Hydrogels for Two‐Photon Polymerization: A Toolbox for Mimicking the Extracellular Matrix

Abstract

The natural extracellular matrix (ECM) represents a complex and dynamic environment. It provides numerous spatio‐temporal signals mediating many cellular functions including morphogenesis, adhesion, proliferation and differentiation. The cell–ECM interaction is bidirectional. Cells dynamically receive and process information from the ECM and remodel it at the same time. Theses complex interactions are still not fully understood. For better understanding, it is indispensable to deconstruct the ECM up to the point of investigating isolated characteristics and cell responses to physical, chemical and topographical cues. Two‐photon polymerization (2PP) allows the exact reconstruction of cell specific sites in 3D at micro‐ and nanometer precision. Processing biocompatible synthetic and naturally‐derived hydrogels, the microenvironment of cells can be designed to specifically investigate their behavior in respect to key chemical, mechanical and topographical attributes. Moreover, 3D manipulation can be performed in the presence of cells, guiding biological tissue formation in all stages of its development. Here, advances in 2PP microfabrication of synthetic and naturally based hydrogels are reviewed. Key components of photopolymerizable hydrogel precursors, their structure–property relationships and their polymerization mechanisms are presented. Furthermore, it is shown how biocompatible 2PP fabricated constructs can act as biologically relevant matrices to study cell functions and tissue development.

Photopolymerization of coordinated ionic liquid monomers: Realizing the benefits of structured media using only common reagents

“…[1][2][3] Photopolymerization reactions can be performed in bulk (i.e., no cosolvent) wherein reaction mixtures contain only polymerizable species (e.g., monomers, cross-linking agents) and initiator, although the presence of a cosolvent such as water is used in tissue engineering and other applications. [3][4][5] Bulk processes offer multiple advantages including the ability to produce a relatively pure product and control over polymer shape and thickness. 6,7 Photopolymerization reactions are employed in a variety of applications including coatings, adhesives, photolithography, microelectronics and, more recently, in biological applications and additive manufacturing.…”

Smart hydrogels for 3D bioprinting

“…During the curing process, photoinitiators generate free radicals that can initiate the polymerization process [69,74,76] . The use of proper exposure time, light intensity, and photoinitiator allows minimum cell damage as well as crosslinking density [77][78][79] . For example, a tubular tissue construct was printed by a two-step photocrosslinking strategy.…”

Poly(2-oxazoline) hydrogels as next generation three-dimensional cell supports

“…The curing reaction can be "switchedon" at will and proceeds with predictable kinetics 18 using the light source, which is a distinct advantage over ECM protein hydrogels where the gelation process is difficult to control and adds pressure on the user, especially when trying to simultaneously handle cells in multiple parallel experiments. Light curing also opens up possibilities of creating specific hydrogel patterns and gradients in 2D using photomasks 22 or even in 3D using 2-photon initiation methods 23 and 3D printers. 24 The latter of these, using printers to make 3D shapes from hydrogels, is an area of great interest as cells can be incorporated during the printing process and is a method that could be compatible with PAOx via extrusion of the soluble polymer followed by light curing.…”