Network modulation enables 3D-printed citrate-based polymer scaffolds with broadly tunable mechanical performance for regenerative engineering

Abstract

Biomaterials with tunable mechanical properties and tissue-mimetic structural features are critical for diverse biomedical applications. Photopolymerizable citrate-based polymers, such as methacrylate polydiolcitrate (mPDC), enable high-resolution fabrication of biodegradable scaffolds via light-based 3D printing for regenerative engineering. However, their broader utility is limited by intrinsic brittleness and restricted mechanical tunability, associated with highly crosslinked heterogeneous polymer networks. To overcome these limitations, we report facile network-engineering strategies that modulate crosslinking density and network topology through incorporation of acrylate-based reactive diluents and/or a thiol-based chain transfer agent, 3,6-dioxa-1,8-octanedithiol (DOD). This approach yields substantially improved and broadly tunable mechanical properties with Young's modulus spanning 6.9–133.5 MPa, ultimate tensile strength ranging from 1.8 MPa to 18.3 MPa, and strain at break varying from 14.2% to 60.6%. Notably, incorporation of isobornyl acrylate (IBOA) alone increased stiffness and toughness, resulting in a 3.6-fold increase in Young's modulus (50.1 vs. 14.0 MPa) and a 2.8-fold increase in strain at break (39.4% vs. 14.2%). Furthermore, the combined use of IBOA and DOD enabled a 4-fold increase in ductility (up to 60.6% strain at break) while maintaining comparable stiffness. All mPDC composite formulations retained good printability, exhibited tunable biodegradability, and supported cell viability. Importantly, these materials enabled application-specific performance in 3D-printed scaffolds: meniscus scaffolds supported human chondrocyte growth and fibrochondrogenic matrix deposition, while vascular stents supported endothelial monolayer formation. Collectively, this work establishes a versatile photopolymerizable citrate-based biomaterial platform that overcomes brittleness and enables broad mechanical tunability, providing a robust foundation for customized biomedical applications ranging from load-bearing to soft tissue engineering.