro produces a cell culture more capable of responding to environmental stimuli with clinically relevant toxicity biomarkers. This was achieved using kidney proximal tubules in three-dimensional organoid hydrogel culture, with comparisons to conventional monolayer kidney cell cultures on plastic.

A 3-D organoid kidney culture model engineered for high-throughput nephrotoxicity assays.

Cell-cell and cell-matrix interactions control cell phenotypes and functions in vivo. Maintaining these interactions in vitro is essential to both produce and retain cultured cell fidelity to normal phenotype and function in the context of drug efficacy and toxicity screening. Two-dimensional (2-D) cultures on culture plastics rarely recapitulate any of these desired conditions.

A critical evaluation of in vitro cell culture models for high-throughput drug screening and toxicity.

Drug candidate and toxicity screening processes currently rely on results from early-stage in vitro cell-based assays expected to faithfully represent essential aspects of in vivo pharmacology and toxicology. Several in vitro designs are optimized for high throughput to benefit screening efficiencies, allowing the entire libraries of potential pharmacologically relevant or possible toxin molecules to be screened for different types of cell signals relevant to tissue damage or to therapeutic goals. Creative approaches to multiplexed cell-based assay designs that select specific cell types, signaling pathways and reporters are routine.

Thiolated carboxymethyl-hyaluronic-Acid-based biomaterials enhance wound healing in rats, dogs, and horses.

The progression of wound healing is a complicated but well-known process involving many factors, yet there are few products on the market that enhance and accelerate wound healing. This is particularly problematic in veterinary medicine where multiple species must be treated and large animals heal slower, oftentimes with complicating factors such as the development of exuberant granulation tissue. In this study a crosslinked-hyaluronic-acid (HA-) based biomaterial was used to treat wounds on multiple species: rats, dogs, and horses.

Fabrication of Off-the-Shelf Multilumen Poly(Ethylene Glycol) Nerve Guidance Conduits Using Stereolithography.

A manufacturing process for fabricating off-the-shelf multilumen poly(ethylene glycol) (PEG)-based nerve guidance conduits (NGCs) was developed that included the use of stereolithography (SL). A rapid fabrication strategy for complex 3D scaffolds incorporated postprocessing with lyophilization and sterilization to preserve the scaffold, creating an implantable product with improved suturability. SL is easily adaptable to changes in scaffold design, is compatible with various materials and cells, and can be expanded for mass manufacture.

Stereolithography of spatially controlled multi-material bioactive poly(ethylene glycol) scaffolds.

Challenges remain in tissue engineering to control the spatial, mechanical, temporal and biochemical architectures of scaffolds. Unique capabilities of stereolithography (SL) for fabricating multi-material spatially controlled bioactive scaffolds were explored in this work. To accomplish multi-material builds, a mini-vat setup was designed allowing for self-aligning X-Y registration during fabrication.

Mammalian cell-seeded hydrogel microarrays printed via dip-pin technology.

Although significant advances have been made in the development of DNA and protein microarrays, less effort has been put toward developing mammalian cell microarrays. Such cellular microarrays may be useful in examining the effects of biological or chemical agents on cells, particularly in drug development and toxicological applications. Here, mammalian cell-seeded hydrogel microarrays were created using two different commercial microarrayers, with four different pin types.