In situ Tissue Regeneration in the Cornea from Bench to Bedside

2021 ◽  
pp. 1-21
Author(s):  
Bijay K. Poudel ◽  
Marie-Claude Robert ◽  
Fiona C. Simpson ◽  
Kamal Malhotra ◽  
Ludovic Jacques ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Corneal Transplantation ◽  
High Income ◽  
Corneal Transplant ◽  
Middle Income ◽  
In Vivo Models ◽  
Corneal Blindness ◽  
In Situ Gelling

Corneal blindness accounts for 5.1% of visual deficiency and is the fourth leading cause of blindness globally. An additional 1.5–2 million people develop corneal blindness each year, including many children born with or who later develop corneal infections. Over 90% of corneal blind people globally live in low- and middle-income regions (LMIRs), where corneal ulcers are approximately 10-fold higher compared to high-income countries. While corneal transplantation is an effective option for patients in high-income countries, there is a considerable global shortage of corneal graft tissue and limited corneal transplant programs in many LMIRs. In situ tissue regeneration aims to restore diseases or damaged tissues by inducing organ regeneration. This can be achieved in the cornea using biomaterials based on extracellular matrix (ECM) components like collagen, hyaluronic acid, and silk. Solid corneal implants based on recombinant human collagen type III were successfully implanted into patients resulting in regeneration of the corneal epithelium, stroma, and sub-basal nerve plexus. As ECM crosslinking and manufacturing methods improve, the focus of biomaterial development has shifted to injectable, in situ gelling formulations. Collagen, collagen-mimetic, and gelatin-based in situ gelling formulas have shown the ability to repair corneal wounds, surgical incisions, and perforations in in-vivo models. Biomaterial approaches may not be sufficient to treat inflammatory conditions, so other cell-free therapies such as treatment with tolerogenic exosomes and extracellular vesicles may improve treatment outcomes. Overall, many of the technologies described here show promise as future medical devices or combination products with cell or drug-based therapies. In situ tissue regeneration, particularly with liquid formulas, offers the ability to triage and treat corneal injuries and disease with a single regenerative solution, providing alternatives to organ transplantation and improving patient outcomes.

scholarly journals Three-dimensional in situ morphometrics of Mycobacterium tuberculosis infection within lesions by optical mesoscopy and novel acid-fast staining

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Robert J. Francis ◽  
Gillian Robb ◽  
Lee McCann ◽  
Bhagwati Khatri ◽  
James Keeble ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Three Dimensional ◽  
Large Field ◽  
Staining Procedure ◽  
3D Analysis ◽  
Mycobacterium Tuberculosis Infection ◽  
In Vivo Models ◽  
Novel Approach

AbstractTuberculosis (TB) preclinical testing relies on in vivo models including the mouse aerosol challenge model. The only method of determining colony morphometrics of TB infection in a tissue in situ is two-dimensional (2D) histopathology. 2D measurements consider heterogeneity within a single observable section but not above and below, which could contain critical information. Here we describe a novel approach, using optical clearing and a novel staining procedure with confocal microscopy and mesoscopy, for three-dimensional (3D) measurement of TB infection within lesions at sub-cellular resolution over a large field of view. We show TB morphometrics can be determined within lesion pathology, and differences in infection with different strains of Mycobacterium tuberculosis. Mesoscopy combined with the novel CUBIC Acid-Fast (CAF) staining procedure enables a quantitative approach to measure TB infection and allows 3D analysis of infection, providing a framework which could be used in the analysis of TB infection in situ.

scholarly journals In-vivo Evaluation and Characterization of Novel In-Situ Gelling System as Controlled Delivery System Containing Ciprofloxacin for Ocular Drug Delivery

2020 ◽  
Vol 10 (5-s) ◽  
pp. 32-39
Author(s):  
Fatima Eram ◽  
, Vivek
Keyword(s):  
Drug Delivery ◽  
Delivery System ◽  
Average Concentration ◽  
Posterior Segment ◽  
Ocular Infection ◽  
In Vivo Evaluation ◽  
Micro Emulsion ◽  
In Situ Gelling

Objectives: The purpose of this research was to develop the micro emulsion-based in situ gelling systems containing Ciprofloxacin for prophylaxis and treatment of the posterior segment diseases like endophthalmitis. Methods: Ciprofloxacin was encapsulated in small droplets owing to form microemulsion, and then the formed droplets were dispersed in a polymer solution that converted into a gel upon triggered by the electrolyte present in the tear fluid. Results: The formulation approach provides better absorption, penetration, retention, and improves the bioavailability of the drug. The average concentration reached into vitreous humor from topical microemulsion in situ gelling formulation was ~0.4 µg/ml, which is far more than the concentration required for therapeutic effect (i.e.  >0.047 µg/ml or >MIC90 for S. Epidermidis, a pathogen commonly responsible to cause endophthalmitis). Conclusion: Thus, novel micro emulsion-based in situ gelling formulation could be a potential drug delivery system for the treatment of posterior segment diseases like endophthalmitis. Keywords: Microemulsion, ciprofloxacin, endophthalmitis, ocular, infection, in situ

