An in vivo Comparison Study Between Strontium Nanoparticles and rhBMP2

Abstract

The osteoinductive property of strontium was repeatedly proven in the last decades. Compelling in vitro data demonstrated that strontium hydroxyapatite nanoparticles exert a dual action, by promoting osteoblasts-driven matrix secretion and inhibiting osteoclasts-driven matrix resorption. Recombinant human bone morphogenetic protein 2 (rhBMP2) is a powerful osteoinductive biologic, used for the treatment of vertebral fractures and critically-sized bone defects. Although effective, the use of rhBMP2 has limitations due its recombinant morphogen nature. In this study, we examined the comparison between two osteoinductive agents: rhBMP2 and the innovative strontium-substituted hydroxyapatite nanoparticles. To test their effectiveness, we independently loaded Gelfoam sponges with the two osteoinductive agents and used the sponges as agent-carriers. Gelfoam are FDA-approved biodegradable medical devices used as delivery system for musculoskeletal defects. Their porous structure and spongy morphology make them attractive in orthopedic field. The abiotic characterization of the loaded sponges, involving ion release pattern and structure investigation, was followed by in vivo implantation onto the periosteum of healthy mice and comparison of the effects induced by each implant was performed. Abiotic analysis demonstrated that strontium was continuously released from the sponges over 28 days with a pattern similar to rhBMP2. Histological observations and gene expression analysis showed stronger endochondral ossification elicited by strontium compared to rhBMP2. Osteoclast activity was more inhibited by strontium than by rhBMP2. These results demonstrated the use of sponges loaded with strontium nanoparticles as potential bone grafts might provide better outcomes for complex fractures. Strontium nanoparticles are a novel and effective non-biologic treatment for bone injuries and can be used as novel powerful therapeutics for bone regeneration.

Alkaline earth metals for osteogenic scaffolds: From mechanisms to applications

“…It has better clinical application than recombinant human BMP-2, another osteoinductive biologic material. 190 Sr-doped HA scaffolds increase local Sr 2+ concentrations and exhibit specific effects on osteoblasts and osteoclasts. 191 Tests have demonstrated their excellent osteoconductive, osteoconductive, and osseointegration properties in vitro.…”

“…Sr‐doped HA scaffolds can continuously release Sr 2+ for more than 28 days and promote endochondral ossification, inhibiting osteoclasts' activity. It has better clinical application than recombinant human BMP‐2, another osteoinductive biologic material 190 . Sr‐doped HA scaffolds increase local Sr 2+ concentrations and exhibit specific effects on osteoblasts and osteoclasts 191 .…”

Nature-Inspired Unconventional Approaches to Develop 3D Bioceramic Scaffolds with Enhanced Regenerative Ability

“…Many biological investigations were carried out on this doping ion, in particular by verifying its interaction with osteoblast-like cells and human osteoclasts to verify proliferation or inhibition, osteogenic differentiation, and angiogenic factor expression. It has been concluded that the bone cell behaviour is Sr 2+ -ion-dose dependent [ 20 , 21 , 22 ]. It was also shown that Sr doping can stabilise the HA crystal which affects, on the one hand, the mechanical stability of the new bone and, on the other hand, also increases the hardness of ceramic scaffold [ 23 , 24 ].…”

Strontium-doping promotes bone bonding of titanium implants in osteoporotic microenvironment

“…Sr is an important component of bone. It plays a key role in bone integration by promoting osteoblast differentiation and accelerating bone formation, while inhibiting osteoclast differentiation and reducing bone resorption ( Choudhary et al, 2007 ; Bonnelye et al, 2008 ; Montagna et al, 2020 ). Sr-containing drugs play an active role in clinical application for anti-osteoporosis.…”