The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues.

We report indirect measurements of the surface temperature of iron oxide nanoparticles in an alternating magnetic field (AMF) through the temperature induced change in fluorescence of a thermoresponsive/fluorescent polymer consisting of poly(N-isopropylacrylamide) (pNIPAM) copolymerized with a fluorescent modified acrylamide (FMA) monomer with fluorescent intensity that increases as its surroundings change from hydrophilic to hydrophobic. When the particles are suspended in water and subjected to external heating, the fluorescence is observed to remain constant up to about 35 C, above which temperature it increases. When the particles dissipate heat internally in an AMF, the fluorescence intensity increases immediately upon application of the AMF, even though the temperature (as measured by an immersed fiber-optic probe) is below 35 C. The observed increase in fluorescence intensity indicates a change in the microenvironment of the FMA due to the transition of the pNIPAM from hydrophilic to hydrophobic. This in turn suggests that the nanoparticle surface temperature is above 35 C and therefore higher than the temperature of the surrounding medium.

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