Predicting the onset of myopia in children by age, sex, and ethnicity: Results from the CLEERE Study.

SIGNIFICANCE: Clinicians and researchers would benefit from being able to predict the onset of myopia for an individual child. This report provides a model for calculating the probability of myopia onset, year-by-year and cumulatively, based on results from the largest, most ethnically diverse study of myopia onset in the United States. PURPOSE: This study aimed to model the probability of the onset of myopia in previously nonmyopic school-aged children. METHODS: Children aged 6 years to less than 14 years of age at baseline participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study who were nonmyopic and less hyperopic than +3.00 D (spherical equivalent) were followed up for 1 to 7 years through eighth grade. Annual measurements included cycloplegic autorefraction, keratometry, ultrasound axial dimensions, and parental report of children's near work and time spent in outdoor and/or sports activities. The onset of myopia was defined as the first visit with at least -0.75 D of myopia in each principal meridian. The predictive model was built using discrete time survival analysis and evaluated with C statistics. RESULTS: The model of the probability of the onset of myopia included cycloplegic spherical equivalent refractive error, the horizontal/vertical component of astigmatism (J0), age, sex, and race/ethnicity. Onset of myopia was more likely with lower amounts of hyperopia and less positive/more negative values of J0. Younger Asian American females had the highest eventual probability of onset, whereas older White males had the lowest. Model performance increased with older baseline age, with C statistics ranging from 0.83 at 6 years of age to 0.92 at 13 years. CONCLUSIONS: The probability of the onset of myopia can be estimated for children in the major racial/ethnic groups within the United States on a year-by-year and cumulative basis up to age 14 years based on a simple set of refractive error and demographic variables.

Human Cell-Derived Matrix Composite Hydrogels with Diverse Composition for Use in Vasculature-on-chip Models.

Microphysiological and organ-on-chip platforms seek to address critical gaps in human disease models and drug development that underlie poor rates of clinical success for novel interventions. While the fabrication technology and model cells used to synthesize organs-on-chip have advanced considerably, most platforms rely on animal-derived or synthetic extracellular matrix as a cell substrate, limiting mimicry of human physiology and precluding use in modeling diseases in which matrix dynamics play a role in pathogenesis. Here, the development of human cell-derived matrix (hCDM) composite hydrogels for use in 3D microphysiologic models of the vasculature is reported. hCDM composite hydrogels are derived from human donor fibroblasts and maintain a complex milieu of basement membrane, proteoglycans, and nonfibrillar matrix components. The use of hCDM composite hydrogels as 2D and 3D cell culture substrates is demonstrated, and hCDM composite hydrogels are patterned to form engineered human microvessels. Interestingly, hCDM composite hydrogels are enriched in proteins associated with vascular morphogenesis as determined by mass spectrometry, and functional analysis demonstrates proangiogenic signatures in human endothelial cells cultured in these hydrogels. In conclusion, this study suggests that human donor-derived hCDM composite hydrogels could address technical gaps in human organs-on-chip development and serve as substrates to promote vascularization.

The association between pupillary responses and axial length in children differs as a function of season.

The association between pupillary responses to repeated stimuli and adult refractive error has been previously demonstrated. This study evaluated whether this association exists in children and if it varies by season. Fifty children aged 8-17 years (average: 11.55 ± 2.75 years, 31 females) with refractive error between + 1.51 and - 5.69 diopters (non-cycloplegic) participated (n = 27 in summer, and n = 23 in winter). The RAPDx pupilometer measured pupil sizes while stimuli oscillated between colored light and dark at 0.1 Hz in three sequences: (1) alternating red and blue, (2) red-only, and (3) blue-only. The primary outcome was the difference in pupillary responses between the blue-only and red-only sequences. Pupillary constriction was greater in response to blue light than to red for those with shorter eyes in summer (ß = - 9.42, P = 0.034) but not in winter (ß = 3.42, P = 0.54). Greater constriction comprised faster pupillary escape following red light onset and slower redilation following stimulus offset of both colors (P = 0.017, 0.036, 0.035 respectively). The association between axial length and children's pupillary responses in summer, but not winter may be explained by greater light-associated release of retinal dopamine in summer. Shorter eyes' more robust responses are consistent with greater light exposure inhibiting axial elongation and reducing myopia risk.

