CONTROLLED RELEASE OF BIOLOGICAL FACTORS FOR PROGENITOR CELL-MEDIATED ENDOGENOUS REPAIR OF INTERVERTEBRAL DISCS

The recent description of progenitor/stem cells in degenerated intervertebral discs (IVDs) raised the possibility of harnessing their regenerative capacity for endogenous repair. The aim of this work is to develop an intradiscal polysaccharide microbead-based delivery system for the sequential release of chemokines and nucleopulpogenic factors. This delivery system would sequentially contribute to 1) the recruitment of resident progenitors (CXCL12 or CCL5), 2) the differentiation of the mobilized progenitors (TGF-β1 and GDF5), and 3) the subsequent regeneration of NP. To determine the effects of chemokines on in vitro cell recruitment, human mesenchymal stem cells (MSC) were cultured in Transwells for 4h, with or without CXCL12 or CCL5. In parallel, pullulan microbeads (PMBs) (100µm) were prepared by a simultaneous crosslinking protocol coupled to a water-in-oil emulsification process. Freeze-dried PMBs were loaded with biological factors then release assays were performed at 37°C for 21 days and supernat...