Biosynthetic corneal implants for replacement of pathologic corneal tissue: performance in a controlled rabbit alkali burn model.
OBJECTIVE
To evaluate the performance of structurally reinforced, stabilized recombinant human collagen-phosphorylcholine (RHCIII-MPC) hydrogels as corneal substitutes in a rabbit model of severe corneal damage.


METHODS
One eye each of 12 rabbits received a deep corneal alkali wound. Four corneas were implanted with RHCIII-MPC hydrogels. The other eight control corneas were implanted with either allografts or a simple cross-linked RHCIII hydrogel. In all cases, 6.25 mm diameter, 350 μm thick buttons were implanted by anterior lamellar keratoplasty to replace damaged corneal tissue. Implants were followed for nine months by clinical examination and in vivo confocal microscopy, after which implanted corneas were removed and processed for histopathological and ultrastructural examination.


RESULTS
Alkali exposure induced extensive central corneal scarring, ocular surface irregularity, and neovascularization in one case. All implants showed complete epithelial coverage by four weeks postoperative, but with accompanying suture-induced vascularization in 6 out of 12 cases. A stable, stratified epithelium with hemidesmosomal adhesion complexes regenerated over all implants, and subbasal nerve regeneration was observed in allograft and RHCIII-MPC implants. Initially acellular biosynthetic implants were populated with host-derived keratocytes as stromal haze subsided and stromal collagen was remodeled. Notably, RHCIII-MPC implants exhibited resistance to vascular ingrowth while supporting endogenous cell and nerve repopulation.


CONCLUSIONS
Biosynthetic implants based on RHC promoted cell and nerve repopulation in alkali burned rabbit eyes. In RHCIII-MPC implants, evidence of an enhanced resistance to neovascularization was additionally noted.
Hackett
Joanne M
JM
University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
Lagali
Neil
N
Merrett
Kimberley
K
Edelhauser
Henry
H
Sun
Yifei
Y
Gan
Lisha
L
Griffith
May
M
Fagerholm
Per
P
D000818:Animals; D001187:Artificial Organs; D002057:Burns, Chemical / Q000473:pathology / Q000601:surgery*; D024061:Collagen Type III / Q000737:chemistry; D003315:Cornea; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000378:metabolism / Q000601:surgery; D003318:Corneal Opacity / Q000139:chemically induced / Q000378:metabolism / Q000601:surgery*; D016039:Corneal Transplantation; D019573:Epithelium, Corneal / Q000502:physiology; D005126:Eye Burns / Q000139:chemically induced*; D020100:Hydrogels; D008689:Methacrylates / Q000737:chemistry; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D023421:Models, Animal; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D011817:Rabbits; D012038:Regeneration / Q000502:physiology; D012972:Sodium Hydroxide; D014184:Transplantation, Homologous
D024061:Collagen Type III; D020100:Hydrogels; D008689:Methacrylates; D010767:Phosphorylcholine; D012972:Sodium Hydroxide; C070638:2-methacryloyloxyethyl phosphorylcholine