Bioengineering

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16 pages, 3358 KiB

Open AccessArticle

Evolution of Retinal Neuron Fractality When Interfacing with Carbon Nanotube Electrodes

by Aiden P. Dillon, Saba Moslehi, Bret Brouse, Saumya Keremane, Sam Philliber, Willem Griffiths, Conor Rowland, Julian H. Smith and Richard P. Taylor

Bioengineering 2024, 11(8), 823; https://doi.org/10.3390/bioengineering11080823 - 12 Aug 2024

Viewed by 502

Abstract

Exploring how neurons in the mammalian body interact with the artificial interface of implants can be used to learn about fundamental cell behavior and to refine medical applications. For fundamental and applied research, it is crucial to determine the conditions that encourage neurons [...] Read more.

Exploring how neurons in the mammalian body interact with the artificial interface of implants can be used to learn about fundamental cell behavior and to refine medical applications. For fundamental and applied research, it is crucial to determine the conditions that encourage neurons to maintain their natural behavior during interactions with non-natural interfaces. Our previous investigations quantified the deterioration of neuronal connectivity when their dendrites deviate from their natural fractal geometry. Fractal resonance proposes that neurons will exhibit enhanced connectivity if an implant’s electrode geometry is matched to the fractal geometry of the neurons. Here, we use in vitro imaging to quantify the fractal geometry of mouse retinal neurons and show that they change during interaction with the electrode. Our results demonstrate that it is crucial to understand these changes in the fractal properties of neurons for fractal resonance to be effective in the in vivo mammalian system. Full article

(This article belongs to the Special Issue Bioengineering and the Eye—2nd Edition)

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19 pages, 10631 KiB

Open AccessArticle

Dimensionality Matters: Exploiting UV-Photopatterned 2D and Two-Photon-Printed 2.5D Contact Guidance Cues to Control Corneal Fibroblast Behavior and Collagen Deposition

by Cas van der Putten, Gozde Sahin, Rhiannon Grant, Mirko D’Urso, Stefan Giselbrecht, Carlijn V. C. Bouten and Nicholas A. Kurniawan

Bioengineering 2024, 11(4), 402; https://doi.org/10.3390/bioengineering11040402 - 19 Apr 2024

Cited by 1 | Viewed by 1501

Abstract

In the event of disease or injury, restoration of the native organization of cells and extracellular matrix is crucial for regaining tissue functionality. In the cornea, a highly organized collagenous tissue, keratocytes can align along the anisotropy of the physical microenvironment, providing a [...] Read more.

In the event of disease or injury, restoration of the native organization of cells and extracellular matrix is crucial for regaining tissue functionality. In the cornea, a highly organized collagenous tissue, keratocytes can align along the anisotropy of the physical microenvironment, providing a blueprint for guiding the organization of the collagenous matrix. Inspired by this physiological process, anisotropic contact guidance cues have been employed to steer the alignment of keratocytes as a first step to engineer in vitro cornea-like tissues. Despite promising results, two major hurdles must still be overcome to advance the field. First, there is an enormous design space to be explored in optimizing cellular contact guidance in three dimensions. Second, the role of contact guidance cues in directing the long-term deposition and organization of extracellular matrix proteins remains unknown. To address these challenges, here we combined two microengineering strategies—UV-based protein patterning (2D) and two-photon polymerization of topographies (2.5D)—to create a library of anisotropic contact guidance cues with systematically varying height (H, 0 µm ≤ H ≤ 20 µm) and width (W, 5 µm ≤ W ≤ 100 µm). With this unique approach, we found that, in the short term (24 h), the orientation and morphology of primary human fibroblastic keratocytes were critically determined not only by the pattern width, but also by the height of the contact guidance cues. Upon extended 7-day cultures, keratocytes were shown to produce a dense, fibrous collagen network along the direction of the contact guidance cues. Moreover, increasing the heights also increased the aligned fraction of deposited collagen and the contact guidance response of cells, all whilst the cells maintained the fibroblastic keratocyte phenotype. Our study thus reveals the importance of dimensionality of the physical microenvironment in steering both cellular organization and the formation of aligned, collagenous tissues. Full article

