Stem cell spheroid engineering with osteoinductive and ROS scavenging nanofibers for bone regeneration

Abstract Stem cell spheroids have been widely investigated to accelerate bone tissue regeneration. However, the directed differentiation of stem cells into osteoblastic lineage and the prevention of cells from damage by reactive oxygen species (ROS) remain challenge. Here, we developed osteoinductive and ROS scavenging extracellular matrix-mimicking synthetic fibers based on epigallocatechin gallate (EGCG) coating. They were then utilized to fabricate engineered spheroids with human adipose-derived stem cells (hADSCs) for bone tissue regeneration. The EGCG-mineral fibers (EMF) effectively conferred osteoinductive and ROS scavenging signals on the hADSCs within spheroids, demonstrating relative upregulation of antioxidant genes ( SOD-1 (25.8 ± 2.1) and GPX-1 (3.3 ± 0.1) and greater level of expression of osteogenic markers, runt-related transcription factor (5.8 ± 0.1) and osteopontin (5.9 ± 0.1), compared to hADSCs in the spheroids without EMF. The in vitro overexpression of osteogenic genes from hADSCs was achieved from absence of osteogenic supplements. Furthermore, in vivo transplantation of hADSCs spheroids with the EMF significantly promoted calvarial bone regeneration (48.39 ± 9.24%) compared to that from defect only (17.38 ± 6.63%), suggesting that the stem cell spheroid biofabrication system with our novel mineralization method described here is a promising tool for bone tissue regeneration.