الفهرس 
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Abstract
This work studies the recent update in tissue engineering of the cornea to get up a biosynthetic cornea which is similar to that of the natural one. This biosynthetic cornea acts as an alternative substitute for keratoprothesis, or using cadaver corneal tissue for transplants.
Tissue engineering has become a new approach for repairing tissue defects and restoring tissue function in recent years. It is defined as understanding the principles of tissue growth, and applying this to produce functional replacement tissue for clinical use.
In this study we review:
1. Anatomy of the cornea.
2. Needs for corneal replacement
A. Corneal transplantation
B. Keratoprosthesis
C. Indications of tissue engineered cornea
Tissue engineered cornea has been used for some conditions in which penetrating keratoplasty is not acceptable including
1) Multiple graft failure 2) Stevens-Johnson syndrome
3) Ocular burns 4) Bilateral total corneal stem-cell deficiency
5) Corneal opacity with ocular surface disease, or corneal
Vascularization.
3. Concept of tissue engineering
The concept of tissue engineering based on three basics including; scaffold biomaterials, cells used in tissue engineering and growth factors
4. Reconstruction of different corneal layer
A. Reconstruction of corneal epithelium
Oral mucosal epithelial cells have been used to reconstruct the corneal ocular surface in patients with bilateral limbal stem cell deficiency. For this method, temperature responsive cell-culture surface was used as a scaffold.
B. Reconstruction of corneal stroma
In animal trial; dermal fibroblasts were harvested from newborn rabbits and seeded on polyglycolic acid (PGA) scaffolds, cultured in vitro, then implanted into adult rabbit cornea. Nearly transparent corneal stroma was formed with a histological structure similar to that of its native cornea.
C. Reconstruction of corneal endothelium
Amniotic membrane has been used as a carrier for cultivated human corneal endothelial cells (cHCEC). Cells obtained from peripheral corneal tissue have been cultivated, and transplanted onto denuded amniotic membrane. Then transplanted onto rabbit cornea whose Descemet’s membrane and endothelial cells had been completely removed. Then determination whether these cHCEC sheets on amniotic membrane carrier were functional in vivo was assisted. The result indicate that the cHCEC sheet consisted of a fairly continuous layer of flat squamous polygonal endothelial cells that appeared uniform in size with tightly opposed cell junctions in vitro and in vivo after transplantation.
5. Reconstruction of whole cornea
Minami et al, on 1993 reconstructed in vitro a cornea containing the three main layers using bovine corneal cells. Stromal fibroblasts were resuspended in a type I collagen gel, seeded in a dish containing a nitrocellulose membrane base, and cultured upside down. Endothelial cells were then seeded onto the bottom of the nitrocellulose base for two days before returning the dish to its up-right position. Epithelial cells were then finally seeded on top of the collagen gel to complete the construct.
Also, complete tissue-engineered human corneas similar to native cornea have been demonstrated by the self-assembly approach. The three corneal cell types were first isolated from normal human cornea unsuitable for transplantation obtained from eye bank. Corneal and dermal fibroblasts were separately seeded and cultured in fibroblast growth medium .This was supplemented with ascorbic acid to allow fibroblasts to secrete their own extracellular matrix ,and forming a thick sheet which can be superposed to reconstruct a corneal stroma. Endothelial and epithelial cells were seeded on each side of the reconstructed stroma then cultured at the air-liquid interface
6. Results and complications of tissue engineered
cornea
The early clinical results appear promising, especially when autologous-engineered epithelium is used and immune-mediated rejection is avoided. Complete reepithelialization of the corneal surfaces occurred within one week. Corneal transparency was restored and postoperative visual acuity was improved. Although, there are many factors that contribute to the clinical failure of the tissue engineered cornea:
1-One of the major causes is the lack of an appropriate in vivo environment that can support the long-term survival and function of the corneal epithelium and its stem cells.
2-Also, transplanted tissue engineered cornea can be affected by presence of unhealthy tear film, improper eyelid closure, and presence of inflammations. The function and survival of the epithelium is also highly dependent on the structural and biochemical support from the underlying stroma
3- Inherent difficulty of growing specific cell types in large quantities. Even when some organs have a high regenerative capacity in vivo, cell growth and expansion invitro m