Washington: A team of scientists have created a biodegradable scaffold that enables sustained, local delivery of gene-silencing factors called siRNA to promote tissue regeneration.
Craig Duvall, Ph.D., Assistant Professor of Biomedical Engineering at Vanderbilt University, and colleagues reported the use of a novel tissue scaffold that can deliver siRNA to nearby cells over a period of several weeks.
Using an siRNA dose 10-100-fold lower than previous studies, the research team efficiently silenced the expression of PHD2-a protein that normally inhibits blood vessel formation- locally within a biodegradable tissue scaffold.
At 33 days post-implant, the scaffolds that delivered PHD2 siRNA had a three-fold increase in the volume of local blood vessels.
To achieve sustained delivery, the researchers first packaged siRNA into nanoparticles, which protect siRNA from being degraded by enzymes found in the extracellular environment.
They then combined these nanoparticles with varying amounts of a substance called trehalose. This nanoparticle-trehalose combination was then embedded into a biodegradable tissue scaffold, which they implanted under the skin of a mouse.
Trehalose acts as a porogen, meaning it creates pores in the tissue scaffold. As a result, the rate at which nanoparticles are released from the scaffold is directly influenced by the amount of trehalose added. Based on the quantity of trehalose, the system can be tuned to release the nanoparticles to the surrounding cells immediately or over a period of several weeks.
The study has been published online in journal Advanced Materials.
