Bone induction at physiological doses of BMP through localization by clay nanoparticle gels

Bone Morphogenic Protein 2 (BMP2) can induce ectopic bone. This ability, which first motivated the widespread application of BMP2 in fracture healing and spinal arthrodesis has, more recently, been indicated as one of several serious adverse effects associated with the supra-physiological doses of BMP2 relied upon for clinical efficacy. Key to harnessing BMPs and other agents safely and effectively will be the ability to localize activity at a target site at substantially reduced doses. Clay (Laponite) nanoparticles can self assemble into gels under physiological conditions and bind growth factors for enhanced and localized efficacy. Here we show the ability to localize and enhance the activity of BMP2 to achieve ectopic bone formation at doses within the sub-microgram per ml range of concentrations sufficient to induce differentiation of responsive cell populations in vitro and at approximately 3000 fold lower than those employed in clinical practice

Harnessing nanotopography to enhance osseointegration of clinical orthopedic titanium implants-an in vitro and in vivo analysis

Despite technological advancements, further innovations in the field of orthopedics and bone regeneration are essential to meet the rising demands of an increasing aging population and associated issues of disease, injury and trauma. Nanotopography provides new opportunities for novel implant surface modifications and promises to deliver further improvements in implant performance. However, the technical complexities of nanotopography fabrication and surface analysis have precluded identification of the optimal surface features to trigger osteogenesis. We herein detail the osteoinductive potential of discrete nanodot and nanowire nanotopographies. We have examined the ability of modified titanium and titanium alloy (Ti64) surfaces to induce bone-specific gene activation and extracellular matrix protein expression in human skeletal stem cells (SSCs) in vitro, and de novo osteogenic response within a murine calvarial model in vivo. This study provides evidence of enhanced osteogenic response to nanowires 300 surface modifications, with important implications for clinical orthopedic application.</p

Bone induction at physiological doses of BMP through localization by clay nanoparticle gels

Bone Morphogenic Protein 2 (BMP2) can induce ectopic bone. This ability, which first motivated the widespread application of BMP2 in fracture healing and spinal arthrodesis has, more recently, been indicated as one of several serious adverse effects associated with the supra-physiological doses of BMP2 relied upon for clinical efficacy. Key to harnessing BMPs and other agents safely and effectively will be the ability to localize activity at a target site at substantially reduced doses. Clay (Laponite) nanoparticles can self assemble into gels under physiological conditions and bind growth factors for enhanced and localized efficacy. Here we show the ability to localize and enhance the activity of BMP2 to achieve ectopic bone formation at doses within the sub-microgram per ml range of concentrations sufficient to induce differentiation of responsive cell populations in vitro and at approximately 3000 fold lower than those employed in clinical practice

Osteogenic potential of Sr-doped calcium phosphate hollow spheres in vitro and in vivo.

Treatment of osteoporotic fractures with conventional surgical methods is associated with a high rate of complications. Intense search for new treatment options includes development of specific biomaterials aimed to be part of the surgical armamentarium. Strontium doped calcium phosphate spheres (SrCPS) is a new material that might be of interest due to the influence on osteoclast and osteoblast activity. In the present study, we successfully constructed hollow spherical SrCPS particles with a diameter of ~700 nm and shell thickness of ~150 nm. The Sr content was about 20 wt %. Cell viability and cytotoxicity were investigated in vitro with concentrations from 0 to 1000 mug/mL of SrCPS in medium extract in a day chase study. The in vivo biocompatibility was tested in a delayed bone-healing model in a rat vertebral defect by histology, muCT, and nanoSPECT. The SrCPS showed no toxicity in vitro with comparable cell number in all concentrations. Increased metabolism was seen in the cell viability study in cells exposed to 400 and 600 mug/mL. SPECT showed good biocompatibility with no local adverse effects and an increased osteoblast activity as compared to adjacent vertebra. SrCPS implantation induced bone formation and resulted in complete resorption and defect consolidation