title: Heparin modification of a biomimetic bone matrix for controlled release of VEGF.
abstract: Bone regeneration using tissue engineered constructs requires strategies to effectively stimulate vascularization within such a construct that is crucial for its supply and integration with the host tissue. In this work, porous scaffolds of a collagen/hydroxyapatite nanocomposite were modified with heparin to generate biomimetic bone matrices which are able to release angiogenic factors in a controlled manner. Heparin was either integrated during material synthesis (in situ) or added to the scaffolds after their fabrication (post). Both approaches resulted in stable incorporation of heparin into the matrix of mineralized collagen. Investigations of binding and release of the vascular endothelial growth factor (VEGF-A₁₆₅) loaded onto the scaffolds revealed an enhanced binding capacity as well as a sustained and nearly constant delivery of VEGF as result of both heparin modification methods. The release rate could be controlled by varying the quantity of incorporated heparin and the modification method. Although the biological activity of VEGF released after 7 days from the unmodified scaffolds was reduced in comparison to control VEGF, it was maintained after release from post or even enhanced after release from in situ modified scaffolds. In conclusion, the heparin-modified scaffolds of mineralized collagen exhibited favorable growth factor binding and release properties and may be beneficial to stimulate vascularization.
authors.affiliation: Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Medical Faculty of Technische Universität Dresden, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Knaack
authors.forename: Anja
authors.initials: A
authors.lastname: Lode
authors.forename: Birgit
authors.initials: B
authors.lastname: Hoyer
authors.forename: Angela
authors.initials: A
authors.lastname: Rösen-Wolff
authors.forename: Anastasia
authors.initials: A
authors.lastname: Gabrielyan
authors.forename: Ingo
authors.initials: I
authors.lastname: Roeder
authors.forename: Michael
authors.initials: M
authors.lastname: Gelinsky
mesh_terms: D000327:Adsorption; D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry*; D001857:Bone Matrix / Q000737:chemistry*; D002417:Cattle; D003094:Collagen / Q000737:chemistry; D003692:Delayed-Action Preparations; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D054457:Tissue Scaffolds / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D003692:Delayed-Action Preparations; D042461:Vascular Endothelial Growth Factor A; D006493:Heparin; D003094:Collagen
keywords: angiogenesis; collagen; endothelial cells; heparin; hydroxyapatite