Characterization and biological evaluation of a novel flavonoid-collagen antioxidant hydrogel with cytoprotective properties.

Reactive oxygen species (ROS) play a critical and important role during wound healing but excess ROS at the wound site can lead to cellular damage and sub-optimal healing. Minimizing oxidative damage to the wound site and any supplemental therapeutic cells can be achieved by delivering exogenous antioxidants. Collagen hydrogels are ideal wound care materials due to their biocompatibility, high water content, and porous, three-dimensional architecture. Yet, they lack the inherent antioxidant activity that could help mitigate excess ROS at a wound site. This work formulates and evaluates the in vitro biocompatibility and antioxidant capabilities of collagen-fibroblast hydrogels combined with the polyphenolic antioxidant luteolin. Collagen solutions mixed with luteolin readily assembled into robust hydrogels with increasing gel strength due to increasing concentrations of luteolin. SEM images confirmed a mean pore size of 2.2 µm and a drastically different macromolecular ultrastructure with extensive fine crosslinking relative to collagen. Adequate cell viability and metabolic activity of dermal fibroblasts cultured within the gels were measured across all formulations, resulting in higher antioxidant activity and more than double the protection to cells from oxidative damage than traditional collagen hydrogels. Given these results, luteolin-collagen hydrogels demonstrate the potential for superior wound-healing properties when compared to collagen alone.

Practical Guide to Measuring Wetland Carbon Pools and Fluxes.

Wetlands cover a small portion of the world, but have disproportionate influence on global carbon (C) sequestration, carbon dioxide and methane emissions, and aquatic C fluxes. However, the underlying biogeochemical processes that affect wetland C pools and fluxes are complex and dynamic, making measurements of wetland C challenging. Over decades of research, many observational, experimental, and analytical approaches have been developed to understand and quantify pools and fluxes of wetland C. Sampling approaches range in their representation of wetland C from short to long timeframes and local to landscape spatial scales. This review summarizes common and cutting-edge methodological approaches for quantifying wetland C pools and fluxes. We first define each of the major C pools and fluxes and provide rationale for their importance to wetland C dynamics. For each approach, we clarify what component of wetland C is measured and its spatial and temporal representativeness and constraints. We describe practical considerations for each approach, such as where and when an approach is typically used, who can conduct the measurements (expertise, training requirements), and how approaches are conducted, including considerations on equipment complexity and costs. Finally, we review key covariates and ancillary measurements that enhance the interpretation of findings and facilitate model development. The protocols that we describe to measure soil, water, vegetation, and gases are also relevant for related disciplines such as ecology. Improved quality and consistency of data collection and reporting across studies will help reduce global uncertainties and develop management strategies to use wetlands as nature-based climate solutions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13157-023-01722-2.

CRISPR/Cas9 mutagenesis of the Arabidopsis GROWTH-REGULATING FACTOR (GRF) gene family.

Genome editing in plants typically relies on T-DNA plasmids that are mobilized by Agrobacterium-mediated transformation to deliver the CRISPR/Cas machinery. Here, we introduce a series of CRISPR/Cas9 T-DNA vectors for minimal settings, such as teaching labs. Gene-specific targeting sequences can be inserted as annealed short oligonucleotides in a single straightforward cloning step. Fluorescent markers expressed in mature seeds enable reliable selection of transgenic or transgene-free individuals using a combination of inexpensive LED lamps and colored-glass alternative filters. Testing these tools on the Arabidopsis GROWTH-REGULATING FACTOR (GRF) genes, we were able to create a collection of predicted null mutations in all nine family members with little effort. We then explored the effects of simultaneously targeting two, four and eight GRF genes on the rate of induced mutations at each target locus. In our hands, multiplexing was associated with pronounced disparities: while mutation rates at some loci remained consistently high, mutation rates at other loci dropped dramatically with increasing number of single guide RNA species, thereby preventing a systematic mutagenesis of the family.

Peripheral Defocus, Pupil Size, and Axial Eye Growth in Children Wearing Soft Multifocal Contact Lenses in the BLINK Study.

