Optimization of an Injectable, Resorbable, Bioactive Cement Able to Release the Anti-Osteoclastogenic Biomolecule ICOS-Fc for the Treatment of Osteoporotic Vertebral Compression Fractures

Abstract

Vertebral compression fractures are typical of osteoporosis and their treatment can require the injection of a cement through a minimally invasive procedure to restore vertebral body height. This study reports the development of an injectable calcium sulphate-based composite cement able to stimulate bone regeneration while inhibiting osteoclast bone resorption. To this aim, different types of strontium-containing mesoporous glass particles (Sr-MBG) were added to calcium sulphate powder to impart a pro-osteogenic effect, and the influence of their size and textural features on the cement properties was investigated. Anti-osteoclastogenic properties were conferred by incorporating into poly(lactic-co-glycolic)acid (PLGA) nanoparticles, a recombinant protein able to inhibit osteoclast activity (i.e., ICOS-Fc). Radiopaque zirconia nanoparticles (ZrO2) were also added to the formulation to visualize the cement injection under fluoroscopy. The measured cement setting times were suitable for the clinical practice, and static mechanical testing determined a compressive strength of ca. 8 MPa, comparable to that of human vertebral bodies. In vitro release experiments indicated a sustained release of ICOS-Fc and Sr2+ ions up to 28 days. Overall, the developed cement is promising for the treatment of vertebral compression fractures and has the potential to stimulate bone regeneration while releasing a biomolecule able to limit bone resorption.

Noninvasive and Microinvasive Nanoscale Drug Delivery Platforms for Hard Tissue Engineering

“…As previously mentioned, a study involving calcium sulfate cement with dispersed strontium-containing mesoporous glass particles and combined with recombinant inducible T-cell costimulator (ICOS-Fc) loaded in PLGA NPs resulted in promising possibilities for the treatment of osteoporosis caused by vertebral compression fractures. This gave the whole formulation the capacity to promote bone tissue regeneration (by osteoblast stimulation) while at the same time limiting the resorption activity of the osteoclasts . According to another performed study, mesoporous silica nanoparticles conjugated with polyethylenimine had successfully delivered osteostatin (a parathyroid hormone-related protein fragment) and siRNA as an IO injection.…”

“…This gave the whole formulation the capacity to promote bone tissue regeneration (by osteoblast stimulation) while at the same time limiting the resorption activity of the osteoclasts. 27 According to another performed study, 141 mesoporous silica nanoparticles conjugated with polyethylenimine had successfully delivered osteostatin 188 (a parathyroid hormone-related protein fragment) and siRNA as an IO injection. As proposed, the codelivery of these two entities had a synergic effect and were to be further examined for a potential gene therapy for the treatment of osteoporosis.…”

“…23,24 Nevertheless, nanoscale-based formulations and platforms have already been studied postsurgically 25−27 to cope with some of these physical limitations. In rat models, researchers 26,27 have achieved promotion of hard tissue formation after a defect was induced, which marks a promising position of these systems to be applied to humans. Related to the physical limitations, similar issues arise with another fracture complication type, termed nonunion 28−30 (lack of stability and/or blood flow for adequate healing), where in most cases a surgical intervention or the application of ultrasound emitters 31 (noninvasive, but physical method) is required for bone regeneration stimulation.…”

“…The physical limitations are related to the treatment of different fractures, which inevitably infer a surgical approach. In addition to naturally occurring fractures that have occurred because of different incidents, , the physical limitation to the use of nanoscale drug delivery systems also includes secondary bone tissue conditions , (those directly connected with surgical outcomes) and malunion types of fracture (abnormal healing of a broken bone). , Nevertheless, nanoscale-based formulations and platforms have already been studied postsurgically − to cope with some of these physical limitations. In rat models, researchers , have achieved promotion of hard tissue formation after a defect was induced, which marks a promising position of these systems to be applied to humans.…”

“…In addition to naturally occurring fractures that have occurred because of different incidents, , the physical limitation to the use of nanoscale drug delivery systems also includes secondary bone tissue conditions , (those directly connected with surgical outcomes) and malunion types of fracture (abnormal healing of a broken bone). , Nevertheless, nanoscale-based formulations and platforms have already been studied postsurgically − to cope with some of these physical limitations. In rat models, researchers , have achieved promotion of hard tissue formation after a defect was induced, which marks a promising position of these systems to be applied to humans. Related to the physical limitations, similar issues arise with another fracture complication type, termed nonunion − (lack of stability and/or blood flow for adequate healing), where in most cases a surgical intervention or the application of ultrasound emitters (noninvasive, but physical method) is required for bone regeneration stimulation .…”