Novel gene-encoding bio-patch that can regrow bone
A group of researchers at the University of Iowa (UI) have developed an implantable bio-patch to regenerate missing or damaged bone in a living body, using existing cells. They put DNA into a nano-sized particle that delivers bone-producing instructions directly into cells. The bio-patch could have several potential uses in dentistry and could also be used to repair birth defects in children who are missing critical areas of a bone.
The bone-regeneration kit consists of a collagen platform seeded with particles containing the genes that are necessary for bone production. The research team directly delivered bone-production instructions to existing bone cells in vivo, allowing those cells to produce the proteins that led to more bone production. The particles contain DNA molecules that encode for a platelet-derived growth factor called PDGF-B, which prompts the cells to make proteins that stimulate bone production.
In laboratory experiments, the bio-patches fully regrow enough bone to cover wounds in the skulls of live rats. Also, they stimulated new growth in human bone marrow stromal cells. Previous attempts to regrow bone relied on repeated applications of proteins, which are costly and harder to replicate consistently.
”If you deliver just the protein, you have to keep delivering it with continuous injections to maintain the dose. With our method, you get local, sustained expression over a prolonged period of time without having to give continued doses of protein”, said Aliasger Salem, professor at the UI’s College of Pharmacy.
According to the researchers, the bio-patch can have several uses in dentistry. It could be used to rebuild bone in the gum area that serves as a foundation for dental implants. This could be helpful for patients who need implants and don’t have enough bone in the surrounding area. Also, it could be used to repair birth defects where there’s missing bone around the head or face.
“We can make a scaffold in the actual shape and size of the defect site, and you’d get complete regeneration to match the shape of what should have been there”, said Satheesh Elangovan, assistant professor at the UI’s College of Dentistry.
The researchers started with the patch consisted of a collagen scaffold, which is loaded with synthetically created plasmids, each of which is outfitted with the genetic instructions for producing bone. They inserted the scaffold on to a 5-millimeter by 2-millimeter missing area of the skulls in test animals.
After four weeks, the research team compared the effectiveness of the bio-patch with inserted plasmids and the bio-patch without inserted plasmids. The bio-patch with inserted plasmids grew 44 times more bone and soft tissue in the treated area than the bio-patch alone, and it was 14 fold higher than the affected area with no manipulation.
How do plasmids work? Bone cells that are already in the body migrate into the scaffold, where they meet with the plasmid. Cells then take up the plasmid and then get the encoding to start producing previously mentioned platelet-derived growth factor PDGF-B, which enhances bone regeneration.
The team used a polymer to shrink the particle’s size and to give plasmid positive electrical charge that would make it easier for the resident bone cells to take them in. Also, plasmids don’t have viral origin, which means that they are less likely to cause an undesired immune response and are easier to produce in large quantities, which lowers the cost.
UI researchers next hope to create a bio platform that promotes growth of new blood vessels that are needed for extended and sustained bone growth.
For more information, read the article published in the journal Biomaterials: “The enhancement of bone regeneration by gene activated matrix encoding for platelet derived growth factor”.