Table 1.
Cell types, model studies, and advantages/disadvantages of biomaterials used in ocular tissue engineering.
| Tissue | Material | Biomaterial | Cell types | Model study | Advantage | disadvantage | Ref. |
|---|---|---|---|---|---|---|---|
| Conjunctiva | Natural | autologous fibrin | CjECs | NZW strain rabbits | The availability, cost-effectiveness, and high tolerance to culture conditions, degrading swiftly without any detrimental impact on the survival of the cultivated limbal epithelial cells | not being contracted by stromal cells, in contrast to using collagen as substrate, | [73] |
| Biohybrid | (SF/PLCL) | rCjECs | mice | having outstanding biocompatibility, demonstrating exceptional manifestation of CjEC genes and decreasing manifestation of inflammatory mediators, the capability to create a well-organized conjunctival epithelium, which includes the presence of goblet cells | Not applicable | [96] | |
| (PLA/EFMs) surface coated by CNF and/or SP loaded with LF | CjECs | NZW (New Zealand white) rabbits | Effective suppression of bacterial growth and reduction of antibiotic usage after surgery | Not applicable | [93] | ||
| SF-rGo | CJMSCs | In vitro | offering advantageous mechanical and cytocompatibility characteristics, as well as a larger surface-to-area ratio compared to alternative manufacturing techniques by using SF, exhibiting exceptional electrical conductivity by use of rGO | Not applicable | [94] | ||
| (collagen/PLCL) | CjECs | in vitro | displaying advantageous mechanical properties, wettability, and the ability to promote cell proliferation/mimicking the ECM and supporting the growth and differentiation of goblet cells/not induce an upregulation of IL-4, IL-5, and IL-6 expression, unlike what is observed in TCPS (tricalcium phosphate scaffold) culture | Not applicable | [95] | ||
| Cornea | Natural | microgrooved collagen films | CEC | In vitro | displaying comparable optical clarity, swelling and biodegradability Compared to the natural cornea, which promoted epithelial cell migration, wound healing, and keratocyte fibrosis retardation | Not applicable | [74] |
| collagen-glycosaminoglycan | corneal keratocyte cell | In vitro | Characteristics include transparency, strength, elasticity, cell development, and resistance to collagenase destruction | Decreasing collagen synthesis | [75] | ||
| Biohybrid | PCL microfibrous scaffold infused with rat tail collagen type I | LSSCs (in vitro)-keratocytes (in vivo) | Rat | Enhancing the organization of collagen and reducing the presence of fibroblasts and myofibroblasts in injured corneas, promoting the ECM-related pathway and increasing the expression of various ECM-related genes in the injured group | Not applicable | [10] | |
| biodegradable silk fibroin-based scaffolds containing GDNF | – | mice | promoting epithelialization, keratocyte and epithelial cell proliferation, stromal nerve plexus development, and anti-apoptotic activity | Not applicable | [12] | ||
| (GelMA-HA) | Rabbit CS cell | In vitro | supplying CS cells with cues for spatial and directional organization and ECM remodeling | Not applicable | [101] | ||
| (PVA-COL) | Human and rabbit CEC | In vitro/rabbit | Making stratified epithelial histologically and functionally similar to healthy epithelial surface | Not expressing collagen type IV and VII even with soluble laminin and the protease inhibitor aprotinin, Failure to achieve stable epithelialization in vivo |
[19] | ||
| (AM)- (PVA-AM) | rabbit CEC | Japanese white rabbits | Being easy to handle and transplant to the cornea, Benefiting from AM tissue's inherent basement membrane and PVA's transparency and durability | Stabilizing the AM component of PVA-AM is still an issue remaining to be resolved | [97] | ||
| (GP/PVA/SF/n-HA) | HCFs cells | In vitro | Regularizing PVA/SF/n-HA composite hydrogel, enhancing heat stability, and reducing moisture | Not applicable | [98] | ||
| VH | – | rabbit | Biomechanical stability and optical transparency, preventing infections caused by S. aureus in implanted devices. in vivo and in vitro | Not applicable | [99] | ||
| Aligned (PVA-COL) | HKs and HCECs | In vitro | Similar mechanical strength to real corneal tissue, enhancing electrospun scaffold mechanical characteristics | Not applicable | [100] | ||
