Controlled Release Microparticle Platform for Localized Prevention of Tissue Calcification and Ossification
This system employs bioerodible polymer microparticles made from PLGA to enable the local, sustained release of a BMP type I receptor inhibitor such as dorsomorphin. The microparticles gradually degrade at the treatment site to maintain effective local drug levels, which suppress SMAD1/5/8 phosphorylation and prevent unwanted chondrocyte terminal differentiation and subsequent calcification. This targeted release can be integrated into hydrogels, scaffolds, or even clotting blood, making it well-suited for cartilage repair procedures like microfracture, autologous chondrocyte implantation, and mesenchymal stem cell implantation, as well as for applications aimed at preventing ectopic calcification in other tissues.
Description
What differentiates this technology is its capacity to deliver localized, controlled therapy while minimizing systemic exposure and associated risks. The release profile can be customized by adjusting polymer molecular weight, particle size distribution, and drug loading, ensuring prolonged effectiveness in diverse clinical scenarios. Preclinical validation in human osteochondral models has demonstrated a significant reduction of calcification markers, highlighting its therapeutic potential over traditional systemic treatments and offering a transformative approach for managing tissue calcification and ossification.Applications
Cartilage repair proceduresEctopic calcification prevention
Heterotopic ossification prevention
Controlled drug release scaffolds
Advantages
Localized delivery minimizes systemic exposure and associated side effects.Sustained release maintains effective inhibitor concentrations, reducing calcification.
Versatile integration with scaffolds, hydrogels, and other matrices enhances cartilage repair procedures.
Customizable release profiles allow for tailored therapeutic approaches across different tissues.
Broad clinical application potential, including prevention of ectopic and heterotopic ossification.