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

• Published in: Journal of biomedical materials research. Part B, Applied biomaterials Vol. 110; no. 6; pp. 1245 - 1254
• Main Authors: Suematsu, Yoshitaka, Nagano, Hisato, Kiyosawa, Tomoharu, Takeoka, Shinji, Fujie, Toshinori
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-06-2022; Wiley Subscription Services, Inc
• 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; poly(d,l-lactic acid) (PDLLA); diabetic skin ulcer; porous structure; adipose-tissue derived stem cells (ASCs); polymeric nanosheet; spheroid
• ISSN: 1552-4973; 1552-4981
• DOI: 10.1002/jbm.b.34995

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.