| sHAPN copolymers | rabbit cornea cells | In vitro/rabbit | Being a thermo-responsive carrier, enhancing the ocular bioavailability of multiple ophthalmic medications, delivering crucial therapeutic benefits such as anti-inflammatory properties and corneal protection | Not applicable | [103] | ||
| oHA | keratocytes | rabbit | enhancing gelatin microcarriers for greater oHA grafting by leveraging oxidation levels in aldehyde HA | Not applicable | [102] | ||
| Decellular | LCs | primary corneal endothelial cells | In vitro | Increasing the surface area of focal adhesions in cells cultured on coated liquid crystals by at least twofold compared to other settings | completed digestion after 13 h for LC and amniotic membrane, whereas the DM was digested after 17 h | [109] | |
| decellularized (SMILE) lenticule (SL), (AM), and collagen-coated plates | hADSCs | New Zealand male rabbits | can culture Keratocytes better | Not applicable | [108] | ||
| carbodiimide crosslinked RHC | – | Human | Being stable for four years without rejection episodes and without immunosuppression, correcting visual acuity of 20/54 and gaining more than 5 Snellen lines on an eye chart | Not applicable | [110] | ||
| Native porcine conjunctiva | CEC | rabbit | Better optical transmittance, tensile strength, stability, biocompatibility, and degradation resistance in vitro and in vivo, longer survive of donor cells | Not applicable | [111] | ||
| Porcine | rabbit corneal limbal epithelial cells | In vitro | Not applicable | The necessity of Future research to assess the endurance of the treated cornea and study in vitro cell recellularization and penetration in the corneal matrix | [112] | ||
| decellularized Human doner cornea | LEPC, LMSC and LM | In vitro | Using non-immunogenic tissue scaffolds for transplantation and having the ability to be repopulated by host cells either in situ or in vitro | Not applicable | [113] | ||
| (FD-APCS) | CEC | In vitro/NZW rabbits | Having no major differences from the APCS-transplanted or native cornea, providing a void area for cells and a collagen lamellae ultrastructure identical to native cornea stroma | Not applicable | [114] | ||
| Decellularized murine corneas | (hESC-CEC) | In vitro | Not applicable | Not applicable | [119] | ||
| decellularized human cornea | hCEC and hLEC | In vitro | Presenting characteristic indicators of (hCEC) and (hLEC) on their respective surfaces. | The vitality of Further research to evaluate if corneal structures are suitable for transplantation. | [120] | ||
| lacrimal gland | Synthetic | polyester membrane | pLGACs | In Vitro | Not applicable | Not applicable | [82] |
| PES | Lacrimal acinar epithelial cells of Sprague-Dawley rats | In Vitro | Excellent oxidative, thermal, and hydrolytic stability | Not being biodegradable | [81] | ||
| Decellular | SIS-Muc | Porcine LG epithelial cells | In Vitro | Promoting normal lacrimal fluid production in epithelial cells grown on SIS-Muc, mimicking natural LG acini polarization | Failure to observe polarization or acini-like features in synthetic tissue | [116] | |
| NZW rabbit lacrimal glands ECM | adult rabbit lacrimal gland progenitor cells | In vitro | keeping cells alive and secreting for four weeks | Further research is needed to optimize decellularization | [13] | ||
| DC-LG | LG epithelial cells | In vitro | A three-dimensional, supporting, and accessible matrix provides LG-specific ECM protein amounts, distribution, and composition | Requiring to Further evaluation of this LG construct by functional research in vivo | [115] | ||
| Lens | Biohybrid | biodegradable HA and nondegradable polymeric gel | – | Dutch Belt pigmented and NZW rabbits | Excellent cortical anatomy and lens clarity | Transparent regrowth in the lens and peripheral capsule bag, with opacified regrowth behind the polymeric scaffold | [104] |
| Retina | Natural | GCH | Human embryonic stem cells | mouse | promoting retinal cell differentiation over other anterior forebrain cells and inducing a modest immune response, allowing the implant to survive 12 weeks | basic retinal lamination and cytoplasmic transfer instead of photoreceptor layer implantation | [77] |
| Cask and Caskin1 | – | In vitro | Having Global synaptic function | Not applicable | [76] | ||
| RS1 | – | In vitro | stabilizing retinal integrity | Not applicable | [79] | ||
