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Corneal Tissue Engineering

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Tissue EngineeringHello everyone, in the previous session, we have learnt about anatomy and other basicaspects of corneal tissue and in today session, we will talk about Tissue Engineering aspectsof cornea.The topic that has to be, that will be covered in today’s session will be, prerequisitesfor designing scaffolds for corneal tissue and polymers and cells that have been alreadyused in corneal tissue engineering and commercially available corneal replacements.Let us begin with prerequisites for designing tissue engineering scaffold for corneal tissue.The first prerequisite is protection.As we know, the eye is exposed to external environment and it has to be protected frombacterial and other microbial infections.The outermost epithelial layer contains tight junctions and also microvilli and it preventsfrom microbial invasion and the microbial invasion and transparency.As we know, the cornea the cornea is transparent in nature, the transparency of cornea is maintainedby hydration level of the stroma layer.The excess of water in this stromal layer is removed from the bottom endothelium layerby using the metallic pump and thereby it maintains the transparency of eye cornea.Hence the tissue engineering construct must have transparency, required for transparency.The cornea is responsible for 80 percent of the refraction of the eye, hence the refractionthat is required for the cornea.And as like any other tissues the scaffold which we prepare for cornea should be compatiblewith the host tissue.And the most important thing is in integration.The tissue engineering construct which we prepare for cornea much integrate with thehost tissue, thereby not allowing any type of microbial invasion.Here are the few of the work that have been done on various tissue layers of cornea.And as you see here, there are many types of polymers have been used both natural andsynthetic polymers, as you see here the full thickness cornea is a full thickness corneaI mean to say is all five layers of corneal layer are tried to reconstruct in these studies.As you see, for this studies cornea, collagen, chitosan and synthetic polymers like PEG andpolyacrylic acids have been used and stromal layer; stromal layer of cornea are also triedto construct, try to construct.And as you see here there are many types of polymers have been used keratin, polylacticacid, gelatin, we will talk about all this polymers in coming in coming slides.And various types of cell sources have been used for constructing the corneal tissue.For example, primary animal derived corneal epithelial cells and primary animal derivedcorneal stromal cells, dorsal root ganglion cells and they have also used human cornealepithelial cells, human corneal fibroblast cells, endothelial cells and human cornealstromal cells for as a cell source for constructing the corneal tissue.And now, we will talk about the various polymers that have been used for constructing the cornealtissue.The primarily used polymer is collagen.As you as we have learnt in the previous session, collagen the stromal layer collagen is thepredominant is the most predominant polymer present in the cornea.And its present in the stromal it is the main component of the human stromal cells, stromaltissue.The drawback of collagen is insufficient mechanical toughness and elasticity, that is requiredfor corneal tissue.And to overcome the drawback of collagen, they tried to crosslink collagen to improvethe mechanical strength and the type of collagen that is used has it is own role.For example, type I and type III collagen hydrogels have adequate tensile strength andelasticity, whereas a type III collagen hydrogels tend to be mechanically and optically superior.And crosslinking of collagen are done using the using various methods that are classifiedunder physical chemical and enzymatic methods.Physic under physical method UV light is been used, dehydrothermal method is also usedUnder chemical method formaldehyde, glutaraldehyde and genipin are used to crosslink the collagen.And in enzymatic method, transglutaminase is used to crosslink the collagen and therebyovercome the drawbacks that are associated with the collagen.We will go on to the silk.Silk fibroin, silk fibroin is the structural protein that is derived from the silkwormBombyx mori.The inherent optical property of silk fibroin makes it more suitable for corneal tissueengineering.And this silk fibroin, silk fibroin is used as a substrate for corneal epithelial cells.Though silk fibroin provide scaffolding material for epithelial cells, but it is cell attachmentproperty are not as superior as collagen, as it lacks the natural ECM protein.To come that, what they have done is they have introduced RGD domain into the silk fibroinmembranes and thereby they tried to improve the cell attachment property of silk fibroin.And compared a compared with collagen, the advantages of using silk fibroin is it issimple to produce and modify and as well as it is easier to produce the porous scaffoldusing silk fibroin.And we will go on to the decellularized cornea.The corneal tissue, they decellularize, remove all the cellular cell cells and the cell debrisfrom the