3D Printed Silicone–Hydrogel Scaffold with Enhanced Physicochemical Properties

Abstract

Scaffolds with multiple functionalities have attracted widespread attention in the field of tissue engineering due to their ability to control cell behavior through various cues, including mechanical, chemical, and electrical. Fabrication of such scaffolds from clinically approved materials is currently a huge challenge. The goal of this work was to fabricate a tissue engineering scaffold from clinically approved materials with the capability of delivering biomolecules and direct cell fate. We have used a simple 3D printing approach, that combines polymer casting with supercritical fluid technology to produce 3D interpenetrating polymer network (IPN) scaffold of silicone-poly(2-hydroxyethyl methacrylate)-co-poly(ethylene glycol) methyl ether acrylate (pHEMA-co-PEGMEA). The pHEMA-co-PEGMEA IPN materials were employed to support growth of human mesenchymal stem cells (hMSC), resulting in high cell viability and metabolic activity over a 3 weeks period. In addition, the IPN scaffolds support 3D tissue formation inside the porous scaffold with well spread cell morphology on the surface of the scaffold. As a proof of concept, sustained doxycycline (DOX) release from pHEMA-co-PEGMEA IPN was demonstrated and the biological activity of released drug from IPN was confirmed using a DOX regulated green fluorescent reporter (GFP) gene expression assay with HeLa cells. Given its unique mechanical and drug releasing characteristics, IPN scaffolds may be used for directing stem cell differentiation by releasing various chemicals from its hydrogel network.

Extrusion 3D Printing of Polymeric Materials with Advanced Properties

“…The shape stability of the printed features could be significantly enhanced through a second step of covalent crosslinking. For example, through photoinitiated covalent crosslinking, [ 86,91,94,95,102–105 ] strong ionic interactions of alginate with calcium, [ 92,101,106 ] or horseradish peroxidase/hydrogen peroxide crosslinking (H 2 O 2 ). [ 95 ] Burdick and co‐workers reported that despite achieving 3D layer‐by‐layer grid structures using hydrogels crosslinked with only a supramolecular network, the filaments were still fused together when printing multilayers due to the dynamic nature of supramolecular interactions (Figure 3D).…”

“…Besides UV induced free radical polymerization, the photoinitiated thiol−ene, [ 107 ] thiol‐yne click chemistry [ 108 ] and thiol‐Michael reactions, [ 109 ] which can form a more homogeneous (step‐growth) hydrogel network [ 110 ] compared to that of a free radical polymerized diacrylates were utilized for post‐crosslinking after extrusion. [ 106 ] The strong metal coordination bond between Fe 3+ and COOH − was also employed to encourage fast gelation of the highly viscous linear polymer solutions after extrusion, [ 39,111 ] which significantly simplified the 3D printing process of hydrogels.…”

“…The use of dynamic bonds which undergo reversible breaking, exchange and reformation could be utilized to modify the printability of polymers as well as imparting various advanced functions. [ 41–58,62–67,59,68,60,69,70,72,61,73,71,82,86–88,74–81,83–85,89–133,244,258 , …”

Paving the Way Toward Complex Blood-Brain Barrier Models Using Pluripotent Stem Cells

“…Another advantage of hydrogels is that they can be loaded with chemicals, mimicking ECM-bound regulatory factors in vivo [129,137]. The ECM is known to provide important cues on cells both through its structure and its release of stimulating factors [138].…”

Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications

“…This results in high-resolution, albeit 2.5D, topographical features which are nevertheless useful in studying the effect of topographical cues in cell culturing [70]. In another recent work [71], a silicone-elastomer/hydrogel interpenetrating network was fabricated by 3D printing PVA filament into a scaffold, pattern transfer into PDMS, and pattern transfer again into silicone-poly(2-hydroxyethyl methacrylate)-co-poly(ethylene glycol) methyl ether acrylate (pHEMA-co-PEGMEA), providing excellent mechanical properties and controlled drug release of the elastomer combined with the biocompatibility and hydrophilicity of the hydrogel.…”