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. 2016 Nov 22;113(47):13295-13300.
doi: 10.1073/pnas.1609603113. Epub 2016 Nov 7.

Hydrogel Films and Coatings by Swelling-Induced Gelation

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Free PMC article

Hydrogel Films and Coatings by Swelling-Induced Gelation

David Moreau et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

Hydrogel films used as membranes or coatings are essential components of devices interfaced with biological systems. Their design is greatly challenged by the need to find mild synthesis and processing conditions that preserve their biocompatibility and the integrity of encapsulated compounds. Here, we report an approach to produce hydrogel films spontaneously in aqueous polymer solutions. This method uses the solvent depletion created at the surface of swelling polymer substrates to induce the gelation of a thin layer of polymer solution. Using a biocompatible polymer that self-assembles at high concentration [poly(vinyl alcohol)], hydrogel films were produced within minutes to hours with thicknesses ranging from tens to hundreds of micrometers. A simple model and numerical simulations of mass transport during swelling capture the experiments and predict how film growth depends on the solution composition, substrate geometry, and swelling properties. The versatility of the approach was verified with a variety of swelling substrates and hydrogel-forming solutions. We also demonstrate the potential of this technique by incorporating other solutes such as inorganic particles to fabricate ceramic-hydrogel coatings for bone anchoring and cells to fabricate cell-laden membranes for cell culture or tissue engineering.

