In a recent study published in Nanomedicine by a group of researchers from both Keele University and the University of Nottingham in the United Kingdom, magnetic nanoparticles (MNPs) were used to enable Frizzled stimulation - a process that has a direct effect on accelerating mineralized matrix formation. This repair process has been shown to upregulate tissue formation during bone fracture repair processes, therefore this study has demonstrated promising results for future clinical applications.
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The Process of Bone Fracture Repair
There are two principle mechanisms in which bone fracture repair occurs, of which include primary bone healing, which is a less commonly seen mechanism of repair, and secondary bone healing that can be divided into four main steps. The four main steps of secondary bone healing include:
- The formation of a hematoma (a localized collection of blood) at the site of the fracture, which typically results in inflammation and osteocyte death at the site.
- Cartilaginous and granulation tissue surrounds the fracture site to serve as a splint for the fracture for 3-4 weeks. During this time, blood capillaries arise in the hematoma, which is followed by the invasion of phagocytic cells that clean up any debris remaining at the site of the injury.
- Osteoblasts and osteocytes replicate to transform the fibrocartilaginous calluses into bony calluses.
- Excess material of the bony calluses is removed and compact bone is laid down to remodel the bone.
During these repair processes, adequate blood supply to the site of the fracture plays an important role in the repair process, as this blood contains nutrients and oxygen that ensure repair can occur. When there is a lack in adequate blood flow or stability through the use of compression, tension or torsion methods during bone fracture repair, impaired or delayed healing of bones can result.
The Use of Nanoparticles in Bone Repair
Currently, the primary materials used for bone fracture repair include bone, bone cement, metal, ceramics and polymer. While these materials are typically inexpensive and exhibit good hardening properties for bone repair, they also have their individual limitations, such as poor flexibility and resistance. A number of clinical applications of nanomaterials for the repair or regeneration of bone tissue has been shown to improve vascularization and immobilize growth factors in bone fracture repair. Some examples include:
- The use of fluorescent nanoparticles, such as quantum dots and upconversion nanoparticles, to track mesenchymal stem cells (MSCs) both in vitro and in vivo
- Gold nanoparticles to promote the differentiation of MSCs toward osteoblast cells
- The delivering of nanoengineered cells to target tissues for regenerative therapy in bone fracture repair1
The use of ‘smart’ nanomaterials, such as magnetic nanoparticles, have been postulated as an innovative approach in improving the overall performance of bone fracture materials. Magnetic fields have the potential to change the physiological and biochemical processes in cells by changing their natural charge particle movement and permeability of the cell membrane. Therefore, the use of magnetic nanoparticles has the potential to deliver mechanical stimuli through a direct targeting of the cell-surface.
Magnetic Nanoparticles and the Wnt Pathway
Wnt proteins play an important role in the aforementioned bone repair process, as they can affect the polarity and differentiation of cells, thereby affecting their behavior. While researchers have found that initiating the overexpression of Wnt proteins accelerates the bone repair process, its use has thus far been limited as a result of the complex and expensive production methods associated with this protein. In the Nanomedicine study, researchers conjugated MNPs with UM206, a synthetic peptide and ligand for the Wnt protein receptor2. By initiating the Frizzled signal transduction, the researchers demonstrated that the peptide conjugated MNPs are capable of regulating controlled bone tissue formation.
The ease of production and reduced expenses associated with the production of magnetic nanoparticles allows this approach to have a promising future in clinical applications. The conjugated MNPs can be activated by an external magnet, which also provides an additional degree of external control and temporal regulation to activating the Wnt pathway. The researchers in this study are not only hopeful that these MNPs will have a future in bone tissue engineering for fracture repair, but could also be successful for reducing the invasiveness of injectable cell therapies.