Scientists at the Royal College of Surgeons Ireland (RCSI) University of Medicine and Health Sciences say they have developed a new biomaterial that has the potential to accelerate bone regeneration by promoting an immune response that encourages repair and lowers the risk of inflammation.

The study “Rapid bone repair with the recruitment of CD206+M2-like macrophages using non-viral scaffold-mediated miR-133a inhibition of host cells,”conducted by researchers at RCSI Tissue Engineering Research Group (TERG) and AMBER, the SFI Research Centre for Advanced Materials and BioEngineering Research, is published in Acta Biomaterialia.

“microRNAs offer vast therapeutic potential for multiple disciplines. From a bone perspective, inhibition of miR-133a may offer potential to enhance Runx2 activity and increase bone repair. This study aims to assess the therapeutic capability of antagomiR-133a delivery from collagen-nanohydroxyapatite (coll-nHA) scaffolds following cell-free implantation in rat calvarial defects (7 mm diameter). This is, to the best of our knowledge, the first report of successful in vivo antagomiR uptake in host cells of fully immunocompetent animals without distribution to other off-target tissues,” write the investigators.

“Our results demonstrate the localized release of antagomiR-133a to the implant site at 1 week post-implantation with increased calcium deposits already evident in the antagomiR-133a loaded scaffolds at this early timepoint. This was followed by an approximate 2-fold increase in bone volume versus antagomiR-free scaffolds and a significant 10-fold increase over the empty defect controls, after just 4 weeks.”

“An increase in host CD206+ cells suggests an accelerated pro-remodeling response by M2-like macrophages accompanying bone repair with this treatment. Overall, this non-viral scaffold-mediated antagomiR-133a delivery platform demonstrates capability to accelerate bone repair in vivo—without the addition of exogenous cells—and underlines the role of M2 macrophage-like cells in directing accelerated bone repair. Expanding the repertoire of this platform to deliver alternative miRNAs offers exciting possibilities for a variety of therapeutic indications.”

The researchers have developed a technology that is a combination of nanoparticles and a collagen-based biomaterial called a scaffold, specifically designed by RCSI TERG that can be surgically implanted to aid bone tissue repair. The material allows for the delivery of a microRNA silencer, a molecule capable of influencing the way our cells function.

In laboratory conditions, researchers successfully demonstrated that damaged bone tissue is restored as the particular microRNA delivered by the biomaterial works to increase cells responsible for bone repair. The technology also assists in promoting a pro-repair immune system response, lowering the risk of inflammation and other complications.

“The results of our research are a promising step towards improving health outcomes for patients with fractures that fail to repair naturally or have degenerative bone diseases such as osteoporosis, although further pre-clinical and clinical trials are still required before the technology could be used to treat humans,” said Caroline Curtin, lecturer in anatomy and regenerative medicine at RCSI.

“We are confident that this biomaterial system will have several potential applications beyond bone repair, as it can be tailored to deliver other therapeutic molecules that address degenerated or diseased tissue in the body,” said Fergal O’Brien, PhD, RCSI director of research and innovation, professor of bioengineering and regenerative medicine and deputy director of the SFI AMBER Centre.

“At RCSI Tissue Engineering Research Group, we are exploring these possibilities through the development of similar methods to repair articular joints like the knee and hip, and attempting to apply the microRNA delivery systems to inhibit breast cancer cell growth and other novel research.”

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