Hong, Yu-Tong Teo, Jye Yng Jeon, Hojeong Kong, Hyunjoon 2024-01-19T15:01:21Z 2024-01-19T15:01:21Z 2021-10-21 2021-04 1944-8244 https://pubs.kist.re.kr/handle/201004/117120 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 PLGAHA-RGD, can form nanostimulators that remain on the cell surface stably during the injection. The resulting HA-CD44 and RGDintegrin 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. English American Chemical Society Shear-Resistant, Biological Tethering of Nanostimulators for Enhanced Therapeutic Cell Paracrine Factor Secretion Article 10.1021/acsami.1c01520 1 ACS Applied Materials & Interfaces, v.13, no.15, pp.17276 - 17288 ACS Applied Materials & Interfaces 13 15 17276 17288 N scie scopus 000643578300012 2-s2.0-85104917957 Nanoscience & Nanotechnology Materials Science, Multidisciplinary Science & Technology - Other Topics Materials Science Article MESENCHYMAL STEM-CELLS GROWTH-FACTOR BONE-MARROW IN-VIVO PROGENITOR CELLS STRESS ANGIOGENESIS BINDING SURFACE CONSEQUENCES mesenchymal stromal cells hyaluronic acid RGD peptide poly(lactic-co-glycolic acid) surface tethering flow-induced shear stress