IADR Abstract Archives
On-demand Bone Regeneration Using Ultrasound-Triggered Nanocomplexes for Delivery of BMP-2
Objectives: On-demand localized control over delivery of biologics is a significant challenge in clinical regenerative medicine. The advantages of using bone morphogenetic protein (BMP-2) for bone regeneration are offset by safety concerns due to the high doses required to compensate for diffusional loss.
Objective: We propose to develop a novel protein delivery system, where liposomes sequester BMP-2 at the bone defect site until its controlled release by application of ultrasound (US).
Methods: Methods: Nanocomplexes for sonodisruptable delivery of BMP-2 (NSD) were synthesized and characterized by TEM, zeta potential, dynamic light scattering, and ELISA for encapsulation efficiency. In vitro, parameters for US disruption, and time course for controlled delivery were tested. In vivo, efficacy of the implant was evaluated in a standardized animal model (16 cohorts, 10 mice each, subjected to different US delivery profiles). Cohorts contained individual US treatment on days 0, 7 and 14, and second treatments on days 0 and 7 or days 7 and 14 to match natural bone healing timepoints (compared with commercial BMP-2 implants). MicroCT and histology were carried out on harvested tissue, 28 days after the last US treatment.
Results: Results: Physical characterization of NSD revealed nanocomplexes (145±20 nm, -36 mV zeta potential) that stably encapsulated BMP-2 (74.3% efficiency). In vitro, BMP-2 release from NSD occurred only on US exposure, and was pressure, frequency and time dependent. In vivo animal studies revealed bone formation only in US treated tissue. Increased bone formation was observed in cohorts that received second treatments on days 0 and 7, compared with single treatments.
Conclusions: Conclusions: We successfully developed and validated in vivo a nanocomplex implant system for controlled US-triggered release of BMP-2 for bone formation. Characterization further showed that multiple US treatments induced greater bone formation compared with either single treatments, or with commercial BMP-2 implants.
Objective: We propose to develop a novel protein delivery system, where liposomes sequester BMP-2 at the bone defect site until its controlled release by application of ultrasound (US).
Methods: Methods: Nanocomplexes for sonodisruptable delivery of BMP-2 (NSD) were synthesized and characterized by TEM, zeta potential, dynamic light scattering, and ELISA for encapsulation efficiency. In vitro, parameters for US disruption, and time course for controlled delivery were tested. In vivo, efficacy of the implant was evaluated in a standardized animal model (16 cohorts, 10 mice each, subjected to different US delivery profiles). Cohorts contained individual US treatment on days 0, 7 and 14, and second treatments on days 0 and 7 or days 7 and 14 to match natural bone healing timepoints (compared with commercial BMP-2 implants). MicroCT and histology were carried out on harvested tissue, 28 days after the last US treatment.
Results: Results: Physical characterization of NSD revealed nanocomplexes (145±20 nm, -36 mV zeta potential) that stably encapsulated BMP-2 (74.3% efficiency). In vitro, BMP-2 release from NSD occurred only on US exposure, and was pressure, frequency and time dependent. In vivo animal studies revealed bone formation only in US treated tissue. Increased bone formation was observed in cohorts that received second treatments on days 0 and 7, compared with single treatments.
Conclusions: Conclusions: We successfully developed and validated in vivo a nanocomplex implant system for controlled US-triggered release of BMP-2 for bone formation. Characterization further showed that multiple US treatments induced greater bone formation compared with either single treatments, or with commercial BMP-2 implants.