Mitigating heavy metal accumulation in tobacco: Strategies, mechanisms, and global initiatives.

The threat of heavy metal (HM) pollution looms large over plant growth and human health, with tobacco emerging as a highly vulnerable plant due to its exceptional absorption capacity. The widespread cultivation of tobacco intensifies these concerns, posing increased risks to human health as HMs become more pervasive in tobacco-growing soils globally. The absorption of these metals not only impedes tobacco growth and quality but also amplifies health hazards through smoking. Implementing proactive strategies to minimize HM absorption in tobacco is of paramount importance. Various approaches, encompassing chemical immobilization, transgenic modification, agronomic adjustments, and microbial interventions, have proven effective in curbing HM accumulation and mitigating associated adverse effects. However, a comprehensive review elucidating these control strategies and their mechanisms remains notably absent. This paper seeks to fill this void by examining the deleterious effects of HM exposure on tobacco plants and human health through tobacco consumption. Additionally, it provides a thorough exploration of the mechanisms responsible for reducing HM content in tobacco. The review consolidates and synthesizes recent domestic and international initiatives aimed at mitigating HM content in tobacco, delivering a comprehensive overview of their current status, benefits, and limitations.

Highly drug/target-tolerant neutralizing antibody (NAb) assay development through target-based drug depletion and drug-based NAb extraction for an anti-EGFR therapeutic monoclonal antibody.

The reduction of immunogenicity is fundamental for the development of biobetter Erbitux, given that the development of an immune response reduces treatment efficacy and may lead to potential side effects. One of the requirements for the clinical research of a Erbitux biobetter candidate (CMAB009) is to develop a neutralizing antibody (NAb) assay, and sufficient drug and target tolerance for the assay is necessary. Here, we describe the development of a competitive ligand binding (CLB) assay for CMAB009 with high drug and target tolerance through target-based drug depletion and drug-based NAb extraction, the integrated experimental strategy was implemented to simultaneously mitigate drug interference and enhance target tolerance. Following troubleshooting and optimization, the NAb assay was validated for clinical sample analysis with the sensitivity of 92 ng/mL, drug tolerance of 70 µg/mL and target tolerance of 798 ng/mL. The innovative drug depletion and NAb extraction achieved though the combination of drug and target beads would enable the development of reliable NAb assays for many other therapeutics that overcome drug and its target interference for more precise and sensitive NAb assessment.

Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Reply to Finsterer et al.

This letter acknowledges Finsterer and colleagues' insightful comments on pesticide use in fruits and vegetables and impact on eye health. Pesticides can harm eyes through various exposures. Adverse effects occur due to direct entry into ocular tissues, with absorption through eye components. While the potential of organic diets to reduce pesticide exposure is acknowledged, the original paper's cited studies lack clarity on whether organic diet interventions were used. Future systematic reviews comparing organic and nonorganic diets could provide further insights.

Exploration of adaptation process and experience among the HIV/AIDS patients based on the comprehensive task-based adaptation model. / 基于综合任务模型探索HIV/AIDSæ‚£è€ çš„ç–¾ç— é€‚åº”è¿‡ç¨‹å’Œä½“éªŒ.

OBJECTIVES: Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) confront multiple difficulties during the disease adaptation process. Based on the comprehensive task-based adaptation model, this study aims to explore the process and experience of adapting to living with HIV among HIV/AIDS patients and to provide evidence for promoting the adaptation of this population. METHODS: With the design of the phenomenon study, we purposefully recruited 43 HIV/AIDS patients and conducted semi-structural interviews. The qualitative data was analyzed by Van Manen method. RESULTS: There were 1 307 significant quotes and 6 themes with 14 sub-themes. "The shadow comes along with the sunshine" was proposed to describe the process of adapting to life with HIV. Another 5 themes emerged to represent the tasks as follows: the direction of the mental anchor, the management of physical tasks, social network and support, the occupational dilemma and benefits, and the consideration of the future. CONCLUSIONS: The adapting process possesses both common and personalized characteristics. Future intervention development should address the integrality and interaction of the adaptation tasks, contributing to the positive adaptation outcomes of HIV/AIDS patients.

Impacts of regular consumption of grapes on macular pigment accumulation in Singapore older adults: a randomized controlled trial.

