Collagen Cross-Linking: Current Status and Future Directions

Hovakimyan, Marina; Guthoff, Rudolf; Stachs, Oliver

doi:10.1155/2012/406850

Cited by 67 publications

(56 citation statements)

References 119 publications

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“…We have not observed chronic corneal oedema, which would have been a clinical sign of endothelial decompensation, during the follow up period up to 19 months. Furthermore, light corneal scarring has been reported in a low number of patients with keratoconus treated with CXL [45-47]. Postoperative scarring was present but limited in the 8 horses where CXL was successful in this study and all these horses retained useful vision.…”

Section: Discussionmentioning

confidence: 55%

Corneal cross-linking in 9 horses with ulcerative keratitis

et al. 2013

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BackgroundCorneal ulcers are one of the most common eye problems in the horse and can cause varying degrees of visual impairment. Secondary infection and protease activity causing melting of the corneal stroma are always concerns in patients with corneal ulcers. Corneal collagen cross-linking (CXL), induced by illumination of the corneal stroma with ultraviolet light (UVA) after instillation of riboflavin (vitamin B2) eye drops, introduces crosslinks which stabilize melting corneas, and has been used to successfully treat infectious ulcerative keratitis in human patients. Therefore we decided to study if CXL can be performed in sedated, standing horses with ulcerative keratitis with or without stromal melting.ResultsNine horses, aged 1 month to 16 years (median 5 years) were treated with a combination of CXL and medical therapy. Two horses were diagnosed with mycotic, 5 with bacterial and 2 with aseptic ulcerative keratitis. A modified Dresden-protocol for CXL could readily be performed in all 9 horses after sedation. Stromal melting, diagnosed in 4 horses, stopped within 24 h. Eight of nine eyes became fluorescein negative in 13.5 days (median time; range 4–26 days) days after CXL. One horse developed a bacterial conjunctivitis the day after CXL, which was successfully treated with topical antibiotics. One horse with fungal ulcerative keratitis and severe uveitis was enucleated 4 days after treatment due to panophthalmitis.ConclusionsCXL can be performed in standing, sedated horses. We did not observe any deleterious effects attributed to riboflavin or UVA irradiation per se during the follow-up, neither in horses with infectious nor aseptic ulcerative keratitis. These data support that CXL can be performed in the standing horse, but further studies are required to compare CXL to conventional medical treatment in equine keratitis and to optimize the CXL protocol in this species.

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Section: Discussionmentioning

confidence: 55%

Corneal cross-linking in 9 horses with ulcerative keratitis

et al. 2013

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“…Therefore, UVA irradiation afterward causes an effect only on the area where it is absorbed, without disturbing other adjacent tissues 40. By adjusting the duration of riboflavin application and UVA irradiation in the CXL procedure, keratocytes in the central cornea were reduced significantly in CXL groups compared with naïve corneas, which can reproduce with a repopulation process 41. Furthermore, via adjustment of the dose of applied UVA irradiation and riboflavin, in contrast to an earlier study,42 we were able to save corneal endothelial cells, which are essential to maintain corneal transparency and cannot be reproduced in the adult organism,43 and we succeeded in avoiding damage to the iris and lens.…”

Section: Discussionmentioning

confidence: 99%

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

Hou

Tóth

et al. 2018

American Journal of Transplantation

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Immunologic graft rejection is the main complication after corneal transplant into pathologically prevascularized so‐called high‐risk eyes. The aim of this study was to evaluate whether ultraviolet (UV) light crosslinking can regress pathologic corneal blood and lymphatic vessels and thereby improve subsequent graft survival. Using the murine model of suture‐induced corneal neovascularization, we found that corneal crosslinking with UVA light and riboflavin regressed both preexisting blood and lymphatic vessels significantly via induction of apoptosis in vascular endothelial cells. In addition, macrophages and CD45+ cell counts were significantly reduced. Consistently, corneal crosslinking reduced keratocyte density and corneal thickness without affecting corneal nonvascular endothelial cells, iris, and lens depending on the crosslinking duration. Furthermore, using the murine model of corneal transplant, long‐term graft survival was significantly promoted (P < .05) and CD4+ CD25+FoxP3+ T regulatory cells were upregulated (P < .01) in high‐risk eyes preoperatively treated with crosslinking. Our results suggest UV light crosslinking as a novel method to regress both pathologic corneal blood and lymphatic vessels and to reduce CD45+ inflammatory cells. Furthermore, this study demonstrates for the first time that preoperative corneal crosslinking in prevascularized high‐risk eyes can significantly improve subsequent graft survival and may become a promising novel therapy in the clinic.

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“…The increased fiber diameter also for the radical system is likely due to the rapid formation of the radically cross-linked network (4 minutes) in which the PEG is cross-linking to itself and multiple fibers. Increase in fiber diameter has been seen with other methods of cross-linking collagen based materials [13]. …”

Section: Discussionmentioning

confidence: 99%

Myocardial matrix–polyethylene glycol hybrid hydrogels for tissue engineering

Grover¹,

Rao²,

Christman³

2013

Nanotechnology

111

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Similar to other protein-based hydrogels, extracellular matrix (ECM) based hydrogels, derived from decellularized tissues, have a narrow range of mechanical properties and are rapidly degraded. These hydrogels contain natural cellular adhesion sites, form nanofibrous networks similar to native ECM, and are biodegradable. In this study, we expand the properties of these types of materials by incorporating poly(ethylene glycol) (PEG) into the ECM network. We use decellularized myocardial matrix as an example of a tissue specific ECM derived hydrogel. Myocardial matrix-PEG hybrids were synthesized by two different methods, cross-linking the proteins with an amine-reactive PEG-star and photo-induced radical polymerization of two different multi-armed PEG-acrylates. We show that both methods allow for conjugation of PEG to the myocardial matrix by gel electrophoresis and infrared spectroscopy. Scanning electron microscopy demonstrated that the hybrid materials still contain a nanofibrous network similar to unmodified myocardial matrix and that the fiber diameter is changed by the method of PEG incorporation and PEG molecular weight. PEG conjugation also decreased the rate of enzymatic degradation in vitro, and increased material stiffness. Hybrids synthesized with amine-reactive PEG had gelation rates of thirty minutes, similar to the unmodified myocardial matrix, and incorporation of PEG did not prevent cell adhesion and migration through the hydrogels, thus offering the possibility to have an injectable ECM hydrogel that degrades more slowly in vivo. The photo-polymerized radical systems gelled in four minutes upon irradiation allowing for 3D encapsulation and culture of cells, unlike the soft unmodified myocardial matrix. This work demonstrates PEG incorporation into ECM-based hydrogels can expand material properties, thereby opening up new possibilities for in vitro and in vivo applications.

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Collagen Cross-Linking: Current Status and Future Directions

Cited by 67 publications

References 119 publications

Corneal cross-linking in 9 horses with ulcerative keratitis

Corneal cross-linking in 9 horses with ulcerative keratitis

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

Myocardial matrix–polyethylene glycol hybrid hydrogels for tissue engineering

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