Self‐Assembling Copolymers Encapsulating Single Endothelial Cells Induce Endogenous ECM Deposition and Vascular Regeneration
4 affiliations
- 1Department of Medicine Division of Cardiology Emory University School of Medicine Atlanta Georgia USA
- 2Southern Regional Medical Center Atlanta Heart Associates McDonough Georgia USA
- 3Severance Biomedical Science Institute Yonsei University College of Medicine Seoul South Korea
- 4Wallace H. Coulter Department of Biomedical Engineering Emory University and Georgia Institute of Technology Atlanta Georgia USA
Abstract
Cell therapy combined with biomimetic polymer engineering offers a promising strategy for cardiovascular regeneration. Compartmentalizing single cells in hydrogels creates three‐dimensional (3D) micro‐niches that enhance bio‐responsiveness and the therapeutic efficacy of cell therapy. A non‐microfluidic strategy for single‐cell encapsulation using a stimuli‐responsive amphiphilic copolymer, gelatin‐poly(glycerol sebacate)‐methacrylate (GPM) is developed. When incubated with cells at room temperature, GPM self‐assembled into single‐cell vesicles via ligand–receptor–mediated interactions, creating a nanoscale matrix around each cell with near 100% encapsulation efficiency. The presence of bioactive moieties, dynamic mechanical properties, and matrix metalloproteinase mediated degradability enabled reciprocal, cell‐matrix interactions. Consequently, 3D cultures of GPM vesicles encapsulating single endothelial cell (GPM/EC vesicles) promoted deposition of thread‐like extracellular matrix (ECM), which facilitated cell migration and served as a guidance scaffold for vessel‐like network formation. For enhanced in vivo distribution and immunoprotection, GPM/reprogrammed EC vesicles were assembled into injectable microspheres, termed mGPM‐rEC. Upon injection into a mouse hindlimb ischemia model, mGPM‐rEC demonstrated robust cell survival and intramuscular migration with the deposition of dense ECM. This ECM functioned as a reservoir for growth factors and signaling molecules, recruiting host vasculature to promote neovascularization and providing structural and mechanical support for implanted cells to form de novo blood vessels.
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BibTeX
@article{morris2026selfassembling,
title = {{Self‐Assembling Copolymers Encapsulating Single Endothelial Cells Induce Endogenous ECM Deposition and Vascular Regeneration}},
author = {Viola B. Morris and Sangho Lee and Kalp Soni and Simon He and Matthew Huang and Dandan Chen and Dae Hoon Lee and Kyung Hee Kim and Seonggeon Cho and Laura Pencea and Divit Jain and Young‐Sup Yoon},
journal = {Advanced Materials (Deerfield Beach, Fla.)},
year = {2026},
month = sep,
doi = {10.1002/adma.74874},
url = {https://doi.org/10.1002/adma.74874},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Self‐Assembling Copolymers Encapsulating Single Endothelial Cells Induce Endogenous ECM Deposition and Vascular Regeneration
AU - Viola B. Morris
AU - Sangho Lee
AU - Kalp Soni
AU - Simon He
AU - Matthew Huang
AU - Dandan Chen
AU - Dae Hoon Lee
AU - Kyung Hee Kim
AU - Seonggeon Cho
AU - Laura Pencea
AU - Divit Jain
AU - Young‐Sup Yoon
PY - 2026
DA - 2026/09/02
JO - Advanced Materials (Deerfield Beach, Fla.)
DO - 10.1002/adma.74874
UR - https://doi.org/10.1002/adma.74874
AB - Cell therapy combined with biomimetic polymer engineering offers a promising strategy for cardiovascular regeneration. Compartmentalizing single cells in hydrogels creates three‐dimensional (3D) micro‐niches that enhance bio‐responsiveness and the therapeutic efficacy of cell therapy. A non‐microfluidic strategy for single‐cell encapsulation using a stimuli‐responsive amphiphilic copolymer, gelatin‐poly(glycerol sebacate)‐methacrylate (GPM) is developed. When incubated with cells at room temperature, GPM self‐assembled into single‐cell vesicles via ligand–receptor–mediated interactions, creating a nanoscale matrix around each cell with near 100% encapsulation efficiency. The presence of bioactive moieties, dynamic mechanical properties, and matrix metalloproteinase mediated degradability enabled reciprocal, cell‐matrix interactions. Consequently, 3D cultures of GPM vesicles encapsulating single endothelial cell (GPM/EC vesicles) promoted deposition of thread‐like extracellular matrix (ECM), which facilitated cell migration and served as a guidance scaffold for vessel‐like network formation. For enhanced in vivo distribution and immunoprotection, GPM/reprogrammed EC vesicles were assembled into injectable microspheres, termed mGPM‐rEC. Upon injection into a mouse hindlimb ischemia model, mGPM‐rEC demonstrated robust cell survival and intramuscular migration with the deposition of dense ECM. This ECM functioned as a reservoir for growth factors and signaling molecules, recruiting host vasculature to promote neovascularization and providing structural and mechanical support for implanted cells to form de novo blood vessels.
SN - 0935-9648
SN - 1521-4095
ER -