Architecture mechanics mediated osteogenic progression in bone regeneration of artificial scaffolds

Scaffold architecture exerts a considerable influence on the osteogenic
effect through stress transmission, as the deformation of scaffolds alters
the mechanical microenvironment of cells adhering to scaffold surface.
Despite extensive researches on bone regeneration influenced by scaffold
architecture, present studies have not addressed the biological mechanism
underlying scaffold architecture-induced stress stimulation (SASS) on
cells yet, posing a great challenge in revealing the biomechanical cues
between scaffold architecture and osteogenic progression. Therefore,
Graphite (GP), Fullerene (FL), and Diamond (DM) scaffolds with gradient
stress-stimulation to cells after deformation were prepared. Moreover, we
analyzed the results of the finite element simulation of the compression
and recovery process of the three types of scaffolds, and tested the
macroscopic mechanical and viscoelastic properties. The cellular
biomechanical mechanisms of SASS through single-cell RNA sequencing
indicated that architectures providing SASS can induce the enrichment of
focal adhesion and osteogenic differentiation pathways of bone mesenchymal
stem cells, and balance bone resorption of osteoclasts and bone formation
of osteoblasts. Besides, SASS enhances bone regeneration for repairing
critical-sized defects in vivo. These results provide insights for
artificial bone scaffold design and clarify the biomechanical cues between
SASS and osteogenic progression.