May Griffith

Université de Montréal | UdeM · Department of Ophthalmology

Sterilization of biodegradable, collagen-based implants is challenging as irradiation sterilization methods can alter their mechanical properties. Electron beam (EB) irradiation is a terminal sterilization method that has been used for biologically-derived implants. Here, recombinant human collagen type III-phosphorylcholine (RHCIII-MPC) hydrogels...

Nociceptor Neuron Silencing In article number 2103364, Sebastien Talbot, Christos Boutopoulos, and co‐workers report a nanotechnology‐enabled strategy to silence subsets of unmodified nociceptor neurons. It uses laser stimulation of neurons targeted with gold nanoparticles to heat‐activate TRPV1, turning this channel into a cell‐specific entry port...

The sensory nervous and immune systems work in concert to preserve homeostasis. While this endogenous interplay protects from danger, it may drive chronic pathologies. Currently, genetic engineering of neurons remains the primary approach to interfere selectively with this potentially deleterious interplay. However, such manipulations are not feasi...

Purpose: To evaluate long-term in vivo functionality of corneas regenerated using a cell-free, liquid hydrogel filler (LiQD Cornea) after deep corneal trauma in the feline model. Methods: Two healthy cats underwent 4 mm diameter stepwise 250/450 µm deep surgical corneal ablation with and without needle perforation. The filler comprising 10% (w/w) c...

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 1–2% of the population aged 65 and over. Additionally, non-motor symptoms such as pain and gastrointestinal dysregulation are also common in PD. These impairments might stem from a dysregulation within the gut-brain axis that alters immunity and the inflammator...

We have studied the suitability of using a molecular rotor-based steady-state fluorometric assay for evaluating changes in both the conformation and the viscosity of collagen-like peptide solutions. Our results indicate...

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), w...

Purpose To determine feasibility of plant-derived recombinant human collagen type I (RHCI) for use in corneal regenerative implants Methods RHCI was crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to form hydrogels. Application of shear force to liquid crystalline RHCI aligned the collagen fibr...

The long-term survival of biomaterial implants is often hampered by surgery-induced inflammation that can lead to graft failure. Considering that most corneas receiving grafts are either pathological or inflamed before implantation, the risk of rejection is heightened. Here, we show that bioengineered, fully synthetic, and robust corneal implants c...

Biofilm formation in living organisms is associated to tissue and implant infections and it has also been linked to the contribution of antibiotic resistance. Thus, understanding biofilm development and being able to mimic such processes is vital for the successful development of anti-biofilm treatments and therapies. Several decades of research ha...

A rapid and precise route to graft a nano-bactericidal barrier is reported.

Recombinant or artificial designer collagens have developed to a point where they are viable candidates for replacing extracted animal collagens in regenerative medicine applications. Biomimetic corneas made have shown promise as replacements for human donor corneas, and have previously been fabricated from several different collagens or collagen-l...

Transplantation with donor corneas is the mainstay for treating corneal blindness, but a severe worldwide shortage necessitates the development of other treatment options. Corneal perforation from infection or inflammation is sealed with cyanoacrylate glue. However, the resulting cytotoxicity requires transplantation. LiQD Cornea is an alternative...

Introduction: Corneal transplantation surgery faces several fundamental problems, including graft failure, especially in complicated cases, and a marked shortage of human donor corneas. The purpose of this review is to examine several developments in biosynthetic alternatives to donor corneal transplantation. In particular, we focus on the regulato...

In current clinical practice, corneas with perforations that are repaired by cyanoacrylate gluing and those with recurrent ulcerations are often treated by corneal grafting as the treatment to restore vision. However, there is a severe shortage of donor corneas worldwide. More importantly, when someone has a toothache and visits the dentist, the de...

Herpes Simplex Virus-1 (HSV-1) infections in the eye often originate in the cornea before assuming a latent state in the trigeminal ganglion. During primary infection and upon injury or reactivation, HSV-1 can lead to significant corneal damage. Nanoparticles (NPs) are an emerging strategy for drug delivery to the cornea because they improve the lo...

Activated T cells are known to promote fibrosis, a major complication limiting the range of polymeric hydrogels as artificial corneal implants. As T cells are activated by dendritic cells (DC), minimally activating hydrogels would be optimal. In this study, we evaluated the ability of a series of engineered (manufactured/fabricated) and natural col...