Purpose: The purpose of this study was to evaluate the relationship between peripheral defocus and pupil size on axial growth in children randomly assigned to wear either single vision contact lenses, +1.50 diopter (D), or +2.50 D addition multifocal contact lenses (MFCLs). Methods: Children 7 to 11 years old with myopia (-0.75 to -5.00 D; spherical component) and ≤1.00 D astigmatism were enrolled. Autorefraction (horizontal meridian; right eye) was measured annually wearing contact lenses centrally and ±20 degrees, ±30 degrees, and ±40 degrees from the line of sight at near and distance. Photopic and mesopic pupil size were measured. The effects of peripheral defocus, treatment group, and pupil size on the 3-year change in axial length were modeled using multiple variables that evaluated defocus across the retina. Results: Although several peripheral defocus variables were associated with slower axial growth with MFCLs, they were either no longer significant or not meaningfully associated with eye growth after the treatment group was included in the model. The treatment group assignment better explained the slower eye growth with +2.50 MFCLs than peripheral defocus. Photopic and mesopic pupil size did not modify eye growth with the +2.50 MFCL (all P ≥ 0.37). Conclusions: The optical signal causing slower axial elongation with +2.50 MFCLs is better explained by the lens type worn than by peripheral defocus. The signal might be something other than peripheral defocus, or there is not a linear dose-response relationship within treatment groups. We found no evidence to support pupil size as a criterion when deciding which myopic children to treat with MFCLs.

Genome-scale phylogeny and comparative genomics of the fungal order Sordariales.

The order Sordariales is taxonomically diverse, and harbours many species with different lifestyles and large economic importance. Despite its importance, a robust genome-scale phylogeny, and associated comparative genomic analysis of the order is lacking. In this study, we examined whole-genome data from 99 Sordariales, including 52 newly sequenced genomes, and seven outgroup taxa. We inferred a comprehensive phylogeny that resolved several contentious relationships amongst families in the order, and cleared-up intrafamily relationships within the Podosporaceae. Extensive comparative genomics showed that genomes from the three largest families in the dataset (Chaetomiaceae, Podosporaceae and Sordariaceae) differ greatly in GC content, genome size, gene number, repeat percentage, evolutionary rate, and genome content affected by repeat-induced point mutations (RIP). All genomic traits showed phylogenetic signal, and ancestral state reconstruction revealed that the variation of the properties stems primarily from within-family evolution. Together, the results provide a thorough framework for understanding genome evolution in this important group of fungi.

Repeated Low-level Red-light Therapy: The Next Wave in Myopia Management?

SIGNIFICANCE: Exposure to long-wavelength light has been proposed as a potential intervention to slow myopia progression in children. This article provides an evidence-based review of the safety and myopia control efficacy of red light and discusses the potential mechanisms by which red light may work to slow childhood myopia progression.The spectral composition of the ambient light in the visual environment has powerful effects on eye growth and refractive development. Studies in mammalian and primate animal models (macaque monkeys and tree shrews) have shown that daily exposure to long-wavelength (red or amber) light promotes slower eye growth and hyperopia development and inhibits myopia induced by form deprivation or minus lens wear. Consistent with these results, several recent randomized controlled clinical trials in Chinese children have demonstrated that exposure to red light for 3 minutes twice a day significantly reduces myopia progression and axial elongation. These findings have collectively provided strong evidence for the potential of using red light as a myopia control intervention in clinical practice. However, several questions remain unanswered. In this article, we review the current evidence on the safety and efficacy of red light as a myopia control intervention, describe potential mechanisms, and discuss some key unresolved issues that require consideration before red light can be broadly translated into myopia control in children.

Quality of life after wearing multifocal contact lenses for myopia control for 2 weeks in the BLINK Study.

