scholarly journals LiQD Cornea: Pro-regeneration collagen mimetics as patches and alternatives to corneal transplantation

2020 ◽  
Vol 6 (25) ◽  
pp. eaba2187 ◽  
Author(s):  
Christopher D. McTiernan ◽  
Fiona C. Simpson ◽  
Michel Haagdorens ◽  
Chameen Samarawickrama ◽  
Damien Hunter ◽  
...  

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 to conventional corneal transplantation and sealants. It is a cell-free, liquid hydrogel matrix for corneal regeneration, comprising short collagen-like peptides conjugated with polyethylene glycol and mixed with fibrinogen to promote adhesion within tissue defects. Gelation occurs spontaneously at body temperature within 5 min. Light exposure is not required—particularly advantageous because patients with corneal inflammation are typically photophobic. The self-assembling, fully defined, synthetic collagen analog is much less costly than human recombinant collagen and reduces the risk of immune rejection associated with xenogeneic materials. In situ gelation potentially allows for clinical application in outpatient clinics instead of operating theaters, maximizing practicality, and minimizing health care costs.

Author(s):  
Alejandro Juarez ◽  
Mohamed Djallali ◽  
Marilyse Piché ◽  
Mathieu Thériault ◽  
Marc Groleau ◽  
...  

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) collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and 1% fibrinogen and crosslinked with 2% (w/w) 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), was applied to the wound bed previously coated with thrombin (250 U/ml). In situ gelation occurred within 5 min, and a temporary tarsorrhaphy was performed. Eyes were examined weekly for 1 month, then monthly over 12 months. Outcome parameters included slit-lamp, Scheimpflug tomography, optical coherence tomography, confocal and specular microscopy, and immunohistochemistry studies.Results: The gelled filler was seamlessly incorporated, supporting smooth corneal re-epithelialization. Progressive in-growth of keratocytes and nerves into the filler corresponding to the mild haze observed faded with time. The regenerated neo-cornea remained stably integrated throughout the 12 months, without swelling, inflammation, infection, neovascularization, or rejection. The surrounding host stroma and endothelium remained normal at all times. Tomography confirmed restoration of a smooth surface curvature.Conclusion: Biointegration of this hydrogel filler allowed stable restoration of corneal shape and transparency in the feline model, with less inflammation and no neovascularization compared to previous reports in the minipig and rabbit models. It offers a promising alternative to cyanoacrylate glue and corneal transplantation for ulcerated and traumatized corneas in human patients.


2020 ◽  
Vol 11 (2) ◽  
pp. 181-188
Author(s):  
Matias Iglicki ◽  
Anat Loewenstein ◽  
Manuel Manera ◽  
Claudia Castro ◽  
Catharina Busch ◽  
...  

Background: To report a case of autologous corneal transplant in a patient with corneal leukoma and choroidal melanoma in the fellow eye. Case Presentation: A 56-year-old woman was complaining about decrease in vision in her left eye. The patient was on the waiting list for a corneal transplant on her right eye due to corneal leucoma after a previous herpes infection. The patient was diagnosed with choroidal melanoma in her left eye. Due to the tumor size (longitudinal diameter >10 mm; anterior-posterior diameter >16 mm) the patient decided to undergo enucleation, after being informed about different treatment options (brachytherapy and enucleation). The patient showed her willingness to use the cornea of the left eye as a transplant for her right eye. After discussion with the ethical committee and its approval, and signing informed consent, the patient underwent enucleation of her left eye. The sample was examined by a pathologist and found to be free of melanoma cells in the corneolimbal tissue. Afterwards, trepanation of the donor cornea button was performed and transplanted to the left eye. Conclusion: Autologous corneal transplantation is a safe and feasible procedure in selected cases.


2019 ◽  
Vol 10 ◽  
pp. 204173141882338 ◽  
Author(s):  
Hyeonji Kim ◽  
Moon-Nyeo Park ◽  
Jisoo Kim ◽  
Jinah Jang ◽  
Hong-Kyun Kim ◽  
...  

Corneal transplantation is a typical surgical procedure for severe corneal diseases. However, the waiting time for a donor cornea has gradually increased due to a decrease in supply caused by an aging population and increased cases of laser-based surgeries. Artificial corneas were developed to meet the increase in demand; however, these approaches have suffered from material deterioration resulted by the limited tissue integration. Here, we introduce a cornea-derived decellularized extracellular matrix (Co-dECM) as a bioink for corneal regeneration. The developed Co-dECM bioink had similar quantitative measurement results for collagen and GAGs compared with that of the native cornea and also had the proper transparency for vision. The differentiation potential of human turbinate-derived mesenchymal stem cells (hTMSCs) to a keratocyte lineage was only observed in the Co-dECM group. Moreover, the developed bioink did not have any cytotoxic effect on encapsulated cells for three-dimensional (3D) culture and has great biocompatibility evident by the xeno-implantation of the Co-dECM gel into mice and rabbits for two and one month, respectively. An in vivo safety similar to clinical-grade collagen was seen with the Co-dECM, which helped to maintain the keratocyte-specific characteristics in vivo, compared with collagen. Taken together, the Co-dECM bioink has the potential to be used in various types of corneal diseases based on its corneal-specific ability and design flexibility through 3D cell printing technology.


Biomaterials ◽  
2014 ◽  
Vol 35 (8) ◽  
pp. 2420-2427 ◽  
Author(s):  
Per Fagerholm ◽  
Neil S. Lagali ◽  
Jeb A. Ong ◽  
Kimberley Merrett ◽  
W. Bruce Jackson ◽  
...  

