Artificial corneas: a regenerative medicine approach

Griffith, May; Jackson, W. B.; Lagali, Neil; Merrett, Kimberley; Li, F; Fagerholm, Per

doi:10.1038/eye.2008.409

Cited by 66 publications

(41 citation statements)

References 30 publications

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“…The collagen-based materials are designed to function as temporary scaffolds that maintain tissue structure, while the surrounding tissue regenerates and replaces the original scaffold over time [9]. Previous studies, while confirming epithelial cell coverage and innervation of scaffolds, have not definitively demonstrated migration of individual cells into the biomaterial to actively regenerate the stroma, by turnover of implanted collagen into host collagen [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Regeneration of Corneal Tissue via a Bioengineered Collagen Construct Implanted by a Nondisruptive Surgical Technique

Koulikovska

Rafat

Petrovski

et al. 2015

Tissue Engineering Part A

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Severe shortage of donor corneas for transplantation, particularly in developing countries, has prompted the advancement of bioengineered tissue alternatives. Bioengineered corneas that can withstand transplantation while maintaining transparency and compatibility with host cells, and that are additionally amenable to standardized, low-cost mass production, are sought. In this study, a bioengineered porcine construct (BPC) was developed to function as a biodegradable scaffold to promote corneal stromal regeneration by host cells. Using high purity medical-grade type I collagen, high 18% collagen content and optimized EDC-NHS crosslinker ratio, BPCs were fabricated into hydrogel corneal implants with over 90% transparency and fourfold increase in strength and stiffness compared to previous versions. Remarkably, optical transparency was achieved despite the absence of collagen fibril organization at the nanoscale. In vitro testing indicated the BPC supported confluent human epithelial and stromal-derived mesenchymal stem cell populations. With a novel femtosecond laser-assisted corneal surgical model in rabbits, cell-free BPCs were implanted in vivo in the corneal stroma of 10 rabbits over an 8 week period. In vivo, transparency of implanted corneas was maintained throughout the postoperative period, while healing occurred rapidly without inflammation and without the use of postoperative steroids. BPC implants had a 100% retention rate at 8 weeks, when host stromal cells began to migrate into implants. Direct histochemical evidence of stromal tissue regeneration was observed by means of migrated host cells producing new collagen from within the implants. This study indicates that a cost-effective BPC extracellular matrix equivalent can incorporate cells passively to initiate regenerative healing of the corneal stroma, and is compatible with human stem or organ-specific cells for future therapeutic applications as a stromal replacement for treating blinding disorders of the cornea.3

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Section: Introductionmentioning

confidence: 99%

Enhanced Regeneration of Corneal Tissue via a Bioengineered Collagen Construct Implanted by a Nondisruptive Surgical Technique

Koulikovska

Rafat

Petrovski

et al. 2015

Tissue Engineering Part A

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“…Innervation by the host will also be required for proper function and full integration of many tissues (88,89), and is particularly important in tissues where motor control, as in skeletal tissue, or sensation, as in the epidermis, provides a key function (90,91). Innervation of engineered tissues may be induced by growth factors, as has been shown in the induction of nerve growth from mouse embryonic dorsal root ganglia to epithelial tissue in an in vitro model (92).…”

Section: Therapies At the Preclinical Stage And In Clinical Testingmentioning

confidence: 99%

Regenerative medicine: Current therapies and future directions

Mao

Mooney

2015

Proc. Natl. Acad. Sci. U.S.A.

704

439

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Organ and tissue loss through disease and injury motivate the development of therapies that can regenerate tissues and decrease reliance on transplantations. Regenerative medicine, an interdisciplinary field that applies engineering and life science principles to promote regeneration, can potentially restore diseased and injured tissues and whole organs. Since the inception of the field several decades ago, a number of regenerative medicine therapies, including those designed for wound healing and orthopedics applications, have received Food and Drug Administration (FDA) approval and are now commercially available. These therapies and other regenerative medicine approaches currently being studied in preclinical and clinical settings will be covered in this review. Specifically, developments in fabricating sophisticated grafts and tissue mimics and technologies for integrating grafts with host vasculature will be discussed. Enhancing the intrinsic regenerative capacity of the host by altering its environment, whether with cell injections or immune modulation, will be addressed, as well as methods for exploiting recently developed cell sources. Finally, we propose directions for current and future regenerative medicine therapies.regenerative medicine | tissue engineering | biomaterials | review

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“…The combination of collagen biomaterials and stem cells could be a valuable strategy to treat corneal defects also. Other strategies in collagen-based corneal scaffolds include the utilization of recombinant human collagen (Dravida et al, 2008;Griffith et al, 2009), the secretion of collagen by the fibroblasts themselves (Carrier et al, 2008) and surface modification to reduce extensive endothelialization (Rafat et al, 2009). …”

Section: Cornea and Neural Cellsmentioning

confidence: 99%