Bio Patch Designed to Regrow Bone

Scientists have created a bio patch to regenerate missing or damaged bone by putting DNA into a nanosized particle that delivers bone-producing instructions right into cells.

The bone-regeneration strategy relies on a collagen platform seeded with particles containing the genes required for generation bone. In lab research, the gene-encoding bio patch effectively regrew bone adequately enough to cover skull wounds in test animals. Moreover, it triggered new growth in human bone marrow stromal cells in the lab.

The study is innovative in that the researchers directly delivered bone-producing directives (using piece of DNA that encodes for a platelet-derived growth factor called PDGF-B [platelet-derived growth factor B subunit]) to existing bone cells in vivo, allowing those cells to produce the proteins that led to more bone production. Earlier efforts had relied on repeated applications from the outside, which is expensive, intensive, and more complicated to replicate consistently.

“We delivered the DNA to the cells, so that the cells produce the protein and that’s how the protein is generated to enhance bone regeneration,” explained Dr. Aliasger Salem, a professor in the University of Iowa’s (UI; Iowa City, USA) College of Pharmacy and a co-corresponding author on the paper, planned for publication in the January 2014 issue of the journal Biomaterials. “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.”

The researchers think the patch has several potential uses in dentistry. For example, it could be used to rebuild bone in the gum area that serves as the concrete-like underpinning for dental implants. That possibility would be a “life-changing experience” for patients who need implants and do not have enough bone in the surrounding area, according to Dr. Satheesh Elangovan, assistant professor in the UI’s College of Dentistry and a joint first author, as well as co-corresponding author, on the article. It also can be used to repair birth defects where there is missing bone around the face or head. “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,” Dr. Elangovan stated.

The investigators started with a collagen scaffold. The researchers then loaded the bio patch with synthetically created plasmids, each of which is supplied with the genetic instructions for producing bone. They then inserted the scaffold on to a 5-mm x 2-mm missing region of skull in test animals. Four weeks later, the researchers compared the bio patch’s effectiveness to inserting a scaffold with no plasmids or taking no action at all.

The plasmid-seeded bio patch grew 44-times more bone and soft tissue in the affected area than with the scaffold alone, and was 14-fold higher than the affected area with no manipulation. Aerial and cross-sectional scans showed the plasmid-encoded scaffolds had encouraged enough new bone growth to nearly close the wound area, the researchers report.

The plasmid performs by entering bone cells already in the body, typically those located right around the damaged area that wander over to the scaffold. The team used a polymer to shrink the particle’s size (i.e., such as creating a zip file) and to give the plasmid the positive electrical charge that would make it easier for the resident bone cells to take them in. “The delivery mechanism is the scaffold loaded with the plasmid,” Dr. Salem stated. “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.”

The researchers also stressed that their delivery strategy is nonviral, meaning the plasmid is less apt to cause an undesired immune response and is easier to generate in mass quantities, which lowers the cost. “The most exciting part to me is that we were able to develop an efficacious, nonviral-based gene-delivery system for treating bone loss,” said Sheetal D'mello, a graduate student in pharmacy and a joint first author on the article.

The scientists next phase of their research will be to create a bio-platform that spurs new blood vessel growth, needed for extended and sustained bone growth.

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