A Review on Stimuli-Actuated 3D Micro/Nanostructures for Tissue Engineering and the Potential of Laser-Direct Writing via Two-Photon Polymerization for Structure Fabrication

Abstract

In this review, we present the most recent and relevant research that has been done regarding the fabrication of 3D micro/nanostructures for tissue engineering applications. First, we make an overview of 3D micro/nanostructures that act as backbone constructs where the seeded cells can attach, proliferate and differentiate towards the formation of new tissue. Then, we describe the fabrication of 3D micro/nanostructures that are able to control the cellular processes leading to faster tissue regeneration, by actuation using topographical, mechanical, chemical, electric or magnetic stimuli. An in-depth analysis of the actuation of the 3D micro/nanostructures using each of the above-mentioned stimuli for controlling the behavior of the seeded cells is provided. For each type of stimulus, a particular recent application is presented and discussed, such as controlling the cell proliferation and avoiding the formation of a necrotic core (topographic stimulation), controlling the cell adhesion (nanostructuring), supporting the cell differentiation via nuclei deformation (mechanical stimulation), improving the osteogenesis (chemical and magnetic stimulation), controlled drug-delivery systems (electric stimulation) and fastening tissue formation (magnetic stimulation). The existing techniques used for the fabrication of such stimuli-actuated 3D micro/nanostructures, are briefly summarized. Special attention is dedicated to structures’ fabrication using laser-assisted technologies. The performances of stimuli-actuated 3D micro/nanostructures fabricated by laser-direct writing via two-photon polymerization are particularly emphasized.

Femtosecond laser direct writing of functional stimulus-responsive structures and applications

“…Thus, the photopolymerization reactions of monomers and photo-initiator molecules can only be induced at the laser focus without impact on other positions. Through precise control of either the laser focus or the sample's relative movement, the target materials can gradually polymerize along the focus scanning path, which can realize the fabrication of intricate micro/nanoscale structures with arbitrary morphology and resolution less than the applied diffraction limit in a maskless and facile process [86,[104][105][106][107][108][109]. Micro/nanostructure fabrication through the principle of two-photon or multiphoton polymerization using a femtosecond laser represents an advanced processing technology for photosensitive polymers, which synergistically integrates the versatility of 3D printing with exceptional resolution of photolithography technology and holds great potential for the precision manufacturing of micro/nanoarchitectures with customized and complicated constructs [103,110,111].…”

Temperature Tunable 4D Polymeric Photonic Crystals

“…To date, spatio-temporal control is mainly exploited for milli and micrometer structures while scaling these properties at the nanoscale is still an open challenge. At the same time, the possibility of developing programmable nano-voxels, achieving a dynamic control on the nano/ micro (hierarchical) structures, would open to important breakthroughs in soft nanotechnology, such as in bio-medicine and tissue engineering, [7][8][9][10] nanophotonics, [11,12] nanoelectronics, [13,14] and nanorobotics [15] (Figure 1a). In these fields, responsive 3D nanostructures can be employed as stimuli-responsive actuators or tunable devices.…”

Ultrafast Humidity Sensing Layers Made by Two‐Photon Polymerization and Initiated Chemical Vapor Deposition

“…[7] Further examples for complex hydrogel structures which are, for example, needed for cell and tissue engineering by 2PP are reported in ref. [25,26]. 2PP printers offer a high potential to directly print structures on substrates without intermediate steps or post preparation.…”