Recent Advances in Hydrogels: Ophthalmic Applications in Cell Delivery, Vitreous Substitutes, and Ocular Adhesives
Abstract
:1. Introduction
2. Hydrogel Types and Classifications
3. Hydrogels Used in Cell and Stem Cell Delivery
4. Hydrogels Used as Vitreous Substitutes
5. Hydrogels Used as Ocular Adhesives in Corneal Wounds and Incisions
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
BDDE | 1,4-Butanediol diglycidyl ether |
MTT | 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide |
AMD | age-related macular degeneration |
ADA | alginate dialdehyde |
CGP | β-glycerophosphate-bound chitosan |
BM-MSC | bone marrow mesenchymal stem cells |
CMCTS | carboxymethyl chitosan |
CS | chitosan |
CPX | ciprofloxacin |
CCI | clear corneal incisions |
CT | cross-linking time |
FD | degree of methacrylation |
DMEK | Descemet membrane endothelial keratoplasty |
Alg-DA | dopamine-modified alginate |
dsDNA | double stranded DNA |
CE | European Conformity |
ECM | extracellular matrix |
FDA | Food and Drug Administration |
FT-IR | Fourier-transform infrared spectroscopy |
GE | gelatin |
GelMA | gelatin methacryloyl |
GELGYM | gelatin-glycidyl-methacrylate hydrogel |
gel-HA | gelatin-hyaluronic acid |
Gtn-HPA | gelatin-hydroxyphenyl propionic acid |
GelCORE + MC | GelCORE loaded with micelles |
GG | Gellan Gum |
DFG | Gellan gum grafted with dopamine |
AuNRs | gold nanorods |
hRPCs | human RPCs |
HAA | hyaluronan modified with aldehyde |
HKA | hyaluronan modified with ketone |
HPCTS | hydroxypropyl chitosan |
ISO | International Organization for Standardization |
IOL | intraocular lens |
IOP | Intraocular pressure |
HA-MA | methacrylated hyaluronic acid |
D-MA | methacrylated hydroxyl dendrimer |
NIR | near infrared |
VC | N-vinylcaprolactam |
OHA | oxidized hyaluronic acid |
PEGOA₄ | PEG-tetraoxyamine |
C3F8 | perfluorocarbon |
PBS | phosphate buffered saline |
PTT | photothermal therapy |
iPSC | pluripotent stem cells |
PCL | poly(3-caprolactone) |
PASA | poly(aspartic acid) |
PEGDA | poly(ethylene glycol) diacrylate |
PEGMA | poly(ethylene glycol) methacrylate |
PGS | poly(glycerol-sebacate) |
PHIS | poly(histidine) |
PGA | poly(L-glutamic acid) |
PLLA/PLGA | poly(L-lactic acid)/poly(lactic-co-glycolic acid) |
poly(MAM-co-MAA-co-BMAC | poly(methacrylamide-co-methacrylate-co-bis(methylacryloyl-cystamine)) |
PNIPAM | poly(N-isopropylacrylamide) |
PHBHx | poly(PHBHx/PEG/PPG urethane) (PHxEP), poly(ε-caprolactone) (PCL), poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate] |
PDA | polydopamine |
PEG | polyethylene glycol |
PPG | polypropylene glycol |
RD | retinal degenerative diseases |
RGCs | retinal ganglion cells |
RPE | retinal pigment epithelium |
RPC | retinal progenitor cell |
RP | retinitis pigmentosa |
SF6 | Sulfur hexafluoride |
SIA | surgical induced astigmatism |
TEA | triethanolamine |
UV | ultraviolet |
UM | uveal melanoma |
%wt | weight percent |
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Type of Hydrogel | Polymer(s) | Retinal Cell Type | In Vitro Cytocompatibility | In Vivo Biocompatibility | Notes |
---|---|---|---|---|---|
PEG/GG [64] | Polyethylene glycol and gellan gum | RPE | Yes—Live/Dead assay, MTT analysis, and gene expression analysis | Not conducted | None |
Ge/GG/Cs [38] | Gelatin, gellan gum, and glycol chitosan | RPE | Yes—Live/Dead staining and gene expression analysis | Not conducted | Inclusion of Cs lead to higher proliferation rates |
DFG [73] | Gellan gum grafted with dopamine | RPE | Yes—Live/Dead staining and gene expression analysis | Not conducted | Dopamine confers superior hydrogel injectability and a favorable microenvironment |
CS-Odex [79] | Chitosan hydrochloride and oxidized dextran | RPC | Yes—Live/Dead assay and inflammatory and apoptotic factor expression analysis | Yes—H&E staining and Masson’s trichrome staining | Hydrogel is able to self-heal. CS increases preferential differentiation towards retinal neurons. |
