Research led by the University of Iowa has tested a "bio patch" that regenerates missing or damaged bone by inserting DNA into nano-sized particles to deliver bone-making genetic instructions directly into cells.
The method succeeded in regrowing enough bone to fully cover skull wounds in live rats. And, in test tubes, it also stimulated new growth in human bone marrow stromal cells.
Using pieces of DNA that encode for a platelet-derived growth factor called PDGF-B, the researchers delivered genetic instructions directly into living bone cells, causing them to make the proteins that lead to more bone production.
They report their work in the latest issue of the journal Biomaterials.
DNA delivered directly into cells
While other researchers have also reported success in encouraging new bone regrowth, they relied on repeated applications that deliver the bone-making proteins from the outside which is costly, intensive and has to be done again and again.
This study is different because it tackled cells from the inside, causing them to produce proteins that led to more bone growth.
Corresponding author Aliasger Salem, professor at Iowa's College of Pharmacy, explains the benefit of directly delivering the DNA to cells:
"If you deliver just the protein, you have 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."
Nano-sized plasmids carry the genetic instructions for making bone
To make their bio patch the team made a scaffold from collagen then seeded it with synthetically made, nano-sized plasmids, each carrying DNA pieces of genetic instructions for making bone.
The researchers then placed DNA-seeded and unseeded scaffolds onto small 5mm x 2 mm holes in the skulls of rats. They found after four weeks that the seeded scaffolds grew 44 times more bone and soft tissue than unseeded scaffolds and 14 times more than untreated wounds.
Scans also revealed that the seeded scaffolds resulted in new bone growth that nearly closed the wound.
The plasmids enter bone cells already present in the body. These are located near the wound site and drift over to the scaffold. The researchers found the plasmids transport easily into cells once they are shrunk in size and given a positive electrical charge.
Prof. Salem explains:
"The delivery mechanism is the scaffold loaded with the plasmid. When cells migrate into the scaffold, they meet with the plasmid, they take up the plasmid and they get the encoding to start producing PDGF-B, which enhances bone regeneration."
Potential applications in dentistry
The researchers say their bio patch could be used in dentistry to rebuild bone in gum areas to provide foundations for dental implants. This would be of great benefit to patients who need implants but do not have enough bone in the surrounding area.
Another potential use for the bio patch could be to repair birth defects where bone is missing, for instance around the head or face.
The bio patch could be made in the shape and size of the defect site so when the new bone grows it is a perfect fit.
The researchers are now working on a way to adapt the techniques to generate new blood vessels to support bone growth.
Funds from the International Team for Implantology, the National Cancer Institute at the National Institutes of Health and the American Cancer Society helped to finance the research.
Earlier this year, UK researchers reported in the journal Advanced Functional Materials how they were working on a method that would one day use stem cells and plastic to mend broken bones. The techique would grow new bone from patients' own stem cells that attached themselves to an implanted plastic scaffold that gradually degrades as the new bone regenerates.