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A Tenon's capsule/bulbar conjunctiva interface biomimetic to model fibrosis and local drug delivery.

ABSTRACT: Glaucoma filtration surgery is one of the most effective methods for lowering intraocular pressure in glaucoma. The surgery efficiently reduces intra-ocular pressure but the most common cause of failure is scarring at the incision site. This occurs in the conjunctiva/Tenon's capsule layer overlying the scleral coat of the eye. Currently used antimetabolite treatments to prevent post-surgical scarring are non-selective and are associated with potentially blinding side effects. Developing new treatments to target scarring requires both a better understanding of wound healing and scarring in the conjunctiva, and new means of delivering anti-scarring drugs locally and sustainably. By combining plastic compression of collagen gels with a soft collagen-based layer, we have developed a physiologically relevant model of the sub-epithelial bulbar conjunctiva/Tenon's capsule interface, which allows a more holistic approach to the understanding of subconjunctival tissue behaviour and local drug delivery. The biomimetic tissue hosts both primary human conjunctival fibroblasts and an immune component in the form of macrophages, morphologically and structurally mimicking the mechanical proprieties and contraction kinetics of ex vivo porcine conjunctiva. We show that our model is suitable for the screening of drugs targeting scarring and/or inflammation, and amenable to the study of local drug delivery devices that can be inserted in between the two layers of the biomimetic. We propose that this multicellular-bilayer engineered tissue will be useful to study complex biological aspects of scarring and fibrosis, including the role of inflammation, with potentially significant implications for the management of scarring following glaucoma filtration surgery and other anterior ocular segment scarring conditions. Crucially, it uniquely allows the evaluation of new means of local drug delivery within a physiologically relevant tissue mimetic, mimicking intraoperative drug delivery in vivo.

SUBMITTER: Kozdon K

PROVIDER: S-EPMC7608904 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Tenon's capsule/bulbar conjunctiva interface biomimetic to model fibrosis and local drug delivery.

Kozdon Katarzyna K Caridi Bruna B Duru Iheukwumere I Ezra Daniel G DG Phillips James B JB Bailly Maryse M

PloS one 20201103 11

Glaucoma filtration surgery is one of the most effective methods for lowering intraocular pressure in glaucoma. The surgery efficiently reduces intra-ocular pressure but the most common cause of failure is scarring at the incision site. This occurs in the conjunctiva/Tenon's capsule layer overlying the scleral coat of the eye. Currently used antimetabolite treatments to prevent post-surgical scarring are non-selective and are associated with potentially blinding side effects. Developing new trea ...[more]

PMID: 33141875

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Project description:Musculoskeletal disorders are a significant burden on the global economy and public health. Advanced drug delivery plays a key role in the musculoskeletal field and holds the promise of enhancing the repair of degenerated and injured musculoskeletal tissues. Ideally, drug delivery should have the ability to directly deliver therapeutic agents to the diseased/injured sites with a desirable drug level over a period of time. Here, we present a mini-review of the current state-of-the-art research associated with local drug delivery and its use for the treatment of musculoskeletal disorders. First, an overview of drug delivery strategies, with a focus on issues related to musculoskeletal pathology, potential therapeutic strategies, conventional and non-conventional drugs, and various delivery systems, is introduced. Then, we highlight recent advances in the emerging fields of musculoskeletal local drug delivery, involving therapeutic drugs (e.g., genes, small molecule therapeutics, and stem cells), novel delivery vehicles (e.g., 3D printing and tissue engineering techniques), and innovative delivery approaches (e.g., multi-drug delivery and smart stimuli-responsive delivery). The review concludes with future perspectives and associated challenges for developing local drug delivery for musculoskeletal applications. STATEMENT OF SIGNIFICANCE: Three important aspects are highlighted in this manuscript: 1) The advanced musculoskeletal drug delivery is introduced from the aspects ranging from musculoskeletal disorders, potential therapeutic solutions, and various drug delivery systems. 2) The recent advances in the emerging fields of musculoskeletal local drug delivery, involving therapeutic drugs (e.g., genes, small molecule therapeutics, and stem cells), novel delivery vehicles (e.g., 3D printing and tissue engineering technique), and innovative delivery approaches (e.g., multi-drug delivery and smart stimuli-responsive delivery), are highlighted. 3) The challenges and perspectives of future research directions in the development of musculoskeletal local drug delivery are presented.

Project description:ImportanceLissamine green (LG) staining of the conjunctiva is a key biomarker in evaluating ocular surface disease. The disease currently is assessed using relatively coarse subjective scales. Objective assessment would standardize comparisons over time and between clinicians.ObjectiveTo develop a semiautomated, quantitative system to assess lissamine green staining of the bulbar conjunctiva on digital images.Design, setting, and participantsUsing a standard photography protocol, 35 digital images of the conjunctiva of 11 patients with a diagnosis of dry eye disease based on characteristic signs and symptoms were obtained after topical administration of preservative-free LG, 1%, solution. Images were scored independently by 2 masked ophthalmologists in an academic medical center using the van Bijsterveld and National Eye Institute (NEI) scales. The region of interest was identified by manually marking 7 anatomic landmarks on the images. An objective measure was developed by segmenting the images, forming a vector of key attributes, and then performing a random forest regression. Subjective scores were correlated with the output from a computer algorithm using a cross-validation technique. The ranking of images from least to most staining was compared between the algorithm and the ophthalmologists. The study was conducted from April 26, 2012, through June 2, 2016.Main outcomes and measuresCorrelation and level of agreement among computerized algorithm scores, van Bijsterveld scale clinical scores, and NEI scale clinical scores.ResultsThe scores from the automated algorithm correlated well with the mean scores obtained from the gradings of 2 ophthalmologists for the 35 images using the van Bijsterveld scale (Spearman correlation coefficient, rs = 0.79), and moderately with the NEI scale (rs = 0.61) scores. For qualitative ranking of staining, the correlation between the automated algorithm and the 2 ophthalmologists was rs = 0.78 and rs = 0.83.Conclusions and relevanceThe algorithm performed well when evaluating LG staining of the conjunctiva, as evidenced by good correlation with subjective gradings using 2 different grading scales. Future longitudinal studies are needed to assess the responsiveness of the algorithm to change of conjunctival staining over time.

Dataset Information

A Tenon's capsule/bulbar conjunctiva interface biomimetic to model fibrosis and local drug delivery.

Publications

A Tenon's capsule/bulbar conjunctiva interface biomimetic to model fibrosis and local drug delivery.

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