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[Preprint]. 2026 Feb 13:2026.02.12.705586. [Version 1] doi: 10.64898/2026.02.12.705586

Network Modulation Enables 3D-Printed Citrate-Based Polymer Scaffolds with Broadly Tunable Mechanical Performance for Regenerative Engineering

Ni Chen, Nolan Schlessman, Rao Fu, Yonghui Ding
PMCID: PMC12918902  PMID: 41726909

Abstract

Biomaterials with highly tunable mechanical properties and tissue-mimetic structural features are critical for diverse biomedical applications. Photopolymerizable citrate-based polymers (CBP), such as methacrylate polydiolcitrate (mPDC), enable high-resolution fabrication of biodegradable scaffolds via light-based 3D printing for regenerative engineering. However, mPDC scaffolds typically exhibits substantial brittleness due to the formation of highly crosslinked and heterogeneous polymer network, an intrinsic limitation of many acrylate-based polymers, thereby restricting their use across a broad range of tissue types. Herein, we report facile network-engineering strategies to modulate crosslinking density and network topology of CBPs through the incorporation of acrylate-based reactive diluents and/or a thiol-based chain transfer agent, 3,6-dioxa-1,8-octanedithiol (DOD). These approaches enabled significantly improved and broadly tunable mechanical properties, with Young’s modulus spanning 6.8-134 MPa, ultimate tensile strength ranging from 1.8 MPa to 18 MPa, and strain at break varying from 14% to 61%. Notably, incorporation of isobornyl acrylate (IBOA) alone significantly enhanced toughness, yielding a 3.6-fold increase in Young’s modulus (50 MPa vs. 14 MPa) and a 2.8-fold increase in strain at break (39% vs. 14%). Moreover, combined incorporation of IBOA and DOD remarkably improved ductility, achieving a 4-fold increase in strain at break to 61% while maintaining comparable stiffness. All mPDC composites exhibited tunable biodegradability, good cytocompatibility, and excellent 3D printability. Using these composite inks, 3D-printed meniscus scaffolds supported the human chondrocyte growth and fibrochondrogenic matrix deposition, while 3D-printed vascular stents supported endothelial monolayer formation. Collectively, this study establishes a versatile photopolymerizable citrate-based biomaterial platform with broadly tunable mechanical performance, controllable biodegradability, good cytocompatibility, and high printability, offering strong potential for customized biomedical applications ranging from load-bearing to soft tissue engineering.

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