학술논문
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.
Document Type
Academic Journal
Author
Rath SN; Department of Plastic and Hand Surgery, University of Erlangen Medical Center, Krankenhausstrasse 12, 91054, Erlangen, Germany.; Pryymachuk G; Bleiziffer OA; Lam CX; Arkudas A; Ho ST; Beier JP; Horch RE; Hutmacher DW; Kneser U
Source
Publisher: Springer Country of Publication: United States NLM ID: 9013087 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-4838 (Electronic) Linking ISSN: 09574530 NLM ISO Abbreviation: J Mater Sci Mater Med Subsets: MEDLINE
Subject
Language
English
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.