TY - JOUR
T1 - 3D Stem Cell Spheroids with 2D Hetero-Nanostructures for In Vivo Osteogenic and Immunologic Modulated Bone Repair
AU - Liu, Xifeng
AU - Astudillo Potes, Maria D.
AU - Dashtdar, Babak
AU - Schreiber, Areonna C.
AU - Tilton, Maryam
AU - Li, Linli
AU - Elder, Benjamin D.
AU - Lu, Lichun
N1 - Publisher Copyright:
© 2024 Wiley-VCH GmbH.
PY - 2024
Y1 - 2024
N2 - 3D stem cell spheroids have immense potential for various tissue engineering applications. However, current spheroid fabrication techniques encounter cell viability issues due to limited oxygen access for cells trapped within the core, as well as nonspecific differentiation issues due to the complicated environment following transplantation. In this study, functional 3D spheroids are developed using mesenchymal stem cells with 2D hetero-nanostructures (HNSs) composed of single-stranded DNA (ssDNA) binding carbon nanotubes (sdCNTs) and gelatin-bind black phosphorus nanosheets (gBPNSs). An osteogenic molecule, dexamethasone (DEX), is further loaded to fabricate an sdCNTgBP-DEX HNS. This approach aims to establish a multifunctional cell-inductive 3D spheroid with improved oxygen transportation through hollow nanotubes, stimulated stem cell growth by phosphate ions supplied from BP oxidation, in situ immunoregulation, and osteogenesis induction by DEX molecules after implantation. Initial transplantation of the 3D spheroids in rat calvarial bone defect shows in vivo macrophage shifts to an M2 phenotype, leading to a pro-healing microenvironment for regeneration. Prolonged implantation demonstrates outstanding in vivo neovascularization, osteointegration, and new bone regeneration. Therefore, these engineered 3D spheroids hold great promise for bone repair as they allow for stem cell delivery and provide immunoregulative and osteogenic signals within an all-in-one construct.
AB - 3D stem cell spheroids have immense potential for various tissue engineering applications. However, current spheroid fabrication techniques encounter cell viability issues due to limited oxygen access for cells trapped within the core, as well as nonspecific differentiation issues due to the complicated environment following transplantation. In this study, functional 3D spheroids are developed using mesenchymal stem cells with 2D hetero-nanostructures (HNSs) composed of single-stranded DNA (ssDNA) binding carbon nanotubes (sdCNTs) and gelatin-bind black phosphorus nanosheets (gBPNSs). An osteogenic molecule, dexamethasone (DEX), is further loaded to fabricate an sdCNTgBP-DEX HNS. This approach aims to establish a multifunctional cell-inductive 3D spheroid with improved oxygen transportation through hollow nanotubes, stimulated stem cell growth by phosphate ions supplied from BP oxidation, in situ immunoregulation, and osteogenesis induction by DEX molecules after implantation. Initial transplantation of the 3D spheroids in rat calvarial bone defect shows in vivo macrophage shifts to an M2 phenotype, leading to a pro-healing microenvironment for regeneration. Prolonged implantation demonstrates outstanding in vivo neovascularization, osteointegration, and new bone regeneration. Therefore, these engineered 3D spheroids hold great promise for bone repair as they allow for stem cell delivery and provide immunoregulative and osteogenic signals within an all-in-one construct.
KW - 2D materials
KW - bone repair
KW - hetero-nanostructures (HNSs)
KW - immunomodulation
KW - stem cell spheroids
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U2 - 10.1002/adhm.202303772
DO - 10.1002/adhm.202303772
M3 - Article
C2 - 38271276
AN - SCOPUS:85184473721
SN - 2192-2640
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
ER -