| Fibrin hydrogel | CJMSCs | In vitro | promoting cell growth and proliferation without harming cells Because of its flexibility and continual disintegration, fibrin hydrogel | Not applicable | [78] | ||
| Synthetic | PCL | Mouse and Human RPCs | In vitro/Adult Rho -/- or wildtype mice | the ability to engage with mRPCs and human RPCs and drive them toward a photoreceptor fate, allowing cell differentiation before transplantation | Not applicable | [17] | |
| PLLA and PLGA | RPCs | In vitro/rat | Being desired to simulate retinal polarization | Not applicable | [83] | ||
| PLGA | RGCs | rabbits and monkeys | been discovered in rabbits' intraocular environments after 3 months | The necessity of Future studies to adjust the molecular weight of PLGA substance and extending the observation duration to determine the scaffold's biodegradability in vivo | [85] | ||
| Laminin coated novel nanowire PCL | Mouse RPCs | Rho −/− mice | Showing Biocompatibility by cell attachment and sustained proliferation | Not applicable | [84] | ||
| polyethylene terephthalate or poly(L-lactide-co-ε-caprolactone) | hfRPE | In vitro/female Chinchilla Bastard rabbit | showing favorable subretinal biocompatibility | Not applicable | [86] | ||
| microfabricated poly(glycerol-sebacate) | RPCs | In vitro | having a 10-fold higher maximum elongation at failure than earlier RPC scaffolds, significantly improving mechanical characteristics and reducing scaffold thickness | Not applicable | [87] | ||
| PCL, PGS and POC | RPCs | In vitro | enhancing scaffold hydrophilicity and degradation, accelerating human retinal pigment epithelial cell proliferation, decreasing fiber diameter, and boosting tensile modulus | Not applicable | [18] | ||
| 3-D PCL cell encapsulation scaffold | Mouse RPC | In vitro | Enabling regulated, accurate, targeted administration of cells to the subretinal area, providing various benefits compared to earlier 2 and 2.5-D structures used for retinal progenitor cell transplantation/having the structure which is highly porous, facilitating diffusion and potential cell interactions from both the neural retina and the RPE | Not applicable | [88] | ||
| PLGA | hiPSC -derived retinal progenitor cells | In vitro | Modifications in the dimensions of the pores, the distance between the slices, the distance between the hatches, and the type of hatching. | Not applicable | [89] | ||
| PLGA | hiPSC retinal organoid derived RGCs | rhesus monkey | allowing transplanted tissues to survive 1 year without tumorigenesis with enough graft–host contact | Not applicable | [14] | ||
| PCL and PEG included taurine | CJMSCs | In vitro | assisting CJMSCs develop into photoreceptors by Taurine | Not applicable | [16] | ||
| Biohybrid | (RWSF/PCL/Gt) | RPE | rabbits | Having good in vitro and in vivo cytocompatibility for RPE implantation as a prosthetic Bruch's membrane | Not applicable | [15] | |
| (SF/PLCL) | RPCs | in vitro | greatly increasing RPC proliferation, including photoreceptors with high porosity and ECM topography | Not applicable | [105] | ||
| gelatin/chitosan | RPE | in vitro | imitating additional cellular matrix and Bruch's membrane nanofibrous structure, without cytotoxicity, and not modifying grown hRPE cells on gelatin/scaffold | needing further clinical trials to prove these scaffolds can treat retinal disorders | [106] | ||
| HAMP/PCL | RPE cells | In vitro | Optimizing porosity, degradation, and biocompatibility | The necessity to use more realistic RPE cultures obtained from primary or stem cell cultures in Future investigations | [107] | ||
| Optic Nerve | Natural | Netrin-1 gradient | RGCs | In vitro | increasing the amount of transplanted RGCs whose axons reach the optic nerve head | not noticing polarized cell directionality | [80] |
| Synthetic | PCL and PBG | RGCP | In vitro | successfully constructed, supporting cell survival and durable long neurite development along fibers | Not applicable | [91] | |
| PCL coated by tosylate + PEDOT | chick dorsal root ganglia and a mouse neuroblastoma cell line | In vitro | directing the nerve bundle | Not applicable | [90] | ||
| PPy-G | RGCs | In vitro | Increasing RGC density and directing neurite outgrowth and nanofiber direction | Not applicable | [92] | ||
