Magnetically-directed nanoparticles could help heal broken bones

When a bone is severely broken in the human body, or a bone-fused prosthesis is implanted, a bone graft is also often required to ensure a solid mechanical repair. However, a graft that removes bone from another area of the body can be a painful and invasive procedure, and the mechanical stimulation required for continued bone regeneration in post-operative therapy becomes problematic if a patient is severely immobilized. To address these problems, researchers have discovered that coating magnetic nanoparticles with proteins and then directing them magnetically to the site of the injury can help stimulate stem cells to regenerate bone.

Bones that have been grafted are best healed using methods of dynamic loading – that is, movement and exercise – to promote what is known as mechanotransduction, where the physical bonding and subsequent mechanical stimulation of grafted bone causes a cascade effect of biochemical signals, hormone release, stem cell regeneration, tissue growth, and a myriad other processes that all combine to ensure efficient repair.

Unfortunately, when complications, such as the immobilization of a patient, precludes the application of dynamic loading or a medical condition, such as a skeletal disorder, means that they simply lack the extra bone required for grafting, then recovery is often a long, slow, complicated process that is all too often partially or completely unsuccessful.

The coated magnetic nanoparticle method used by medical researchers from Keele and Nottingham universities in the UK, however, is claimed to be able to direct materials straight to an injury site without the need for surgery. It is then possible to remotely manipulate the nanoparticles to produce mechanical forces and maintain the bone regeneration process through the delivery of stem cells and a staged release of a growth stimulating protein.

"Injectable therapies for regenerative medicine show great potential as a minimally invasive route for introducing therapeutic stem cells, drug delivery vehicles and biomaterials efficiently to wound sites," said James Henstock, Ph.D. who led the study. "In our investigation we coated magnetic nanoparticles with specific targeting proteins then controlled them remotely with an external magnetic field to simulate exercise. We wanted to learn how this might affect the injected stem cells and their ability to restore functional bone."

The initial trials of this method were conducted on fetal chicken femurs (thigh bones) and tissue-engineered collagen hydrogel (animal structural protein suspended in a high water content polymer). In both cases, the researchers claim that there was a marked increase in bone development and density without causing any mechanical stress to the construct or surrounding tissue.

"This work demonstrates that providing the appropriate mechanical cues in conjunction with controlled release of growth factors to these injectable cell therapies can have a significant impact on improving bone growth," said Dr. Henstock. "It also could potentially improve tissue engineering approaches for translational medicine."

The unique upshot of this research is not that it is just another use for magnetic nanoparticles, which also hold potential in cleaning up oil spills, improving cancer detection and helping shrink digital storage bulk. This time, nanoparticles are being used for both their unique physical properties in aiding mechanical stimulation and providing the potential for targeted biomaterial delivery as a total medical solution in a single package.

The research was a Biotechnology and Biological Sciences Research Council (BBSRC)-funded study led by James Henstock, Ph.D., in collaboration with Alicia El Haj, Ph.D., and colleagues at Keele University’s Institute for Science and Technology in Medicine, and Dr. Kevin Shakesheff, from the University of Nottingham’s School of Pharmacy.

The research was recently published in the journal Stem Cells Translational Medicine.

Source: Keele University