We showed previously that 1‐ethyl‐3‐(3‐dimethylamino‐propyl)‐carbodiimide hydrochloride (EDC) crosslinked recombinant human collagen III (RHCIII) hydrogels promoted stable regeneration of the human cornea (continued nerve and stromal cell repopulation) for over four years. However, as EDC crosslinking kinetics were difficult to control we additiona...

Purpose: To investigate the efficacy of recombinant human collagen type I (RHC I) and collagen-like peptide (CLP) hydrogels as alternative carrier substrates for the cultivation of limbal epithelial stem cells (LESC) under xeno-free culture conditions. Methods: Human LESC were cultivated on seven different collagen-derived hydrogels: (1) unmodif...

The severe worldwide shortage of donor organs, and severe pathologies placing patients at high risk for rejecting conventional cornea transplantation, have left many corneal blind patients untreated. Following successful pre-clinical evaluation in mini-pigs, we tested a biomaterials-enabled pro-regeneration strategy to restore corneal integrity in...

Recently, we found a mistake in Figure 4D in our previously published paper[...]

Unoperated cornea. Epithelium is pseudocoloured blue.

RHCIII-MPC implanted cornea.

Extracellular vesicles (gold colour) in CLP-PEG implanted cornea.

CLP-PEG implanted cornea.

Statement of significance: Although biomaterials comprising full-length recombinant human collagen and extracted animal collagen have been evaluated and used clinically, these macromolecules provide only a limited number of functional groups amenable to chemical modification or crosslinking and are demanding to process. Synthetic, customizable ana...

Currently, full-thickness transplantation with human donor corneas is the most widely accepted treatment for corneal blindness. However, due to a severe shortage of human donor corneas as well as problems associated with the storage, screening, and immune response to allogeneic tissues, there has been a push to develop alternative therapies and mat...

The term artificial cornea is used loosely to refer to a wide range of bioengineered implants from prostheses that are designed to replace the minimal function of the cornea to implants that promote regeneration of the different corneal structures and nerves. The trend is towards the use of biomaterials that promote corneal regeneration, with impla...

Ocular fluid is an extracellular fluid excreted from the tear gland. Several important markers from ocular fluid have been identified as having significant clinical diagnostic value for various diseases. The contact lens is disposable, relatively cheap and serves as a platform to obtain direct intimate contact with ocular fluid and is therefore an...

Age-associated diseases are becoming more prevalent as the worldwide population is getting older. This chapter reviews the current developments in nanotechnology directed at combating the rise of diseases and ailments stemming from ageing. The major complications that are discussed are cancers, cardiovascular disease, and neurodegeneration. Medical...

Sulfated polysaccharides and synthetic glycopolymers are promising candidates as antiviral drugs but have failed in clinical trials most likely due to lack of virucidal activity. However, studies have shown that incorporation of lipophilic end groups to oligosaccharide chains is a mean to gain the desired virucidal properties. Here, we describe the...

Purpose: To describe the use of collagen-based alternatives to cyanoacrylate glue for the sealing of acute corneal perforations. Methods: A collagen analog comprising a collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and its chemical crosslinker were tested for biocompatibility. These CLP-PEG hydrogels, which are designed to ac...

Statement of significance: The manuscript addresses the significance of bone marrow-derived mesenchymal stem cell therapy for retro-corneal membrane (RCM) formation in full-thickness transplantation of biosynthetic corneal equivalents. This work reports the pathophysiological changes in the anterior chamber of the mouse eye following full-thicknes...

Human mesenchymal stromal cells (hMSCs) are adult-source cells that have been extensively evaluated for cell-based therapies. hMSCs delivered by intravascular injection have been reported to accumulate at sites of injury to promote tissue repair and can also be employed as vectors for delivery of therapeutic genes. However, the full potential of hM...

Purpose of Review Corneal disease affects 12.7 million individuals globally, and the current gold standard therapy using a human donor cornea (HDC) in low-risk patients or keratoprosthesis in high-risk patients is prone to graft rejection. New techniques are currently being investigated to regenerate corneal tissue to provide a more effective treat...

Cultured epidermal cell sheets (CES) containing undifferentiated cells are useful for treating skin burns and have potential for regenerative treatment of other types of epithelial injuries. The undifferentiated phenotype is therefore important for success in both applications. This study aimed to optimize a method for one-week storage of CES for t...

Correction for ‘Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications’ by R. Ravichandran et al., J. Mater. Chem. B, 2016, 4, 318–326.

