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

J Mater Sci Mater Med. 2011 May;22(5):1279-91. doi: 10.1007/s10856-011-4300-0. Epub 2011 Mar 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Demineralization Technique
  • Bone Morphogenetic Protein 2 / chemistry
  • Bone Morphogenetic Protein 2 / pharmacology
  • Bone Substitutes
  • Calcium Phosphates / chemistry*
  • Heparin / chemistry*
  • Humans
  • Hyaluronic Acid
  • Hydrogels / chemistry*
  • Male
  • Neovascularization, Physiologic / drug effects
  • Osteoblasts / physiology
  • Polyesters / chemistry*
  • Rats
  • Rats, Inbred Lew
  • Tissue Scaffolds

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Substitutes
  • Calcium Phosphates
  • Hydrogels
  • Polyesters
  • beta-tricalcium phosphate
  • polycaprolactone
  • poly(lactide)
  • Hyaluronic Acid
  • Heparin