PURPOSE: To validate Pediatric Refractive Error Profile 2 (PREP2) subscales that can be used to evaluate contact lens wearers and compare vision-specific quality of life measurements between children wearing multifocal and single vision contact lenses for 2 weeks. METHODS: Two hundred and ninety-four myopic children aged 7-11 years (inclusive) were enrolled in the 3-year, double-masked Bifocal Lenses In Nearsighted Kids (BLINK) Study. Participants completed the PREP2 survey after having worn contact lenses for 2 weeks. The Vision, Symptoms, Activities and Overall PREP2 subscales were used to compare participants' subjective assessment while wearing +1.50 or +2.50 D add multifocal or single vision contact lenses. Rasch analysis was used to validate each subscale and to compare participants' subjective assessment of contact lens wear. RESULTS: Item fit to the Rasch model was good for all scales, with no individual items having infit mean square statistics outside the recommended range (0.7-1.3). Response category function was acceptable for all subscales, with ordered category thresholds. Measurement precision, assessed by the Rasch person reliability statistic, was less than ideal (≥0.8) for three of the subscales, but met the minimum acceptable standard of 0.5. Scores for the Vision subscale differed by treatment assignment (p = 0.03), indicating that participants with the highest add power reported statistically worse quality of vision, although the difference was only 3.9 units on a scale of 1-100. Girls reported fewer symptoms than boys (p = 0.006), but there were no other differences between boys and girls. CONCLUSIONS: Rasch analysis demonstrates that the PREP2 survey is a valid instrument for assessing refractive error-specific quality of life. These results suggest that vision-related quality of life is not meaningfully affected by 2 weeks of soft multifocal contact lens wear for myopia control.

Low-dose intrapulmonary drug delivery device for studies on next-generation therapeutics in mice.

Although nebulizers have been developed for delivery of small molecules in human patients, no tunable device has been purpose-built for targeted delivery of modern large molecule and temperature-sensitive therapeutics to mice. Mice are used most of all species in biomedical research and have the highest number of induced models for human-relevant diseases and transgene models. Regulatory approval of large molecule therapeutics, including antibody therapies and modified RNA highlight the need for quantifiable dose delivery in mice to model human delivery, proof-of-concept studies, efficacy, and dose-response. To this end, we developed and characterized a tunable nebulization system composed of an ultrasonic transducer equipped with a mesh nebulizer fitted with a silicone restrictor plate modification to control the nebulization rate. We have identified the elements of design that influence the most critical factors to targeted delivery to the deep lungs of BALB/c mice. By comparing an in silico model of the mouse lung with experimental data, we were able to optimize and confirm the targeted delivery of over 99% of the initial volume to the deep portions of the mouse lung. The resulting nebulizer system provides targeted lung delivery efficiency far exceeding conventional nebulizers preventing waste of expensive biologics and large molecules during proof-of-concept and pre-clinical experiments involving mice. (Word Count =207).

Accommodation in Children after 4.7 Years of Multifocal Contact Lens Wear in the BLINK Study Randomized Clinical Trial.

SIGNIFICANCE: When worn for myopia control in children, soft multifocal contact lenses with a +2.50 D add reduced the accommodative response over a 3-year period, but wearing them for more than 4 years did not affect accommodative amplitudes, lag, or facility. PURPOSE: This study aimed to compare the accommodative response to a 3D stimulus between single-vision, +1.50-D add, and +2.50-D add multifocal contact lens wearers during 3 years of contact lens wear and then to compare accommodative amplitude, lag, and facility between the three groups after an average of 4.7 years of wear. METHODS: Bifocal Lenses In Nearsighted Kids study participants aged 7 to 11 years old were randomly assigned to wear single-vision, +1.50-D add, or +2.50-D add soft contact lenses (CooperVision, Pleasanton, CA). The accommodative response to a 3D stimulus was measured at baseline and annually for 3 years. After 4.7 years, we measured objective accommodative amplitudes, lead/lag, and binocular facility with ±2.00-D flippers. We compared the three accommodative measures using multivariate analysis of variance (MANOVA), adjusting for clinic site, sex, and age group (7 to 9 or 10 to 11 years). RESULTS: The +2.50-D add contact lens wearers exhibited lower accommodative response than the single-vision contact lens wearers for 3 years, but the +1.50-D add contact lens wearers exhibited only lower accommodative response than did the single-vision contact lens wearers for 2 years. After adjustment for clinic site, sex, and age group, there were no statistically significant or clinically meaningful differences between the three treatment groups for accommodative amplitude (MANOVA, P = .49), accommodative lag (MANOVA, P = .41), or accommodative facility (MANOVA, P = .87) after an average of 4.7 years of contact lens wear. CONCLUSIONS: Almost 5 years of multifocal contact lens wear did not affect the accommodative amplitude, lag, or facility of children.

Scalable and High-Throughput In Vitro Vibratory Platform for Vocal Fold Tissue Engineering Applications.

