Three-Dimensional Patterning of Poly(Ethylene Glycol) Hydrogels Through Surface-Initiated Photopolymerization

Abstract

Photopolymerizable hydrogels have been investigated extensively for biomedical applications, specifically in the area of tissue engineering. While fabrication approaches have shown promise in designing hydrogel scaffolds that guide cell function, the ability to spatially control localization in three-dimensions has been limited. We have developed a method for generating two-dimensional and three-dimensional (3D) patterns within multilayered poly(ethylene glycol) diacrylate (PEG-DA) hydrogels. Covalently attached hydrogel layers are formed using precursor solutions with a 10:1 mole ratio of PEG-DA to PEG-aminoacrylate (Acr-PEG-NH2). Upon illumination of the precursor with visible light (wavelength = 514 nm), a hydrogel layer forms with pendant amine groups induced by the presence of Acr-PEG-NH2 macromer. Pendant amine groups are further functionalized with free carboxyl groups present on the visible light photoinitiator eosin, allowing for the formation of subsequent hydrogel layers. Using noncontact photolithography, the prepolymer solution is polymerized through a photomask, resulting in hydrogel structures with distinct pattern formation in each layer. Unreacted regions immobilized with eosin can be subsequently filled with a different PEG hydrogel. The technique presented shows a great potential for tissue engineering applications, for biosensors, and in the formation of cell and protein patterning for biotechnology.

Controlling Stem Cell Fate with Material Design

“…In another additive polymerization process, PEGDA combined with amino-functionalized PEG allowed for multi-layered assemblies of gels that resembled microvascular networks through multiple photopolymerization steps. [126] Another means to spatially control cell morphology is through the combination of sequential crosslinking steps that occur by distinct methods. This has been demonstrated by groups using HA as the base network, which is first crosslinked with chemical crosslinks (e.g., Michael addition) and then exposed to UV light in order to crosslink remaining methacrylate or acrylate functional groups.…”

The Natural and Engineered 3D Microenvironment as a Regulatory Cue During Stem Cell Fate Determination

“…This alternative approach critically links 2D mechanistic studies to the in vivo application, however, the mechanisms of cellular interaction and subcellular functioning within these environments are not well known. Using both natural (protein and polysaccharide) and synthetic polymers, material scientists can engineer patterns of adhesion (55,56,55), composition(57,58), growth factor(59,60,61) and mechanical gradients (62,63), cell positioning (64,65,66,67,68), degradation rates(69,70,71,72) and geometry(73) to direct tissue morphogenesis (74,75,76,77). The application of these materials with a cellular component has been well reviewed recently for a range of tissue targets including but not limited to bone(78,79,80), cardiac(81,82), tendon(83,84), nerve(85,86), cartilage(87,88) and fat(89,90,91).…”

Strategies for Vascularization of Polymer Scaffolds

“…2, A and B). 43 Interfacial photopolymerization was induced by the addition of the PEG-DA precursor solution onto a surface that was covalently immobilized with a photoinitiator (eosin Y) followed by exposure to visible light ( λ = 514 nm). This resulted in the formation of a hydrogel that grew from the surface outward with thickness controlled solely as a function of polymerization conditions without the need of spacers or molds.…”