Injectable Modular Cellularized Blocks via Dual‐Photocrosslinking for Enhanced Cell Therapy

Cell-based regenerative medicine is limited by poor survival of transplanted cells and the lack of scalable, ready-to-use delivery platforms. Here, we developed an injectable dual-photocrosslinking microsphere (DP-MS) bioink composed of Ru/SPS, o-nitrobenzyl-modified hyaluronic acid (HANB), and gelatin methacryloyl (GelMA). Orthogonal green (525 nm) and UV (365 nm) light enable sequential crosslinking: first to generate cell-laden microspheres, and the second step requires only 10 s to induce inter-microsphere imine bonding without external adhesives. The dual-photocrosslinking strategy preserved inter-microsphere spaces, facilitated rapid vascular ingrowth, and enhanced cell survival. In a subcutaneous implantation model, vascular volume in the DP-MS group was approximately 7-fold greater than that of constructs lacking inter-microsphere voids; furthermore, encapsulated stem cells maintained persistent viability over 14 days. Importantly, this superior performance translated into significantly accelerated bone regeneration in a rat mandibular defect model. This platform thus provides a versatile and scalable strategy for developing cellularized products with clinical translation potential.

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Publication Details

Journal
Advanced Healthcare Materials
Published
2026-08-27
DOI
https://doi.org/10.1002/adhm.71624
Primary Topic
3D Printing in Biomedical Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Injectable Modular Cellularized Blocks via Dual‐Photocrosslinking for Enhanced Cell Therapy

Wentao Jiang, Huijiao Yan, Licheng Wan, Wenjie Zhang et al.
Advanced Healthcare Materials
3D Printing in Biomedical Research
article

Injectable Modular Cellularized Blocks via Dual‐Photocrosslinking for Enhanced Cell Therapy

Wentao Jiang, Huijiao Yan, Licheng Wan, Wenjie Zhang, Rongpu Liu, Shaoyi Wang, Hansen Ma, Shuhan Duan, Rong Yang, Junyi Wang, Jiajia Wang
article en

Abstract

Cell-based regenerative medicine is limited by poor survival of transplanted cells and the lack of scalable, ready-to-use delivery platforms. Here, we developed an injectable dual-photocrosslinking microsphere (DP-MS) bioink composed of Ru/SPS, o-nitrobenzyl-modified hyaluronic acid (HANB), and gelatin methacryloyl (GelMA). Orthogonal green (525 nm) and UV (365 nm) light enable sequential crosslinking: first to generate cell-laden microspheres, and the second step requires only 10 s to induce inter-microsphere imine bonding without external adhesives. The dual-photocrosslinking strategy preserved inter-microsphere spaces, facilitated rapid vascular ingrowth, and enhanced cell survival. In a subcutaneous implantation model, vascular volume in the DP-MS group was approximately 7-fold greater than that of constructs lacking inter-microsphere voids; furthermore, encapsulated stem cells maintained persistent viability over 14 days. Importantly, this superior performance translated into significantly accelerated bone regeneration in a rat mandibular defect model. This platform thus provides a versatile and scalable strategy for developing cellularized products with clinical translation potential.

Advanced Healthcare Materials
Shanghai Ninth People's Hospital (CN)
National Natural Science Foundation of China, Shanghai Education Development Foundation, Shanghai Municipal Education Commission, National Key Research and Development Program of China
Openalex Percentile: Top 19%
3D Printing in Biomedical Research
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