Two-photon polymerization for 3D biomedical scaffolds: Overview and updates

Abstract

The needs for high-resolution, well-defined and complex 3D microstructures in diverse fields call for the rapid development of novel 3D microfabrication techniques. Among those, two-photon polymerization (TPP) attracted extensive attention owing to its unique and useful characteristics. As an approach to implementing additive manufacturing, TPP has truly 3D writing ability to fabricate artificially designed constructs with arbitrary geometry. The spatial resolution of the manufactured structures via TPP can exceed the diffraction limit. The 3D structures fabricated by TPP could properly mimic the microenvironment of natural extracellular matrix, providing powerful tools for the study of cell behavior. TPP can meet the requirements of manufacturing technique for 3D scaffolds (engineering cell culture matrices) used in cytobiology, tissue engineering and regenerative medicine. In this review, we demonstrated the development in 3D microfabrication techniques and we presented an overview of the applications of TPP as an advanced manufacturing technique in complex 3D biomedical scaffolds fabrication. Given this multidisciplinary field, we discussed the perspectives of physics, materials science, chemistry, biomedicine and mechanical engineering. Additionally, we dived into the principles of tow-photon absorption (TPA) and TPP, requirements of 3D biomedical scaffolders, developed-to-date materials and chemical approaches used by TPP and manufacturing strategies based on mechanical engineering. In the end, we draw out the limitations of TPP on 3D manufacturing for now along with some prospects of its future outlook towards the fabrication of 3D biomedical scaffolds.

Knowledge domain and hotspots analysis concerning applications of two-photon polymerization in biomedical field: A bibliometric and visualized study

“…The main citation path indicated by the dual-map further illustrates that this is an interdisciplinary research field, due to most of the cited sources and citing sources being both chemistry, materials, physics and biomedicine-related journals. For example, a recent paper discussed TPP for 3D biomedical scaffolds from the perspectives of physics, chemistry, material science, and biomedicine (Jing et al, 2022). This also shows that the development of TPP applied in biomedical field requires the full cooperation of experts from all relevant disciplines.…”

“…The light source used by TPP is usually near-infrared femtosecond laser. By focusing the femtosecond laser on the photoresist, a photoinitiator (PI) molecule in the photopolymer is excited by absorbing two photons at the same time (i.e., two-photon absorption), thereby inducing local radical polymerization in the focal volume (Jing et al, 2022). TPP is an additive manufacturing (AM) technology, which belongs to the category of optical three-dimensional printing (3DP) (Jonušauskas et al, 2018).…”

“…However, due to the threshold and properties of TPP, compared to the common used optical 3DP techniques such as selective laser sintering (SLS), stereolithography (SLA), and digital light processing (DLP), the 3D structures fabricated by TPP has higher spatial resolution and can exceed the diffraction limit. Structures with a resolution of less than 100 nm have been repeatedly reported (Sakellari et al, 2012;Jing et al, 2022). Meanwhile, the wavelength of the laser used for TPP is transparent to the photopolymer processed, so the focus can move freely in the material, which makes this technique gets rid of the limitations of layer-by-layer processing of other 3DP technologies and realize truly three-dimensional arbitrary writing (Baldacchini et al, 2021).…”

“…Therefore, compared with other high-resolution manufacturing technologies, such as traditional photolithography, dip-pen nanolithography, capillary force lithography, nanoimprint lithography, and others, features available in 3D structures fabricated using TPP would be comparable to what can be achieved in 2D. In addition, compared with traditional 3D manufacturing technologies applied in the biomedical field, including particulate leaching, solvent casting, freeze-drying, electrospinning etc., TPP not only has higher processing resolution but also can more precisely reproduce complex artificially designed 3D structures (Jing et al, 2022). TPP is currently the only technique capable of fabricating complex 3D microstructures with finely adjusted geometry on the cell and sub-cell scale.…”

Knowledge domain and hotspots concerning photosensitive hydrogels for tissue engineering applications: A bibliometric and visualized analysis (1996-2022)

“…The tissue substitutes, wound dressings, or substrates for TE all put forward various requirements for biomaterials. In particular, the engineering extracellular matrices (ECMs), or the mimics of the microenvironment for cell growth, and 3D cell culture models, are usually called the tissue engineering scaffolds, which interact with cells as ECMs before forming new tissues ( Yao et al, 2013 ; Jafari et al, 2017 ; Jing et al, 2022 ). TE scaffold is the crux to achieve the goal of TE ( Langer and Vacanti 1993 ; Wu et al, 2020 ).…”