A Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma

Abstract

A significant challenge in oncology is the need to develop in vitro models that accurately mimic the complex microenvironment within and around normal and diseased tissues. Here, we describe a self-folding approach to create curved hydrogel microstructures that more accurately mimic the geometry of ducts and acini within the mammary glands, as compared to existing three-dimensional block-like models or flat dishes. The microstructures are composed of photopatterned bilayers of poly (ethylene glycol) diacrylate (PEGDA), a hydrogel widely used in tissue engineering. The PEGDA bilayers of dissimilar molecular weights spontaneously curve when released from the underlying substrate due to differential swelling ratios. The photopatterns can be altered via AutoCAD-designed photomasks so that a variety of ductal and acinar mimetic structures can be mass-produced. In addition, by co-polymerizing methacrylated gelatin (methagel) with PEGDA, microstructures with increased cell adherence are synthesized. Biocompatibility and versatility of our approach is highlighted by culturing either SUM159 cells, which were seeded postfabrication, or MDA-MB-231 cells, which were encapsulated in hydrogels; cell viability is verified over 9 and 15 days, respectively. We believe that self-folding processes and associated tubular, curved, and folded constructs like the ones demonstrated here can facilitate the design of more accurate in vitro models for investigating ductal carcinoma.

Self‐Folded Hydrogel Tubes for Implantable Muscular Tissue Scaffolds

“…Here, the internal part of the folded tube was formed by the soft or high molecular weight PEGDA, while the external part was represented by the low molecular weight PEGDA. Despite in the literature, the preferential arrangement was represented by the wrapping of the low molecular weight PEGDA in the internal part, the addition of the sacrificial layer during fabrication influenced the rolling behavior of PEGDA bilayers. The internal stresses generated at the interface between gelatin and the first photo‐crosslinked PEGDA, due to of interpenetration between the two polymers, promoted the bilayer rolling toward the freer side (as shown in Video S1, Supporting Information), promoting the above‐mentioned spatial organization (see the Supporting Information for a detailed discussion).…”

“…Development of 3D scaffolds with encapsulated cells has been a mainstream approach for engineering tissues, regenerative medicine applications, and developing biohybrid systems. In previous examples, cells were exposed to UV light either during the photopolymerization reaction or after the cell seeding, as UV light was used to trigger folding . This technique, however, leads to several issues, such as photoinitiator toxicity, UV‐induced DNA damage, and too‐rigid hydrogels that restrict cell spreading lower cell viability.…”

“…In vitro 3D models have been proposed to encapsulate cells within hydrogels for mimicking in vivo structural cues. Gracias and co‐workers reported the use of self‐folding PEGDA bilayer system as an in vitro model for studying ductal carcinoma . In another study, photodegredation induced self‐folding was demonstrated by Kasko and co‐workers using ortho ‐nitrobenzyl incorporated PEGDA thin films .…”

“…Here, the formation of self‐folded tubular structures with encapsulated cells from poly(ethylene glycol) diacrylate (PEGDA) hydrogel bilayers is reported. PEGDA hydrogels have previously been used in developing self‐folding structures, microrobots, and tissue scaffolds upon swelling . In vitro 3D models have been proposed to encapsulate cells within hydrogels for mimicking in vivo structural cues.…”

Remotely Controlled Microscale 3D Self‐Assembly Using Microwave Energy

“…Self‐folding, a deterministic self‐assembly process, provides a desirable strategy for creating 3D microscale structures for 3D sensing, 3D metamaterials, microrobots, drug delivery, cell cultures, cell encapsulation, and microscale chemical container applications . Self‐assembly of 3D microscale structures can be accomplished by different trigger mechanisms including magnetic force‐driven self‐assembly, electric force‐driven assembly, pneumatic force‐driven assembly, differential stress‐driven assembly, shape memory assembly, and surface tension‐driven assembly .…”