Bone breakages are a common injury worldwide. Some of these heal readily, whereas other injuries do not and this leads to long-term injuries and this risk of disability. Slow-healing or non-healing bone fractures in otherwise healthy people may be caused by gene variants.
With the more problematic cases, figures for the U.S. suggest there are over 100,000 broken bone incidences each year that fail to heal properly. The outcome of this is nonunion fractures. The term is reserved for permanent failures of healing following a broken bone. It relates to serious complication of a fracture and may occur when the fracture moves too much. There are two main types:
Hypertrophic non-union: Here a callus is formed, but the bone fractures have not joined.
Atrophic non-union: In this case no callus is formed. This is often due to impaired bony healing.
To overcome the nonunion fractures globally it has been estimated that medics perform over 2 million bone grafts in attempts to treat these challenging injuries. This level is anticipated to rise as the global population becomes older; one recent study into the incidence and costs of osteoporotic fractures in China found that the cases would double by 2035
A bone graft is a surgical procedure used to fix problems with bones or joints. The process involves the transplanting of bone tissue and this helps to fix bones that are damaged from trauma. Grafting is additionally useful for growing bone around an implanted device (an example is with a total knee replacement).
The process of bone grafting involves harvesting fresh bone from patients. The process can be unpleasant for the patient and painful. A further concern is that the donated grafts provided by tissue banks often fail to integrate.
To overcome this problem, Dr. Maxim Bez has come up with a two-step gene therapy method. The process also uses am FDA-approved ultrasound system (the deployment of sound waves with frequencies higher than the upper audible limit of human hearing). The ultrasonics create microbubbles (or ‘colloidal bubbles’). Microbubbles are a type of bubble smaller than one millimeter in diameter. They have begun to be used in both life sciences and medicine. The composition of the bubble shell and filling material determine factors like buoyancy, crush strength, thermal conductivity, and acoustic properties. For drug delivery, microbubbles have been used to release drugs at target sites. This happens when ultrasonic waves trigger the release and local delivery of drugs from the microbubble shell.
To test out the new system, Bez’s research team used pigs and the results demonstrate that the process fully-healed nonunion fractures in pigs, with complete healing occurring within eight weeks of treatment.
For the research, as Medicine India reports, the scientists placed a collagen scaffold at the site of the bone break. This served as a niche for bone progenitor cells (a biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell). Following this the scientists injected microbubbles that had been mixed with genetic material, with the genetic material functioning as a bone growth factor. Next pulses of sound from an ultrasound wand led to the uptake of the growth factor DNA by progenitor cells. This served to stimulate bone growth.
What was novel about the new process was that, in contrast to other gene therapies which use viral vectors, the ultrasound and microbubbles did not trigger inflammation. As well as the risk of inflammation from viral vectors, the use of viruses can also lead to integration into the genome which could lead to the development of cancer.
The research assessment is that the technique was minimally invasive, safe, and it successfully promoted total bone healing. The time taken to achieve this was equal to or better than bone grafting. The next step is to further develop the method and then lead into human trials. Here it is hoped that as well as reducing hospitalization terms the technology should result in fewer cases of disability and well as reduce the costs placed on the health system.
The research is published in the journal Science Translational Medicine with the research titled “In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs.”
Essential Science
This article is part of Digital Journal’s regular Essential Science columns. Each week Tim Sandle explores a topical and important scientific issue. Last week we reviewed research into Parkinson’s disease that suggested the progression of the disease can be controlled through the use of antibiotics. The week before we found out what the rings of Saturn sounded like thanks to some audio files released by NASA.
