Advancements in Polymer Biomaterials as Scaffolds for Corneal Endothelium Tissue Engineering


Silicone and
collagenHexagonal structures, 1.52 to 2.02 µm depth, 10–20 µm widthHuman mesenchymal stem cells (hMSCs)Differentiation of hMSCs into corneal endothelial-like cellsCorneal endothelium tissue engineering, potential autologous stem cell therapyTwo-photon lithography2019[107]Tissue culture
polystyrene
(TCPS)1 μm pillars, 1 μm wells, and 250 nm pillars; FNC coating containing fibronectin, collagen I, and albuminHuman corneal endothelial cells
(HCECs)Enhanced proliferation, maintenance of functional markers like ZO-1 and
Na+/K+-ATPaseCorneal endothelium tissue engineering, cell therapy, and drug screeningHeat embossing2015[109]PDMS (polydimethylsiloxane)1 μm pillars, 1 μm wells, 250 nm pillars, and 250 nm wellsBovine corneal
endothelial cells (BCECs)Enhanced cell density on pillars, maintenance of functional markers
like Na+/K+-ATPaseCorneal endothelium tissue engineering and drug screeningSoft lithography2012[110]PDMS (polydimethylsiloxane)Nanopillars: 250 nm diameter,
250 nm height; micropillars:
1 µm diameter, 1 µm height;
FNC coating containing
fibronectin, collagen I, laminin,
and chondroitin sulfateHuman corneal endothelial cell line B4G12 (HCEC-B4G12)Increased cell proliferation; improved Na+/K+-ATPase and ZO-1 expressionCorneal endothelium
tissue engineeringSoft lithography2014[111]Gelatin methacrylate (GelMA)1 μm pillars with 6 μm spacing
(1 × 6 μmpS pillars);
250 nm pillarsHuman corneal endothelial cells
(HCECs)Enhanced cell adhesion and mechanical strength, customizable degradation rates, increased amount of ZO-1 expression for 1 × 6 μmpS pillarsCorneal endothelium
tissue engineering-Hybrid crosslinking method (which combines physical crosslinking followed by UV crosslinking to improve the material’s mechanical strength)
-PET stamp-based nano-molding for high-resolution patterns2017[112]Silk nanofibrils (SNF) and gelatin methacryloyl (GelMA)Nanoscale fibrillar structures with 30/70 volume ratio of SNF/GelMAHuman corneal
stromal cellsEnhanced transparency, mechanical strength, cell attachment, spreading, and proliferation with customizable degradation ratesCornea regenerationUV crosslinking for GelMA; calcium chloride–formic acid dissolution and stirring for nanofibril formation. Casting followed by UV crosslinking for fabrication of SNF/GelMA hybrid films.2021[75]Acrylated star-shaped poly(ethylene oxide-stat-propylene oxide) (Acr-sP(EO-stat-PO)) hydrogelsMicrometer-sized surface patterns (posts and grooves). Groove width: 10 μm, depth: 5 μm (grooves separated by 20 μm space). Wider pattern: 25 μm wide grooves, 10 μm depth (separated by 25 μm spaces)Mouse fibroblast cell line (L929) and human mesenchymal stem cells (hMSC)Induced vitronectin (VN) adsorption
and strong cell adhesion, alignment,
and spreadingUse topographic patterning to promote cell adhesion even on non-adhesive materials without additional surface chemistry modificationsUV-based imprinting2011[122]Star-shaped poly (ethylene glycol)Posts: 3 µm diameter, 3 µm height; lines: 5–50 µm spacing, 5–50 µm width, 5 µm depthMouse fibroblast (L929)Enhanced cell adhesion and spreading.
