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Gene-activated constructs lead to accelerated bone healing

(12.09.2018)

Dr Ara Hacobian, head of the molecular biology group at the LBI for Experimental and Clinical Traumatology, has exciting research findings to share. As he recently published in the Journal of Controlled Release, a genetically optimized BMP-2 plasmid enhances the functionality of a gene-activated construct, leading to accelerated bone healing.

The gene activated construct consists of chitosan nanoparticles embedded in a bone mimicking collagen-hydroxyapatite scaffold. The nanoparticles carry plasmid DNA, coding for bone morphogenetic proteins (BMPs).

Plasmids – small, double-stranded circular DNA pieces that can replicate autonomously – are an important tool in molecular biology. They are used to express genes and form proteins, such as BMPs which are potent mediators of osteogenesis (bone-formation). Through genetic engineering of a plasmin, such as optimization of the gene sequence or the addition of certain non-coding gene sequences (introns), the efficiency of a plasmid can be enhanced. The team around Dr. Hacobian inserted a genetically modified BMP-2 plasmid (BMP-2-Advanced plasmid) into mesenchymal stem cells. This lead to an increase in BMP-2 formation and thus an improved osteogenesis rate. Moreover the insertion of the BMP-2-Advanced plasmid in a collagen-hydroxyapatite scaffold resulted in significantly higher calcium production.

Only four weeks after implantation into vital bone, µCT imaging showed an equally significant increase in bone tissue formation. Further experiments proved that the BMP-2-Advanced plasmid promoted the differentiation of bone progenitor cells to osteoblasts, resulting in fast healing of the bone defect. The study confirms that by optimizing the plasmid construct, the functionality of a gene-activated construct can be enhanced, leading to accelerated bone healing after injury.