Tissue engineering polymeric formulations enable lymphangiogenesis for myocardial repair.
- 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, 138 Yixueyuan Rd., Shanghai, 200032, PR China.
- 2Multidisciplinary Innovation Centre for Bioadditive Manufacturing, Institute for Frontier Medical Technology, School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Rd., Shanghai, 201620, PR China.
- 3Department of Plastic Surgery, Jinan Clinical Research Center for Tissue Engineering Skin Regeneration and Wound Repair, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, 16766 Jingshi Rd., Jinan, Shandong, 250014, PR China.
Abstract
Purpose
Emerging evidence emphasizes the pivotal contribution of cardiac lymphatic activation following ischemic heart injury, with induced lymphangiogenesis driving edema resolution and inflammatory cell clearance. The aim of this study was to identify a bioactive small molecule with pro-lymphangiogenic activity and to develop a tissue engineering polymeric formulation for sustained local delivery in myocardial repair.Methods
Through a high-throughput screen, we identified the bioactive molecule β-(3,4-dihydroxyphenyl) lactic acid (3,4-DHPLA) as a potent stimulator of lymphatic endothelial cells (LECs). To leverage this finding, we engineered a tissue engineering polymeric formulation (TEPF) to promote lymphangiogenesis during myocardial repair. The TEPF was fabricated via an integrated strategy combining 3D printing and near-field electrospinning to incorporate 3,4-DHPLA into a biodegradable polyurethane scaffold. The resulting structure mimics the microstructure of the cardiac extracellular matrix while supporting the microenvironment-responsive release of 3,4-DHPLA.Results
We evaluated the therapeutic efficacy of TEPF in rat and porcine ischemia/reperfusion injury models, which markedly improved cardiac function and significantly attenuated adverse ventricular remodeling. Single-cell RNA sequencing and in vitro data further revealed the dual mechanisms of TEPF, not only promoting lymphangiogenesis but also orchestrating a pro-regenerative niche via expansion of Tregs, M2 macrophages, and pro-regenerative fibroblasts (COL12A1⁺, COL11A1⁺, NRG1⁺).Conclusions
Thus, the tissue engineering polymeric formulations may enable sustained drug release during myocardial tissue repair, thereby alleviating the pain of injection administration for patients with cardiovascular diseases and potentially facilitating patient-friendly use of other functional molecules-based therapeutic tissue engineering formulations through durable delivery.
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BibTeX
@article{liu2026tissue,
title = {{Tissue engineering polymeric formulations enable lymphangiogenesis for myocardial repair.}},
author = {Zhuo Liu and Ruizhi Li and Wenxin Huang and Jinyi Zhang and Ying Qu and Wenke Dong and Yonghang Liu and Qingze Li and Xiaoyang Lin and Huitang Xia and Tonghe Zhu and Chen Xu},
journal = {Bioactive materials},
year = {2026},
month = oct,
doi = {10.1016/j.bioactmat.2026.08.048},
url = {https://europepmc.org/article/MED/42908871},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Tissue engineering polymeric formulations enable lymphangiogenesis for myocardial repair.
AU - Zhuo Liu
AU - Ruizhi Li
AU - Wenxin Huang
AU - Jinyi Zhang
AU - Ying Qu
AU - Wenke Dong
AU - Yonghang Liu
AU - Qingze Li
AU - Xiaoyang Lin
AU - Huitang Xia
AU - Tonghe Zhu
AU - Chen Xu
PY - 2026
DA - 2026/10/12
JO - Bioactive materials
DO - 10.1016/j.bioactmat.2026.08.048
UR - https://europepmc.org/article/MED/42908871
AB - Purpose Emerging evidence emphasizes the pivotal contribution of cardiac lymphatic activation following ischemic heart injury, with induced lymphangiogenesis driving edema resolution and inflammatory cell clearance. The aim of this study was to identify a bioactive small molecule with pro-lymphangiogenic activity and to develop a tissue engineering polymeric formulation for sustained local delivery in myocardial repair.Methods Through a high-throughput screen, we identified the bioactive molecule β-(3,4-dihydroxyphenyl) lactic acid (3,4-DHPLA) as a potent stimulator of lymphatic endothelial cells (LECs). To leverage this finding, we engineered a tissue engineering polymeric formulation (TEPF) to promote lymphangiogenesis during myocardial repair. The TEPF was fabricated via an integrated strategy combining 3D printing and near-field electrospinning to incorporate 3,4-DHPLA into a biodegradable polyurethane scaffold. The resulting structure mimics the microstructure of the cardiac extracellular matrix while supporting the microenvironment-responsive release of 3,4-DHPLA.Results We evaluated the therapeutic efficacy of TEPF in rat and porcine ischemia/reperfusion injury models, which markedly improved cardiac function and significantly attenuated adverse ventricular remodeling. Single-cell RNA sequencing and in vitro data further revealed the dual mechanisms of TEPF, not only promoting lymphangiogenesis but also orchestrating a pro-regenerative niche via expansion of Tregs, M2 macrophages, and pro-regenerative fibroblasts (COL12A1⁺, COL11A1⁺, NRG1⁺).Conclusions Thus, the tissue engineering polymeric formulations may enable sustained drug release during myocardial tissue repair, thereby alleviating the pain of injection administration for patients with cardiovascular diseases and potentially facilitating patient-friendly use of other functional molecules-based therapeutic tissue engineering formulations through durable delivery.
SN - 2452-199X
ER -