(This article belongs to the Special Issue Bioengineering and the Eye—2nd Edition)

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9 pages, 1560 KiB

Open AccessCommunication

Neurovascular Relationships in AGEs-Based Models of Proliferative Diabetic Retinopathy

by Juan S. Peña, Ranjini K. Ramanujam, Rebecca A. Risman, Valerie Tutwiler, Francois Berthiaume and Maribel Vazquez

Bioengineering 2024, 11(1), 63; https://doi.org/10.3390/bioengineering11010063 - 8 Jan 2024

Cited by 2 | Viewed by 1456

Abstract

Diabetic retinopathy affects more than 100 million people worldwide and is projected to increase by 50% within 20 years. Increased blood glucose leads to the formation of advanced glycation end products (AGEs), which cause cellular and molecular dysfunction across neurovascular systems. These molecules [...] Read more.

Diabetic retinopathy affects more than 100 million people worldwide and is projected to increase by 50% within 20 years. Increased blood glucose leads to the formation of advanced glycation end products (AGEs), which cause cellular and molecular dysfunction across neurovascular systems. These molecules initiate the slow breakdown of the retinal vasculature and the inner blood retinal barrier (iBRB), resulting in ischemia and abnormal angiogenesis. This project examined the impact of AGEs in altering the morphology of healthy cells that comprise the iBRB, as well as the effects of AGEs on thrombi formation, in vitro. Our results illustrate that AGEs significantly alter cellular areas and increase the formation of blood clots via elevated levels of tissue factor. Likewise, AGEs upregulate the expression of cell receptors (RAGE) on both endothelial and glial cells, a hallmark biomarker of inflammation in diabetic cells. Examining the effects of AGEs stimulation on cellular functions that work to diminish iBRB integrity will greatly help to advance therapies that target vision loss in adults. Full article

(This article belongs to the Special Issue Bioengineering and the Eye—2nd Edition)

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13 pages, 5886 KiB

Open AccessArticle

Electrospun Nanofiber Membrane for Cultured Corneal Endothelial Cell Transplantation

by Euisun Song, Karen M. Chen, Mathew S. Margolis, Thitima Wungcharoen, Won-Gun Koh and David Myung

Bioengineering 2024, 11(1), 54; https://doi.org/10.3390/bioengineering11010054 - 5 Jan 2024

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Abstract

The corneal endothelium, comprising densely packed corneal endothelial cells (CECs) adhering to Descemet’s membrane (DM), plays a critical role in maintaining corneal transparency by regulating water and ion movement. CECs have limited regenerative capacity within the body, and globally, there is a shortage [...] Read more.

The corneal endothelium, comprising densely packed corneal endothelial cells (CECs) adhering to Descemet’s membrane (DM), plays a critical role in maintaining corneal transparency by regulating water and ion movement. CECs have limited regenerative capacity within the body, and globally, there is a shortage of donor corneas to replace damaged corneal endothelia. The development of a carrier for cultured CECs may address this worldwide clinical need. In this study we successfully manufactured a gelatin nanofiber membrane (gelNF membrane) using electrospinning, followed by crosslinking with glutaraldehyde (GA). The fabricated gelNF membrane exhibited approximately 80% transparency compared with glass and maintained a thickness of 20 µm. The gelNF membrane demonstrated desirable permeability and degradability for a Descemet’s membrane analog. Importantly, CECs cultured on the gelNF membrane at high densities showed no cytotoxic effects, and the expression of key CEC functional biomarkers was verified. To assess the potential of this gelNF membrane as a carrier for cultured CEC transplantation, we used it to conduct Descemet’s membrane endothelial keratoplasty (DMEK) on rabbit eyes. The outcomes suggest this gelNF membrane holds promise as a suitable carrier for cultured CEC transplantation, offering advantages in terms of transparency, permeability, and sufficient mechanical properties required for successful transplantation. Full article

