Microfluidic nanocomplex-based localized gene delivery platform for bone tissue engineering.

Atefeh Malek-khatabi,1,* Hamid akbari javar,2 Mohammad mahdi hasani-sadrabadi ,3

1. Department of Pharmaceutical biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences.
2. Department of Pharmaceutical biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences.
3. California NanoSystems Institute, University of California, 570 Westwood Plaza



Annually more than 2.2million bone graft procedures take place in worldwide. biomaterials-based bone tissue engineering as a solution for bone regeneration has attracted significant interest due to its potential in reducing the costs and surgical trauma affiliated with the treatment of bone defects.


Gene therapy is an effective method of bone regeneration, in such a way that uses plasmid dna to encode the common growth factors like human bone morphogenetic protein-2 (hbmp2). hbmp2-plasmid (p-hbmp2) causes to a longer bioavailability of the protein, and the resulting protein will have a better post-translational modification and tertiary structure formation as it is produced in-vivo and it also stimulates human bone marrow mesenchymal stem cells (hbmmscs) to differentiate to osteoblastic lineage. likewise, p-hbmp2 obviates some disadvantages of hbmp2 such as high cost and short half-life.


In this study, a microfluidic platform has been developed to synthesis chitosan-based nanoparticles (csnps) in order to encapsulate p-hbmp2 through ionic gelation which will provide a sustained release of the target gene over two weeks. the release regimes can be tuned by controlling the size and compactness of csnps. csnps immobilized on the surface of electrospun polycaprolactone nanofiber scaffold to induce a long-term gene expression of hbmp2 by cultured hbmmscs.


Osteogenic differentiation of cells was also achieved by the overexpression of hbmp2 as well as other osteogenic markers (runx-2, col-1 and ocn) in medium free of osteogenic supplementation. in-vivo results also confirmed the functionality of engineered delivery system which can be implemented toward next-generation bone tissue regeneration.


Microfluidic nanoparticles. gene delivery. stem cell differentiation. bone tissue engineering.