Non-rigid calcium phosphate cement containing hydrogel microbeads and absorbable fibres seeded with umbilical cord stem cells for bone engineering

Abstract

The need for bone repair has increased as the population ages. Non-rigid calcium phosphate scaffolds could provide compliance for micro-motions within the tissues and yet have load-supporting strength. The objectives of this study were to: (a) develop a non-rigid calcium phosphate cement (CPC) with microbeads and fibre reinforcement; and (b) investigate human umbilical cord mesenchymal stem cell (hUCMSC) proliferation, osteodifferentiation and mineralization on non-rigid CPC for the first time. Non-rigid CPC was fabricated by adding extra tetracalcium phosphate in the traditional CPC and by incorporating chitosan, absorbable fibres and hydrogel microbeads. The non-rigid CPC-microbead scaffold possessed a strain-at-failure of 10.7%, much higher than the traditional CPC's strain of 0.05% which is typical for brittle bioceramics. Flexural strength of non-rigid CPC-microbead was 4-fold that of rigid CPC-microbead scaffold, while work-of-fracture (toughness) was increased by 20-fold. The strength of non-rigid CPC-microbead-fibre scaffold matched that of cancellous bone. hUCMSCs on non-rigid CPC proliferated from 100 cells/mm(2) at 1 day to 600 cells/mm(2) at 8 days. Alkaline phosphatase, osteocalcin and collagen gene expressions of hUCMSCs were greatly increased, and the cells synthesized bone minerals. hUCMSCs on non-rigid CPC-microbead-fibre constructs had higher bone markers and more mineralization than those on rigid CPC controls. In conclusion, this study developed the first non-rigid, in situ-setting calcium phosphate-microbead-fibre scaffold with a strain-at-failure exceeding 10%. hUCMSCs showed excellent proliferation, osteodifferentiation and mineralization on non-rigid CPC scaffold. The novel non-rigid CPC-hUCMSC construct with good strength, high strain-at-failure and toughness, as well as superior stem cell proliferation, osteodifferentiation and mineralization, is promising for load-bearing bone regeneration applications.