4d Bioprinting via Molecular Network Contraction for Membranous Tissue Fabrication.

Abstract

Generation of thin membranous tissues (TMT), such as the cornea, epidermis, and periosteum, presents a difficult fabrication challenge in tissue engineering (TE). TMTs consist of several cell layers that are less than 100μm in thickness per layer. While traditional methods provide the necessary resolution for TMT fabrication, they require significant handling and incorporation of several layers is limited. Extrusion bioprinting offers precise control over deposition of different biomaterials and cell populations within the same construct but lacks the resolution to generate biomimetic TMTs. W e have developed, for the first time, a 4D bioprinting strategy that allows for the generation of cell-laden TMTs. Anionic gelatin methacrylate (GelMA) hydrogels are treated with cationic poly-L-lysine (PLL), which induces charge attraction, microscale network collapse, and macroscale hydrogel shrinking. The impact of shrinking on hydrogel properties, print resolution, and cell viability are presented. Additionally, o ur work suggests that a novel mechanism is occurring, where PLL exhibits a contractile force on GelMA and PLL molecular weight drives GelMA shrinking capabilities. Finally, w e show that this phenomenon can occur while maintaining an encapsulated cell population. These findings address a critical barrier in TE by generating macroscale tissue structures with their microscale TMT counterparts in the same print. This article is protected by copyright. All rights reserved.