Chitosan-chondroitin sulphate nanoparticles for controlled delivery of platelet lysates in bone regenerative medicine

In this study, a new formulation of nanoparticles (NPs) based on the electrostatic interaction between chitosan and chondroitin sulphate (CH-CS NPs) is proposed for the controlled release of proteins and growth factors (GFs), specifically platelet lysates (PLs). These nanoparticulate carriers are particularly promising for protein entrapment because the interactions between the polysaccharides and the entrapped proteins mimic the interactions between chondroitin sulphate and proteins in the native extracellular matrix (ECM). Spherical non-cytotoxic NPs were successfully produced, exhibiting high encapsulation efficiency for physiological levels of GFs and a controlled protein release profile for > 1 month. Moreover, it was also observed that these NPs can be uptaken by human adipose-derived stem cells (hASCs), depending on the concentration of NPs in the culture medium and incubation time. This shows the versatility of the developed NPs, which, besides acting as a protein delivery system, can also be used in the future as intracellular carriers for bioactive agents, such as nucleotides. When the PL-loaded NPs were used as a replacement of bovine serum for in vitro hASCs culture, the viability and proliferation of hASCs was not compromised. The release of PLs from CH-CS NPs also proved to be effective for the enhancement of in vitro osteogenic differentiation of hASCs, as shown by the increased levels of mineralization, suggesting not only the effective role of the delivery system but also the role of PLs as an osteogenic supplement for bone tissue engineering and regenerative medicine applications.