title: 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.
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.
authors: Department of Plastic and Hand Surgery, University of Erlangen Medical Center, Krankenhausstrasse 12, 91054, Erlangen, Germany.
authors: Subha N
authors: SN
authors: Rath
authors: Galyna
authors: G
authors: Pryymachuk
authors: Oliver A
authors: OA
authors: Bleiziffer
authors: Christopher X F
authors: CX
authors: Lam
authors: Andreas
authors: A
authors: Arkudas
authors: Saey T B
authors: ST
authors: Ho
authors: Justus P
authors: JP
authors: Beier
authors: Raymund E
authors: RE
authors: Horch
authors: Dietmar W
authors: DW
authors: Hutmacher
authors: Ulrich
authors: U
authors: Kneser
mesh_terms: D000818:Animals; D018775:Bone Demineralization Technique; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology; D018786:Bone Substitutes; D002130:Calcium Phosphates / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid; D020100:Hydrogels / Q000737:chemistry*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010006:Osteoblasts / Q000502:physiology; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D011917:Rats, Inbred Lew; D054457:Tissue Scaffolds
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D002130:Calcium Phosphates; D020100:Hydrogels; D011091:Polyesters; C485817:beta-tricalcium phosphate; C016240:polycaprolactone; C033616:poly(lactide); D006820:Hyaluronic Acid; D006493:Heparin