The vocal folds (VFs) are constantly exposed to mechanical stimulation leading to changes in biomechanical properties, structure, and composition. The development of long-term strategies for VF treatment depends on the characterization of related cells, biomaterials, or engineered tissues in a controlled mechanical environment. Our aim was to design, develop, and characterize a scalable and high-throughput platform that mimics the mechanical microenvironment of the VFs in vitro. The platform consists of a 24-well plate fitted with a flexible membrane atop a waveguide equipped with piezoelectric speakers which allows for cells to be exposed to various phonatory stimuli. The displacements of the flexible membrane were characterized via Laser Doppler Vibrometry (LDV). Human VF fibroblasts and mesenchymal stem cells were seeded, exposed to various vibratory regimes, and the expression of pro-fibrotic and pro-inflammatory genes was analyzed. Compared to current bioreactor designs, the platform developed in this study can incorporate commercial assay formats ranging from 6- to 96-well plates which represents a significant improvement in scalability. This platform is modular and allows for tunable frequency regimes.

Evaluation of a Pilot Protocol for Detecting Infant Hyperopia.

SIGNIFICANCE: Highly hyperopic children are at greater risk for developing conditions such as strabismus, amblyopia, and early literacy and reading problems. High hyperopia is a common finding in infants in a pediatric medical practice, and early detection can be done effectively in that setting with tropicamide autorefraction. PURPOSE: This study aimed to evaluate the effectiveness of a pilot screening program to detect high hyperopia in 2-month-old infants in a pediatric medical practice in Columbus, Ohio. METHODS: Cycloplegic refractive error (1% tropicamide) was measured by retinoscopy and autorefraction with the Welch Allyn SureSight (Welch Allyn/Hillrom, Skaneateles Falls, NY) in 473 infants (55.4% female) who were undergoing their 2-month well-baby visit at their pediatrician's medical practice. Cycloplegic retinoscopy (1% cyclopentolate) was repeated at a subsequent visit in 35 infants with ≥+5.00 D hyperopia in the most hyperopic meridian during the screening. RESULTS: Twenty-eight infants (5.9%) had high hyperopia (spherical equivalent, ≥+5.00 D), and 61 (12.9%) had high hyperopia (≥+5.00 D in at least one meridian of at least one eye) by retinoscopy with 1% tropicamide. The mean ± standard deviation spherical equivalent tropicamide cycloplegic refractive error measured with retinoscopy was +2.54 ± 1.54 D (range, -3.25 to +7.00 D) and with SureSight was +2.29 ± 1.64 D (range, -2.90 to +7.53 D). Retinoscopy done using 1% cyclopentolate was 0.44 ± 0.54 D more hyperopic in spherical equivalent than with 1% tropicamide ( P < .001). CONCLUSIONS: High hyperopia was a common finding in 2-month-old infants in a pediatric medical setting that could be detected effectively by cycloplegic autorefraction using tropicamide. Greater cooperation between pediatric primary vision and medical care could lead to effective vision screenings designed to detect high hyperopia in infants.

Compensation for Vitreous Chamber Elongation in Infancy and Childhood.

SIGNIFICANCE: The ratios of diopters of change in refractive error produced per millimeter of eye elongation (D/mm) are rarely those predicted from geometric optics because of changes in other ocular components. Quantifying this optical compensation in millimeters instead of ratios reveals some important principles about eye growth and refractive error. PURPOSE: The study purpose was to sort total vitreous chamber elongation into millimeters that either contributed (uncompensated) or did not contribute to change in refractive error (compensated). METHODS: Participants were infants in the Berkeley Infant Biometry Study (n = 271, ages 3 months to 6 years) or schoolchildren in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (n = 456 emmetropes and 522 myopes, ages 6 to 14 years). Refractive error was measured using cycloplegic retinoscopy in infants (cyclopentolate 1%) and cycloplegic autorefraction in schoolchildren (tropicamide 1% or combined with cyclopentolate 1%). Axial dimensions were assessed using A-scan ultrasonography. Uncompensated millimeters were estimated from ratios of change in refractive error per millimeter of elongation using Gullstrand eye models. Compensated millimeters were the difference between measured elongation and uncompensated millimeters. RESULTS: Compensated millimeters exceeded uncompensated millimeters in emmetropic children across ages, but uncompensated millimeters exceeded compensated millimeters in myopic children. Compensated millimeters were highest in infancy and decreased with age, reaching less than 0.10 mm per year by age 10 years in both myopic and emmetropic children. There were no statistically significant differences in compensated millimeters between myopic and emmetropic children between ages 8 and 14 years ( P values from .17 to .73). CONCLUSIONS: The ability of the ocular components, primarily crystalline lens, to compensate for vitreous elongation is independent of the higher demands of myopic eye growth. The limited compensation after age 10 years suggests the target for elongation in myopia control needed to arrest myopia progression may be that seen in emmetropes or less.

