Shear-Resistant, Biological Tethering of Nanostimulators for Enhanced Therapeutic Cell Paracrine Factor Secretion

Yu Tong Hong, Jye Yng Teo, Hojeong Jeon, Hyunjoon Kong

Research output: Contribution to journalArticlepeer-review


Mesenchymal stromal cells (MSCs) secreting multiple growth factors and immunomodulatory cytokines are promising for regenerative medicine. To further enhance their secretory activity, efforts have emerged to tether nanosized carriers of secretory stimuli, named nanostimulators, to the MSC surface by forming nonchemical bonds. Despite some successes, there is a great need to improve the retention of nanostimulators during transport through a syringe needle, where high shear stress exerted on the cell surface separates them. To this end, we hypothesize that poly(lactic-co-glycolic acid)-block-hyaluronic acid (PLGA-HA) conjugated with integrin-binding RGD peptides, denoted PLGA-HA-RGD, can form nanostimulators that remain on the cell surface stably during the injection. The resulting HA-CD44 and RGD-integrin bonds would synergistically increase the adhesion strength of nanostimulators. Interestingly, nanostimulators prepared with PLGA-HA-RGD show 3- to 6-fold higher retention than those made with PLGA-HA. Therefore, the PLGA-HA-RGD nanostimulators induced MSCs to secrete 1.5-fold higher vascular endothelial growth factors and a 1.2-fold higher tissue inhibitor of matrix metalloproteinase-1 as compared to PLGA-HA nanostimulators. Consequently, MSCs tethered with PLGA-HA-RGD nanostimulators served to stimulate endothelial cell activities to form a blood vessel-like endothelial lumen with increased length and number of junctions. The nanostimulator design strategy would also be broadly applicable to regulate, protect, and home a broad array of therapeutic or immune cells by tethering carriers with bioactive molecules of interest.

Original languageEnglish (US)
Pages (from-to)17276-17288
Number of pages13
JournalACS Applied Materials and Interfaces
Issue number15
StatePublished - Apr 21 2021


  • RGD peptide
  • flow-induced shear stress
  • hyaluronic acid
  • mesenchymal stromal cells
  • poly(lactic- co-glycolic acid)
  • surface tethering

ASJC Scopus subject areas

  • Materials Science(all)


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