3D Printing of large-scale and highly porous biodegradable tissue engineering scaffolds from poly(trimethylene-carbonate) using two-photon-polymerization

Abstract

The introduction of two-photon polymerization (2PP) to the field of tissue engineering and regenerative medicine (TERM) has led to great expectations for the production of scaffolds with an unprecedented degree of complexity and tailorable architecture. Unfortunately, resolution and size are usually mutually exclusive when using 2PP, resulting in a lack of highly-detailed scaffolds with a relevant size for clinical application. Through the combination of using a highly reactive photopolymer and optimizing key printing parameters, we propose for the first time a biodegradable and biocompatible poly(trimethylene-carbonate) (PTMC)-based scaffold of large size (18 × 18 × 0.9 mm) with a volume of 292 mm3 produced using 2PP. This increase in size results in a significant volumetric increase by almost an order of magnitude compared to previously available large-scale structures (Stichel 2010 J. Laser Micro./Nanoeng. 5 209–12). The structure’s detailed design resulted in a highly porous scaffold (96%) with excellent cytocompatibility, supporting the attachment, proliferation and differentiation of human adipose-derived mesenchymal stem cells towards their osteogenic and chondrogenic lineages. This work strongly attests that 2PP is becoming a highly suitable technique for producing large-sized scaffolds with a complex architecture. We show as a proof-of-concept that an arrayed design of repetitive units can be produced, but a further perspective will be to print scaffolds with anisotropic features that are more representative of human tissues.

Two-Photon Polymerization: Functionalized Microstructures, Micro-Resonators, and Bio-Scaffolds

“…For instance, some researchers have expended efforts to develop photocrosslinkable gelatin hydrogels for biofabrication applications [ 66 , 67 , 68 , 69 , 70 ]. For tissue engineering applications, photoreactive resin based on poly(trimethylenecarbonate) (PTMC) has been modified through chemical reactions, aiming at the fabrication of highly porous and biodegradable scaffolds [ 71 ].…”

“…The growing interest in the tissue engineering and regenerative medicine fields has motivated the development of several bio-applicable materials. For instance, the use of a highly reactive photopolymer in TPP experiments, with their fabrication parameters optimized, allows the production of scaffolds with large size (in the order of millimeters in the three dimensions), with relevant size for clinical application [ 71 ].…”

“…Scaffolds sculpted from a biodegradable and biocompatible poly(trimethylene-carbonate) (PTMC)-based material by TPP ( Figure 17 a) supported the adhesion and proliferation of human adipose-derived stem cells (hASCs) [ 71 ]. Two days post-seeding, hASCs attached to the scaffold exhibited elongated filopodia ( Figure 17 b).…”

“…Figure 17 e presents live/dead staining conducted after 28 days, showing a high cellular viability. The proliferation of the hASCs was validated by the significant increase of DNA ( Figure 17 f) and the presence of ki67-positive cells ( Figure 17 g) [ 71 ].…”

Additive Manufacture of Small-Scale Metamaterial Structures for Acoustic and Ultrasonic Applications

“…Soft materials, like hydrogel, can also be printed for use in active metamaterial micro-devices [134]. There is significant interest in MPP printing of hydrogels for drug delivery and tissue scaffolding, due to the method's high spatial resolution and composite-printing capabilities [135,136]. Other medical applications for this printing method have been realized [137], for example with an MPP-printed, porous filter being used to filter blood cells in a microfluidic chip [138].…”