Elucidating the role of size of hydroxyl apatite particles toward the development of competent antiosteoporotic bioceramic materials: In vitro and in vivo studies

Abstract

Osteoporosis caused by overdose of steroids is one of the major concerns for the orthopedic surgeons. Current therapeutic strategies offer limited success due to their inability to regenerate damaged bone at osteoporosis site. Therefore, there is an urgent need to develop a material having bone regeneration ability and also, ability to cure osteoporosis simultaneously. In this work, nanosized and microsized hydroxyl apatite (HAp) particles doped with europium (Eu) were prepared for diagnostic and therapeutic applications in biomedical engineering. Particles were characterized by X‐ray diffraction to confirm the formation of HAp phase and transmission electron microscopy technique has been used to explore the size of microparticle and nanoparticle. In vitro release of antibiotic drug and degradation behavior in two different pHs of phosphate buffered saline was checked. Controlled drug release behavior and conversion of degraded ions into HAp is estimated by Higuchi's and 3D diffusion model, respectively. Osteoporosis was induced in 36 female Wistar rats by administering dexamethasone once a week for four consecutive weeks. Rats were treated with different doses of nano‐HAp (25, 50, and 100 μg/kg intravenous single dose) and single dose of microsized HAp (100 μg/kg). After treatment, authors have evaluated sensitive biochemical markers of bone in serum. Continuous improvement in ultimate stiffness and Young's modulus of femur shaft of rats was observed with the increase in the dose of nano‐HAp from 25 to 100 μg/kg. Results strongly suggest that europium‐doped nano‐HAp is more effective for treating severe osteoporosis in humans. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1723–1735, 2019.

Applications of Calcium-Based Nanomaterials in Osteoporosis Treatment

“…Various methods can be applied to prepare and functionalize CBNMs, including a simple, mild liquid-phase mineralization reaction. ,,− This provides an opportunity to achieve uniform nanomorphology and diversified functionalization of CBNMs using many hydrophilic drugs and organic ingredients via mineralization reactions. CBNMs, especially CaP, are also structurally able to accept many ionic substitutions, such as strontium, ,− cobalt, boron and europium . These substituted inorganic ions not only endow CBNMs with different properties but can also aid in osteoporosis treatment.…”

“…Various preparation methods allow for the construction of different forms of antiosteoporotic CBNMs. The preparation methods discussed here include coprecipitation, ,,,− ,,,− sol–gel, ,− ,,− ,− hydrothermal, ,,, electrochemical deposition, ,, electrostatic spray deposition, vapor diffusion, sonochemical synthesis, and physical crushing. − Each preparation method has unique advantages and is accordingly suitable for the preparation of specific forms of CBNMs. The physicochemical properties of CBNMs prepared by different methods are summarized in Table .…”

“…Although the reaction conditions of the hydrothermal method are harsher, CBNMs with high crystallinity and hierarchical structures can easily be obtained by controlling the reaction conditions. Products with high crystallinity can be obtained directly in one step with this method, avoiding the shortcomings of the coprecipitation and sol–gel methods, such as agglomeration caused by sintering and impurities introduced by grinding. , Therefore, nHA with high crystallinity and uniform morphology is commonly prepared with the hydrothermal method. ,,, Ion-doped nano-HA can also be obtained by adding specific ions during the reaction.…”

“…There are two ways to rebalance bone remodeling: (1) using a single ingredient that has the properties of both promoting osteogenesis and inhibiting osteoclasts; or (2) the one plus one strategy (a combination strategy with one component promoting osteogenesis and the other component inhibiting osteoclasts). There are three categories of single ingredients that have both properties: inorganic elements (e.g., strontium, ,,,− ,,,,,, europium, and gallium), clinical drugs (e.g., PTH, cholecalciferol, simvastatin, and estradiol), and MSCs . Additionally, although estradiol is classified as an antiabsorption drug in clinical applications, its dual effects on osteoclasts and osteoblasts have been demonstrated by some researchers. , Therefore, in recent studies, it has been used as an antiosteoporotic ingredient with dual effects. , Strontium ions have both pro-osteogenic and antiosteoclastogenic effects, but the low oral bioavailability and side effects associated with dose accumulation limit its clinical application. , Calcium and strontium have similar properties because they are within the same group of elements, so the substitution of strontium for calcium can be achieved in CBNMs through a simple process.…”

“…This was a result of the bone remodeling regulatory effect of Sr and the stimulation effect on MSC of the needlelike nanoapatite coating . Not only strontium but also europium , and gallium have this dual regulatory ability for bone remodeling, and europium-doped nHA additionally has fluorescence emission at 738 nm due to its inherent lanthanide element properties . For local delivery of clinical drugs, nHA can directly load cholecalciferol by surface adsorption and encapsulate simvastatin with the poly­( N -isopropylacrylamide) brush modified mesoporous .…”