Background: Oxidative stress is a key risk factor for visual impairment and consuming dietary antioxidant-rich foods may help in managing visual impairments. However, a limited number of studies have investigated the effect of dietary antioxidant-rich food including grapes on eye health in older adults. Objectives: To assess the effects on macular pigment accumulation of regular consumption of grapes in Singapore older adults. Methods: This was a 16 week, double-blind, randomized, placebo-controlled trial. Thirty-four Singapore older adults were randomized into regularly consuming either 46 g day-1 of freeze-dried table grape powder (the intervention group) or the same amount of placebo powder (the control group). Macular pigment optical density (MPOD), skin carotenoid status, advanced glycation end product (AGEs) status and dietary lutein intake were assessed every 4 weeks, and plasma lutein concentration, total antioxidant capacity and total phenolic content were measured every 8 weeks. Results: A significant time effect (p = 0.007) was observed for MPOD, and this is largely attributed to the improvement in the MPOD for the intervention group, as a significant increase was observed only in this group (week 0: 0.56 ± 0.04 D.U.; week 16: 0.61 ± 0.04 D.U., p < 0.01). Additionally, a significant increase in plasma total antioxidant capacity (week 0: 0.26 ± 0.13 mM TEAC; week 16: 0.36 ± 0.20 mM TEAC, p < 0.01) and total phenolic content (week 0: 10.50 ± 0.44 mg L-1 GAE; week 16: 12.58 ± 0.55 mg L-1 GAE, p < 0.001) was observed for the intervention group only. In contrast, a significant increase in skin AGE status was observed in the control group (week 0: 2.47 ± 0.24; week 16: 2.99 ± 0.12, p < 0.05) while this was mitigated in the intervention group. There were no differences in dietary lutein intake, plasma lutein concentration and skin carotenoid status between groups throughout the study. Conclusions: Regular intake of grapes may improve eye health in Singapore older adults, specifically in augmenting MPOD, which can be explained by an increase in plasma total antioxidant capacity and phenolic content, and the downregulation of AGEs. This study was registered at clinicatrials.gov as NCT05064865.

SIRIUS, Ultra-Scintillating Upconversion Breast Implant for Remote Orthotopic Photodynamic Therapy.

Present day strategies for delivery of wireless photodynamic therapy (PDT) to deep-seated targets are limited by the inadequacy of irradiance and insufficient therapeutic depth. Here we report the design and preclinical validation of a flexible wireless upconversion nanoparticle (UCNP) implant (SIRIUS) that is capable of large field, high intensity illumination for PDT of deep-seated tumors. The implant achieves this by incorporating submicrometer core-shell-shell NaYF4 UCNPs into its design, which significantly enhances upconversion efficiency and mitigates light loss from surface quenching. We demonstrate the efficacy of SIRIUS UCNP implant mediated PDT in preclinical breast cancer disease models. In our in vitro experiments, SIRIUS directed 5-Aminolevulinic Acid (5-ALA) based wireless PDT leads to significant reactive oxygen species (ROS) generation and tumor apoptosis in hormonal receptor+/HER2+ (MCF7) and triple-negative (MDA-MB-231) breast cancer cell lines. In our in vivo rodent model, SIRIUS-driven PDT is shown to be significant in regressing tumors when applied to orthotopically inoculated breast tumors. Following successful preclinical validation, we also describe a clinical prototype of UCNP breast implant with potential dual cosmetic and onco-therapeutic functions. SIRIUS is an upconversion breast implant for wireless PDT that fulfils all the design prerequisites necessary for seamless clinical translation.

Single-cell transcriptomics reveals maturation of transplanted stem cell-derived retinal pigment epithelial cells toward native state.