Posts: cells spread, wrapped around posts. Lines: cells aligned along grooves, best alignment in 5–10 µm grooves.Use topographic patterning to promote cell adhesion even on non-adhesive materials without additional surface chemistry modificationsNanoimprinting and replica molding2009[123]Poly(vinyl alcohol) (PVA) hydrogelGratings, pillars, convex lens, concave lens (gratings: 250 nm, 10 μm, 2 μm; pillars: 10 μm, 2 μm; convex lens: 10 μm, 2 μm, 1.8 μm; concave lens: 1.8 μm)Human endothelial cells (EA.hy926)The 2 μm gratings on PVA hydrogels were found to increase hydrophobicity and were the most effective in promoting endothelial cell adhesion and density. Convex and concave lenses also performed well but were slightly less effective than gratings. Pillars were moderately effective and were the least optimal.Corneal endothelium tissue engineeringCasting method (for the creation of micro-sized features), nanoimprint lithography (for the creation of nano-sized features), and nitrogen plasma modification2016[113]PHEMA hydrogelsLotus leaf topography (3 ± 1 µm height, 9 ± 2 µm width)Human corneal epithelial cells (HCE-T)Enhanced cell adhesion and proliferation, increased hydrophobicity with static contact angle of 86 ± 2°, and the presence of trapped air pockets.Tissue engineering, especially in applications requiring enhanced cell adhesion and hydrophobic surfacesPolymerization in mold-nanoimprint lithography (PIM-NIL), which involves the use of Teflon AF molds to capture the hierarchical structure of the lotus leaf, both at the micro- and nanoscale, and then polymerizing PHEMA within the mold to create a structured hydrogel.2016[142]PHEMA (poly(hydroxyethyl methacrylate))Pillar structures (aspect ratio up to 100:1, 30 µm diameter, 1 mm height, 50–500 µm spacing)Not specifiedMicrostructured surfaces showed higher contact angles compared to smooth surfaces, indicating increased hydrophobicityBiomimetic surfaces and hydrophobic surface designCombination of molding and radical polymerization2005[143]Collagen filmsGroove widths of 25 µm, 50 µm, and 100 µm, with a depth of 50 µm and a ridge width of 200 µmRabbit corneal
epithelial cells (CECs)
and keratocytesSwelling capacity and optical clarity comparable to natural cornea, similar degradation rate to unpatterned films (14 h), significant cell alignment along grooves (alignment index 20% to 60%), normal exponential cell growth (slightly slower on wider grooves), accelerated wound healing with narrower grooves, and inhibition of keratocyte transformation into myofibroblasts (reduced CTGF, aSMA, COL1A1 gene expression).Design surfaces that promote cell alignment, guide direction migration of cells, accelerate wound healing, and inhibit fibrosis.
Epithelialization of corneal epithelial cells.Combination of soft lithography and solvent casting2019[114]Polydimethylsiloxane (PDMS)Rose-petal-topography-mimicked surface. Microgroove mean depths of 12.9 µm (red rose) and 6.6 µm (white rose). White rose petal patterned PDMS exhibited hexagonal patterns similar to CEC.Bovine corneal
endothelial cells (BCE C/D-1b)Collagen IV-functionalized PDMS (PDMS-C4) significantly enhanced CEC proliferation, but white-rose-patterned PDMS-C4 (PDMS-C4-R) provided the highest proliferation rate and cell density. PDMS-C4-R also maintained CEC-specific phenotype.Corneal endothelium tissue engineeringSoft lithography, followed by functionalization with collagen IV and hyaluronic acid to enhance cell attachment and proliferation.2021[108]Gold with SAMs of oligo(ethylene oxide)Self-assembled monolayers
(SAMs) with variable
chain lengthsProteins
(e.g., fibrinogen, lysozyme)Prevention of nonspecific
protein adsorptionDesign of non-fouling surfaces for biomedical applicationsAdsorption of alkanethiols onto gold surfaces using ethanol solutions, leading to the creation of monolayers with oligo(ethylene oxide) chains1993[118]Glass, silicon, and
titanium panesUltrathin film (30 +/- 5 nm) of reactive star-shaped poly(ethylene glycol) prepolymers (star PEG).Human dermal
fibroblasts (HDFs), sarcoma osteogenic cells (SaOS-2), human mesenchymal stem
cells (hMSCs)Prevention of unspecific
protein adsorption.
Promotion of specific cell adhesion and proliferation while preserving normal differentiation process.Non-fouling implant coatings that promote cell adhesion and proliferationNot mentioned1991[119]Linear RGD peptide (gRGDsc)-modified star PEG coatings.



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Kevin Y. Wu www.mdpi.com