Novel Dendrimer nanoparticles for iPS generation in bone and cartilage regeneration

Promising formulations for bone and cartilage regeneration comprise the use of edge nanotechnology such as dendrimers.  Dendrimers can act as drug delivery systems for controlling cellular fate from inside cells by being engineered for its chemistry, bioavailabitility and biocompatibility (1). They also allow the design of interfaces with various classes of biochemically-active functional groups. Indeed, other polymeric nanoparticles have already been reported and studied as carriers for drugs, gene, and image contrast agents, therefore finding many possibilities in tissue engineering and regenerative medicine. The aim of this project is to develop carboxymethylchitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles  for the intracellular delivery of genetic material: recent synthetic gene vector Minicircle carrying factors such as Oct4, Sox2, NANOG and Lin28) for iPS cell Reprogramming (2). iPS constitutes an exciting new field that created powerful new opportunities for modeling human diseases and offers hope for personalized regenerative cell therapies (3).

Studies on the internalization and cellular trafficking of the dendrimer nanoparticles achieved by grafting fluorescent label probes such as Fluorescein -5(6)-isothiocyanate (FITC) have been done (4). After confirming their pluripotency iPS cells will be cultured in osteogenic and chondrogenic differentiation medium (2D) and will then be seeded in hydroxyapatite and polymeric gellan gum-based scaffolds (3D) and investigated for their osteogenic and chondrogenic potential  in vitro and in vivo. Also iPS cells will be cultured in the presence of Dex-loaded CMCht/PAMAM dendrimer nanoparticles followed by overnight seeding in the previous mentioned scaffolds and subcutaneous implantation in a rat model.