Keywords: associative polymers; cell culture; hydrogel coating; hydrogel film; tissue engineering.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Formation of hydrogel films by swelling-induced gelation. (A) Schematic representation of the solvent depletion created near the surface of a swelling polymer network. Upon immersion in a polymer solution, the dry network (dark green) swells. Free polymer chains (red) are pushed away from the volume spanned by the swelling network (light green) and accumulate near its surface. This creates a local excess in polymer concentration in the solution, which is redistributed by thermal diffusion. (B) Illustration of the design strategy using swelling of a hydrophilic polymer substrate to induce the formation of hydrogel films.
Fig. 2.
Fig. 2.
Formation of PVA hydrogel films on swelling PAAm substrates. (A) Schematic representation of the experimental protocol: (i) a dry PAAm substrate is immersed in a PVA aqueous solution; (ii) the PAAm substrate swells inducing the formation of a PVA hydrogel film (dark red); (iii) the sample is collected and rinsed in water; (iv) the PVA hydrogel film can be peeled off from the swollen PAAm substrate. (B) Peeling of a PVA hydrogel film after 3-h immersion in a 15 wt% PVA aqueous solution. (C and D) Stability in water of the same films as in B: right after fabrication (C and D, Left) and after storage at 20 °C for 1 wk (C, Right) or after storage at 90 °C for 1 h (D, Right). (Scale bar: 1 cm.)
Fig. S1.
Fig. S1.
X-ray diffraction profile of PVA hydrogel films produced at the surface of 3-mm-thick PAAm films after immersion in a 15 wt% PVA solution for 3 h (red), 8 h (blue), and 22 h (green). The spectra are compared with those of water (black) and of a physical PVA hydrogel film prepared by five cycles of freezing at −18 °C and thawing at 20 °C. The dashed line indicates the known position of the main Bragg peak of PVA crystals calculated from Bunn (42).
Fig. 3.
Fig. 3.
Observation of hydrogel film growth. (A) Schematic representation of the experimental setup enabling the simultaneous observation of the size of the substrate (light green) and of the thickness of the hydrogel film (dark red). (B) Spherical PAAc–PAAm substrates: dry (Left) and swollen to equilibrium in water (Right). (C–E) Pictures of the equatorial region of PAAc–PAAm spheres after 1-h immersion in different conditions: the sphere is immersed dry in water (C); the sphere is immersed dry in a 10 wt% PVA solution, which reveals the formation of a PVA hydrogel film (D); the sphere is first swollen to equilibrium in pure water and then immersed in a 10 wt% PVA solution (E). (F) Time series of a PAAc–PAAm sphere swelling in a 10 wt% PVA solution: substrate swelling (Top) and close-up showing film growth at the sphere surface (Bottom).
Fig. S2.
Fig. S2.
Time series showing the equator of PAAc–PAAm spheres swelling in PVA aqueous solutions with different concentrations: 1 wt% (A), 2.5 wt% (B), 5 wt% (C), 10 wt% (D), and 15 wt% (E).
Fig. S3.
Fig. S3.
(A) Microscopic observation of the in situ detachment of a PVA hydrogel film formed at the surface of a PAAc–PAAm sphere after 1-h swelling in a 10 wt% PVA aqueous solution. (B) Close-up showing the interfaces of the PVA hydrogel film with the PAAc–PAAm substrate (black arrow) and with the PVA solution (white arrow).
Fig. S4.
Fig. S4.
Measurement protocol to determine the radius of PAAc–PAAm spheres and the thickness of PVA hydrogel films. (A) The interface between the PVA hydrogel film and the PVA solution is revealed by in-lens lighting. The outer radius is measured by fitting with a circle. (B) The interface between the PVA hydrogel film and the PAAc–PAAm substrate is revealed by in-plane lighting. The inner radius is measured by fitting with a circle. The film thickness is determined from the difference between these two radii.
Fig. 4.
Fig. 4.
Relationship between substrate swelling and hydrogel film growth. (A) Increase in the radius of PAAc–PAAm spheres as a function of immersion time in aqueous solutions with different PVA concentrations: 0 wt% (○), 1 wt% (▸), 2.5 wt% (◆), 5 wt% (▼), 7.5 wt% (■), 10 wt% (▲), and 15 wt% (●). Full lines show best fits by Eq. 1 for the first hour of swelling. (B) Substrate diffusivity measured from fits as a function of PVA concentration. The overlap concentration C* indicates the transition from dilute to semidilute PVA solutions. (C) Thickness of PVA hydrogel films as a function of immersion time for the same experiments as in A. Full lines show model predictions with Eq. 4 for a spherical substrate (Φc = 0.35 wt%). Dashed lines show the results of numerical simulations. (D) Same as C in log-log scale. In all graphs, error bars represent the maximum SD in a time series. They are not shown when smaller than the symbols.
Fig. 5.
Fig. 5.
Modeling of swelling-induced gelation. (A) Schematic representations of the analytical model predicting hydrogel film growth for 1D swelling (Top) and for swelling of a spherical substrate (Bottom). (B) Calculated concentration profiles as a function of the distance from the substrate surface at different times during swelling for two initial polymer concentrations: 1 vol% (Right) and 10 vol% (Left).
Fig. S5.
Fig. S5.
Formation of a PVA hydrogel film by swelling-induced gelation around a hydrosoluble PEG substrate: (A) dry un–cross-linked PEG substrate obtained by melt pressing, (B) formation of a PVA hydrogel film during immersion of the substrate in a 10 wt% PVA aqueous solution, and (C) PVA hydrogel film after complete dissolution of the PEG substrate and immersion in water.
Fig. S6.
Fig. S6.
Equator of PAAc–PAAm spheres swelling in hydrogel forming (A and B) or nonhydrogel forming (C and D) solutions: (A) Pluronic F127 aqueous solution (10 wt%), (B) PVA aqueous solution (10 wt%), (C) PVP aqueous solution (10 wt%), and (D) PEG aqueous solution (10 wt%). (Immersion time, 20 min.)
Fig. 6.
Fig. 6.
Fabrication of composite ceramic-hydrogel coatings and cell encapsulation. (A–E) Fabrication of composite hydroxyapatite–PVA hydrogel coatings. (A and B) Coating by immersion of dry PAAc–PAAm spheres in 10 wt% PVA solutions containing dispersions of hydroxyapatite nanoparticles (5 wt%) (A) or microparticles (20 wt%) (B, Top) Pictures of spheres after immersion (30 min for nanoparticles, 60 min for microparticles) and rinsing in water (15 min). (Bottom) Cross-section images by optical microscopy. (C) Same observations as B showing the absence of coating when the PAAc–PAAm sphere is swollen to equilibrium in pure water before immersion in the PVA solution with hydroxyapatite microparticles. (D and E) Low-vacuum SEM observations of the surface of the spheres coated with nanoparticles (D) and with microparticles (E). (F–J) Encapsulation of mouse fibroblasts NIH 3T3 in PVA hydrogel films using swelling of dry PEG films. (F) Cell-laden PVA hydrogel film obtained after the encapsulation protocol. (G) Cross-section of the PVA hydrogel film showing the gradient in film thickness. The picture is constructed by juxtaposing several images. The bottom surface was in contact with the PEG substrate, and the top surface with the cell suspension. Dotted line delimitates the upper region where clusters of living cells are revealed by MTT staining. (H–J) Confocal microscopy observations near the top surface of the hydrogel films for different film thicknesses: less than 1-mm thickness after 24 h (H); more than 1-mm thickness after 24 h (I) and 48 h (J). Green staining by calcein reveals the cytoplasm of living cells. Red staining by ethidium reveals the nucleus of dead cells.
Fig. S7.
Fig. S7.
Schematic representations of the encapsulation and control protocols. (A) Encapsulation protocol. (B) Positive control for cell viability. (C) Negative control for cell encapsulation.
Fig. S8.
Fig. S8.
Pictures of the encapsulation process. (A) PEG substrates (black arrow) are placed in sterile glass wells. (B) The PVA/cell solution is poured in the wells. (C) Glass wells after incubation at 37 °C for 3 h. (D) Glass wells are soaked in a large excess of growth medium. (E) The obtained PVA hydrogel films (white arrow) are collected and rinsed in PBS solutions. (F) The films (white arrow) are stored individually in cell culture wells and incubated in growth medium at 37 °C.
Fig. S9.
Fig. S9.
Epifluorescence microscopy observations of the positive control for cell viability (A and B) and of the negative control for cell encapsulation (C and D) after 24 and 48 h, respectively.

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