Effects of VEGF loading on scaffold-confined vascularization

• Published in: Journal of biomedical materials research. Part A 2010-12, Vol.95A (3), p.783-792
• Main Authors: Lindhorst, Daniel, Tavassol, Frank, von See, Constantin, Schumann, Paul, Laschke, Matthias W., Harder, Yves, Bormann, Kai-Hendrik, Essig, Harald, Kokemüller, Horst, Kampmann, Andreas, Voss, André, Mülhaupt, Rolf, Menger, Michael D., Gellrich, Nils-Claudius, Rücker, Martin
• Format: Article
• Language: English
• Subjects: angiogenesis; Animals; biocompatibility; Biocompatible Materials - chemistry; Biocompatible Materials - metabolism; Biological and medical sciences; Biotechnology; bone tissue engineering; Calcium Phosphates - chemistry; Calcium Phosphates - metabolism; coating; dorsal skinfold chamber; Fundamental and applied biological sciences. Psychology; Health. Pharmaceutical industry; Hemodynamics; Implants, Experimental; Industrial applications and implications. Economical aspects; Inflammation; intravital fluorescence microscopy; Lactic Acid - chemistry; Lactic Acid - metabolism; Materials Testing; Medical sciences; Mice; Mice, Inbred BALB C; Miscellaneous; Neovascularization, Physiologic - drug effects; Polyglycolic Acid - chemistry; Polyglycolic Acid - metabolism; Porosity; scaffold; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology. Biomaterials. Equipments; Tissue Engineering - methods; Tissue Scaffolds - chemistry; Vascular Endothelial Growth Factor A - chemistry; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor A - pharmacology; VEGF
• ISSN: 1549-3296; 1552-4965; 1552-4965
• DOI: 10.1002/jbm.a.32902

Adequate vascularization of tissue‐engineered constructs remains a major challenge in bone grafting. In view of this, we loaded ß‐tricalcium‐phosphate (ß‐TCP) and porous poly(L‐lactide‐co‐glycolide) (PLGA) scaffolds via collagen coating with vascular endothelial growth factor (VEGF) and studied whether the VEGF loading improves scaffold angiogenesis and vascularization. Dorsal skinfold chambers were implanted into 48 balb/c mice, which were assigned to 6 groups (n = 8 each). Uncoated (controls), collagen‐coated, and additionally VEGF‐loaded PLGA and ß‐TCP scaffolds were inserted into the chambers. Angiogenesis, neovascularization, and leukocyte‐endothelial cell interaction were analyzed repeatedly during a 14‐day observation period using intravital fluorescence microscopy. Furthermore, VEGF release from PLGA und ß‐TCP scaffolds was studied by ELISA. Micromorphology was studied from histological specimens. Unloaded ß‐TCP scaffolds showed an accelerated and increased angiogenic response when compared with unloaded PLGA scaffolds. In vitro, PLGA released significantly higher amounts of VEGF compared with ß‐TCP at the first two days resulting in a rapid drop of the released amount at the following days up to day 7 where the VEGF release was negligible. Nonetheless, in vivo VEGF loading increased neovascularization, especially in ß‐TCP scaffolds. This increased vascularization was associated with a temporary leukocytic response with pronounced leukocyte‐endothelial cell interaction at days 3 and 6. Histology revealed adequate host tissue response and engraftment of both ß‐TCP and PLGA scaffolds. Our study demonstrates that ß‐TCP scaffolds offer more suitable conditions for vascularization than PLGA scaffolds, in particular if they are loaded with VEGF. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.