title: Optimizing Biomaterials for Tissue Engineering Human Bone Using Mesenchymal Stem Cells.
abstract: BACKGROUND
  Adequate biomaterials for tissue engineering bone and replacement of bone in clinical settings are still being developed. Previously, the combination of mesenchymal stem cells in hydrogels and calcium-based biomaterials in both in vitro and in vivo experiments has shown promising results. However, results may be optimized by careful selection of the material combination.
  
  
  METHODS
  β-Tricalcium phosphate scaffolds were three-dimensionally printed with five different hydrogels: collagen I, gelatin, fibrin glue, alginate, and Pluronic F-127. The scaffolds had eight channels, running throughout the entire scaffold, and macropores. Mesenchymal stem cells (2 × 10) were mixed with each hydrogel, and cell/hydrogel mixes were dispersed onto the corresponding β-tricalcium phosphate/hydrogel scaffold and cultured under dynamic-oscillating conditions for 6 weeks. Specimens were harvested at 1, 2, 4, and 6 weeks and evaluated histologically, radiologically, biomechanically and, at 6 weeks, for expression of bone-specific proteins by reverse-transcriptase polymerase chain reaction. Statistical correlation analysis was performed between radiologic densities in Hounsfield units and biomechanical stiffness.
  
  
  RESULTS
  Collagen I samples had superior bone formation at 6 weeks as demonstrated by volume computed tomographic scanning, with densities of 300 HU, similar to native bone, and the highest compression values. Bone specificity of new tissue was confirmed histologically and by the expression of alkaline phosphatase, osteonectin, osteopontin, and osteocalcin. The bone density correlated closely with histologic and biomechanical testing results.
  
  
  CONCLUSIONS
  Bone formation is supported best by β-tricalcium phosphate/collagen I hydrogel and mesenchymal stem cells in collagen I hydrogel.
  
  
  METHODS
  Therapeutic, V.
authors.affiliation: Neubrandenburg, Germany; Boston and Cambridge, Mass.; and Kyoto, Japan From the Department of Plastic and Aesthetic Surgery, Hand Surgery, and Burns, Dietrich-Bonhoeffer-Hospital, University of Greifswald; the Laboratory for Tissue Engineering and Organ Fabrication, Massachusetts General Hospital, Harvard Medical School; the Massachusetts Institute of Technology; and the Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University.
authors.forename: Christian
authors.initials: C
authors.lastname: Weinand
authors.forename: Craig M
authors.initials: CM
authors.lastname: Neville
authors.forename: Eli
authors.initials: E
authors.lastname: Weinberg
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacanti
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D001696:Biomechanical Phenomena; D002130:Calcium Phosphates / Q000737:chemistry; D002454:Cell Differentiation / Q000502:physiology*; D019245:Compressive Strength; D017077:Culture Media, Conditioned; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D066298:In Vitro Techniques; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D012680:Sensitivity and Specificity; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D017077:Culture Media, Conditioned; D020100:Hydrogels; C485817:beta-tricalcium phosphate