Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels

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Abstract

We engineered a photocrosslinkable and transparent bioadhesive hydrogel for quick sealing, and repair of corneal defects.

Abstract

Corneal injuries are common causes of visual impairment worldwide. Accordingly, there is an unmet need for transparent biomaterials that have high adhesion, cohesion, and regenerative properties. Herein, we engineer a highly biocompatible and transparent bioadhesive for corneal reconstruction using a visible light cross-linkable, naturally derived polymer, GelCORE (gel for corneal regeneration). The physical properties of GelCORE could be finely tuned by changing prepolymer concentration and photocrosslinking time. GelCORE revealed higher tissue adhesion compared to commercial adhesives. Furthermore, in situ photopolymerization of GelCORE facilitated easy delivery to the cornea, allowing for bioadhesive curing precisely according to the required geometry of the defect. In vivo experiments, using a rabbit stromal defect model, showed that bioadhesive could effectively seal corneal defects and induce stromal regeneration and re-epithelialization. Overall, GelCORE has many advantages including low cost and ease of production and use. This makes GelCORE a promising bioadhesive for corneal repair.

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Progress in corneal wound healing.

Alexander V. Ljubimov, Mehrnoosh Saghizadeh (2015)

Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β (TGF-β) system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and nanocarriers for corneal drug delivery are discussed. Attention is also paid to problems in wound healing understanding and treatment, such as lack of specific epithelial stem cell markers, reliable identification of stem cells, efficient prevention of haze and stromal scar formation, lack of data on wound regulating microRNAs in keratocytes and endothelial cells, as well as virtual lack of targeted systems for drug and gene delivery to select corneal cells.

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Engineering a sprayable and elastic hydrogel adhesive with antimicrobial properties for wound healing

Anthony S. Weiss, Roberto Portillo-Lara, Mohammad Fares … (2017)

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Engineering a highly elastic human protein–based sealant for surgical applications

Nasim Annabi, Yi-Nan Zhang, Alexander Assmann … (2017)

Surgical sealants have been used for sealing or reconnecting ruptured tissues but often have low adhesion, inappropriate mechanical strength, cytotoxicity concerns, and poor performance in biological environments. To address these challenges, we engineered a biocompatible and highly elastic hydrogel sealant with tunable adhesion properties by photocrosslinking the recombinant human protein tropoelastin. The subcutaneous implantation of the methacryloyl-substituted tropoelastin (MeTro) sealant in rodents demonstrated low toxicity and controlled degradation. All animals survived surgical procedures with adequate blood circulation by using MeTro in an incisional model of artery sealing in rats, and animals showed normal breathing and lung function in a model of surgically induced rat lung leakage. In vivo experiments in a porcine model demonstrated complete sealing of severely leaking lung tissue in the absence of sutures or staples, with no clinical or sonographic signs of pneumothorax during 14 days of follow-up. The engineered MeTro sealant has high potential for clinical applications because of superior adhesion and mechanical properties compared to commercially available sealants, as well as opportunity for further optimization of the degradation rate to fit desired surgical applications on different tissues.

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Author and article information

Journal

Journal ID (nlm-ta): Sci Adv

Journal ID (iso-abbrev): Sci Adv

Journal ID (publisher-id): SciAdv

Journal ID (hwp): advances

Title: Science Advances

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2375-2548

Publication date Collection: March 2019

Publication date (Electronic): 20 March 2019

Volume: 5

Issue: 3

Electronic Location Identifier: eaav1281

Affiliations

[1 ]Chemical and Biomolecular Engineering Department, University of California, Los Angeles, Los Angeles, CA, USA.

[2 ]Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

[3 ]Department of Chemical Engineering, Northeastern University, Boston, MA, USA.

[4 ]Biomaterials Innovation Research Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.

[5 ]Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.

[6 ]Center for Minimally Invasive Therapeutics (C-MIT), California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA, USA.

[7 ]Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Author notes

[*]

These authors contributed equally to this work.

[† ]Corresponding author. Email: nannabi@ 123456ucla.edu (N.A.), reza_dana@ 123456meei.harvard.edu (R.D.)

Author information

Ehsan Shirzaei Sani http://orcid.org/0000-0002-4609-1505

Ahmad Kheirkhah http://orcid.org/0000-0003-4217-3367

Zhongmou Sun http://orcid.org/0000-0003-2355-0534

William Foulsham http://orcid.org/0000-0002-7088-605X

Amir Sheikhi http://orcid.org/0000-0002-4495-6675

Article

Publisher ID: aav1281

DOI: 10.1126/sciadv.aav1281

PMC ID: 6426459

PubMed ID: 30906864

SO-VID: 4a7130b3-865d-46a8-a902-0c8f833cf6b6

Copyright © Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

History

Date received : 17 August 2018

Date accepted : 31 January 2019

Funding

Funded by: doi http://dx.doi.org/10.13039/100000005, U.S. Department of Defense;

Award ID: W81XWH-18-1-0654

Funded by: doi http://dx.doi.org/10.13039/100000005, U.S. Department of Defense;

Award ID: W81XWH-18-1-0654

Funded by: doi http://dx.doi.org/10.13039/100000052, NIH Office of the Director;

Award ID: R01EB023052

Funded by: doi http://dx.doi.org/10.13039/100000052, NIH Office of the Director;

Award ID: R01HL140618

Funded by: doi http://dx.doi.org/10.13039/100000968, American Heart Association;

Award ID: 16SDG31280010

Funded by: doi http://dx.doi.org/10.13039/100001818, Research to Prevent Blindness;

Award ID: Stein Innovation Award

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Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels

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Most cited references 36

Progress in corneal wound healing.

Engineering a sprayable and elastic hydrogel adhesive with antimicrobial properties for wound healing

Engineering a highly elastic human protein–based sealant for surgical applications

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