Hydroxyapatite -- bone substitute in the new century

Due to the influence of diseases, aging, frequent traffic accidents and other factors, bone injury cases increase year by year. According to statistics, there are 3 million orthopedic cases in China every year, so the demand for bone substitute materials is increasing. In recent years, Hydroxyapatite as a representative of bone substitute materials has gradually become a favorite in clinical application.
Hydroxyapatite is the main component of vertebrate bones and teeth, which has good bioactivity and biocompatibility. Compared with the traditional metal (stainless steel, titanium alloy) and ceramic (alumina, silicon nitride) bone substitute materials, Hydroxyapatite not only has strong corrosion resistance and bone induction, but also eliminates the safety risks of the former by its degradation in vivo. At present, the research on Hydroxyapatite in bone substitute materials mainly focuses on two aspects: Hydroxyapatite coating and human bone biomimetic regeneration materials.
Hydroxyapatite coating is a kind of hard tissue implant material prepared by coating Hydroxyapatite on the surface of titanium alloy by physical and chemical means. After implanted into human body, titanium alloy can provide enough mechanical strength, and the Hydroxyapatite coating on the surface of the material is easy to combine with human bone, which can induce the formation of new bone on the surface of human bone, and generally can induce the formation of new bone in a few months. The Hydroxyapatite coating prepared by Shanghai Silicate Research Institute of Chinese Academy of Sciences by plasma spraying technology has high bonding strength with substrate and good biological activity, and has been applied in artificial hip joint and other parts. So far, more than 70000 Hydroxyapatite coated implants have been applied, and good clinical effects have been achieved, as shown in Figure 1. However, Hydroxyapatite coating has the disadvantage of insufficient adhesion, which leads to the phenomenon of coating falling off after implantation in vivo. The solution to this problem is still under constant exploration.

Figure 1. Some clinical application of Hydroxyapatite coated bone substitutes and in vivo osteogenesis experiments. (a) Hydroxyapatite coated hip arthroplasty; (b) one month after implantation, new bone formed and filled the pores between the coating and bone tissue; (c) three months after implantation, the new bone was replaced by mature bone tissue.

Human bone biomimetic regeneration material is a new composite material that simulates the formation environment of natural bone in vitro, obtains nano Hydroxyapatite crystal with the same size as natural bone through nanotechnology, and composes with collagen to realize the lifelike composition, structure and function with human natural bone at different scales (micro and macro). According to the analysis of high resolution electron microscope and atomic force magnifier, human skeleton has a set of very delicate structures: bundles of collagen and layers of nano Hydroxyapatite crystals are embedded together in an extremely uniform and orderly manner, as shown in Fig. 2. This kind of multi-layer composite self-assembly structure also makes the bone have both hardness and bending resistance. Therefore, imitating the special structure of human bone, it can theoretically achieve biological activity and mechanical compatibility matching with human bone. In addition, the presence of collagen makes the biomimetic bone substitute easy to bond with autologous bone tissue. At present, the research on this aspect is still in progress. Because it is difficult for the outside world to accurately imitate the osteogenic environment in vivo, it is still very difficult for human bone bionics. Due to the different functions of cortical bone and cancellous bone, there are still some differences in the structural composition, which undoubtedly increases the workload and difficulty of bone bionics.

Whether it is Hydroxyapatite coating or biomimetic regeneration material of human bone, Hydroxyapatite is the key of bone substitute material. It endows bone with compressive strength, and is the main load-bearing of bone tissue. In addition, its ability to induce new bone formation is incomparable with other materials. Although there are many difficulties in the research of bone substitute materials, with the continuous penetration of nanotechnology and biotechnology in the field of medical materials, we believe that patients will see the dawn of "bone regeneration" in the near future.

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