2016 ◽  
Vol 31 (1_suppl) ◽  
pp. 80-87 ◽  
Author(s):  
Mark H Meissner

Varicose veins affect one-quarter to one-third of Western adult populations and consume an increasing amount of health care resources. Much of this increased utilization has been driven by the advent of minimally invasive technology including endovenous thermal ablation, foam sclerotherapy, and more recently mechanicochemical and cyanoacrylate glue ablation. This has largely been driven by patient and physician preferences in the absence of robust evidence that one therapy is truly superior to another. This partially arises from misunderstandings about appropriate outcomes measures and what truly constitutes effective treatment of varicose veins. Technical outcomes, such as saphenous closure rates, have frequently been used as surrogates for effective treatment but are poorly correlated with symptom improvement, quality of life, and risk of recurrence. Although there does appear to be a trend towards higher recurrence with ultrasound-guided foam sclerotherapy, the data are occasionally conflicting and there does not appear to be substantial differences between the various modalities. Similarly, there do not appear to be major differences in late quality of life measures between these treatment options. As long-term differences in recurrence and quality of life are small, overall cost effectiveness is driven primarily by initial treatment costs and ultrasound-guided foam sclerotherapy is the most cost-effective strategy in many models. However, there continues to be substantial uncertainty surrounding cost estimates and other factors of importance to the patient may ultimately drive treatment decisions. The benefits of some adjuncts to the treatment of axial superficial reflux, such as the concurrent versus staged management of tributary varicosities, remain ill-defined while that of others, such as routine post-procedural ultrasound surveillance and compression, need critical re-evaluation.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5745
Author(s):  
Ana Karen Mendoza-Martinez ◽  
Daniela Loessner ◽  
Alvaro Mata ◽  
Helena S. Azevedo

Ovarian cancer (OvCa) is one of the leading causes of gynecologic malignancies. Despite treatment with surgery and chemotherapy, OvCa disseminates and recurs frequently, reducing the survival rate for patients. There is an urgent need to develop more effective treatment options for women diagnosed with OvCa. The tumor microenvironment (TME) is a key driver of disease progression, metastasis and resistance to treatment. For this reason, 3D models have been designed to represent this specific niche and allow more realistic cell behaviors compared to conventional 2D approaches. In particular, self-assembling peptides represent a promising biomaterial platform to study tumor biology. They form nanofiber networks that resemble the architecture of the extracellular matrix and can be designed to display mechanical properties and biochemical motifs representative of the TME. In this review, we highlight the properties and benefits of emerging 3D platforms used to model the ovarian TME. We also outline the challenges associated with using these 3D systems and provide suggestions for future studies and developments. We conclude that our understanding of OvCa and advances in materials science will progress the engineering of novel 3D approaches, which will enable the development of more effective therapies.


Abstract Keratoconus is an ectatic corneal disorder characterized by progressive corneal thinning and protrusion. Keratoconus recurrence after corneal transplantation although rare is present and has been confirmed histologically. Host, donor, genetic, mechanical and environmental factors have been proposed as predisposing factors to initiate keratoconus recurrence. The time-to-recurrence post-deep anterior lamellar keratoplasty seems to occur earlier than after penetrating keratoplasty. Wound dehiscence and high astigmatism post-transplant are plausible differential diagnosis for this entity. The treatment options are similar to primary keratoconus. Since, the era of collagen corneal cross-linking, early diagnosis is desirable as it could halt the progression of recurrent keratoconus. How to cite this article Barbara R, Barbara A. Recurrent Keratoconus. Int J Kerat Ect Cor Dis 2013;2(2):65-68.


Materials ◽  
2019 ◽  
Vol 12 (5) ◽  
pp. 832 ◽  
Author(s):  
Scott Elgersma ◽  
Michelle Ha ◽  
Jung-Lynn Yang ◽  
Vladimir Michaelis ◽  
Larry Unsworth

Self-assembling peptides are a promising class of biomaterials with desirable biocompatibility and versatility. In particular, the oligopeptide (RADA)4, consisting of arginine (R), alanine (A), and aspartic acid (D), self-assembles into nanofibers that develop into a three-dimensional hydrogel of up to 99.5% (w/v) water; yet, the organization of water within the hydrogel matrix is poorly understood. Importantly, peptide concentration and polarity are hypothesized to control the internal water structure. Using variable temperature deuterium solid-state nuclear magnetic resonance (2H NMR) spectroscopy, we measured the amount of bound water in (RADA)4-based hydrogels, quantified as the non-frozen water content. To investigate how peptide polarity affects water structure, five lysine (K) moieties were appended to (RADA)4 to generate (RADA)4K5. Hydrogels at 1 and 5% total peptide concentration were prepared from a 75:25 (w/w) blend of (RADA)4:(RADA)4K5 and similarly analyzed by 2H NMR. Interestingly, at 5% peptide concentration, there was lower mobile water content in the lysinated versus the pristine (RADA)4 hydrogel. Regardless of the presence of lysine, the 5% peptide concentration had higher non-frozen water content at temperatures as low as 217 ± 1.0 K, suggesting that bound water increases with peptide concentration. The bound water, though non-frozen, may be strongly bound to the charged lysine moiety to appear as immobilized water. Further understanding of the factors controlling water structure within hydrogels is important for tuning the transport properties of bioactive solutes in the hydrogel matrix when designing for biomedical applications.


Author(s):  
Kazuhiko Ishihara ◽  
Miu Kaneyasu ◽  
Kyoko Fukazawa ◽  
Ren Zhang ◽  
Yuji Teramura

The effects of differentiated cells on stem cell differentiation were analyzed by co-culture using a cell-encapsulated double-layered hydrogel system. As a polymer hydrogel matrix, a water-soluble zwitterionic polymer having both...


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