DEVELOPMENT OF MULTIFUNCTIONAL BETA-TRICALCIUM PHOSPHATE SCAFFOLDS FOR ANGIOGENESIS AND OSTEOGENESIS

Rapid and efficient vascularization is still a considerable challenge of a tissue engineered β-tricalcium phosphate (β-TCP) scaffold. To overcome this challenge, branched channels were created in the porous scaffold to stimulate the instant flow of blood supply. The branched channeled porous β-TCP scaffold was fabricated using 3D printing and template-casting method. Human bone mesenchymal stem cells (hBMSC) and human umbilical vein endothelial cells (HUVEC) were seeded in the scaffolds and characterized through double-stranded DNA (dsDNA) assay, alkaline phosphatase (ALP) assay and cell migration. Scaffolds were then implanted in the subcutaneous pockets in mice. Hematoxylin and eosin staining and Immunohistochemical staining on vascularization, bone-related markers were carried out. Results showed that branched channels significantly promoted HUVECs’ infiltration, migration, proliferation, and angiogenesis and also promote the proliferation and osteogenesis differentiation of hBMSCs. Scaffolds did not show significant pro-inflammatory effects. In vivo results showed that in the early stage after implantation, cells significantly migrated into branched channeled scaffolds compared to non-channeled and straight channeled scaffolds. More and matured blood vessels formed in the branched channeled scaffolds compared to in non-channeled and straight channeled scaffolds. Besides promoting vascularization, the branched channels also stimulated the infiltration of bone-related cells into the scaffolds. These results suggested that the geometric design of branched channels in the porous β-TCP scaffold promoted rapid vascularization and potentially stimulated bone cell recruitment. To further enhance the function of the scaffold to promote the MSCs differentiation, MnO2 hollow and solid nanoparticles were doped into the scaffold with different concentrations.