Table 3.
Methods to Create Surface Chemistry Gradients on 2D Substrates Including Functional Group Gradients and Oligomer/Polymer-Grafted Surfaces
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| Method | Possible gradient controlling parameter(s) | Grafted species | Substrate | Final-graded functionality/surface characteristics | Gradient type(s) characterized | Bioactive or model factors used (if any) | Cell type(s) investigated (if any)b | References |
| Diffusive deposition (vapor or liquid phase adsorbent) | Diffusion controlling factors | Dichlorodimethylsilane or other organosilanes (hydrophobic) | Hydrophilic substrates (silicon dioxide, silica, quartz) | Hydrophobic (methyl groups) gradient on hydrophilic substrate | Functional group density, wettability | Fibrinogen, γ-globulin, lysozyme, kininogen, IgG | – | 79–83 |
| Grafting from initiator gradients generated via diffusion (ATRP and/or NMRP)c | Time, monomer concentration, temperature# | PAA/(PMM & PS) grafted from organosilane-based initiators | Silicon wafer | (−COOH) functionality | Polymer graft density, thickness, wettability | – | – | 86, 87 |
| Continuous depletion of monomer solution (ATRP) | Monomer solution removal rate, MCI2 concentration (governing reaction rate and polydispersity)& | PMM, (PHEMA and PMM) | Silicon wafer with chemisorbed initiator | (−COOH) functionality | Molecular weight (orthogonal), thickness | – | – | 86, 88 |
| Initiator gradient via diffusion–continuous depletion of monomer solution (ATRP) | (As mentioned above)#,& | PDMAEMA, PHEMA | Silicon wafer | (−COOH) functionality | Polymer graft density & molecular weight (orthogonal) (others, e.g., thickness, wettability) | Lysozyme, fibronectin | Osteoblast-like cells | 88, 105 |
| Thermochemical manipulation of aliphatic tert-butyl ester functionalized SAM | Temperature(s), pH, nanoparticle colloidal solution properties | (−NR2) and (−COOH) functionalized polystyrene nanospheres | Gold substrate with functionalized SAM | Nanosphere gradient (built on SAM containing −COOH gradient) | Functional group density, nanoparticle density | – | – | 89 |
| Density gradient method | Reactant concentration, reaction time (i.e., flow rates) | Dichlorodimethylsilane or other organosilanes (hydrophobic) | Hydrophilic substrates (silicon dioxide, silica, quartz) | Hydrophobic (methyl groups) gradient on hydrophilic substrate | Functional group density, wettability | Fibrinogen, IgG, lysozyme | – | 84 |
| Hyperthermal polyatomic ion deposition | Flurocarbon (C3F5+) ion fluence (ions/cm2) | Flurocarbon | PMM, PS | Fluorocarbon | Functional group density, wettability | – | – | 85 |
| Spatially varying electrochemical desorption/adsorption of alkanethiols | Applied potentials, time | Carboxylic acid–modified PS nanospheres | Gold electrode with assembled amine-terminated alkanethiol layer | (−NH2) functionality translated into PS surface | Functional group density, nanosphere surface density | – | – | 45 |
| Continuous immersion in NaOH solution | Immersion speed (time), temperature, [OH] | (Hydrolysis of the surface groups) | PVC films | Carbonate (hydrophobic) and hydroxyl (hydrophilic) groups | Functional group density, wettability | – | Endothelial cells | 44 |
| Continuous immersion of gold substrate in alkanethiol solution | Immersion speed (time) | Methyl- and hydroxyl-terminated alkanethiol | Gold-coated silicon wafers | (−CH3) or (−OH) groups | Functional group density, wettability | – | – | 90 |
| Continuous immersion in initiator solution (ATRP) | Immersion speed (time) | PHEMA | Silicon wafer | (−COOH) functionality | Functional group density | Fibronectin | Fibroblasts | 78 |
