Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants

Jangamreddy, Jaganmohan Reddy; Haagdorens, Michel; Islam, Mohammad Mirazul; Lewis, Philip N.; Samanta, Ayan; Fagerholm, Per; Liszka, Aneta; Ljunggren, Monika Kozak; Buznyk, Oleksiy; Alarcon, Emilio I.; Zakaria, Nadia; Meek, Keith Michael Andrew; Griffith, May

doi:10.1016/j.actbio.2018.01.011

Cited by 52 publications

(45 citation statements)

References 38 publications

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“…In that respect, a 36 amino-acid long CMP chain (O'Leary et al, 2011) was modified by addition of a two-amino acid linker (Islam et al, 2016), covalently conjugated to a backbone of mechanically tougher polyethylene glycol (PEG), and subsequently crosslinked (Rubert Pérez et al, 2015). The resulting CMP-PEG stabilised hydrogels were as effective as full-length collagen gels in promoting corneal functional repair as recently shown in mini-pigs (Jangamreddy et al, 2018).…”

Section: Introductionmentioning

confidence: 92%

“…In contrast, full thickness implants, where the integrity of host endothelium is compromised, depend upon minimising the wound healing response and development of opaque scar tissue (retro‐corneal membrane [RCM] formation) to retain transparency. Accordingly, lamellar implants have enjoyed some degree of success (P. Fagerholm et al, ; Islam et al, ; Jangamreddy et al, ), whereas full thickness implants do not remain clear due to RCM formation in many cases (Hicks & Hamilton, ; Obata & Tsuru, ; Rajendran, Netuková, Griffith, Forrester, & Kuffová, ; Yum, Kim, & Kim, ). However, they can function as tectonic grafts allowing preservation of the eye in the case of a nonhealing wound and later replacement with a full thickness, endothelium‐intact, penetrating allograft.…”

Section: Introductionmentioning

confidence: 99%

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Activation of dendritic cells by crosslinked collagen hydrogels (artificial corneas) varies with their composition

Moelzer¹,

Shankar

Griffith

et al. 2019

J Tissue Eng Regen Med

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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 collagen matrices to either activate DC or conversely induce DC apoptosis in vitro. Bone marrow DC were cultured on a series of singly and doubly crosslinked hydrogels (made from recombinant human collagen III [RHCIII] or collagen mimetic peptide [CMP]) or on natural collagen‐containing matrices, MatrigelTM and de‐cellularised mouse corneal stroma. DC surface expression of major histocompatibility complex Class II and CD86 as well as apoptosis markers were examined. Natural matrices induced low levels of DC activation and maintained a “tolerogenic” phenotype. The same applied to singly crosslinked CMP‐PEG gels. RHCIII gels singly crosslinked using either N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide with the coinitiator N‐hydroxy succinimide (EDC‐NHS) or N‐cyclohexyl‐N‐(2‐morpholinoethyl)carbodiimide metho‐p‐toulenesulfonate with NHS (CMC‐NHS) induced varying levels of DC activation. In contrast, however, RHCIII hydrogels incorporating an additional polymeric network of 2‐methacryloyloxyethyl phosphorylcholine did not activate DC but instead induced DC apoptosis, a phenomenon observed in natural matrices. This correlated with increased DC expression of leukocyte‐associated immunoglobulin‐like receptor‐1. Despite low immunogenic potential, viable tolerogenic DC migrated into and through both natural and manufactured RHCIII gels. These data show that the immunogenic potential of RHCIII gels varies with the nature and composition of the gel. Preclinical evaluation of hydrogel immunogenic/fibrogenic potential is recommended.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Activation of dendritic cells by crosslinked collagen hydrogels (artificial corneas) varies with their composition

Moelzer¹,

Shankar

Griffith

et al. 2019

J Tissue Eng Regen Med

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“…ALK was used to implant the hydrogels into minipig eyes and the transplanted corneas were followed up for 12 months. Implanted corneas remained clear and both epithelium and stroma regenerated successfully [204].…”

