Angiogenic efficacy of ASC spheroids filtrated on porous nanosheets for the treatment of a diabetic skin ulcer

Stem cell transplantation is expected to be an effective treatment for intractable skin ulcers by promoting angiogenesis; however, it is challenging to quickly realize a sufficient bloodstream for the ulcers. For this treatment, sheet‐like materials with monolayer cells such as cell sheets have been...

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Published in:Journal of biomedical materials research. Part B, Applied biomaterials Applied biomaterials, 2022-06, Vol.110 (6), p.1245-1254
Main Authors: Suematsu, Yoshitaka, Nagano, Hisato, Kiyosawa, Tomoharu, Takeoka, Shinji, Fujie, Toshinori
Format: Article
Language:English
Subjects:
Adipose Tissue - metabolism
adipose‐tissue derived stem cells (ASCs)
Angiogenesis
Animal models
Animals
Biomedical materials
Cell interactions
Cell number
Cytology
Diabetes
Diabetes mellitus
Diabetes Mellitus - metabolism
diabetic skin ulcer
Diameters
Growth factors
Healing
Lactic acid
Materials research
Materials science
Mice
Monolayers
Nanosheets
Nutrients
poly(d,l‐lactic acid) (PDLLA)
Polymer films
polymeric nanosheet
Polymers
Porosity
porous structure
Secretion
Skin
Skin Ulcer - metabolism
spheroid
Spheroids
Spheroids, Cellular - metabolism
Stem cell transplantation
Stem cells
Stem Cells - metabolism
Thin films
Tissues
Transplantation
Ulcers
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - metabolism
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Summary:Stem cell transplantation is expected to be an effective treatment for intractable skin ulcers by promoting angiogenesis; however, it is challenging to quickly realize a sufficient bloodstream for the ulcers. For this treatment, sheet‐like materials with monolayer cells such as cell sheets have been investigated. However, they have a limitation of cell number that can be transplanted at one time due to the two‐dimensional, monolayer cell structure, and sufficient secretion of growth factors cannot be expected. In this regard, cellular aggregates, such as spheroids, can reproduce three‐dimensional cell‐cell interactions that cause biological functions of living tissues more representative than monolayer cells, which is important to achieving efficient secretion of growth factors. In this study, we focused on free‐standing porous polymer ultrathin films (“porous nanosheets”) comprising poly(d,l‐lactic acid) (PDLLA) and succeeded in developing a spheroid‐covered nanosheet, on which more than 1000 spheroids from adipose‐tissue derived stem cells (ASCs) were loaded. The porous structure with an average pore diameter of 4 μm allowed for facile filtration and carrying spheroids on the nanosheet, as well as sufficient oxygen and nutrients inflow to the cells. The spheroid‐covered nanosheet achieved homogeneous transference of spheroids to a whole skin defect in diabetic model mice. Given the continuous release of vascular endothelial growth factor (VEGF) from the spheroids, the transplanted spheroids promoted healing with more accelerated angiogenesis than a nanosheet with a monolayer of cells. The spheroid‐covered nanosheet may be a new regenerative material for promoting intractable skin ulcer healing.
ISSN:1552-4973
1552-4981
DOI:10.1002/jbm.b.34995