Functionalized PLGA-doped zirconium oxide ceramics for bone tissue regeneration
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Functionalized PLGA-doped zirconium oxide ceramics for bone tissue regeneration Yael Lupu-Haber & Oded Pinkas & Stefanie Boehm & Thomas Scheper & Cornelia Kasper & Marcelle Machluf
# Springer Science+Business Media New York 2013
Abstract Bone tissue engineering is an alternative approach to bone grafts. In our study we aim to develop a composite scaffold for bone regeneration made of doped zirconium oxide (ZrO2) conjugated with poly(lactic-co-glycolic acid) (PLGA) particles for the delivery of growth factors. In this composite, the PLGA microspheres are designed to release a crucial growth factor for bone formation, bone morphogenetic protein-2 (BMP2). We found that by changing the polymer’s molecular weight and composition, we could control microsphere loading, release and size. The BMP2 released from PLGA microspheres retained its biological activity and increased osteoblastic marker expression in human mesenchymal stem cells (hMSCs). Uncapped PLGA microspheres were conjugated to ZrO2 scaffolds using carbodiimide chemistry, and the composite scaffold was shown to support hMSCs growth. We also demonstrated that human umbilical vein endothelial cells (HUVECs) can be co-cultured with hMSCs on the ZrO2 scaffold for future vascularization of the scaffold. The ZrO2 composite scaffold could serve as a bone substitute for bone grafting applications with the added ability of releasing different growth factors needed for bone regeneration. Keywords PLGA . BMP2 . Scaffold . Drug delivery . Bone tissue engineering
Y. Lupu-Haber : O. Pinkas : M. Machluf Faculty of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel 32000 S. Boehm : T. Scheper : C. Kasper Institute of Technical Chemistry, Leibniz University of Hannover, Callinstr. 5, 30167 Hannover, Germany M. Machluf (*) The Laboratory of Cancer Drug Delivery & Cell Based Technologies, Faculty of Biotechnology & Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel 32000 e-mail: [email protected]
1 Introduction Bone is a dynamic tissue with the ability to heal and repair without scaring. Nevertheless, in cases of delayed union or large non-healing fractures resulting from trauma, tumors, infections or congenital abnormalities, bone graft procedures are required (Braddock et al. 2001). Current treatments for bone loss are autograft procedures, allograft procedures or bone graft substitutes such as metals and ceramics (Mourino and Boccaccini 2010; Porter et al. 2009). Such procedures are limited due to restricted availability and have high rates of complications such as donor site morbidity, pain, deep infections, hematomas, inflammations, and immune rejection (Khan et al. 2008; Salgado et al. 2004). Bone tissue engineering, involving scaffolds, cells and growth factors, has emerged as an alternative approach to bone grafting that could overcome the above mentioned problems. Scaffolds for tissue engineering should be porous, three-dimensional, biocompatible and provide an environment that enables cells to pr
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