Luis M. Rodríguez-Lorenzo
Felisa Reyes-Ortega
May Griffith- 1Department Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology (ICTP), Madrid, Spain
- 2Department Ophthalmology, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital and University of Cordoba, Cordoba, Spain
- 3Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC, Canada
- 4Department Ophthalmology, Université de Montréal, Montreal, QC, Canada
- 5Institute of Biomedical Engineering, Université de Montréal, Montreal, QC, Canada
Editorial on the Research Topic
Biomaterials used in tissue engineering for the restoration of ocular disorders
The goal of tissue engineering is the construction of bioartificial tissues to restore, improve, or maintain failing or failed tissue and organs. The concept was born and is still driven by the necessity of addressing the critical gap between the growing number of patients awaiting tissue or organ transplantation and the severe shortfall of donated organs/tissues (Chandra et al., 2020). Tissue engineering has been very broadly described to use cells, scaffolds, and tissue-inducing factors (Langer and Vacanti, 1993), which translate to the use of biomaterials, bioengineering, and associated regenerative medicine technologies.
Ocular disorders affect a large percentage of the world population: at least 1 billion people have vision impairment that could have been prevented or has yet to be addressed. Vision impairment impacts the lives of people everywhere and affects people of all ages, with the majority being over the age of 50 (World Health Organization, 2019). Tissue engineering is a promising tool to produce treatments for ophthalmologic disorders; however, several obstacles need to be overcome.
The required range of properties for biomaterials to be used in the restoration of the eye from damage by ocular disorders is limited by the optimal combination of thickness, mechanical properties, and composition, ensuring bio- and immune-compatibility. Ideally, the biomaterials should resist the build-up of proteins and other substances that would hinder the intended function, and they should be resistant to infection. The ultimate challenge is the capacity to surgically implant the engineered tissue with no complications for the patient.
From a biomaterials standpoint, the first-in-human report of biomimetic material engineered implants that stimulated stable regeneration of human corneal tissues and nerves was published just over a decade ago. Griffith, Fagerholm, and their team used cell-free recombinant human collagen-based implants to discover that the adult human cornea was capable of regeneration by inducing the patients’ endogenous cells to make the repairs in an early clinical trial (Fagerholm et al., 2010). More recent developments come from advanced manufacturing technologies. 3D printing and bioprinting are becoming the technologies of choice for the manufacture of scaffolds and constructs in tissue engineering because they enable the design of personalized tissue and organ constructs for precision medicine. The current challenge is to find the right combination of printable materials and printing technology. There is growing use of decellularized tissues as a base for the printable ink to provide an adequate environment for recellularization with healthy biological material. However, not only do recellularization techniques need to be optimized, but also the most suitable therapeutic cells, from pluripotent stem cells (iPSCs) to human embryonic stem cells (hESCs). An alternate approach has been the development of fully synthetic mimetic macromolecules that can be designed to be fully chemically controlled and safe from pathogen transmission, as well as being cost effective as there is no need for expensive screening to minimize the risk of transmissible pathogens, particularly zoonotic transmission. For example, short peptide mimics of full-length proteins have been tested for tissue restoration (Rubert Pérez et al., 2015).
As alternatives to fully engineered ocular scaffolds or implants, biomaterials have been tested as pro-regeneration sealants and fillers. These biosealant fillers could be either the hydrogel matrices based on collagen-like peptides and polyethylene glycols, mixed with fibrinogen to promote adhesion within tissue defects (McTiernan et al., 2020) or chemically modified gelatin with polymethacrylates, like GeIMA (Yan et al., 2022), GELCORE (Sani et al., 2019), or GELGYM (Sharifi et al., 2021). They are less costly and reduce any risk of allergy or immune rejection associated with xenogeneic materials.
