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International

Journal of Bioprinting

RESEARCH ARTICLE
High-resolution 3D printing of collagen I-based

scaffolds via Schiff-base interaction for enhanced
osteogenic differentiation

Kaixuan Li 1,2† id , Hanxiao Huang 1,2,3† id , Peng Ge 1,2 id , and Cailiang Shen *
1,2 id
1 Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei,
Anhui, China
2 Laboratory of Spinal and Spinal Cord Injury Regeneration and Repair, Department of Spine
Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
3
Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Hefei,
Anhui, China

Abstract

Collagen I is a key extracellular matrix (ECM) component in bone tissue and one of
the most important biomaterials for bone tissue engineering applications. However,
printing high-resolution mesh scaffold from collagen I remains challenging due
to its relatively weak ink shape fidelity. While previous efforts have attempted to
improve printability by increasing ink viscosity, such approaches often compromise
† These authors contributed equally ink flowability and yield only modest improvements in printing resolution. To
to this work. solve this issue, we blended oxidized cellulose with collagen I to form a Schiff-base
interaction. The resulting hydrogel exhibited lower viscosity but a more apparent
*Corresponding author:
Cailiang Shen linear rheological characteristic, as demonstrated by our large amplitude oscillation
(shencailiang@ahmu.edu.cn) sweep results. This enhanced rheological profile enabled the fabrication of scaffolds
Citation: Li K, Huang H, Ge P, with a printing resolution approaching 150 μm—one of the highest reported for
Shen C. High-resolution 3D printing collagen I-based scaffolds. Scaffolds with this scale of rod diameter and pore size
of collagen I-based scaffolds via greatly enhanced the proliferation and osteogenic differentiation of mesenchymal
Schiff-base interaction for enhanced
osteogenic differentiation. stem cells. Correspondingly, the expression of key osteogenic markers, including
Int J Bioprint. 2025;11(4):225-241. N-cadherin, HIF-1α, and β-catenin, was upregulated. These findings broaden our
doi: 10.36922/IJB025140116 understanding of scaffold design and processing optimization of collagen I-based
Received: April 1, 2025 scaffolds and may advance their application in bone tissue engineering.
1st revised: May 23, 2025
2nd revised: May 28, 2025
Accepted: May 29, 2025 Keywords: 3D printing; Collagen I; Osteogenic differentiation; Printing resolution
Published online: June 3, 2025
Copyright: © 2025 Author(s).
This is an Open Access article
distributed under the terms of the
Creative Commons Attribution 1. Introduction
License, permitting distribution,
and reproduction in any medium, Collagen I is a key extracellular matrix (ECM) compound in bone tissue and has been
provided the original work is considered one of the most ideal biomaterials for bone tissue engineering. It is highly
1,2
properly cited. biocompatible and contains surface Arg-Gly-Asp (RGD) groups that bind to specific cell
3,4
Publisher’s Note: AccScience receptors, promoting cell adhesion. Therefore, it is superior to general thermoplastic
Publishing remains neutral with biopolymers and ceramics for a broad field of tissue engineering applications. Also,
regard to jurisdictional claims in
published maps and institutional collagen I has been shown to promote osteogenic differentiation of stem cells more
5
affiliations. effectively than many other natural biopolymers like gelatin. For these reasons,

Volume 11 Issue 4 (2025) 225 doi: 10.36922/IJB025140116