Transplantation of stem cell-derived retinal pigment epithelial (RPE) cells is considered a viable therapeutic option for age-related macular degeneration (AMD). Several landmark Phase I/II clinical trials have demonstrated safety and tolerability of RPE transplants in AMD patients, albeit with limited efficacy. Currently, there is limited understanding of how the recipient retina regulates the survival, maturation, and fate specification of transplanted RPE cells. To address this, we transplanted stem cell-derived RPE into the subretinal space of immunocompetent rabbits for 1 mo and conducted single-cell RNA sequencing analyses on the explanted RPE monolayers, compared to their age-matched in vitro counterparts. We observed an unequivocal retention of RPE identity, and a trajectory-inferred survival of all in vitro RPE populations after transplantation. Furthermore, there was a unidirectional maturation toward the native adult human RPE state in all transplanted RPE, regardless of stem cell resource. Gene regulatory network analysis suggests that tripartite transcription factors (FOS, JUND, and MAFF) may be specifically activated in posttransplanted RPE cells, to regulate canonical RPE signature gene expression crucial for supporting host photoreceptor function, and to regulate prosurvival genes required for transplanted RPE's adaptation to the host subretinal microenvironment. These findings shed insights into the transcriptional landscape of RPE cells after subretinal transplantation, with important implications for cell-based therapy for AMD.

Dysfunctional Autophagy, Proteostasis, and Mitochondria as a Prelude to Age-Related Macular Degeneration.

Retinal pigment epithelial (RPE) cell dysfunction is a key driving force of AMD. RPE cells form a metabolic interface between photoreceptors and choriocapillaris, performing essential functions for retinal homeostasis. Through their multiple functions, RPE cells are constantly exposed to oxidative stress, which leads to the accumulation of damaged proteins, lipids, nucleic acids, and cellular organelles, including mitochondria. As miniature chemical engines of the cell, self-replicating mitochondria are heavily implicated in the aging process through a variety of mechanisms. In the eye, mitochondrial dysfunction is strongly associated with several diseases, including age-related macular degeneration (AMD), which is a leading cause of irreversible vision loss in millions of people globally. Aged mitochondria exhibit decreased rates of oxidative phosphorylation, increased reactive oxygen species (ROS) generation, and increased numbers of mitochondrial DNA mutations. Mitochondrial bioenergetics and autophagy decline during aging because of insufficient free radical scavenger systems, the impairment of DNA repair mechanisms, and reductions in mitochondrial turnover. Recent research has uncovered a much more complex role of mitochondrial function and cytosolic protein translation and proteostasis in AMD pathogenesis. The coupling of autophagy and mitochondrial apoptosis modulates the proteostasis and aging processes. This review aims to summarise and provide a perspective on (i) the current evidence of autophagy, proteostasis, and mitochondrial dysfunction in dry AMD; (ii) current in vitro and in vivo disease models relevant to assessing mitochondrial dysfunction in AMD, and their utility in drug screening; and (iii) ongoing clinical trials targeting mitochondrial dysfunction for AMD therapeutics.

Effect of xanthophyll-rich food and supplement intake on visual outcomes in healthy adults and those with eye disease: a systematic review, meta-analysis, and meta-regression of randomized controlled trials.

CONTEXT: Xanthophyll intake is known to improve eye health; however, its benefits on visual outcomes have not been systematically studied, particularly in a population with eye diseases. OBJECTIVE: A systematic review, meta-analysis, and meta-regression were conducted to investigate the effect of xanthophyll intake on visual outcomes, and further subgroup analysis was performed on the basis of eye disease status. DATA SOURCES: The PubMed, Scopus, Embase, CINAHL, Cochrane, and Web of Science databases were searched, and relevant randomized controlled trials were identified. DATA EXTRACTION: For systematic review, meta-analysis, and meta-regression, 43, 25, and 21 articles were selected, respectively. DATA ANALYSIS: Xanthophyll intake enhanced macular pigment optical density (MPOD) for both heterochromatic flicker photometry (weighted mean difference [WMD], 0.05; 95% confidence interval [CI], 0.03-0.07) and autofluorescence imaging (WMD, 0.08; 95%CI, 0.05-0.11) measurements and decreased photostress recovery time (WMD, -2.35; 95%CI, -4.49 to -0.20). While enhancement in visual acuity logarithm of the minimum angle of resolution was observed in response to the xanthophyll-rich food and supplement intake only for patients with eye disease (WMD, -0.04; 95%CI, -0.07 to -0.01). Meta-regression showed a positive correlation between change in MPOD (heterochromatic flicker photometry) and the corresponding change in serum lutein levels (regression coefficient = 0.068; P = 0.00). CONCLUSION: Intake of xanthophyll-rich food or supplements can improve eye health. Additional improvement in visual acuity was observed in patients with eye disease. A positive association between MPOD and serum lutein level, while absent with dietary xanthophyll intake, suggests the importance of bioavailability when examining the effect of xanthophyll on eye health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021295337.