The current Research Topic covers cutting-edge research on several aspects of ocular tissue engineering mentioned above. For Fuchs endothelial corneal dystrophy (FECD), the characteristics of the different biomaterials proposed for the engineering of a monolayer of corneal endothelium for the treatment of FECD, and a retinal pigment epithelium (RPE) monolayer for the treatment of dry age macular degeneration (AMD), are reviewed. It is noteworthy to read the reasons for not reaching ample clinical usage and the distance of the described properties from the clinical needs (Sasseville et al.). How highly effective modulator therapies (HEMT) targeting cystic fibrosis transmembrane conductance regulator (CFTR) protein influence the dynamic and interdependent processes of healthy and abnormal lens development during pregnancy and breastfeeding is also analyzed, highlighting the need for further research that clarifies the potential secondary effects of these therapies (Zhu et al.). The need for tissue engineered approaches for the treatment of corneal opacity is also covered, including a proposal for a new model of keratoprostheses based on the combination of 3D printing and decellularization techniques, where decellularized corneal tissue is used as the base material for the 3D ink (Wang et al.). In the same direction, a high-throughput strategy for designing a simplified, inexpensive, and scalable corneal xenograft platform is presented. The advantages and limitations of this decellularization technique are described (Wang et al.). The introduction of new approaches for healing corneal tissue is also included in this Research Topic. Corneal alkali burns are usually treated with corticosteroids; however, the side effects of these treatments advocate the continued search for alternatives. The paper (Thathapudi et al.) proposes and describes the potential of an alternative based on a cannabinoid receptor 2 (CB2r) agonist that is effective but extremely insoluble, necessitating the use of biomaterials as micelles for drug delivery to restore tissue morphology and function.
Author contributions
LR-L: Conceptualization, Writing–original draft. FR-O: Validation, Writing–review and editing. MG: Supervision, Validation, Writing–review and editing.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Project PID2021-128985OB-I00 funded by MCIN/AEI/10.13039/501100011033/FEDER Una manera de hacer Europa, is acknowledged. FR-O acknowledges funding from Plan Andaluz de Investigacion, “Desarrollo e Innovacion” (PAIDI2020) Fellowship supported by Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía co-funded by Fondo Social Europeo de Andalucía 2014-2020.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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References
Chandra, P. K., Soker, S., and Atala, A. (2020). “Chapter 1 - tissue engineering: current status and future perspectives,” in Principles of tissue engineering. Editors R. Lanza, R. Langer, and P. Joseph (Academic Press), 1–35.
Fagerholm, P., Lagali, N. S., Merrett, K., Jackson, W. B., Munger, R., Liu, Y., et al. (2010). A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study. Sci. Transl. Med. 2 (46), 46ra61. doi:10.1126/scitranslmed.3001022
Langer, R., and Vacanti, J. P. (1993). Tissue engineering. Science 260 (5110), 920–926. doi:10.1126/science.8493529
McTiernan, C. D., Simpson, F. C., Haagdorens, M., Samarawickrama, C., Hunter, D., Buznyk, O., et al. (2020). LiQD Cornea: pro-regeneration collagen mimetics as patches and alternatives to corneal transplantation. Sci. Adv. 6 (25), eaba2187. doi:10.1126/sciadv.aba2187
Rubert Pérez, C. M., Stephanopoulos, N., Sur, S., Lee, S. S., Newcomb, C., and Stupp, S. I. (2015). The powerful functions of peptide-based bioactive matrices for regenerative medicine. Ann. Biomed. Eng. 43 (3), 501–514. doi:10.1007/s10439-014-1166-6
Sani, E. S., Kheirkhah, A., Rana, D., Sun, Z., Foulsham, W., Sheikhi, A., et al. (2019). Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels. Sci. Adv. 5 (3), eaav1281. doi:10.1126/sciadv.aav1281
Sharifi, S., Islam, M. M., Sharifi, H., Islam, R., Koza, D., Reyes-Ortega, F., et al. (2021). Tuning gelatin-based hydrogel towards bioadhesive ocular tissue engineering applications. Bioact. Mater 6 (11), 3947–3961. doi:10.1016/j.bioactmat.2021.03.042
Keywords: ocular disorders, 3D bioprinting, short peptide, clinical trial, cornea, biosealants, fillers, decellularized tissues
Citation: Rodríguez-Lorenzo LM, Reyes-Ortega F and Griffith M (2024) Editorial: Biomaterials used in tissue engineering for the restoration of ocular disorders. Front. Pharmacol. 15:1369505. doi: 10.3389/fphar.2024.1369505
Received: 12 January 2024; Accepted: 17 January 2024;
Published: 31 January 2024.
Edited and reviewed by:
Heike Wulff, University of California, Davis, United StatesCopyright © 2024 Rodríguez-Lorenzo, Reyes-Ortega and Griffith. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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