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<p>Low retention of transplanted stem cells at target sites remains a major barrier to the clinical translation of cell-based therapies. Conventional strategies, including genetic modification, chemical functionalization, and biomaterial encapsulation, often face limitations in translational feasibility, safety, or procedural complexity. Here, we present a nanoparticle-enabled biophysical approach to enhance cell retention. We incorporate cell-settling nanoparticles composed of clinically approved materials into mesenchymal stem cells, increasing cellular density to accelerate gravitational settling and improve adhesion and survival. Building on this, we develop copper-chaperone-activatable nanoparticles, which enhance tissue regeneration and anti-fibrotic signaling through activation of fibroblast growth factor 2 and a positive feedback loop. In a mouse skin wound model, we show that copper-chaperone-activatable nanoparticle-treated mesenchymal stem cells exhibit enhanced vascularization and reduced fibrosis. These findings demonstrate that modulation of cellular density and physical forces can improve stem cell engraftment, establishing a biophysical framework for safe and translationally relevant cell-based therapies.</p>

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Nanoparticle-enabled tuning of cell density for enhanced adhesion and tissue repair

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月9日

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  • Hyun Su Park,
  • Gwang-Bum Im,
  • So Yun Jeong,
  • Jongseok Lee,
  • Amélie Ferran,
  • Jihyun Lee,
  • Sung-Won Kim,
  • Jiyu Hyun,
  • Young-Ju Jang,
  • Eun-Cheol Lee,
  • Younghoon Lee,
  • Jong Wook Bae,
  • Suk Ho Bhang

摘要

Low retention of transplanted stem cells at target sites remains a major barrier to the clinical translation of cell-based therapies. Conventional strategies, including genetic modification, chemical functionalization, and biomaterial encapsulation, often face limitations in translational feasibility, safety, or procedural complexity. Here, we present a nanoparticle-enabled biophysical approach to enhance cell retention. We incorporate cell-settling nanoparticles composed of clinically approved materials into mesenchymal stem cells, increasing cellular density to accelerate gravitational settling and improve adhesion and survival. Building on this, we develop copper-chaperone-activatable nanoparticles, which enhance tissue regeneration and anti-fibrotic signaling through activation of fibroblast growth factor 2 and a positive feedback loop. In a mouse skin wound model, we show that copper-chaperone-activatable nanoparticle-treated mesenchymal stem cells exhibit enhanced vascularization and reduced fibrosis. These findings demonstrate that modulation of cellular density and physical forces can improve stem cell engraftment, establishing a biophysical framework for safe and translationally relevant cell-based therapies.