Restoration of vasculogenic microtissue sprouting in osteogenic niches using PDGF-BB for prevascularized bone...

Prevascularization is critical for successful bone tissue engineering, yet the osteogenic niche generated by osteogenic microtissues and osteogenic induction medium (OIM) often impairs vascular network formation. In this study, vasculogenic microtissues were fabricated by seeding human umbilical vein endothelial cells (HUVECs) alone or in combination with human umbilical cord mesenchymal stem cells (hUCMSCs) on gelatin microcarriers. The effects of the osteogenic niche on microvascular sprouting were assessed using conditioned media derived from osteogenic microtissues. Results demonstrated that the osteogenic environment significantly inhibited the sprouting and migration of both HUVECs and hUCMSCs, promoting osteogenic differentiation at the cost of stemness and angiogenic potential. To counteract these effects, Platelet-derived growth factor-BB (PDGF-BB) supplementation was introduced. Consistent with previous reports showing that platelet-derived factors promote directional migration of perivascular and endothelial cells(Khosravi et al., 2021) (Khosravi et al., 2021), PDGF-BB restored hUCMSC migration even under osteogenic conditions, upregulated stemness-related genes (SOX2, KLF4, OCT4), and enhanced vascular network formation within vasculogenic microtissues. PDGF-BB restored hUCMSC migration, upregulated stemness-related genes (SOX2, KLF4, OCT4), and enhanced vascular network formation within vasculogenic microtissues even under osteogenic conditions. These findings suggest that PDGF-BB modification of the osteogenic niche offers a promising strategy to optimize the assembly of prevascularized engineered bone tissues, potentially improving bone regeneration outcomes and implant integration.