(This article belongs to the Special Issue Bioengineering and the Eye—2nd Edition)

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12 pages, 5011 KiB

Open AccessArticle

Biocompatibility and Transplantation Efficacy of the C-Clear Artificial Cornea in a Rabbit Chemical Burn Model

by Ho-Seok Chung, Sanghyu Nam, Ko-Eun Lee, Do-Sun Jeong, Seheon Oh, Jeong-Hye Sunwoo, Hun Lee, Jae-Yong Kim and Hungwon Tchah

Bioengineering 2023, 10(10), 1235; https://doi.org/10.3390/bioengineering10101235 - 21 Oct 2023

Viewed by 1534

Abstract

We investigated the bioavailability and stability of a C-Clear artificial cornea in a rabbit chemical burn model. Thirty-six rabbits were divided into a control group (n = 16) and a chemical burn group that used NaOH solution (n = 20). After [...] Read more.

We investigated the bioavailability and stability of a C-Clear artificial cornea in a rabbit chemical burn model. Thirty-six rabbits were divided into a control group (n = 16) and a chemical burn group that used NaOH solution (n = 20). After lamellar dissection, the central posterior lamella was excised using a 3 mm diameter trephine, and an artificial cornea was transplanted into the lamellar pocket. After 2 weeks, the central anterior lamella was excised using a 3 mm diameter trephine to secure a clean visual axis. We examined the anterior segment of the eyes weekly for 12 weeks after transplantation. Successful subjects whose artificial corneas were maintained stably for 12 weeks were euthanized and underwent histologic examinations. Artificial corneas remained stable for up to 12 weeks in 62.5 and 50% of rabbits in the control and chemical burn groups, respectively. Two rabbits in the chemical burn group showed the formation of a retroprosthetic membrane, and one rabbit with visual axis blockage underwent membrane removal using a Nd:YAG laser. In histologic examinations, adhesion between artificial cornea and peripheral corneal stoma was observed. In conclusion, we confirmed structural stability and biocompatibility of the C-Clear artificial cornea for up to 12 weeks after implantation in control and chemical burn groups. Full article

(This article belongs to the Special Issue Bioengineering and the Eye—2nd Edition)

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Review

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17 pages, 295 KiB

Open AccessReview

Innovative Bioscaffolds in Stem Cell and Regenerative Therapies for Corneal Pathologies

by Federico Visalli, Federico Fava, Matteo Capobianco, Mutali Musa, Fabiana D’Esposito, Andrea Russo, Davide Scollo, Antonio Longo, Caterina Gagliano and Marco Zeppieri

Bioengineering 2024, 11(9), 859; https://doi.org/10.3390/bioengineering11090859 - 23 Aug 2024

Viewed by 319

Abstract

Corneal diseases, which can result in substantial visual impairment and loss of vision, are an important worldwide health issue. The aim of this review was to investigate the novel application of bioscaffolds in stem cell and regenerative treatments for the treatment of corneal [...] Read more.

Corneal diseases, which can result in substantial visual impairment and loss of vision, are an important worldwide health issue. The aim of this review was to investigate the novel application of bioscaffolds in stem cell and regenerative treatments for the treatment of corneal disorders. The current literature reports that organic and artificial substances create bioscaffolds that imitate the inherent structure of the cornea, facilitating the attachment, growth, and specialization of stem cells. Sophisticated methods such as electrospinning, 3D bioprinting, and surface modification have been reported to enhance the characteristics of the scaffold. These bioscaffolds have been shown to greatly improve the survival of stem cells and facilitate the regrowth of corneal tissue in both laboratory and live animal experiments. In addition, the incorporation of growth factors and bioactive compounds within the scaffolds can promote a favorable milieu for corneal regeneration. To summarize, the advancement of these groundbreaking bioscaffolds presents a hopeful treatment strategy for the regeneration of the cornea, which has the potential to enhance the results for individuals suffering from corneal disorders. This study highlights the possibility of utilizing the fields of biomaterials science and stem cell treatment to tackle medical demands that have not yet been satisfied in the field of ophthalmology. Full article

