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.

Multiscale fluid–structure interaction modelling to determine the mechanical stimulation of bone cells in a tissue engineered scaffold

“…Current bone tissue engineering (TE) approaches involve growing mesenchymal stem cells (MSCs) under in vitro conditions on either natural or synthetic biomaterial scaffolds. Using such approaches, it has been shown that MSCs can differentiate along the osteogenic pathway in the presence of various biochemical factors and various biomaterial scaffolds, for example PLGA and collagen, and can elicit tissue differentiation in vitro that is indicative of bone formation (Lupu-Haber et al 2013;Li et al 2013;Park et al 2012;Xie et al 2013;Vozzi et al 2013). However, existing TE approaches have not been able to regenerate tissue in vitro that can be used clinically to replace degenerated bone, support loading and enhance the growth and differentiation of new bone tissue in vivo.…”

In vitro and in vivo characterization of a novel tricalcium silicate-based ink for bone regeneration using laser-assisted bioprinting

“…It was therefore difficult to retrieve the printed cells to perform a reliable cell counting, and cell proliferation was assumed to be equivalent to control, since the same amount of cells were printed in each condition at the start of the experiment. In vitro, even though literature suggested that BioRoot RCS® might induce angiogenesis [54], zirconium oxide (ZrO 2 ) (which accounts for 5% of BioRoot RCS® powder composition, according to the manufacturer), was reported to have a cytotoxic effect on HUVECs (figure S2) [27] but did not affect SCAPs metabolism, whatever the applied quantity. Thus, only the influence of LAB-delivered dose of MI was assessed for the rest of the experimental study.…”

“…Zirconium oxide (ZrO 2 ), the radio-opacifier element, is used for clinical follow-up of the BioRoot RCS®. ZrO 2 was found to be not only non-cytotoxic at least for MSCs [27], but also to upregulate osteogenic-related genes [28]. Altogether, the BioRoot RCS® seemed to be a great candidate to promote bone repair, offering both a solid substrate as osteoconductive support by its physical properties, and an osteoinducer material based on its mineral composition enhancing osteogenic cell lines potentials.…”

Polymeric microspheres: a delivery system for osteogenic differentiation

“…ZrO 2 scaffold turned brown because of high calcium deposition after 60 days. [31] PLGA MSs loaded with rhBMP-2 and fluorinated fingolimod GF in microgel scaffold composed of chitosan and inorganic phosphates improved defect vascularization and bone formation in critical-size cranial defects of Sprague Dawley rats. [32] Other GFs like TGF, BMP-7, IGF, and BGF are also coated on PLGA MS. Osteogenic markers like collagen 1 (Col-1), Cbfa1, and OCN expression from hMSC embedded in dexamethasone (DEX) nanosphere-coated MSs carrying BMP-7 are significantly higher than TGFb3 and IGF/bFGF groups.…”

“…BMP‐2 loaded MS after 2 weeks of treatment of hMSC showed increased expression of collegen‐I and osteogenin genes that suggest osteogenic differentiation. ZrO 2 scaffold turned brown because of high calcium deposition after 60 days . PLGA MSs loaded with rhBMP‐2 and fluorinated fingolimod GF in microgel scaffold composed of chitosan and inorganic phosphates improved defect vascularization and bone formation in critical‐size cranial defects of Sprague Dawley rats …”