Functionalized PLGA-doped zirconium oxide ceramics for bone tissue regeneration

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.