Journal of Materials Science: Materials in Medicine

, Volume 22, Issue 5, pp 1279–1291

Hyaluronan-based heparin-incorporated hydrogels for generation of axially vascularized bioartificial bone tissues: in vitro and in vivo evaluation in a PLDLLA–TCP–PCL-composite system

Authors

  • Subha N. Rath
    • Department of Plastic and Hand SurgeryUniversity of Erlangen Medical Center
    • Division of BioengineeringNational University of Singapore
  • Galyna Pryymachuk
    • Department of Plastic and Hand SurgeryUniversity of Erlangen Medical Center
  • Oliver A. Bleiziffer
    • Department of Plastic and Hand SurgeryUniversity of Erlangen Medical Center
  • Christopher X. F. Lam
    • Division of BioengineeringNational University of Singapore
  • Andreas Arkudas
    • Department of Plastic and Hand SurgeryUniversity of Erlangen Medical Center
  • Saey T. B. Ho
    • Graduate Programme in Bioengineering, Yong Loo Lin School of MedicineNational University of Singapore
  • Justus P. Beier
    • Department of Plastic and Hand SurgeryUniversity of Erlangen Medical Center
  • Raymund E. Horch
    • Department of Plastic and Hand SurgeryUniversity of Erlangen Medical Center
  • Dietmar W. Hutmacher
    • Faculty of Engineering, Faculty of Science, Institute of Health and Biomedical InnovationQueensland University of Technology
    • Department of Plastic and Hand SurgeryUniversity of Erlangen Medical Center
Article

DOI: 10.1007/s10856-011-4300-0

Cite this article as:
Rath, S.N., Pryymachuk, G., Bleiziffer, O.A. et al. J Mater Sci: Mater Med (2011) 22: 1279. doi:10.1007/s10856-011-4300-0

Abstract

Smart matrices are required in bone tissue-engineered grafts that provide an optimal environment for cells and retain osteo-inductive factors for sustained biological activity. We hypothesized that a slow-degrading heparin-incorporated hyaluronan (HA) hydrogel can preserve BMP-2; while an arterio–venous (A–V) loop can support axial vascularization to provide nutrition for a bio-artificial bone graft. HA was evaluated for osteoblast growth and BMP-2 release. Porous PLDLLA–TCP–PCL scaffolds were produced by rapid prototyping technology and applied in vivo along with HA-hydrogel, loaded with either primary osteoblasts or BMP-2. A microsurgically created A–V loop was placed around the scaffold, encased in an isolation chamber in Lewis rats. HA-hydrogel supported growth of osteoblasts over 8 weeks and allowed sustained release of BMP-2 over 35 days. The A–V loop provided an angiogenic stimulus with the formation of vascularized tissue in the scaffolds. Bone-specific genes were detected by real time RT-PCR after 8 weeks. However, no significant amount of bone was observed histologically. The heterotopic isolation chamber in combination with absent biomechanical stimulation might explain the insufficient bone formation despite adequate expression of bone-related genes. Optimization of the interplay of osteogenic cells and osteo-inductive factors might eventually generate sufficient amounts of axially vascularized bone grafts for reconstructive surgery.

Abbreviations

HA

Hyaluronic acid/hyaluronan hydrogel

BMP

Bone morphogenetic protein

CT

Computerized tomography

A–V

Arterio–venous

PLDLLA

Poly(L-lactide-co-D,L-lactide)

PCL

Poly(ε-caprolactone)

TCP

β-Tri-calcium phosphate

Copyright information

© Springer Science+Business Media, LLC 2011