Scientists at Penn State developed a method to print a ‘bone’ construct during a surgical procedure. The technique is intended to allow surgeons to rapidly fill bony defects that would not easily heal by themselves, and the researchers have turbo-charged the technique by including genes that promote bone formation. Consequently, they describe the resulting printed bioconstruct as a “gene-activated matrix”. The genes include platelet derived-growth factor (PDGF-B), which stimulates nearby cells to invade and proliferate within the construct, and bone morphogenetic protein (BMP-2), which stimulates bone formation. The technique could allow for long-term healing, as the genes are expressed by cells within the construct for a long time.
Getting large defects in bone to heal is a challenge, and scientists have spent a long time testing different biomaterials in this context with the aim of creating a ‘scaffold’ that can support and encourage the body’s own cells during bone healing. They have have also begun experimenting with incorporating genetic material into biomaterial implants to enhance the healing process and guide cells down a desired path.
Typically, biomaterials involve pre-formed constructs that must be cut to fit the area they are implanted in. However, this new approach is interesting in that it involves bioprinting directly into the defect during surgery, which could be more convenient and allow a surgeon to easily fill irregular defects.
“Growth factors are essential for cell growth,” said Ibrahim Ozbolat, one of the developers of the new technique. “We use two different genes encoding two different growth factors. These growth factors help stem cells to migrate into the defect area and then help the progenitor cells to convert into bone.”
The genes were delivered in the form of plasmids, which are small loops of DNA that are typically found in bacteria. The researchers cleverly designed the construct to release the genes over different periods, helping to mimic the biochemical cascades and sequential gene expression that naturally occur during physiological processes in the body. The PDGF-B was delivered as a simple plasmid, enabling it to be released rapidly over the space of 10 days. However, the BMP-2 was encapsulated in chitosan nanoparticles, which allowed for a much longer release of 5 weeks.
So far, the Penn State team tested the technology in a bony defect rat model, and found that the gene-activated material enabled approximately 90% bone coverage of a bony defect over a six week period, compared with only 25% in control rats who received no treatment.
Study in journal Biomaterials: Controlled Co-delivery of pPDGF-B and pBMP-2 from intraoperatively bioprinted bone constructs improves the repair of calvarial defects in rats
Via: Penn State