TY - JOUR

T1 - Functionalized PLGA-doped zirconium oxide ceramics for bone tissue regeneration

AU - Lupu-Haber, Yael

AU - Pinkas, Oded

AU - Boehm, Stefanie

AU - Scheper, Thomas

AU - Kasper, Cornelia

AU - Machluf, Marcelle

N1 - Funding information: Acknowledgments The research was supported by the Niedersachsen Foundation. The partial support of the Russell Berrie Nanotechnology Institute, Technion–Israel Institute of Technology (IIT), is thankfully acknowledged. bFGF was kindly donated by Prof. Gera Neufeld, from the Department of Anatomy and Cell Biology, Faculty of Medicine, IIT. BMP2 was kindly donated by Prof. Walter Sebald, from Biozentrum University, Würzburg, Germany. We further wish to thank Ilana Schoenbrun for her technical assistance.

PY - 2013/7/28

Y1 - 2013/7/28

N2 - 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.

AB - 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.

KW - BMP2

KW - Bone tissue engineering

KW - Drug delivery

KW - PLGA

KW - Scaffold

UR - http://www.scopus.com/inward/record.url?scp=84890570604&partnerID=8YFLogxK

U2 - 10.1007/s10544-013-9797-1

DO - 10.1007/s10544-013-9797-1

M3 - Article

C2 - 23893013

AN - SCOPUS:84890570604

VL - 15

SP - 1055

EP - 1066

JO - Biomedical microdevices

JF - Biomedical microdevices

SN - 1387-2176

IS - 6

ER -