(This article belongs to the Special Issue Bioengineering and the Eye—2nd Edition)

41 pages, 1213 KiB

Open AccessReview

Seeing the Future: A Review of Ocular Therapy

by Maiya Whalen, Monica Akula, Shannon M. McNamee, Margaret M. DeAngelis and Neena B. Haider

Bioengineering 2024, 11(2), 179; https://doi.org/10.3390/bioengineering11020179 - 13 Feb 2024

Cited by 1 | Viewed by 2604

Abstract

Ocular diseases present a unique challenge and opportunity for therapeutic development. The eye has distinct advantages as a therapy target given its accessibility, compartmentalization, immune privilege, and size. Various methodologies for therapeutic delivery in ocular diseases are under investigation that impact long-term efficacy, [...] Read more.

Ocular diseases present a unique challenge and opportunity for therapeutic development. The eye has distinct advantages as a therapy target given its accessibility, compartmentalization, immune privilege, and size. Various methodologies for therapeutic delivery in ocular diseases are under investigation that impact long-term efficacy, toxicity, invasiveness, and delivery range. While gene, cell, and antibody therapy and nanoparticle delivery directly treat regions that have been damaged by disease, they can be limited in the duration of the therapeutic delivery and have a focal effect. In contrast, contact lenses and ocular implants can more effectively achieve sustained and widespread delivery of therapies; however, they can increase dilution of therapeutics, which may result in reduced effectiveness. Current therapies either offer a sustained release or a broad therapeutic effect, and future directions should aim toward achieving both. This review discusses current ocular therapy delivery systems and their applications, mechanisms for delivering therapeutic products to ocular tissues, advantages and challenges associated with each delivery system, current approved therapies, and clinical trials. Future directions for the improvement in existing ocular therapies include combination therapies, such as combined cell and gene therapies, as well as AI-driven devices, such as cortical implants that directly transmit visual information to the cortex. Full article

(This article belongs to the Special Issue Bioengineering and the Eye—2nd Edition)

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14 pages, 1188 KiB

Open AccessReview

Quercetin and Related Analogs as Therapeutics to Promote Tissue Repair

by Tina B. McKay, Kyle A. Emmitte, Carrie German and Dimitrios Karamichos

Bioengineering 2023, 10(10), 1127; https://doi.org/10.3390/bioengineering10101127 - 25 Sep 2023

Cited by 9 | Viewed by 1486

Abstract

Quercetin is a polyphenol of the flavonoid class of secondary metabolites that is widely distributed in the plant kingdom. Quercetin has been found to exhibit potent bioactivity in the areas of wound healing, neuroprotection, and anti-aging research. Naturally found in highly glycosylated forms, [...] Read more.

Quercetin is a polyphenol of the flavonoid class of secondary metabolites that is widely distributed in the plant kingdom. Quercetin has been found to exhibit potent bioactivity in the areas of wound healing, neuroprotection, and anti-aging research. Naturally found in highly glycosylated forms, aglycone quercetin has low solubility in aqueous environments, which has heavily limited its clinical applications. To improve the stability and bioavailability of quercetin, efforts have been made to chemically modify quercetin and related flavonoids so as to improve aqueous solubility while retaining bioactivity. In this review, we provide an updated overview of the biological properties of quercetin and proposed mechanisms of actions in the context of wound healing and aging. We also provide a description of recent developments in synthetic approaches to improve the solubility and stability of quercetin and related analogs for therapeutic applications. Further research in these areas is expected to enable translational applications to improve ocular wound healing and tissue repair. Full article

(This article belongs to the Special Issue Bioengineering and the Eye—2nd Edition)

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