Incorporation of growth factor containing Matrigel promotes vascularization of porous PLGA scaffolds M. W. Laschke, 1 M. Ru ¨ cker, 1,2 G. Jensen, 1 C. Carvalho, 3,4 R. Mu ¨ lhaupt, 3,4 N.-C. Gellrich, 2 M. D. Menger 1 1 Institute for Clinical and Experimental Surgery, University of Saarland, 66421 Homburg/Saar, Germany 2 Department of Oral and Maxillofacial Surgery, Hannover Medical School, 30625 Hannover, Germany 3 Freiburg Materials Research Center, Albert-Ludwigs University, 79104 Freiburg, Germany 4 Institute for Macromolecular Chemistry, Albert-Ludwigs University, 79104 Freiburg, Germany Received 9 February 2007; revised 6 April 2007; accepted 3 May 2007 Published online 9 August 2007 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.a.31503 Abstract: In tissue engineering, rapid ingrowth of blood vessels into scaffolds is a major prerequisite for the sur- vival of three-dimensional tissue constructs. In the present study, we investigated whether the vascularization of implanted poly-D,L-lactic-co-glycolic acid (PLGA) scaffolds may be accelerated by incorporation of Matrigel. For this purpose, we investigated in the aortic ring assay the proangiogenic properties of growth factor reduced Matri- gel (GFRM) and growth factor containing Matrigel (GFCM), which were then incorporated into the pores of PLGA scaffolds. Subsequently, we analyzed vasculariza- tion, biocompatibility, and incorporation of these scaffolds during 14 days after implantation into dorsal skinfold chambers of balb/c mice by means of intravital micros- copy, histology, and immunohistochemistry. Matrigel-free scaffolds served as controls. In the aortic ring assay, GFCM stimulated the development of a network of tubular vessel structures with a significantly increased sprout area and density when compared with GFRM. Accordingly, GFCM accelerated and improved in vivo the ingrowth of new blood vessels into scaffolds, resulting in the formation of a pericyte-coated vascular network with an increased functional capillary density in comparison to the GFRM and control group. Besides, analysis of leukocyte–endothe- lial cell interaction in host tissue venules located in close vicinity to the scaffolds showed no marked differences in numbers of rolling and adherent leukocytes between the observation groups, indicating that incorporation of Matri- gel did not affect biocompatibility of PLGA scaffolds. These findings demonstrate that the combination of proan- giogenic extracellular matrices with solid scaffold biomate- rials may represent a novel approach to accelerate adequate vascularization of tissue engineering constructs. Ó 2007 Wiley Periodicals, Inc. J Biomed Mater Res 85A: 397–407, 2008 Key words: scaffold; PLGA; matrigel; vascularization; bio- compatibility INTRODUCTION The basic principle of tissue engineering is the de- velopment of biological tissue substitutes that can restore, maintain, or improve tissue function. 1 For this purpose, a tissue construct may be engineered in vitro by seeding stem cells or differentiated tissue specific cells within a three-dimensional scaffold, which provides biomechanical stability during the first weeks after implantation into the host site. 1,2 Correspondingly, an adequate scaffold has to fulfil a multiplicity of material properties, in particular, a good biocompatibility, a timed degradability to non- toxic products, and a porous structure that allows a rapid vascularization. 3,4 Survival and long-term function of cells in the cen- ter of a tissue construct decisively depend on the extend of blood vessel ingrowth during the first days after implantation. Oxygen transport from blood vessels of the surrounding host tissue is lim- ited to a diffusion distance of *150–200 lm, 5,6 sup- plying only the cells on the surface of the construct. However, recent studies indicated that complete vas- cularization of porous scaffolds that are even very thin (250–3000 lm) takes at least 1–2 weeks after im- plantation. 7–9 To overcome this problem, several approaches are currently under investigation to accelerate the vascularization process, including the incorporation of angiogenic growth factors into the scaffold biomaterials. 10 This can be done by simply mixing the growth factor with polymer particles before processing the polymer into a porous scaffold, Correspondence to: M.W. Laschke; e-mail: matthias.laschke@ uniklinik-saarland.de Contract grant sponsor: Deutsche Forschungsgemein- schaft; contract grant numbers: RU 1224/1-1, RU 1224/1-2, GE 820/6-1 ' 2007 Wiley Periodicals, Inc.