Novel mineralized heparin–gelatin nanoparticles for potential application in tissue engineering of bone

  • Yuan Yang
  • Haihao Tang
  • Alexander Köwitsch
  • Karsten Mäder
  • Gerd Hause
  • Joachim Ulrich
  • Thomas Groth


Nanoparticles (NPs) were prepared from succinylated gelatin (s-GL) cross-linked with aldehyde heparin (a-HEP) and used subsequently as a nano-template for the mineralization of hydroxyapatite (HAP). Gelatin was functionalized with succinyl groups that made it soluble at room temperature. Heparin was oxidized to generate aldehyde groups and then used as a cross-linker that can react with s-GL to form NPs via Schiff’s base linkage. The polymer concentrations, feed molar ratios and pH conditions were varied to fabricate NPs suspension. NPs were obtained with a spheroid shape of an average size of 196 nm at pH 2.5 and 202 nm at pH 7.4. These NPs had a positive zeta potential of 7.3 ± 3.0 mV and a narrow distribution with PDI 0.123 at pH 2.5, while they had a negative zeta potential of −2.6 ± 0.3 mV and formed aggregates (PDI 0.257) at pH 7.4. The NPs prepared at pH 2.5 with a mean particle size of 196 nm were further used for mineralization studies. The mineralization process was mediated by solution without calcination at 37 °C. The HAP formed on NPs was analyzed by Fourier transform infrared spectroscopy and X-ray diffraction. HAP coated s-GL/a-HEP NPs developed in this study may be used in future as osteoinductive fillers enhancing the mechanical properties of injectable hydrogel or use as potential multifunctional device for nanotherapeutic approaches.


Gelatin Hyaluronic Acid Dynamic Light Scattering Aldehyde Group Genipin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We are very thankful to Dr. Hendrik Metz for zeta potential experiment, Mrs. Ute Mentzel for FFFF and DLS measurements and Ms. Kristin Wendt for XRD analysis. This work was supported by the European Union Seventh Framework Program (FP7/2007–2013) under Grant agreement no. NMP4-SL-2009-229292 (“Find and Bind”).

Supplementary material

10856_2013_5111_MOESM1_ESM.tif (600 kb)
Zeta-potential of s-GL at different pH conditions. At pH 4, the s-GL is nearly zero charged (TIFF 599 kb)


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Yuan Yang
    • 1
  • Haihao Tang
    • 1
  • Alexander Köwitsch
    • 1
  • Karsten Mäder
    • 2
  • Gerd Hause
    • 3
  • Joachim Ulrich
    • 4
  • Thomas Groth
    • 1
  1. 1.Biomedical Materials Group, Department of Pharmaceutical Technology and Biopharmacy, Institute of PharmacyMartin Luther University Halle-WittenbergHalle (Saale)Germany
  2. 2.Pharmaceutical Technology Group, Department of Pharmaceutical Technology and Biopharmacy, Institute of PharmacyMartin Luther University Halle-WittenbergHalle (Saale)Germany
  3. 3.Microscopy Unit, BiocenterMartin Luther University Halle-WittenbergHalle (Saale)Germany
  4. 4.Thermal Process Engineering, Center for Engineering ScienceMartin Luther University Halle-WittenbergHalle (Saale)Germany

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