Microencapsulation and delivery of CNP in 3D tissue-engineered model (Wolfson Foundation).

Principal investigator: A. De Souza
Co-investigator(s): N. Peake, A. Pavlov, A.J. Hobbs, Gleb SUKHORUKOV and Tina CHOWDHURY

Microcapsules (A) encapsulated with fluorescein labelled CNP (B). Image in (C) is merged. Inflammatory explant model shows presence of CNP containing microcapsules (white arrows) released from the cartilage defect site (D). White bars represent 2 M. Our recent work identified that a natural protein called the C-type Natriuretic Peptide (CNP) maintains homeostatic function in human cartilage. We established that CNP function declines with age and the differences in the mechanism of natriuretic peptide signalling affects the ability of the peptide to function normally. These findings will have widespread impact due to the role of CNP in maintaining homeostasis in multiple tissues including cartilage or bone and function in vascular, cardiac, renal and central nervous systems. This project will develop a CNP delivery system that will be tested in 3D tissue engineered systems with the ultimate aim for use in patients with cartilage degeneration. This work involves cross-disciplinary expertise to encapsulate CNP (Prof Adrian Hobbs, WHRI) in a microcapsule delivery system with technology developed by Prof Gleb Sukhorukov (IOM). The microparticles will be engineered for sustained release of CNP into the local environment, and this funding will be used to perform studies with a human ex vivo moded to establish a) release profile and stability of microparticle delivery system ex vivo, b) sustained release of fluorescent-tagged CNP into the local environment, c) sustained response of human cartilage to microparticle-delivered CNP. Pilot data shows successful labelling and encapsulation of CNP in microcapsules (Fig. 1). This system will be highly attractive to investors because it represents patentable technology to augment a natural pathway with known beneficial effects in cartilage, bone and cardiovascular tissue. The project is funded by the Wolfson Foundation and supports Alveena De Souza.