Scaffold-Free Spheroids with Two-Dimensional Heteronano-Layers (2DHNL) Enabling Stem Cell and Osteogenic Factor Codelivery for Bone Repair
journal contributionposted on 2022-01-24, 16:44 authored by Xifeng Liu, Linli Li, Bipin Gaihre, Sungjo Park, Yong Li, Andre Terzic, Benjamin D. Elder, Lichun Lu
Scaffold-free spheroids offer great potential as a direct supply of cells for bottom-up bone tissue engineering. However, the building of functional spheroids with both cells and bioactive signals remains challenging. Here, we engineered functional spheroids with mesenchymal stem cells (MSCs) and two-dimensional heteronano-layers (2DHNL) that consisted of black phosphorus (BP) and graphene oxide (GO) to create a 3D cell-instructive microenvironment for large defect bone repair. The effects of the engineered 2D materials on the proliferation, osteogenic differentiation of stem cells was evaluated in an in vitro 3D spheroidal microenvironment. Excellent in vivo support of osteogenesis of MSCs, neovascularization, and bone regeneration was achieved after transplanting these engineered spheroids into critical-sized rat calvarial defects. Further loading of osteogenic factor dexamethasone (DEX) on the 2DHNL showed outstanding in vivo osteogenic induction and bone regrowth without prior in vitro culture in osteogenic medium. The shortened overall culture time would be advantageous for clinical translation. These functional spheroids impregnated with engineered 2DHNL enabling stem cell and osteogenic factor codelivery could be promising functional building blocks to provide cells and differential clues in an all-in-one system to create large tissues for time-effective in vivo bone repair.
engineered 2d materialsbone tissue engineeringosteogenic factor dexamethasoneosteogenic factor codeliveryenabling stem cellfunctional spheroids impregnatedcreate large tissues3d spheroidal microenvironment2dhnl showed outstandingengineered functional spheroidsmesenchymal stem cellsbone repair scaffoldfunctional spheroidsengineered spheroidsbone repair3d cellstem cellsinstructive microenvironmentbone regenerationosteogenic mediumosteogenic inductionosteogenic differentiationfree spheroidsvivo vitro provide cellsone systemgraphene oxidedirect supplydimensional heteronanodifferential cluesclinical translationblack phosphorus