The Gradual Release of Alendronate for the Treatment of Critical Bone Defects in Osteoporotic and Control Rats

Abstract

Purpose Osteoporosis is a severe health problem with social and economic impacts on society. The standard treatment consists of the systemic administration of drugs such as bisphosphonates, with alendronate (ALN) being one of the most common. Nevertheless, complications of systemic administration occur with this drug. Therefore, it is necessary to develop new strategies, such as local administration. Methods In this study, emulsion/dispersion scaffolds based on W/O emulsion of PCL and PF68 with ALN, containing hydroxyapatite (HA) nanoparticles as the dispersion phase were prepared using electrospinning. Scaffolds with different release kinetics were tested in vitro on the co-cultures of osteoblasts and osteoclast-like cells, isolated from adult osteoporotic and control rats. Cell viability, proliferation, ALP, TRAP and CA II activity were examined. A scaffold with a gradual release of ALN was tested in vivo in the bone defects of osteoporotic and control rats. Results The release kinetics were dependent on the scaffold composition and the used system of the poloxamers. The ALN was released from the scaffolds for more than 22 days. The behavior of cells cultured in vitro on scaffolds with different release kinetics was comparable. The difference was evident between cell co-cultures isolated from osteoporotic and control animals. The PCL/HA scaffold show slow degradation in vivo and residual scaffold limited new bone formation inside the defects. Nevertheless, the released ALN supported bone formation in the areas surrounding the residual scaffold. Interestingly, a positive effect of systemic administration of ALN was not proved. Conclusion The prepared scaffolds enabled tunable control release of ALN. The effect of ALN was proved in vitro and in in vivo study supported peri-implant bone formation.

3D-printed porous zinc scaffold combined with bioactive serum exosomes promotes bone defect repair in rabbit radius

“…Concurrently, zinc ions, as an essential trace element, play a crucial role in improving the cellular immune environment, accelerating bone regeneration, and inhibiting biofilm formation [ 29 ]. Furthermore, Poloxamers, a type of thermosensitive polymer, possess good solubility, low toxicity, strong drug release capability, and good compatibility with numerous biological molecules and chemical excipients [ 30 ]. Specifically, Poloxamers 407 have been widely used in the delivery of drugs and biological molecules through different routes [ 31 ].…”

Electrospun L-Lysine/Amorphous Calcium Phosphate Loaded Core-Sheath Nanofibers for Managing Oral Biofilm Infections and Promoting Periodontal Tissue Repairment

“…The flexibility of PCL has been utilized to improve the ductility and fracture strain of nanofibers made of only inorganic materials. 30 Additionally, COL, the primary component of cementum’s extracellular matrix, can be incorporated into the nanofibers, 38 , 39 promoting tissue regeneration, as those fibers with favorable biocompatibility and minimal immunogenicity, facilitate stem cells’ adhesion, support and protection. 40 …”

“…On one hand, it has evolved from a single-fluid blending process to multiple-fluid processes such as coaxial, 24,25 tri-axial, side-by-side 26 and other multiple-fluid process for creating coreshell, 27 Janus, 28 and combined nanostructures. [29][30][31] On the other hand, electrospun nanofibers are constantly being used in new and innovative applications due to their ability to encapsulate active ingredients for specific purposes. [32][33][34] Additionally, it is easy to load multiple active ingredients into complex electrospun structures with the ability to tailor components, compositions, and spatial distributions within nanofibers.…”

“…The flexibility of PCL has been utilized to improve the ductility and fracture strain of nanofibers made of only inorganic materials. 30 Additionally, COL, the primary component of cementum's extracellular matrix, can be incorporated into the nanofibers, 38,39 promoting tissue regeneration, as those fibers with favorable biocompatibility and minimal immunogenicity, facilitate stem cells' adhesion, support and protection. 40 Thus, we constructed a multi-functional core-sheath nanofibrous membrane as a local drug delivery system (Lys/ACP-CNF) for the therapy of periodontitis with potential post-infection in GTR (table of content image, TOC).…”