Impact of Microplastics on the Ocular Surface.

Plastics are synthetic materials made from organic polymers that are ubiquitous in daily living and are especially important in the healthcare setting. However, recent advances have revealed the pervasive nature of microplastics, which are formed by degradation of existing plastic products. Although the impact on human health has yet to be fully characterised, there is increasing evidence that microplastics can trigger inflammatory damage, microbial dysbiosis, and oxidative stress in humans. Although there are limited studies investigating their effect on the ocular surface, studies of microplastics on other organs provide some insights. The prevalence of plastic waste has also triggered public outcry, culminating in the development of legislation aimed at reducing microplastics in commercial products. We present a review outlining the possible sources of microplastics leading to ocular exposure, and analyse the possible mechanisms of ocular surface damage. Finally, we examine the utility and consequences of current legislation surrounding microplastic regulation.

Orthogonally crosslinked alginate conjugate thermogels with potential for cell encapsulation.

Hydrogels with more than one mode of crosslinking have gained interest due to improved control over hydrogel properties such as mechanical strength using multiple stimuli. In this work, sodium alginate was covalently conjugated onto thermoresponsive polyurethanes to prepare hybrid polymers (EPC-Alg) that are responsive to both temperature and Ca2+, forming orthogonally crosslinked hydrogels which are non-toxic to cells. Notably, the crosslinks are fully reversible, allowing for gel strength to be modulated via selective removal of either stimulus, or complete deconstruction of the hydrogel network by removing both stimuli. Higher alginate fractions increased the hydrophilicity and Ca2+ response of the EPC-Alg hydrogel, enabling tunable modulation of the thermal stability, stiffness and gelation temperatures. The EPC-Alg hydrogel could sustain protein release for a month and encapsulate neural spheroids with high cell viability after 7-day culture, demonstrating feasibility towards 3D cell encapsulation in cell-based biomedical applications such as cell encapsulation and cell therapy.

Treat and extend regimen for diabetic macular oedema-a systematic review and meta-analysis.

PURPOSE: Various treatment regimens are currently practiced in the treatment of CI-DMO (centre-involving diabetic macular oedema). In recent years, there has been a growing body of evidence supporting a treat and extend (T&E) regimen for DMO which offers the promise of comparable visual and anatomical outcomes while reducing injection burden. This meta-analysis was hence performed to evaluate the aforementioned outcomes in the treatment of DMO. Ten studies met the inclusion criteria. METHODS: A search of PubMed, MEDLINE, Current Contents, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. We employed the terms 'treat AND extend AND (diabetic AND macular AND edema OR oedema)' to ensure a comprehensive search. The search workflow adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: The pooled analysis of the mean number of injections in 1 year for T&E-aflibercept (AFL), T&E-ranibizumab (RBZ) and collectively was 9.1 (95% CI: 7.63-10.63), 10.0 (95% CI: 9.55-10.47) and 9.6 (95% CI: 8.62-10.49), respectively. Improvements in vision at 1 year for T&E-AFL, T&E-RBZ and collectively were 6.26 (95% CI: 3.24-9.29), 7.14 (95% CI: 4.76-9.52) and 7.08 (95% CI: 5.32-8.84) letters, respectively. The improvements in central subfield thickness at 1 year for T&E-AFL, T&E-RBZ and collectively were 131.94 (95% CI: 100.29-163.60), 108.64 (95% CI: 82.82-134.46) and 121.32 (95% CI: 102.89-139.75) microns, respectively. CONCLUSION: The meta-analysis of T&E for DMO did not show a clear advantage in reducing the number of injections compared to landmark clinical trials with pro-re-nata (PRN) treatment regimens in the first year of treatment with limited gains in visual and anatomical outcomes. However, the T&E approach offers the potential for fewer patient visits, thereby reducing treatment burden. Longer term studies on T&E with a standardised protocol would be required to assess the longevity of the vision gain in the first year despite a likely reduced treatment burden compared to the PRN trials.

Injectable PTHF-based thermogelling polyurethane implants for long-term intraocular application.

