Poly(Epsilon-lysine) dendrons tethered with phosphoserine increase mesenchymal stem cell differentiation potential of calcium phosphate gels.
Calcium phosphates (CaP) are considered as biomaterials of choice for the treatment of critical-sized bone defects. Novel injectable CaP materials integrating poly(epsilon-lysine) generation 3 dendrons tethered with phosphoserine were obtained by sol-gel synthesis. This type of dendron was integrated to mimic the biochemical structure of noncollagenous proteins present in the forming osteoids during bone repair. Sol-gel synthesis was coupled with a dialysis process able to equilibrate the materials at a physiological pH value. Fourier transform infrared spectroscopy (FTIR) showed the successful retention of the dendrons after gel dialysis, whereas X-ray diffraction analysis demonstrated both the pH-tuned formation of a hydroxyapatite crystalline phase within the gel and the complete removal of ammonium nitrate deriving from the sol-gel reaction solvent. Scanning electron microscopy images confirmed the presence of crystalline domains in gels synthesized at pH 9.0. Injectability tests showed that the optimized formulations fulfilled the rheological properties required to minimally invasive surgical procedures. Cytotoxicity tests on osteoblast-like MG-63 cells as well as morphology and viability studies showed that the dendrons induced a significantly higher level of cell proliferation at early incubation time. Differentiation of the cell was also clearly enhanced at longer incubation time as demonstrated by both alkaline phosphatase activity and expression of typical markers. Altogether, the data from this work indicate the clinical potential of the osteoid-mimicking CaP cements in minimally invasive bone surgery.
1 Institute of Composite and Biomedical Materials , National Research Council of Italy (CNR), Naples, Italy .
Maria Grazia
MG
Raucci
Marco Antonio
MA
Alvarez-Perez
Steven
S
Meikle
Luigi
L
Ambrosio
Matteo
M
Santin
D000469:Alkaline Phosphatase / Q000378:metabolism; D002130:Calcium Phosphates / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D050091:Dendrimers / Q000494:pharmacology*; D005782:Gels / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007267:Injections; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010078:Oxazines / Q000378:metabolism; D010768:Phosphoserine / Q000494:pharmacology*; D011107:Polylysine / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D014966:Xanthenes / Q000378:metabolism
D002130:Calcium Phosphates; D050091:Dendrimers; D005782:Gels; D010078:Oxazines; D014966:Xanthenes; D010768:Phosphoserine; C005843:resazurin; D011107:Polylysine; C020243:calcium phosphate; D000469:Alkaline Phosphatase