Towards a standardized multi-tissue decellularization protocol for the derivation of extracellular matrix materials.

The goal of tissue decellularization is to efficiently remove unwanted cellular components, such as DNA and cellular debris, while retaining the complex structural and molecular milieu within the extracellular matrix (ECM). Decellularization protocols to date are centered on customized tissue-specific and lab-specific protocols that involve consecutive manual steps which results in variable and protocol-specific ECM material. The differences that result from the inconsistent protocols between decellularized ECMs affect consistency across batches, limit comparisons between results obtained from different laboratories, and could limit the transferability of the material for consistent laboratory or clinical use. The present study is the first proof-of-concept towards the development of a standardized protocol that can be used to derive multiple ECM biomaterials (powders and hydrogels) via a previously established automated system. The automated decellularization method developed by our group was used due to its short decellularization time (4 hours) and its ability to reduce batch-to-batch variability. The ECM obtained using this first iteration of a unified protocol was able to produce ECM hydrogels from skin, lung, muscle, tendons, cartilage, and laryngeal tissues. All hydrogels formed in this study were cytocompatible and showed gelation and rheological properties consistent with previous ECM hydrogels. The ECMs also showed unique proteomic composition. The present study represents the first step towards developing standardized protocols that can be used on multiple tissues in a fast, scalable, and reproducible manner.

New Software Interface for Registering Rapid Antigen Test Results to Prevent Fraud.

Donald O. Besong has already documented that the online registration of unsupervised lateral flow test results poses concerns in the case of a serious pandemic where there are not enough medics to read scans or watch videos of candidates' results (Besong Int J Biomed Healthc Sci. 2022;12(1):1-12). Scanning or videorecording requires a high number of available medics (Besong Int J Biomed Healthc Sci. 2022;12(1):1-12) in an adverse pandemic scenario. In the above study (Besong Int J Biomed Healthc Sci. 2022;12(1):1-12), an artificial intelligence (AI) interface with image recognition was suggested as a method to prevent cheating during the online registration of unsupervised test results. The second solution suggested was a method that obscures the meaning of the result the candidate reads from their test device so that a software interface can resolve that from a database (Besong Int J Biomed Healthc Sci. 2022;12(1):1-12). This is an entirely new method. In this study, the latter (entirely new) method is proposed and described in detail. Precisely, this simple but new method is all about blinding the test strips so that the candidate does not know what the face values signify. The software then connects to a database of unique strip identification numbers to determine the test result when the candidate or patient registers their results. Both strip number and the value of their test must be entered to register results. This method has never been proposed or implemented. The technique will be described in detail.

High-Axial-Aspect Tannic Acid Microparticles Facilitate Gelation and Injectability of Collagen-Based Hydrogels.

Injectable collagen-based hydrogels offer great promise for tissue engineering and regeneration, but their use is limited by poor mechanical strength. Herein, we incorporate tannic acid (TA) to tailor the rheology of the corresponding hydrogels while simultaneously adding the therapeutic benefits inherent to this polyphenolic component. TA in the solution form and needle-shaped TA microparticles are combined with collagen and the respective systems studied for their time-dependent sol-gel transitions (from storage to body temperatures, 4-37 °C) as a function of TA concentration. Compared to systems incorporating TA microparticles, those with dissolved TA, applied at a similar concentration, generate a less significant enhancement of the elastic modulus. Premature gelation at a low temperature and associated colloidal arrest of the system are proposed as a main factor explaining this limited performance. A higher yield stress (elastic stress method) is determined for systems loaded with TA microparticles compared to the system with dissolved TA. These results are interpreted in terms of the underlying interactions of TA with collagen, as probed by spectroscopy and isothermal titration calorimetry. Importantly, hydrogels containing TA microparticles show high cell viability (human dermal fibroblasts) and comparative cellular activity relative to the collagen-only hydrogel. Overall, composite hydrogels incorporating TA microparticles demonstrate a new, simple, and better-performance alternative to cell culturing and difficult implantation scenarios.