BACKGROUND: Hydrogels show great potential to be used for intraocular applications due to their high-water content and similarity to the native vitreous. Injectable thermosensitive hydrogels through a small-bore needle can be used as a delivery system for drugs or a tamponading substitute to treat posterior eye diseases with clear clinical potential. However, none of the currently available thermosensitive hydrogels can provide intraocular support for up to 3 months or more. METHOD: In this study, an injectable polytetrahydrofuran (PTHF)-based thermosensitive hydrogel was synthesized by polyurethane reaction. We examined the injectability, rheological properties, microstructure, cytotoxicity, and in vivo compatibility and stability of the hydrogels in rabbit eyes. RESULTS: We found that the PTHF block type and PTHF component ratio could modulate thermogelation properties of the polyurethane polymers. The PTHF-based hydrogel implants retained normal retinal structure and function. Incorporating bioinert PTHF generated highly biocompatible and more stable thermogels in the vitreous cavity, with gel networks and the presence of polymer still observed after 3 months when other thermogels would have been completely cleared. Moreover, despite lacking hydrolytically cleavable linkages, the polymers could be most naturally removed from the native vitreous by bio-erosion without additional surgical interventions. CONCLUSION: Our findings suggest the potential of incorporating hydrophobic bioinert blocks to enhance the in vivo stability of supramolecularly associated hydrogels for long-term intraocular applications.

Treponema denticola Induces Neuronal Apoptosis by Promoting Amyloid-ß Accumulation in Mice.

Background: Neuronal apoptosis is a major contributor to Alzheimer's disease (AD). Periodontitis is a significant risk factor for AD. The periodontal pathogens Porphyromonas gingivalis and Treponema denticola have been shown to initiate the hallmark pathologies and behavioral symptoms of AD. Studies have found that T. denticola infection induced Tau hyperphosphorylation and amyloid ß accumulation in the hippocampi of mice. Aß accumulation is closely associated with neuronal apoptosis. However, the roles of T. denticola in neuronal apoptosis remain unclear and its roles in AD pathology need further study. Objective: This study aimed to investigate whether oral infection with T. denticola induced alveolar bone loss and neuronal apoptosis in mice. Methods: C57BL/6 mice were orally administered with T. denticola, Micro-CT was employed to assess the alveolar bone resorption. Western blotting, quantitative PCR, and TUNEL staining were utilized to detect the apoptosis-associated changes in mouse hippocampi. N2a were co-cultured with T. denticola to verify in vivo results. Results: Mice infected with T. denticola exhibited more alveolar bone loss compared with the control mice. T. denticola oral infection induced neuronal apoptosis in hippocampi of mice. Consistent results of the apoptosis-associated protein expression were observed in N2a cells treated with T. denticola and Aß1-42 in vitro. However, the Aß inhibitor reversed these results, suggesting that Aß1-42 mediates T. denticola infection-induced neuronal apoptosis. Conclusions: This study found that oral infected T. denticola caused alveolar bone loss, and induced neuronal apoptosis by promoting Aß accumulation in mice, providing evidence for the link between periodontitis and AD.

Customized strategies for high-yield purification of retinal pigment epithelial cells differentiated from different stem cell sources.

Retinal pigment epithelial (RPE) cell dysfunction and death are characteristics of age-related macular degeneration. A promising therapeutic option is RPE cell transplantation. Development of clinical grade stem-cell derived RPE requires efficient in vitro differentiation and purification methods. Enzymatic purification of RPE relies on the relative adherence of RPE and non-RPE cells to the culture plate. However, morphology and adherence of non-RPE cells differ for different stem cell sources. In cases whereby the non-RPE adhered as strongly as RPE cells to the culture plate, enzymatic method of purification is unsuitable. Thus, we hypothesized the need to customize purification strategies for RPE derived from different stem cell sources. We systematically compared five different RPE purification methods, including manual, enzymatic, flow cytometry-based sorting or combinations thereof for parameters including cell throughput, yield, purity and functionality. Flow cytometry-based approach was suitable for RPE isolation from heterogeneous cultures with highly adherent non-RPE cells, albeit with lower yield. Although all five purification methods generated pure and functional RPE, there were significant differences in yield and processing times. Based on the high purity of the resulting RPE and relatively short processing time, we conclude that a combination of enzymatic and manual purification is ideal for clinical applications.

