title: 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.
authors.affiliation: Biomaterials and Tissue Engineering Division, Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD, USA.
authors.forename: Wahwah
authors.initials: W
authors.lastname: TheinHan
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weir
authors.forename: Carl G
authors.initials: CG
authors.lastname: Simon
authors.forename: Hockin H K
authors.initials: HH
authors.lastname: Xu
mesh_terms: D000199:Actins / Q000378:metabolism; D000880:Anthraquinones / Q000378:metabolism; D001843:Bone Cements / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology*; D002130:Calcium Phosphates / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D005453:Fluorescence; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D055595:Mechanical Phenomena; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008863:Microspheres; D013194:Staining and Labeling; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D000199:Actins; D000880:Anthraquinones; D001843:Bone Cements; D002130:Calcium Phosphates; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C010078:alizarin; C020243:calcium phosphate