The Effect of Multifocal Soft Contact Lens Wear on Axial and Peripheral Eye Elongation in the BLINK Study.

Purpose: The purpose of this study was to compare axial and peripheral eye elongation during myopia therapy with multifocal soft contact lenses. Methods: Participants were 294 children (177 [60.2%] girls) age 7 to 11 years old with between -0.75 diopters (D) and -5.00 D of myopia (spherical component) and less than 1.00 D astigmatism at baseline. Children were randomly assigned to Biofinity soft contact lenses for 3 years: D-designs with a +2.50 D addition, +1.50 D addition, or single vision. Five measurements of eye length were averaged at the fovea, ±20°, and ±30° in the horizontal and vertical meridians of the right eye using the Haag-Streit Lenstar LS 900. Results: Axial elongation over 3 years with single vision contact lenses was greater than peripheral elongation in the superior and temporal retinal qeuadrants by 0.07 mm (95% confidence interval [CI] = 0.05 to 0.09 mm) and 0.06 mm (95% CI = 0.03 to 0.09 mm) and similar in the inferior and nasal quadrants. Axial elongation with +2.50 D addition multifocal contact lenses was similar to peripheral elongation in the superior retinal quadrant and less than peripheral elongation in the inferior and nasal quadrants by -0.04 mm (95% CI = -0.06 to -0.01 mm) and -0.06 mm (95% CI = -0.09 to -0.02 mm). Conclusions: Wearing +2.50 D addition multifocal contact lenses neutralized or reversed the increase in retinal steepness with single vision lenses. The mismatch between greater inhibition of elongation at the fovea than peripherally despite greater peripheral myopic defocus suggests that optical myopia therapy may operate through extensive spatial integration or mechanisms other than local defocus.

Donor Age and Time in Culture Affect Dermal Fibroblast Contraction in an In Vitro Hydrogel Model.

Current cellular hydrogel-based skin grafts composed of human dermal fibroblasts and a hydrogel scaffold tend to minimize contraction of full-thickness skin wounds and support skin regeneration. However, there has been no comparison between the sources of the dermal fibroblast used. Products using human adult or neonatal foreskin dermal fibroblasts are often expanded in vitro and used after multiple passages without a clear understanding of the effects of this initial production step on the quality and reproducibility of the cellular behavior. Based on the known effects of 2D tissue culture expansion on cellular proliferation and gene expression, we hypothesized that differences in donor age and time in culture may influence cellular properties and contractile behavior in a fibroblast-populated collagen matrix. Using porcine skin as a model based on its similarity to human skin in structure and wound healing properties, we isolated porcine dermal fibroblasts of three different donor ages for use in a 2D proliferation assay and in a 3D cell-populated collagen matrix contractility assay. In 2D cell culture, doubling time remained relatively consistent between all age groups from passage 1 to 6. In the contractility assays, fetal and neonatal groups contracted faster and generated more contractile force than the adult group at passage 1 in vitro. However, after five passages in culture, there was no difference in contractility between ages. These results show how cellular responses in a hydrogel scaffold differ based on donor age and time in culture in vitro, and suggest that consistency in the cellular component of bioengineered skin products could be beneficial in the biomanufacturing of consistent, reliable skin grafts and graft in vivo models. Future research and therapies using bioengineered skin grafts should consider how results may vary based on donor age and time in culture before seeding. Impact statement Little is known about the impact of donor cell age and time in culture on the contraction of cellular, hydrogel-based skin grafts. These results show how cellular phenotypes of porcine fibroblasts differ based on donor age and time in culture. This information is beneficial when addressing important inconsistencies in biomanufacturing of bioengineered skin grafts and in vitro models. These findings are relevant to research and therapies using bioengineered skin graft models and the results can be used to increase reproducibility and consistency during the production of bioengineered skin constructs. The information from this study can be extrapolated to future in vivo studies using human dermal fibroblasts in an in vivo model to help determine the best donor age and time in culture for optimal wound healing outcomes or more reproducible in vitro testing constructs.