Poly-cyclodextrin functionalized porous bioceramics for local chemotherapy and anticancer bone reconstruction.

The progress in bone cancer surgery and multimodal treatment concept achieve only modest improvement in the overall survival, due to failure in clearing out residual cancer cells at the surgical margin and extreme side-effects of adjuvant postoperative treatments. Our study aims to propose a new method based on cyclodextrin polymer (polyCD) functionalized hydroxyapatite (HA) for achieving a high local drug concentration with a sustained release profile and a better control of residual malignant cells via local drug delivery and promotion of the reconstruction of bone defects. PolyCD, a versatile carrier for therapeutic molecules, can be incorporated into HA (bone regeneration scaffold) through thermal treatment. The parameters of polyCD treatment on the macroporous HA (porosity 65%) were characterized via thermogravimetric analysis. Good cytocompatibility of polyCD functionalized bioceramics was demonstrated on osteoblast cells by cell vitality assay. An antibiotic (gentamicin) and an anticancer agent (cisplatin) were respectively loaded on polyCD functionalized bioceramics for drug release test. The results show that polyCD functionalization leads to significantly improved drug loading quantity (30% more concerning gentamicin and twice more for cisplatin) and drug release duration (7 days longer concerning gentamicin and 3 days longer for cisplatin). Conclusively, this study offers a safe and reliable drug delivery system for bioceramic matrices, which can load anticancer agents (or/and antibiotics) to reduce local recurrence (or/and infection).

Optimization of culture conditions for osteogenically-induced mesenchymal stem cells in ß-tricalcium phosphate ceramics with large interconnected channels.

The aim of this study was to optimize culture conditions for human mesenchymal stem cells (hMSCs) in ß-tricalcium phosphate ceramics with large interconnected channels. Fully interconnected macrochannels comprising pore diameters of 750 µm and 1400 µm were inserted into microporous ß-tricalcium phosphate (ß-TCP) scaffolds by milling. Human bone marrow-derived MSCs were seeded into the scaffolds and cultivated for up to 3 weeks in both static and perfusion culture in the presence of osteogenic supplements (dexamethasone, ß-glycerophosphate, ascorbate). It was confirmed by scanning electron microscopic investigations and histological staining that the perfusion culture resulted in uniform distribution of cells inside the whole channel network, whereas the statically cultivated cells were primarily found at the surface of the ceramic samples. It was also determined that perfusion with standard medium containing 10% fetal calf serum (FCS) led to a strong increase (seven-fold) of cell numbers compared with static cultivation observed after 3 weeks. Perfusion with low-serum medium (2% FCS) resulted in moderate proliferation rates which were comparable to those achieved in static culture, although the specific alkaline phosphatase (ALP) activity increased by a factor of more than 3 compared to static cultivation. Gene expression analysis of the ALP gene also revealed higher levels of ALP mRNA in low-serum perfused samples compared to statically cultivated constructs. In contrast, gene expression of the late osteogenic marker bone sialoprotein II (BSPII) was decreased for perfused samples compared to statically cultivated samples.