Ultrasound Activated Bone Morphogenetic -2 (BMP-2) Nanocomplexes that Provides On-Demand, Controlled Release for Bone Regeneration
Year: 2016
Type: dissertation
Abstract: Recombinant bone morphogenetic-2 (BMP-2) delivered on an acellular collagen sponge (ACS) is clinically approved for bone regeneration. Post implantation, BMP-2 is rapidly released as a bolus from the ACS, cleared quickly from the site requiring high doses to compensate for diffusional loss. Additionally, the advantages of using BMP-2 for bone regeneration are offset by safety concerns attributed to the high doses of BMP-2 used. Further the rapid release of BMP-2 does not match the temporal release of endogenous BMP-2 during natural physiological bone healing. To address this, rhBMP-2 polyethylene glycol sonodisruptable liposome nanocomplexes (NSD) that releases BMP- 2 only on ultrasound (US) exposure were developed. I hypothesized that US control release of BMP-2 that matched the expression of endogenous BMP-2 during physiological bone healing would require lower doses of BMP-2 to be effective. To test this hypothesis we investigated two specific objectives: 1. To develop and characterize NSD-BMP and evaluate US controlled release mechanism in vitro and in vivo and, 2. To evaluate in vivo, the temporal effects of US controlled delivery of BMP-2 on bone formation. In vitro, NSD-BMP released bioactive BMP-2 proportional to ultrasound duration and pressure. In vivo these nanocomplexes containing BMP-2 induced bone only upon ultrasound exposure. Further in vivo, US delayed release of BMP-2 was observed to enhance bone formation in comparison to the commercial implants. Most importantly NSD-BMP2 was clinically highly efficacious when multiple combinations of delayed ultrasound treatments were administered. This observation established that a critical window exists where BMP-2 is most effective for the purpose of bone induction. In conclusion, this study demonstrates that an US controlled release nanocomplex system can be used to temporally deliver BMP-2 that mirrors the release of endogenous BMP-2 expression temporally during bone healing. Resulting in less BMP-2 required to be clinically effective and that this system is a potentially a cheaper system with a better safety profile compared to current implants.
Source: TSpace (University of Toronto)
Author: Gazelle Jean Crasto
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W2905853342