Gtn-HPA [66] | Gelatin-hydroxyphenyl propionic acid | RPC | Yes—Live/Dead assay | Yes—immunohistochemistry and anti-leukocyte staining | Gtn-HPA lowers proliferative potential and transplants show persistent retinal detachment |
gel-HA [82] | Thiolated gelatin and methacrylated hyaluronic acid | RPC | Yes—Live/dead staining, inflammatory and apoptotic factor expression levels, and cell adhesion analysis | Not conducted | Improved cell proliferation |
gel-HA-PDA [82] | Thiolated gelatin, methacrylated hyaluronic acid, and polydopamine | RPC | Yes—Live/dead staining, inflammatory and apoptotic factor expression levels, and cell adhesion analysis | Yes—H&E staining and Masson’s trichrome staining | Improved neuronal differentiation and cell migration and adhesion |
Type of Hydrogel | Polymers | In Vitro Cytocompatibility | In Vivo Biocompatibility | Notes |
---|---|---|---|---|
HPCTS-ADA [89] | Hydroxypropyl chitosan and alginate dialdehyde | Yes—MTT assay | No—electroretinogram and histopathologic anaylsis | None |
CMCTS-OHA [90] | Oxidized hyaluronic acid and carboxymethyl chitosan | Yes—MTT assay | Yes—H&E staining | Self-healing properties |
PanaceaGel SPG-178 [91] | 13 amino acid peptide (RLDLRLALRLDLR) | Yes—Live/Dead staining | Yes—slit lamp examination, fundoscopy, electroretinography, histopathology | Self-assembling properties prevent damage from injection |
poly(MAM-co-MAA-co-BMAC [92] | Thiolated gellan and poly(methacrylamide-co-methac -rylate-co-bis(methylacryloyl-cystamine)) | Yes—ECIS and CellTiter-Glo Luminescent Cell Viability end-point assay | Yes—electroretinography, optical coherence tomography, and H&E staining | Thermoresponsive |
PHxEP [47] | Poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate], polyethylene glycol, and polypropylene glycol | Yes—MTT assay | Yes—histopathological examination | Thermoresponsive |
EPC [93] | Poly(ε-caprolactone), polyethylene glycol, and polypropylene glycol | Not conducted | Yes—slit-lamp examinations, fundus evaluation, electroretinography, H&E staining | Degrades and regenerates a vitreous-like body |
HA-oxime [98] | Hyaluronan modified with aldehyde or ketone and PEG-tetraoxyamine | Yes—Live/Dead assay | Yes—H&E examination | Click chemistry cross-linking system obviates the need for cross-linking agents |
PEGDA [105] | Poly(ethylene glycol) diacrylate | Yes—CellTiter-Glo luminescent cell viability assay | Not conducted | Can be loaded with vitamin C to protect against oxidative damage |
PEGDA-co-PEGMA [105] | Poly(ethylene glycol) methacrylate and poly(ethylene glycol) diacrylate | Yes—CellTiter-Glo luminescent cell viability assay | Not conducted | Can be loaded with vitamin C to protect against oxidative damage |
Type of Hydrogel | Polymer | Corneal Incision Length (mm) | Burst Pressure (kPa) |
---|---|---|---|
ReSure® Sealant [121] | Polyethylene glycol | <3.5 | 12.4 |
OcuSeal™ [136] | Poly(glycerol succinic acid) and PEG-aldehyde | <2.8 | 26.4 |
OcuPairTM [126] | Methacrylated hydroxyl dendrimer and methacrylated hyaluronic acid | <6 | 9.3 |
GelCORE [128] | Methacrylated gelatin | <3 | 30.1 |
GELGYM [135] | Glicydlmethacrylated Gelatin | <4 | 26.7 |
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Lin, K.T.; Wang, A.; Nguyen, A.B.; Iyer, J.; Tran, S.D. Recent Advances in Hydrogels: Ophthalmic Applications in Cell Delivery, Vitreous Substitutes, and Ocular Adhesives. Biomedicines 2021, 9, 1203. https://doi.org/10.3390/biomedicines9091203
Lin KT, Wang A, Nguyen AB, Iyer J, Tran SD. Recent Advances in Hydrogels: Ophthalmic Applications in Cell Delivery, Vitreous Substitutes, and Ocular Adhesives. Biomedicines. 2021; 9(9):1203. https://doi.org/10.3390/biomedicines9091203
Chicago/Turabian StyleLin, Kenny T., Athena Wang, Alexandra B. Nguyen, Janaki Iyer, and Simon D. Tran. 2021. "Recent Advances in Hydrogels: Ophthalmic Applications in Cell Delivery, Vitreous Substitutes, and Ocular Adhesives" Biomedicines 9, no. 9: 1203. https://doi.org/10.3390/biomedicines9091203