TY - JOUR
T1 - Microfluidics generation of chitosan microgels containing glycerylphytate crosslinker for in situ human mesenchymal stem cells encapsulation
AU - Mora-Boza, Ana
AU - Mancipe Castro, Lina M.
AU - Schneider, Rebecca S.
AU - Han, Woojin M.
AU - García, Andrés J.
AU - Vázquez-Lasa, Blanca
AU - San Román, Julio
N1 - Funding Information:
The authors thank the Spanish Ministry of Science and Innovation (project, MAT2017-84277-R ) and U.S. National Institutes of Health ( R01 AR062368 ) for financial support. B. Vázquez-Lasa and J. San Román are members of the SusPlast platform (Interdisciplinary Platform for Sustainable Plastics towards a Circular Economy) from the Spanish National Research Council (CSIC). Ana Mora-Boza was supported by “La Caixa” Foundation (ID 100010434, scholarship code LCF/BQ/ES16/11570018) and CIBER-BBN (Health Institute Carlos III) Travel grant.
Funding Information:
The authors thank the Spanish Ministry of Science and Innovation (project, MAT2017-84277-R) and U.S. National Institutes of Health (R01 AR062368) for financial support. B. V?zquez-Lasa and J. San Rom?n are members of the SusPlast platform (Interdisciplinary Platform for Sustainable Plastics towards a Circular Economy) from the Spanish National Research Council (CSIC). Ana Mora-Boza was supported by ?La Caixa? Foundation (ID 100010434, scholarship code LCF/BQ/ES16/11570018) and CIBER-BBN (Health Institute Carlos III) Travel grant.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/1
Y1 - 2021/1
N2 - Human mesenchymal stem cells (hMSCs) are an attractive source for cell therapies because of their multiple beneficial properties, i.e. via immunomodulation and secretory factors. Microfluidics is particularly attractive for cell encapsulation since it provides a rapid and reproducible methodology for microgel generation of controlled size and simultaneous cell encapsulation. Here, we report the fabrication of hMSC-laden microcarriers based on in situ ionotropic gelation of water-soluble chitosan in a microfluidic device using a combination of an antioxidant glycerylphytate (G1Phy) compound and tripolyphosphate (TPP) as ionic crosslinkers (G1Phy:TPP-microgels). These microgels showed homogeneous size distributions providing an average diameter of 104 ± 12 μm, somewhat lower than that of control (127 ± 16 μm, TPP-microgels). The presence of G1Phy in microgels maintained cell viability over time and upregulated paracrine factor secretion under adverse conditions compared to control TPP-microgels. Encapsulated hMSCs in G1Phy:TPP-microgels were delivered to the subcutaneous space of immunocompromised mice via injection, and the delivery process was as simple as the injection of unencapsulated cells. Immediately post-injection, equivalent signal intensities were observed between luciferase-expressing microgel-encapsulated and unencapsulated hMSCs, demonstrating no adverse effects of the microcarrier on initial cell survival. Cell persistence, inferred by bioluminescence signal, decreased exponentially over time showing relatively higher half-life values for G1Phy:TPP-microgels compared to TPP-microgels and unencapsulated cells. In overall, results position the microfluidics generated G1Phy:TPP-microgels as a promising microcarrier for supporting hMSC survival and reparative activities.
AB - Human mesenchymal stem cells (hMSCs) are an attractive source for cell therapies because of their multiple beneficial properties, i.e. via immunomodulation and secretory factors. Microfluidics is particularly attractive for cell encapsulation since it provides a rapid and reproducible methodology for microgel generation of controlled size and simultaneous cell encapsulation. Here, we report the fabrication of hMSC-laden microcarriers based on in situ ionotropic gelation of water-soluble chitosan in a microfluidic device using a combination of an antioxidant glycerylphytate (G1Phy) compound and tripolyphosphate (TPP) as ionic crosslinkers (G1Phy:TPP-microgels). These microgels showed homogeneous size distributions providing an average diameter of 104 ± 12 μm, somewhat lower than that of control (127 ± 16 μm, TPP-microgels). The presence of G1Phy in microgels maintained cell viability over time and upregulated paracrine factor secretion under adverse conditions compared to control TPP-microgels. Encapsulated hMSCs in G1Phy:TPP-microgels were delivered to the subcutaneous space of immunocompromised mice via injection, and the delivery process was as simple as the injection of unencapsulated cells. Immediately post-injection, equivalent signal intensities were observed between luciferase-expressing microgel-encapsulated and unencapsulated hMSCs, demonstrating no adverse effects of the microcarrier on initial cell survival. Cell persistence, inferred by bioluminescence signal, decreased exponentially over time showing relatively higher half-life values for G1Phy:TPP-microgels compared to TPP-microgels and unencapsulated cells. In overall, results position the microfluidics generated G1Phy:TPP-microgels as a promising microcarrier for supporting hMSC survival and reparative activities.
KW - Chitosan lactate
KW - Glycerylphytate
KW - Human mesenchymal stem cells encapsulation
KW - Microfluidics
KW - Microgel
KW - Secretome
UR - http://www.scopus.com/inward/record.url?scp=85096177677&partnerID=8YFLogxK
U2 - 10.1016/j.msec.2020.111716
DO - 10.1016/j.msec.2020.111716
M3 - Article
C2 - 33545868
AN - SCOPUS:85096177677
SN - 0928-4931
VL - 120
JO - Materials Science and Engineering C
JF - Materials Science and Engineering C
M1 - 111716
ER -