In vitro effects of the co-release of icariin and strontium from bioactive glass submicron spheres on the reduced osteogenic potential of rat osteoporotic bone marrow mesenchymal stem cells

Abstract

Osteoporosis is a metabolic disease that affects bone tissue and is highly associated with bone fractures. Typical osteoporosis fracture treatments, such as bisphosphonates and hormone replacement, present important challenges because of their low bioavailability on the site of action. Options to overcome this issue are systems for the local release of therapeutic agents such as bioactive glasses containing therapeutic molecules and ions. These agents are released during the dissolution process, combining the drugs and ion therapeutic effects for osteoporosis treatment. Among the therapeutic agents that can be applied for bone repair are strontium (Sr) ion and phytopharmaceutical icariin, which have shown potential to promote healthy bone marrow stem cells osteogenic differentiation, increase bone formation and prevent bone loss. Submicron Sr-containing bioactive glass mesoporous spheres with sustained ion release capacity were obtained. Icariin was successfully incorporated into the particles, and the glass composition influenced the icariin incorporation efficiency and release rates. In this work, for the first time, Sr and icariin were incorporated into bioactive glass submicron mesoporous spheres and the in vitro effects of the therapeutic agents release were evaluated on the reduced osteogenic potential of rat osteoporotic bone marrow mesenchymal stem cells, and results showed an improvement on the reduced differentiation potential.

The Local Release of Teriparatide Incorporated in 45S5 Bioglass Promotes a Beneficial Effect on Osteogenic Cells and Bone Repair in Calvarial Defects in Ovariectomized Rats

“…In cases of individuals who have chronic diseases associated with the need for bone repair, if necessary, it can be difficult [ 65 , 66 ]. Therefore, there is a growing demand for biomaterials that have adequate properties in relation to bone tissue and that can positively influence tissue regeneration, improving biomechanical properties and accelerating the osteogenesis process [ 31 , 32 , 67 , 68 ].…”

“…According to Kyllonen et al [ 69 ] for the release and transport of the active drug, particles of different sizes can be used; therefore, the drug is incorporated, absorbed, or associated with these particles and thus is protected from the degradation from the environment until its release. In a recent study by Mosqueira et al [ 32 ], the authors concluded that the efficiency of the loading of therapeutic agents in strontium-modified bioglass spheres, as well as the drug release rates, were mainly influenced by the pore size of the particles, thus improving the osteogenic potential of the mesenchymal cells of the bone marrow obtained from rats with osteoporosis. In this study, bioglass particles were reduced to nanometer size for surface increase, as the number of surface atoms increases dramatically as the particle size decreases [ 70 ], which contributes to drug incorporation and release.…”

“…The 45S5 Bioglass ® has great versatility in the fields of biomedicine, orthopedics, and even dentistry, being used for bone repairs in the fields of periodontics [ 27 ], maxillofacial surgery [ 28 ], and even for soft tissue repair [ 29 ]. Furthermore, the ability of bioglasses to incorporate hydrophilic and hydrophobic groups in their structures resulted in their development in association with therapeutic agents [ 30 , 31 , 32 , 33 ].…”

Applications of Calcium-Based Nanomaterials in Osteoporosis Treatment

“…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.…”

“…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, 95,104,106,[115][116][117][118]132,135,146,148,149,153 europium, 122 and gallium 150 ), clinical drugs (e.g., PTH, 99 cholecalciferol, 126 simvastatin, 151 and estradiol 105 ), and MSCs. 125 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.…”