Development of innovative biopolymers and related composites for bone tissue regeneration: study of their interaction with human osteoprogenitor cells.

Purpose: In the framework of a project aiming to improve the properties of poly(?-caprolactone) (PCL)-based devices, we prepared novel composites and tested their in vitro biocompatibility and osteogenic capacity on human mesenchymal stromal cells (MSC) from bone marrow. Methods: We prepared two functionalized derivatives, PCL-g-MAGMA and PCL-DMAEA, by insertion of anhydride groups by radical grafting of maleic anhydride (MA) and glycidyl-methacrylate (GMA) molecules, and by insertion of N-(dimethylamino) ethylacrylate (DMAEA) of tertiary amines groups, respectively. In addition, in order to improve the osteoconductive properties of the materials, we also prepared the corresponding composites containing the mineral component of bone, namely hydroxyapatite (HA). Mesenchymal stromal cells (MSC) derived from bone marrow were prepared, plated onto a number of discs obtained from these functionalized derivatives and tested in terms of adhesion and vitality (by MTT test and SEM observation), and the expression of alkaline phosphatase, the early marker of osteoblastic phenotype. Results: The biological in vitro assessment of the functionalized materials, PCL-g-MAGMA and PCL-DMAEA appeared promising only in part, in particular the cells exhibited very poor adhesion to PCL-MAGMA. On the contrary, the related composites, PCL-g-MAGMA-HA and PCL-DMAEA-HA clearly showed that the addition of HA greatly ameliorated the cell-material interaction. In particular, a surprisingly increased response characterized PCL-g-MAGMA-HA, either in terms of adhesion and vitality or in terms of alkaline phosphatase activity. Conclusions: Altogether these studies showed that the addition of HA nanowhiskers resulted for all basic materials, in particular PCL-MAGMA, in improved cell adhesion and performance.