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      A novel flexible microfluidic meshwork to reduce fibrosis in glaucoma surgery

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          Abstract

          Purpose/Relevance

          Fibrosis and hence capsule formation around the glaucoma implants are the main reasons for glaucoma implant failure. To address these issues, we designed a microfluidic meshwork and tested its biocompatibility in a rabbit eye model. The amount of fibrosis elicited by the microfluidic meshwork was compared to the amount elicited by the plate of conventional glaucoma drainage device.

          Methods

          Six eyes from 3 New Zealand albino rabbits were randomized to receive either the novel microfluidic meshwork or a plate of Ahmed glaucoma valve model PF7 (AGV PF7). The flexible microfluidic implant was made from negative photoresist SU-8 by using micro-fabrication techniques. The overall size of the meshwork was 7 mm × 7 mm with a grid period of 100 μm. Both implants were placed in the subtenon space at the supratemporal quadrant in a standard fashion. There was no communication between the implants and the anterior chamber via a tube. All animal eyes were examined for signs of infection and implant erosion on days 1, 3, 7, and 14 and then monthly. Exenterations were performed in which the entire orbital contents were removed at 3 months. Histology slides of the implant and the surrounding tissues were prepared and stained with hematoxylin-eosin. Thickness of the fibrous capsules beneath the implants were measured and compared with paired student’s t-test between the two groups.

          Results

          The gross histological sections showed that nearly no capsule formed around the microfluidic meshwork in contrast to the thick capsule formed around the plate of AGV PF7. Thickness of the fibrotic capsules beneath the AGV PF7 plate from the 3 rabbit eyes was 90μm, 82μm, and 95 μm, respectively. The thickness at the bottom of fibrotic capsules around the new microfluidic implant were 1μm, 2μm, and 1μm, respectively. The difference in thickness of capsule between the two groups was significant ( P = 0.002). No complications were noticed in the 6 eyes, and both implants were tolerated well by all rabbits.

          Conclusion

          The microfluidic meshwork elicited minimal fibrosis and capsule formation after 3-months implantation in a rabbit model. This provides promising evidence to aid in future development of a new glaucoma drainage implant that will elicit minimal scar formation and provide better long-term surgical outcomes.

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          Most cited references33

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          Syringe-injectable electronics.

          Seamless and minimally invasive three-dimensional interpenetration of electronics within artificial or natural structures could allow for continuous monitoring and manipulation of their properties. Flexible electronics provide a means for conforming electronics to non-planar surfaces, yet targeted delivery of flexible electronics to internal regions remains difficult. Here, we overcome this challenge by demonstrating the syringe injection (and subsequent unfolding) of sub-micrometre-thick, centimetre-scale macroporous mesh electronics through needles with a diameter as small as 100 μm. Our results show that electronic components can be injected into man-made and biological cavities, as well as dense gels and tissue, with >90% device yield. We demonstrate several applications of syringe-injectable electronics as a general approach for interpenetrating flexible electronics with three-dimensional structures, including (1) monitoring internal mechanical strains in polymer cavities, (2) tight integration and low chronic immunoreactivity with several distinct regions of the brain, and (3) in vivo multiplexed neural recording. Moreover, syringe injection enables the delivery of flexible electronics through a rigid shell, the delivery of large-volume flexible electronics that can fill internal cavities, and co-injection of electronics with other materials into host structures, opening up unique applications for flexible electronics.
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            Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes.

            Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron-device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron-probe interactions, consistent with long-term biocompatibility of the device.
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              Antifibrotics and wound healing in glaucoma surgery.