Electrohydrodynamic Jet-Printed Ultrathin Polycaprolactone Scaffolds Mimicking Bruch's Membrane for Retinal Pigment Epithelial Tissue Engineering.

Age-related macular degeneration (AMD) is the leading cause of visual loss and affects millions of people worldwide. Dysfunction of the retinal pigment epithelium (RPE) is associated with the pathogenesis of AMD. The purpose of this work is to build and evaluate the performance of ultrathin scaffolds with an electrohydrodynamic jet (EHDJ) printing method for RPE cell culture. We printed two types of ultrathin (around 7 µm) polycaprolactone scaffolds with 20 µm and 50 µm pores, which possess mechanical properties resembling that of native human Bruch's membrane and are biodegradable. Light microscopy and cell proliferation assay showed that adult human retinal pigment epithelial (ARPE-19) cells adhered and proliferated to form a monolayer on the scaffolds. The progress of culture matured on the scaffolds was demonstrated by immunofluorescence (actin, ZO-1, and Na+/K+-ATPase) and Western blot analysis of the respective proteins. The RPE cells cultured on EHDJ-printed scaffolds with 20 µm pores presented higher permeability, higher transepithelial potential difference, and higher expression level of Na+/K+-ATPase than those cultured on Transwell inserts. These findings suggest that the EHDJ printing can fabricate scaffolds that mimic Bruch's membrane by promoting maturation of RPE cells to form a polarized and functional monolayered epithelium with potential as an in vitro model for studying retinal diseases and treatment methods.

Polymeric biomaterials in the treatment of posterior segment diseases.

Polymeric biomaterials are biological or synthetic substances which can be engineered to interact with biological systems for the diagnosis or treatment of diseases. These biomaterials have immense potential for treating eyes diseases, particularly the retina-a site of many inherited and acquired diseases. Polymeric biomaterials can be engineered to function both as an endotamponade agent and to prevent intraocular scarring in retinal detachment repair surgeries. They can also be designed as a drug delivery platform for treatment of retinal diseases. Finally, they can be used as scaffolds for cellular products and provide non-viral gene delivery solutions to the retina. This perspective article explains the role of polymeric biomaterials in the treatment of retinal conditions by highlighting recent advances being translated to clinical practice. The article will also identify potential hurdles to clinical translation as future research directions in the field.

Injectable Hybrid-Crosslinked Hydrogels as Fatigue-Resistant and Shape-Stable Skin Depots.

Injectable hydrogels have gained considerable attention, but they are typically mechanically weak and subject to repeated physiological stresses in the body. Herein, we prepared polyurethane diacrylate (EPC-DA) hydrogels, which are injectable and can be photocrosslinked into fatigue-resistant implants. The mechanical properties can be tuned by changing photocrosslinking conditions, and the hybrid-crosslinked EPC-DA hydrogels exhibited high stability and sustained release properties. In contrast to common injectable hydrogels, EPC-DA hydrogels exhibited excellent antifatigue properties with >90% recovery during cyclic compression tests and showed shape stability after application of force and immersion in an aqueous buffer for 35 days. The EPC-DA hydrogel formed a shape-stable hydrogel depot in an ex vivo porcine skin model, with establishment of a temporary soft gel before in situ fixing by UV crosslinking. Hybrid crosslinking using injectable polymeric micelles or nanoparticles may be a general strategy for producing hydrogel implants resistant to physiological stresses.

A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway.

One common cause of vision loss after retinal detachment surgery is the formation of proliferative and contractile fibrocellular membranes. This aberrant wound healing process is mediated by epithelial-mesenchymal transition (EMT) and hyper-proliferation of retinal pigment epithelial (RPE) cells. Current treatment relies primarily on surgical removal of these membranes. Here, we demonstrate that a bio-functional polymer by itself is able to prevent retinal scarring in an experimental rabbit model of proliferative vitreoretinopathy. This is mediated primarily via clathrin-dependent internalisation of polymeric micelles, downstream suppression of canonical EMT transcription factors, reduction of RPE cell hyper-proliferation and migration. Nuclear factor erythroid 2-related factor 2 signalling pathway was identified in a genome-wide transcriptomic profiling as a key sensor and effector. This study highlights the potential of using synthetic bio-functional polymer to modulate RPE cellular behaviour and offers a potential therapy for retinal scarring prevention.