Chemical Engineering Journal · Jun 4, 2026
Voronoi curvature scaffolds rejuvenate senescent stem cells and enhance aged bone regeneration
By Lu Z, Babu RS, Rhohani I et al.
Ageing is associated with a progressive decline in stem cell function and regenerative capacity, contributing to impaired bone healing in elderly populations. Cellular senescence and dysregulated mechanotransduction are key factors underlying this age-related deterioration in tissue regeneration. Tissue curvature has recently emerged as an important regulator of cellular behaviour; however, its role in modulating cellular senescence and functional decline remains poorly understood. In this study, we investigate how hyperboloidal curvature regulates senescence and osteogenic differentiation in adipose tissue-derived stem cells (ASCs) and its impact on bone regeneration in vivo . Using high-resolution liquid crystal display (LCD) 3D printing, we fabricated biphasic calcium phosphate (BCP) scaffolds with distinct Gaussian curvature profiles, including Cubic, Gyroid, and Voronoi hyperboloidal architectures, and seeded senescent ASCs onto these scaffolds. ASCs cultured on Voronoi-curved scaffolds exhibited the lowest expression of cell cycle repression genes (P16, P21) and senescence-associated secretory phenotype (SASP) factors, together with markedly enhanced osteogenic differentiation. Mechanistically, Voronoi curvature was associated with reduced αVβ3 integrin expression in senescent ASCs and increased nuclear translocation of Yes-associated protein (YAP), suggesting involvement of mechanosensitive signalling pathways. Blocking αVβ3 integrin signalling rejuvenated senescent ASCs and further enhanced their osteogenic differentiation. In an aged rat critical-sized defect model, Voronoi curvature scaffolds significantly improved bone regeneration compared with Cubic and Gyroid scaffolds. Collectively, these findings identify hyperboloidal Voronoi curvature scaffolds as a powerful geometric cue capable of rejuvenating senescent stem cells and enhancing aged bone repair. This work highlights scaffold geometry as a promising strategy for designing anti-senescent biomaterials to address age-related skeletal regeneration.