| Decellular | porcine decellularized optic nerve | neurotrophin-3-overexpressing Schwann cells | In vitro/Rat | Increasing dorsal root ganglion neurite directional growth, myelin regeneration, neural stem cell adhesion, survival, and migration, and reducing inflammatory cells and chondroitin sulfate proteoglycan expression | The necessity of future studies to modify ECM proteins on the scaffold, assess animal behavior and electrophysiological function, and conduct large animal models for preclinical efficacy testing | [118] | |
| DON | DRG neurites | In vitro | causing lengthier extension, greater distances, and branching on the DON than the ON, selectively removing axon-inhibitory substances including myelin-associated glycoprotein and chondroitin sulfate proteoglycans by Decellularization | Not applicable | [117] |
BrM = Bruch's membrane/ON = optic nerve/RGCs = Retinal Ganglion Cells/WHO = World Health Organization/TE = tissue engineering/NSF = National Science Foundation/AMD = Age-related Macular Degeneration/VEGF= Vascular Endothelial Growth Factor/TENGs = Tissue-engineered nerve grafts/HAM = human amniotic membrane/RS1= Retinoschisin/GCH=Gelatin/Chondroitin sulfate/Hyaluronic Acid/hESC = human embryonic stem cell/ONL= Outer Nuclear Layer/PES= Polyethersulfone/PCL= Polycaprolactone/PLLA= Poly L-lactic Acid/PLGA= Poly Lactic-co-Glycolic Acid/PGS= Poly Glycerol Sebacate/PPy-G = polypyrrole functionalized graphene/PLA= Poly Lactic Acid/EFMs = Electrospun nanofibrous membranes/CNF= Cellulose Nanofibrils/SP= Silk Peptide/LF = levofloxacin/SF= Silk Fibroin/rGo = reduced Graphene oxide/PLCL = poly (L-lactic acid-co-3- caprolactone)/SF/rGO= Silk Fibroin/reduced Graphene oxide/ ECM = extracellular matrix/ Collagen/PLCL = Collagen/poly (L-lactic acid-co-3- caprolactone)/CjECs = Conjunctival Epithelial Cells/SF/PLCL = Silk Fibroin/poly (L-lactic acid-co-3- caprolactone)/GelMA-HA = hyaluronic acid-modified gelatin-methacrylate/PVA-COL= Collagen-Immobilized Poly (Vinyl Alcohol)/AM = Amniotic Membrane/PVA-AM = polyvinyl alcohol hydrogel/GP/PVA/SF/n-HA= Genipin-crosslinked polyvinyl alcohol/silk fibroin/nanohydroxyapatite Hydrogel/PCL/collagen = Polycaprolactone/collagen/HA= Hyaluronic Acid/RWSF= Regenerated wild Antheraea pernyi Silk Fibroin/Gt = Gelatin/HAMP= Human amniotic membrane powder/LCs = Lens Capsules/FD-APCS= Freezing-Dry Acellular Porcine Cornea Stroma/SMILE= Small incision lenticule extraction/SL = lenticule/RHC= Recombinant Human Collagen/NZW= New Zealand White/(SIS-Muc) = Conversely decellularized porcine small intestine submucos/DC-LG = Decellularized porcine LG matrix/DON = Decellularized Optic Nerve/PLA=Poly Lactic Acid/SP= Silk Peptide/CJMSCs= Conjunctiva Mesenchymal Stem Cells/PLCL= Poly L-lactic acid-co-3- Caprolactone/rCjECs = rabbit Conjunctival Epithelial Cells/LCs = Lens Capsules/hADSCs = human Adipose Mesenchymal Stem Cells/PCL= Poly ε-Caprolactone/LSSCs= Limbal Stromal Stem Cells/GDNF = Glial Cell-Derived Neurotrophic Factor/LEPC= Limbal Epithelial Progenitor Cells/LMSC= Limbal Mesenchymal Stromal Cells/LM = Limbal Melanocytes/FD-APCS= Freezing Dry Acellular Porcine Cornea Stroma/GelMA-HA= Hyaluronic Acid-modified Gelatin-Methacrylate/CS= Corneal Stromal/hESC-CEC = human Embryonic Stem Cells- Corneal Epithelial Cells/PVA-COL= Colagen-Immobilized Poly Vinyl Alcohol/CEC= Corneal Epithelial Cells/GP= Genipin/n-HA = nanohydroxyapatite/HCFs = Human Corneal Fibroblasts/VH= Vancomycin-loaded collagen Hydrogels/hCEC = human Corneal Endothelial Cells/hLEC = human Limbal Epithelial Cells/PVA= Aligned Polyvinyl Acetate/HKs = Human Keratocytes/LG = Lacrimal Gland/PLGACs= Purified rabbit Lacrimal Gland Acinar Cells/RPCs= Retinal Progenitor Cells/RS= Retinoschisin/PCL= Polycaprolactone/mRPCs = mouse Retinal Progenitor Cells/hiPSC = human-induced Pluripotent Stem Cell/RPE = Retinal Pigment Epithelial/PEG= Polyethylene Glycol/DRG = Dorsal Root Ganglion/PBG= Poly-gamma-Benzyl-L-Glutamate/RGCP= Retinal Ganglion Cell Progenitors/PEDOT= PSS (polystyrene sulfonate) in water and isopropanol/TCPS = tricalcium phosphate scaffold/LCs = Lens Capsules/DM = Descemet's membrane/DHC = Decellularized Human Cornea/FD-APCS= Freezing Dry Acellular Porcine Cornea Stroma/GelMA-HA= Hyaluronic Acid-modified Gelatin-Methacrylate/PVA= Polyvinyl Alcoholhydrogel/POC= Poly (1,8-Octanediol-co-Citrate)/LSSCs= Limbal Stromal Stem Cells/hfRPE = Human fetal Retinal Pigment Epithelium cells/IL-4, IL-5, and IL-6 = interleukin-4, interleukin-5, Interleukin-6/sHAPN= Sulfated Hyaluronic acid with amine-terminated poly(N-isopropylacrylamide)/oHA = Oxidized hyaluronan.