Guiding Lights: Tissue Bioprinting Using Photoactivated Materials

Abstract

Photo-activated materials have found widespread use in biological and medical applications and are playing an increasingly important role in the nascent field of three-dimensional (3D) bioprinting. Light can be used as a trigger to drive the formation or the degradation of chemical bonds, leading to unprecedented spatiotemporal control over a material's chemical, physical, and biological properties. With resolution and construct size ranging from nanometres to centimeters, light-mediated biofabrication allows multicellular and multimaterial approaches. It promises to be a powerful tool to mimic the complex multiscale organization of living tissues including skin, bone, cartilage, muscle, vessels, heart, and liver, among others, with increasing organotypic functionality. With this review, we comprehensively discuss photochemical reactions, photo-activated materials, and their use in state-of-the-art deposition-based (extrusion and droplet) and vat polymerization-based (one-and two-photon) bioprinting. By offering an up-to-date view on these techniques, we identify emerging trends, focusing on both the chemistry and instrument aspects, thereby allowing the readers to select the best-suited approach. Starting with photochemical reactions and photo-activated materials, we then discuss principles, applications, and limitations of each technique. With a critical eye to the most recent achievements, the reader is guided through this exciting, emerging field with special emphasis on cell-laden hydrogel constructs.

Multiphoton Laser Fabrication of Hybrid Photo-Activable Biomaterials

“…Hydrogels that allow precise control of cells and their 3D microenvironments are needed in tissue engineering [ 7 , 93 ], organoid growth [ 71 , 94 ], and disease modeling [ 95 , 96 , 97 ]. Besides the possibility offered by direct laser writing to spatially tailor these matrices, for real application in biotechnology or experimental medicine, these structures must be compatible with and responsive to cells, so as to support their 3D growth.…”

“…The fields of tissue engineering [ 7 , 117 ] and organoids [ 35 , 94 , 105 ] have gained much interest in recent years, driven by the rising demand for transplants and implants. Artificial tissues are, however, prone to rejection as foreign objects: one mitigation action is the improvement of the vascularization of the implanted biomaterial.…”

“…In particular, we will explore the recent developments in the photolithographic microfabri-cation of biocompatible hydrogel-based structures capable of guiding the cell cycle and fate and monitoring the cell state. Recent comprehensive reviews have appeared on the microfabrication of resins (organics, hybrids, renewables, functionalized) by photolithography and light confinement [4], on the laser ablation of hydrogels [5], on the surface patterning of hydrogels [6] and on the use of different fabrication methods for tissue engineering [7]. However, these three aspects, fabrication, ablation and functionalization, can be combined in a more effective R&D strategy for cell manipulation and stimulation, and our aim here is to review the efforts in this direction.…”

Injectability of Biosynthetic Hydrogels: Consideration for Minimally Invasive Surgical Procedures and 3D Bioprinting

“…Photopolymerization is a widely used crosslinking technique because it offers the ability to easily and precisely control both the temporal and spatial polymerization of the hydrogel. [ 94 ] This is done by controlling the physical positioning and exposure duration of the initiating light. [ 95 ] The initiating light triggers a free‐radical polymerization reaction whereby a liquid polymeric solution is crosslinked to create an insoluble elastic hydrogel.…”

“…[ 88,96 ] The photopolymerization reaction can be carried out by several mechanisms, including chain reaction, H‐abstraction, or cleavage mechanisms, depending on the desired properties of the resulting hydrogel. [ 94b ] These properties include physical characteristics such as gel porosity, degree of crosslinking, and matrix stiffness.…”