Intra-oral Models: Comparison of in situ Substrates

1992 ◽  
Vol 71 (3_suppl) ◽  
pp. 920-923 ◽  
Author(s):  
B. øgaard ◽  
G. Rølla
Keyword(s):  
Clinical Effects ◽  
Hard Tissue ◽  
In Vivo Models ◽  
Caries Model ◽  
Models Comparison ◽  
Risk Patients ◽  
Oral Conditions ◽  
Bovine Enamel

Numerous intra-oral caries models have been designed for clinical and mechanistic purposes. Several factors—such as human vs. bovine enamel, sound vs. demineralized tissues, lesion type, dentin vs. enamel, the severity of the cariogenic challenge, and the microflora—may influence the reactivity of the hard tissue and hence lesion development and progression. Some models use unextracted teeth and are true in vivo models, whereas in situ models are based on hard-tissue substrates in the form of slabs or sections. Models producing a moderate cariogenic challenge usually show a fluoride dose response. However, caries is increasingly becoming a problem limited to some high-risk patients and to lesions located to areas where severe challenges exist (e.g., fissures and pits). There is thus need for models that could mimic such situations. One of the requirements for intra-oral models producing severe cariogenic challenge conditions should probably be that it should be able to demineralize fluorapatite. A challenge for future caries research is to develop agents that have a better clinical effect in fissures and pits than those presently available. Because, in the past, much emphasis has been placed on remineralization of artificial lesions, more research on the demineralization process should be performed in the future, since this may give improved clinical effects. Ideally, an intra-oral caries model should take into account as many of the natural oral conditions as possible and minimize the degree of artificiality.

scholarly journals Regenerative capacity of the corneal transition zone for endothelial cell therapy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicole Ming Sie ◽  
Gary Hin-Fai Yam ◽  
Yu Qiang Soh ◽  
Matthew Lovatt ◽  
Deepinder Dhaliwal ◽  
...  
Keyword(s):  
Transition Zone ◽  
Corneal Endothelium ◽  
Ex Vivo ◽  
Corneal Transplantation ◽  
Corneal Stroma ◽  
Regenerative Capacity ◽  
In Vivo Models ◽  
Endothelial Progenitors ◽  
Donor Corneas

AbstractThe corneal endothelium located on the posterior corneal surface is responsible for regulating stromal hydration. This is contributed by a monolayer of corneal endothelial cells (CECs), which are metabolically active in a continuous fluid-coupled efflux of ions from the corneal stroma into the aqueous humor, preventing stromal over-hydration and preserving the orderly arrangement of stromal collagen fibrils, which is essential for corneal transparency. Mature CECs do not have regenerative capacity and cell loss due to aging and diseases results in irreversible stromal edema and a loss of corneal clarity. The current gold standard of treatment for this worldwide blindness caused by corneal endothelial failure is the corneal transplantation using cadaveric donor corneas. The top indication is Fuchs corneal endothelial dystrophy/degeneration, which represents 39% of all corneal transplants performed. However, the global shortage of transplantable donor corneas has restricted the treatment outcomes, hence instigating a need to research for alternative therapies. One such avenue is the CEC regeneration from endothelial progenitors, which have been identified in the peripheral endothelium and the adjacent transition zone. This review examines the evidence supporting the existence of endothelial progenitors in the posterior limbus and summarizes the existing knowledge on the microanatomy of the transitional zone. We give an overview of the isolation and ex vivo propagation of human endothelial progenitors in the transition zone, and their growth and differentiation capacity to the corneal endothelium. Transplanting these bioengineered constructs into in vivo models of corneal endothelial degeneration will prove the efficacy and viability, and the long-term maintenance of functional endothelium. This will develop a novel regenerative therapy for the management of corneal endothelial diseases.

The in vivo performance of magnetic particle-loaded injectable, in situ gelling, carriers for the delivery of local hyperthermia

Biomaterials ◽  
2010 ◽  
Vol 31 (4) ◽  
pp. 691-705 ◽  
Author(s):  
Pol-Edern Le Renard ◽  
Olivier Jordan ◽  
Antonin Faes ◽  
Alke Petri-Fink ◽  
Heinrich Hofmann ◽  
...  
Keyword(s):  
Magnetic Particle ◽  
Local Hyperthermia ◽  
In Situ Gelling
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