One-Step Fabrication of Bone Morphogenetic Protein-2 Gene Activated, Porous Poly-L-Lactide Scaffold for Bone Induction

Publication date: Available online 7 September 2017
Source:Molecular Therapy - Methods & Clinical Development
Author(s): Jingwen Xue, Hang Lin, Allison Bean, Ying Tang, Jian Tan, Rocky S. Tuan, Bing Wang
Bone morphogenetic protein 2 (BMP2) is an efficacious inducer for the osteogenesis of mesenchymal stem cells (MSCs). Conventional applications of BMP2 have involved either the direct incorporation of BMP2 protein or ex vivo BMP2 gene transfer into stem cells prior to their transplantation. These approaches are able to promote bone formation to some extent, however are hampered either by the lack of stability and sustainability of BMP2 protein or by the time-consuming and cost-prohibitive in vitro cell culture procedure. To overcome these limitations, we have developed a gene-activated poly-L-lactide acid (PLLA) scaffold with the encapsulation of recombinant adeno-associated viral (AAV) vector encoding a full-length cDNA of human BMP2, using an ice-based microparticle porogenization method that was recently developed. Results showed continuous release of AAV particles from the micropores of scaffolds for up to 1 week, subsequently transducing embedded human MSCs and producing functional BMP2. MSCs within scaffolds underwent efficacious osteogenesis, on the basis of osteoinductive gene expression and osteogenic differentiation, which resulted in robust new bone formation in vivo at 4 weeks. These findings show the potential of the technology towards developing clinical applications of a rapid, cost-effective and potentially point-of-care approach for the repair of bone defects.



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