              When medical and laser therapy fail to control intraocular pressure, glaucoma filtration surgery needs to be performed. Glaucoma surgery is unique in that its success is linked to interruption of the wound-healing response in order to maintain patency of the new filtration pathway. In this article we will review the wound-healing pathway and the pharmacologic interventions that have been employed clinically and experimentally to interrupt wound healing, particularly steroids and the antifibrotic agents 5-fluorouracil and mitomycin C. A review of the published literature looking at use of these agents to enhance success as well as the associated complications are presented, critiqued, and interpreted in order to put the studies in proper perspective. Future directions and recommendations regarding use of these agents are available and an introduction to newer wound modulating agents such as anti-transforming growth factor beta 2 is presented.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 March 2017
                2017
                : 12
                : 3
                : e0172556
                Affiliations
                [1 ]Department of Ophthalmology, University of California, San Francisco, California, United States of America
                [2 ]Department of Biomedical Engineering, the University of Texas at Austin, Austin, Texas, United States of America
                [3 ]Department of Physics, the University of Texas at Austin, Austin, Texas, United States of America
                Harvard Medical School, UNITED STATES
                Author notes

                Competing Interests: Authors have applied for provisional patent based on work presented in this paper. The patent’s title is “A Novel Flexible Microfluidic Meshwork for Glaucoma Surgery”. Patent number is 62462132. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

                • Conceptualization: CX YH XW FH ZZ LL.

                • Data curation: CX YH XW FH ZZ LL.

                • Formal analysis: CX YH XW FH ZZ LL.

                • Funding acquisition: CX YH.

                • Investigation: BA CX YH XW FH ZZ LL MB.

                • Methodology: CX YH XW FH ZZ LL.

                • Project administration: BA PC CX YH XW FH ZZ LL.

                • Resources: BA CX YH XW FH ZZ LL.

                • Software: CX YH XW FH ZZ LL.

                • Supervision: CX YH.

                • Validation: CX YH MB.

                • Visualization: CX YH BA JHL PC MB.

                • Writing – original draft: CX YH BA JHL PC.

                • Writing – review & editing: CX YH BA JHL PC.

                ‡ These authors also contributed equally to this work

                Author information
                http://orcid.org/0000-0001-8131-7971
                Article
                PONE-D-16-48984
                10.1371/journal.pone.0172556
                5354370
                28301490
                9ea1f809-feca-4684-a039-60abea190b25

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 11 December 2016
                : 6 February 2017
                Page count
                Figures: 6, Tables: 0, Pages: 11
                Funding
                Funded by: The Clinical and Rehabilitative Medicine Research Program
                Award ID: W81XWH-16-1-0580
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000053, National Eye Institute;
                Award ID: EY00216- Core Grant
                Funded by: funder-id http://dx.doi.org/10.13039/100001818, Research to Prevent Blindness;
                Award ID: Unrestricted grant
                Funded by: funder-id http://dx.doi.org/10.13039/100007826, American Glaucoma Society;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: NCATS UL1 TR000004
                Award Recipient :
                This work was funded by UT Austin Cockrell School of Engineering and Department of Biomedical Engineering start-up fund (CX), by the Office of the Assistant Secretary of Defense for Health Affairs through the Clinical and Rehabilitative Medicine Research Program under Award No. W81XWH-16-1-0580 (CX), by The Man May Seen Seed Grant (YH and CX), by UCSF Catalyst Award (YH and CX), by EY00216- Core Grant (YH) and by Research to Prevent Blindness unrestricted funding (YH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Engineering and Technology
                Fluidics
                Microfluidics
                Medicine and Health Sciences
                Ophthalmology
                Eye Diseases
                Glaucoma
                Biology and Life Sciences
                Anatomy
                Head
                Eyes
                Medicine and Health Sciences
                Anatomy
                Head
                Eyes
                Biology and Life Sciences
                Anatomy
                Ocular System
                Eyes
                Medicine and Health Sciences
                Anatomy
                Ocular System
                Eyes
                Research and Analysis Methods
                Experimental Organism Systems
                Animal Models
                Rabbits
                Biology and Life Sciences
                Organisms
                Animals
                Vertebrates
                Amniotes
                Mammals
                Rabbits
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Ophthalmic Procedures
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Biology and Life Sciences
                Developmental Biology
                Fibrosis
                Medicine and Health Sciences
                Ophthalmology
                Eye Diseases
                Custom metadata
                All relevant data are within the paper.

                Uncategorized
                Uncategorized

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