A 3D prevascularized calcium phosphate cement scaffold for accelerated alveolar bone regeneration and angiogenesis in
Yaxi Sun1, Zeqing Zhao2, Qingchen Qiao1
1Department of Orthodontics, School of Stomatology, Capital Medical University, No.9, Fan Jia Cun Road, Fengtai District, Beijing, 100050, China.
Objectives:
The objective of this study is to develop a load-bearing prevascularized construct by combining calcium phosphate cement (CPC) with cells within a three-dimensional (3D) hydrogel culture system, to accelerate the regeneration of alveolar bone defects.
Methods:
A 3D co-culture system was established by encapsulating human periodontal ligament stem cells (hPDLSCs) and human umbilical vein endothelial cells (hUVECs) within a gelatin methacryloyl (GelMA) hydrogel on 3D-printed porous CPC scaffolds. The mechanical properties, pore structure and angiogenic potency were determined in vitro. In vivo performance was evaluated using a nude rat subcutaneous implantation model and a rat alveolar bone defect model. Four groups were tested: (1) Blank group (surgery-only group); (2) CPC+GelMA group (non-prevascularized group); (3) CPC+GelMA-cell group (prevascularized group)༛(4) Natural Periodontium group.
Results:
The novel construct had good mechanical properties and biocompatibility. The 3D co-culture in GelMA successfully induced microvascular formation in vitro. Subcutaneous implantation in nude rats showed that the CPC+GelMA-cell group exhibited markedly greater angiogenic capacity than the CPC+GelMA group after 6 weeks, with a neovascular density 1.93-fold higher than that of the non-prevascularized group. Among all groups, the CPC+GelMA-cell group exhibited the strongest capacity for repairing rat alveolar bone defects. Compared to CPC+GelMA group, CPC+GelMA-cell group significant enhanced bone regeneration in rats by 1.23-1.37 folds, and increased vascularization by 2.65 folds (p<0.05).
Conclusions:
The novel 3D prevascularized CPC construct combined appropriate mechanical properties with great efficacy for alveolar bone regeneration and vascularization in vivo in an animal model.