| UV (or photo-) irradiation | UV properties, exposure time using a motorized stage, exposure intensity using a mask or filterα | Etching (ozonolysis) | Silane monolayer (on glass), polymeric substrates (PCL) | Hydrophilic functionalities (−OH, −COOH) | Surface energy, wettability | Fibronectin | Osteoblast-like cells | 49, 50 |
| Etching (ozonolysis) | Silane monolayer on silicon substrate masked with a elastomeric stamp | Hydrophilic (−COOH groups) gradient on hydrophobic SAM (methyl groups) | Surface energy, wettability | – | – | 51 | ||
| BP–TEG–PE polymerization (using a heterobifunctional photolinker)/BP-RGD | Glass, alkanethiolate monolayer on gold-coated silicon wafer | Model factor | Graft density, model factor | R-phycoerythrin | – | 65, 66 | ||
| Graded preirradiation to induce −COOH functionality followed by PAAcid grafting | Polyethylene terephthalate | Model factor and −COOH functionality | Graft density, model factor | Laminin (covalently attached) | PC-12 cells | 46 | ||
| EBPDMA, TEGDMA | Glass | Functionality of casted polymers | Methacrylate conversion, mechanical properties | – | – | 41 | ||
| MMA | SBDC monolayer on silicon wafer | (−COOH) functionality | Graft density, thickness, model factor | RGD | Fibroblasts | 67 | ||
| Radio-frequency gas plasma discharge | Plasma composition, electrode-substrate gap width, power, time, exposure area using a graded or partially covering mask/exposure time using a moving mask, diffusionβ | Peroxide initiators (surface oxidation or etching) | Polyethylene (inert), PDMS,PS, PTFE | Oxygen-based functionalities (such as hydroxyl, ester, acid, ether, ketone, or aldehyde groups) | Functional group density, surface energy, wettability | Constituents in blood, albumin, IgG, fibrinogen | Platelets | 52–55 |
| ppAAm and ppHEX (graft copolymerization) | Glass | Hydrophobic alkane groups to hydrophilic allylamine groups | Thickness, functional group density, wettability | – | Fibroblasts | 77 | ||
| ppAAm/octa-1,7-diene and ppAA (graft copolymerization) | Glass | Amine/hydrocarbon and carboxyl functionalities | Thickness, functional group density, wettability | IgG | – | 74–76 | ||
| UV irradiation–plasma discharge | (As mentioned above)α,β | AA | Polymeric substrate | Hydrophilic (−COOH) | Functional group density, wettability | Serum proteins | Neurons | 64 |
| Power-graded corona discharge treatment | Substrate translation velocity, electrode-substrate gap width, power, time | Peroxide initiators (surface oxidation) | Polyethylene (insert) | Oxygen-based functionalities (such as hydroxyl, ester, acid, ether, ketone, or aldehyde groups) | Functional group density,wettability | Fetal bovine serum, calf serum and NGF, human albumin, plasma proteins | CHO cells, fibroblasts, endothelial cells, PC-12 cells, platelets | 56–61 |
| ″ | PLGA/polycarbonate | ″ | ″ | Fetal bovine serum | Fibroblasts | 62, 63 | ||
| PEO-MA | Polyethylene (inert) | PEO | Functional group density, wettability | Plasma proteins | Platelets | 68, 69 | ||
| AA/NaSS/DMAPAA (graft copolymerization), MAPC (graft copolymerization) | Polyethylene (insert) | Charged functionalities (AA/NaSS: −ve, DMAPAA: +ve) | Functional group density, charge density, wettability | Plasma proteins | CHO cells, platelets | 70, 71 | ||
| MAPC (graft copolymerization) | Polyethylene (insert) | Groups with high phospholipid affinity | Functional group density, wettability | Plasma proteins, fibronectin | Platelets, fibroblasts | 72, 73 | ||
| Thin film casting (using knife-edge flow coating) followed by annealing | Polymer solution composition, annealing temperature(s) and time, knife-substrate gap width, coating velocity and acceleration | PS-b-PMM | Silicon wafer | PS (function of film thickness) | Thickness, nanostructure | – | – | 96, 97 |