Transplantation of cultured oral mucosal epithelial cells (OMECs) is a promising treatment strategy for limbal stem cell deficiency. In order to improve the culture method, we investigated the effects of four culture media and tissue harvesting sites on explant attachment, growth, and phenotype of OMECs cultured from Sprague-Dawley rats. Neither ch...

Corneal blindness is a major cause of blindness in the world and corneal transplantation is the only widely accepted treatment to restore sight in these eyes. However, it is becoming increasingly difficult for eye banks to meet the increasing demand for transplantable tissue, which is in part due to population aging. Donor tissue shortage is theref...

We report for the first time the preparation of a fibrous material composed of surface grafted spherical nanosilver and collagen using one-step electrospinning. The resulting composite showed comparable morphology to the control without nanosilver, but had improved electrical conductivity. Under electrical stimulation, fibrous materials containing...

Using a combination of methacrylated collagen and the photosensitizer rose Bengal, a new light-activated biomimetic material for tissue sutureless bonding was developed. This formulation was cross-linked using green light. In vivo tests in mice demonstrate the suitability of the material for sutureless wound closure.

Purpose We fabricated and investigated polymeric scaffolds that can substitute for the conjunctival extracellular matrix to provide a substrate for autologous expansion of human conjunctival goblet cells in culture. Methods We fabricated two hydrogels and two silk films: (1) recombinant human collagen (RHC) hydrogel, (2) recombinant human collagen...

A nanocellulose-reinforced polyvinyl alcohol hydrogel material of exceptionally high water content for ophthalmic applications is presented (>90% wt), which also features hitherto unprecedented combination of optical, mechanical, viscoelastic, oxygen permeability, and biocompatibility properties. The hydrogel combines the desired softness with rema...

Purpose To assess safety and efficacy of biosynthetic collagen-phosphorylcholine implants as corneal substitutes in patients with severe pathologies for whom human donor cornea transplantation carries a high risk of rejection. Methods Recombinant human collagen type III and 2-methacryloyloxyethyl-phosphorylcholine were fabricated into collagen-MPC...

We have previously shown in animal models and in early clinical studies that collagen-based biomaterials promoted functional regeneration of corneal epithelium, stroma and nerves. Recently, we showed that these fabricated implants were made of collagen fibrils that were fine and aligned, like those in human corneas. There were noticeable difference...

The marine sulfated polysaccharide fucoidan displays superior ability to induce platelet aggregation compared to other sulfated polysaccharides. As such, it is an attractive tool for studying molecular and cellular responses in activated platelets. The heterogeneous structure, however, poses a problem in such applications. This study describes the...

Bioresorbable and biodegradable polymers have been heavily used for the treatment of various ocular diseases as well as in basic ophthalmology research. These polymers, owing to their biocompatibility and prolonged biodegradability, are suitable substances as ocular drug delivery vehicles and temporary devices or implants to support ocular tissue r...

Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date, however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunologica...

INTRODUCTION: Limbal Epithelial Stem Cell (LESC) deficiency is an orphan disease leading to corneal blindness. Tissue engineering has become a treatment modality for this condition, as cultivated limbal epithelial transplantation (CLET) can successfully regenerate the anterior cornea [1]. In CLET, a limbal biopsy is cultivated and transplanted with...

Purpose: The current and projected shortage of transplantable human donor corneas has prompted the development of long-term alternatives to human donor tissue for corneal replacement. The biosynthetic stromal substitutes (BSS) characterized herein represent a potentially safe alternative to donor organ transplantation for anterior corneal stromal...

The cornea is the transparent front part of the eye that transmits light to the back of the eye to generate vision. Loss of corneal transparency, if irreversible, leads to severe vision loss or blindness. For decades, corneal transplantation using human donor corneas has been the only option for treating corneal blindness. Despite recent improvemen...

The human cornea is the transparent surface of the eye, which serves as the main refractive element of the visual system. Its function depends upon its optical clarity so irreversible loss of transparency due to disease or damage results in permanent vision loss or blindness, necessitating corneal transplantation (keratoplasty) in entirety or in pa...

Purpose: Storage of cultured human oral keratinocytes (HOK) allows for transportation of cultured transplants to eye clinics worldwide. In a previous study, one-week storage of cultured HOK was found to be superior with regard to viability and morphology at 12°C compared to 4°C and 37°C. To understand more of how storage temperature affects cell p...