Enhanced regeneration of corneal tissue via a bioengineered collagen construct implanted by a nondisruptive surgical technique

Marina Koulikovska, Mehrdad Rafat, G. Petrovski, Zoltán Veréb, Saeed Akhtar, Per Fagerholm, Neil Lagali

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 cross-linker ratio, BPCs were fabricated into hydrogel corneal implants with over 90% transparency and four-fold increase in strength and stiffness compared with previous versions. Remarkably, optical transparency was achieved despite the absence of collagen fibril organization at the nanoscale. In vitro testing indicated that 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.

Original languageEnglish
Pages (from-to)1116-1130
Number of pages15
JournalTissue Engineering - Part A
Volume21
Issue number5-6
DOIs
Publication statusPublished - Mar 1 2015

Fingerprint

Collagen
Transparency
Regeneration
Tissue
Swine
Cornea
Corneal Stroma
Tissue regeneration
Hydrogel
Collagen Type I
Stem cells
Ultrashort pulses
Developing countries
Hydrogels
Scaffolds
Rabbits
Anatomic Models
Costs
Costs and Cost Analysis
Corneal Transplantation

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials

Cite this

Enhanced regeneration of corneal tissue via a bioengineered collagen construct implanted by a nondisruptive surgical technique. / Koulikovska, Marina; Rafat, Mehrdad; Petrovski, G.; Veréb, Zoltán; Akhtar, Saeed; Fagerholm, Per; Lagali, Neil.

In: Tissue Engineering - Part A, Vol. 21, No. 5-6, 01.03.2015, p. 1116-1130.

Research output: Contribution to journalArticle

Koulikovska, Marina ; Rafat, Mehrdad ; Petrovski, G. ; Veréb, Zoltán ; Akhtar, Saeed ; Fagerholm, Per ; Lagali, Neil. / Enhanced regeneration of corneal tissue via a bioengineered collagen construct implanted by a nondisruptive surgical technique. In: Tissue Engineering - Part A. 2015 ; Vol. 21, No. 5-6. pp. 1116-1130.
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