corneal tissue and they use for corneal replacement purposes.But the problem is the availability of the human cornea tissue for preparing the decellularizedcornea, hence are taken from porcine or bovine.And as it is a decellularized cornea, it is optical and mechanical property are similarto the natural corneal tissue.And the approaches to decellularize the cornea tissue are listed over here, they use thevery sorry.They use the various types of detergents like ionic detergents, non ionic detergents, zwitterionicdetergents and freezing thawing and osmotic shock.And apart from these techniques recently, they have tried to use the high hydrostaticpressure and supercritical carbon dioxide.Chitosan; chitosan is derived from the chitin by deacetylation process and it has been reportedthat primary bovine corneal epithelial cell seeded on the pure chitosan membrane, showedimproved proliferation.The incorporation of chitosan can promote the optical transparency and mechanical strengthof the collagen membrane.But the problem with chitosan is it is, it is very poorly soluble in the physiologicalmedium.Hence, the derivatives of chitosan has been tried out for example, hydroxyl ethyl chitosan,which has a very good solubility and also they have tried to use hydroxypropyl chitosan.Compared the hydroxypropyl chitosan has a comparable optical transparency and it hascomparable water content and high glucose permeability compared to the natural humancornea.Also, although chitosan has demonstrated great potential for corneal tissue engineering,it is not used alone, it is blended with other polymer and hence used.So, far we have discussed about the naturally occurring polymers now, we will talk aboutfew of the synthetic polymers.The preliminary, predominantly widely used synthetic polymer for corneal tissue engineeringis, polymethyl methacrylate.Polymethyl methacrylate is a transparent thermoplastic polymer which can be; which can be modifiedto achieve the required mechanical properties like toughness and stiffness.And poly PMMA it has ability to block UV light and hence it is more suited for corneal tissueengineering.However, the usage of PMMA is impeded due to tissue necrosis vitreous, vitreous opacitiesand poor adhesion between the PMMA and host corneal collagen.Vitreous opacities I mean to say is vitreous fluid contains 98 percent of water and 2 percentof hyaluronic acid, what happens is, tiny clots are formed and they form in the eyeballand they move along with the eyeball movement and that hinders the that is known as vitreousopacities.Several efforts have been taken to overcome these drawbacks.For example, coupling PMMA with the PEG polyethylene glycol and they also try to combine otherpolymer polyHEMA with the PMMA and they also tried to improve the antibacterial activityof PMMA by using the antimicrobial agents into these PMMA polymers.And these are the few commercially available corneal replacements and as you see here,most of the core material that are used for this corneal replacements are synthetic innature PMMA polyHEMA, acrylic polymer.And as you see, the major drawbacks of this commercially available corneal replacementsis integration.The poor adhesion between the cornea and the tissue engineering construct.Hence, future study should be focuses on to improve the integration of these tissue engineeringconstructs with the host tissue.One more major aspects of a cornea is cornea corneal wound healing.Like any other wound healing process, which happen that happens in our body even cornealwound healing involves four stages like hemostasis, inflammation, cell proliferation and remodelling.But the problem with the corneal wound healing is cornea contains limbus region.And this limbus region is immune privilege and angiogenic privileges; that means, theit lacks, it naturally lacks neo vascularization and immune cells in the limbus region andthat is required for the transparency of the corneal tissue.And as you see here, the wound healing process involves the step called inflammation anddue to this, the immune cells march into the limbus region.They destroy the limbus region and they will be a neo vascularization takes place as yousee over here and that leads to the corneal opacity.And as as in any other wound healing process, wound healing leads to the scaring of thetissue that ultimates ultimately leads to the loss of vision and there are many attemptsangiogenic privilege and immune privilege of cornea.For example, amniotic membrane.Amniotic membrane contains naturally contains anti-inflammatory antiangiogenic compoundsand using this amniotic membrane for corneal wound healing; corneal wound healing preventsthe or lessen the inflammation stage.And many pharma, pharmaceutical agents that are antiangiogenic or anti-inflammatory agentsare used for corneal wound healing to achieve the immune and angiogenic privilege but atthe same time.Exosomes, exosomes are cell derived nano scale vesicles that are secreted outs secreted outand these exosomes contain several bio active bio active molecules that have various functionalities.The exosomes that have been released by corneal epithelial cells are known to involve in woundhealing process.And usage of these exosomes for wound healing process for corneal wound healing are provenbetter.Thank you.