Section: Hydrogel-based Scaffoldsmentioning

confidence: 89%

Bioengineering Approaches for Corneal Regenerative Medicine

Mahdavi

Abdekhodaie

Mashayekhan

et al. 2020

Tissue Eng Regen Med

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BACKGROUND: Since the cornea is responsible for transmitting and focusing light into the eye, injury or pathology affecting any layer of the cornea can cause a detrimental effect on visual acuity. Aging is also a reason for corneal degeneration. Depending on the level of the injury, conservative therapies and donor tissue transplantation are the most common treatments for corneal diseases. Not only is there a lack of donor tissue and risk of infection/rejection, but the inherent ability of corneal cells and layers to regenerate has led to research in regenerative approaches and treatments. METHODS: In this review, we first discussed the anatomy of the cornea and the required properties for reconstructing layers of the cornea. Regenerative approaches are divided into two main categories; using direct cell/growth factor delivery or using scaffold-based cell delivery. It is expected delivered cells migrate and integrate into the host tissue and restore its structure and function to restore vision. Growth factor delivery also has shown promising results for corneal surface regeneration. Scaffold-based approaches are categorized based on the type of scaffold, since it has a significant impact on the efficiency of regeneration, into the hydrogel and non-hydrogel based scaffolds. Various types of cells, biomaterials, and techniques are well covered. RESULTS: The most important characteristics to be considered for biomaterials in corneal regeneration are suitable mechanical properties, biocompatibility, biodegradability, and transparency. Moreover, a curved shape structure and spatial arrangement of the fibrils have been shown to mimic the corneal extracellular matrix for cells and enhance cell differentiation. CONCLUSION: Tissue engineering and regenerative medicine approaches showed to have promising outcomes for corneal regeneration. However, besides proper mechanical and optical properties, other factors such as appropriate sterilization method, storage, shelf life and etc. should be taken into account in order to develop an engineered cornea for clinical trials.

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“…To address this, new biomaterials, such as collagen gels, synthetic polymers, and tissue-engineered scaffolds, have been developed to repair, regenerate, or replace the damaged cornea [82]. Jangamreddy et al found that one kind of peptide analogs as alternatives to collagen promoted regeneration of corneal tissue by stimulating in-growing corneal epithelium cells to secrete EVs for generating matrix components [55]. During corneal wound healing, mouse corneal epithelial cell-derived exosomes induced fibroblast proliferation and transformation of keratocytes to myofibroblasts, mediating intercellular communication between the corneal epithelium and stroma [56].…”

Section: Corneal Allograft Rejectionmentioning

confidence: 99%

Recent advances of exosomes in immune-mediated eye diseases

Zhao

Wei

et al. 2019

Stem Cell Res Ther

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Exosomes, nanosized extracellular vesicles of 30–150 nm, are shed by almost all cell types. Bearing proteins, lipids, RNAs, and DNAs, exosomes have emerged as vital biological mediators in cell-to-cell communication, affecting a plethora of physiological and pathological processes. Particularly, mounting evidence indicates that immunologically active exosomes can regulate both innate and adaptive immune responses. Herein, we review recent advances in the research of exosomes in several immune-mediated eye diseases, including Sjögren’s syndrome (SS) dry eye, corneal allograft rejection, autoimmune uveitis, and age-related macular degeneration (AMD). Additionally, we discuss the potential of exosomes as novel biomarkers and drug delivery vesicles for the diagnosis and treatment of eye diseases.

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Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants

Abstract: Graphical abstract

Cited by 52 publications

References 38 publications

Activation of dendritic cells by crosslinked collagen hydrogels (artificial corneas) varies with their composition

Activation of dendritic cells by crosslinked collagen hydrogels (artificial corneas) varies with their composition

Bioengineering Approaches for Corneal Regenerative Medicine

Recent advances of exosomes in immune-mediated eye diseases

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