| Thin film casting followed by annealing (utilizing a temperature gradient) | Annealing temperature(s) and timeδ | PLLA | Silanized silicon wafer | Functionality of casted polymers | Crystallinity, nanoscale roughness | Fetal bovine serum | Osteoblast-like cells | 98 |
| (As mentioned above)δ | PS | Silicon wafer | PS | Thickness and temperature (orthogonal) (others, e.g., roughness) | – | – | 106 | |
| Gradient mixing (with a three-syringe pump system)–thin film casting–melt annealing | Sample collection rate, annealing temperature(s) and time, knife-substrate gap width, coating velocityη | PDLLA & PLLA | Glass | Functionality of casted polymers | Material composition, crystallinity, stiffness, roughness | – | Osteoblast-like cells | 99, 100 |
| Gradient mixing–melt annealing (utilizing a temperature gradient) | (As mentioned above)δ,η | (PDLLA & PCL)/(PS & PVME)/(PLGA & PCL) | Glass, silicon wafer | ″ | Material composition and temperature (orthogonal) (others, e.g., chemistry, microstructure, crystallinity, roughness, hydrophilicity, stiffness, degradation rate) | – | Osteoblast-like cells, VSMCs | 101–103 |
| UV (ozonolysis) treatment–thin film casting–annealing | (As mentioned above)α,δ | PS-b-PMM with an underlying oxidized chlorosilane monolayer | Silicon wafer | (PS or PMM) (function of surface energy) | Surface energy and thickness (orthogonal) (others, e.g., microstructure) | – | – | 104 |
| Electrostatic interaction (continuous immersion of a charged substrate into a suspension of nanoparticles carrying the opposite charge) | Immersion rate/colloidal solution filling rate | Anionic nanospheres (silica, gold, silver) | Poly(ethylene imine)-coated silicon wafer, glass slide modified with cationic moieties | PLL-g-PEG-RGD–coated nanospheres/protein-conjugated nanospheres | Nanoparticle density gradient, nanostructure, nanoscale roughness, protein gradient | Bovine serum albumin, ephrin-A5, ephrin B1 | Osteoblasts, hippocampal cells | 92, 93 |
| Electrostatic interaction (continuous immersion of a metal oxide substrate into a solution of polycationic polymer) | Immersion rate | PLL-g-PEG | TiO2/Nb2O5 | Functionality of grafted polymer, surface-adsorbed protein | Polymer graft density, thickness, adsorbed or conjugated protein surface density | Human serum albumin, fibrinogen, IgG, blood serum and blood plasma | – | 91 |
a
PAA: poly(acrylamide); PMM: poly(methyl methacrylate); PS: polystyrene; PHEMA: poly(2-hydroxy ethyl methacrylate); PDMAEMA: poly(dimethyl aminoethyl methacrylate); SAM: self-assembled monolayer; PVC: poly(vinyl carbonate); PCL: poly(ε-caprolactone); BP: benzophenone; TEG: tetraethylene glycol; PE: polyethylene; RGD: (arginine-glycine-aspartic acid); PAAcid: poly(acrylic acid); EBPDMA: ethoxylated bis-dimethacrylate; TEGDMA: triethylene glycol dimethacrylate; MMA: methacrylic acid; SBDC: N,N-(diethyl-aminodithicarbamoylbenzyl(tri-methoxy)silane); PTFE: poly(tetrafluoro ethylene); ppAAm: plasma polymerized allylamine; ppHex: plasma polymerized hexane; ppAA: plasma polymerized acrylic acid; PLGA: poly(lactic-co-glycolic acid); PEO-MA: polyethylene oxide-monomethacrylate; NaSS: sodium p-styrene sulfonate; DMAPAA: N,N-dimethyl aminopropyl acrylamide; MAPC: ω-methacryloyloxyalkyl phosphorylcholine; PS-b-PMM: polystyrene-b-poly(methyl methacrylate); PLLA: poly(L-lactic acid); PDLLA: poly(D,L-lactic acid); PVME: poly(vinyl methyl ether); PLL-g-PEG: poly(L-lysine)-graft-poly(ethylene glycol); PDMS: polydimethylsiloxane.
b
PC-12: pheochromocytoma; CHO: Chinese hamster ovary; VSMCs: vascular smooth muscle cells.
c
ATRP: atom transfer radical polymerization; NMRP: nitroxide-mediated radical polymerization.
NGF: nerve growth factor.