Nanovibrational control of chondrogenic differentiation

Studentship strategic priority area: Healthcare Technologies
Keywords: Osteoarthritis (OA), Tissue Engineering (TE) Nanovibration, Chondrogenesis, PEG-hydrogels

Cartilage is an avascular and aneural tissue and so suffers poor healing and unattended cartilage damage leads to osteoarthritis (OA), a degenerative joint disease. At present, the World Health Organization (WHO) has ranked OA as the second greatest cause of disability and the primary health disease with the fastest rate of growth. As a result, tissue engineering (TE) is an emerging technique for cartilage regeneration. In this new project, we will use a novel bioreactor that delivers tiny, nanoscale (30 nm, 1000 Hz) vibrations to MSCs to expand and differentiate them into chondrocytes that produce the correct hyaline cartilage phenotype. This nanovibrational control of cells has as a result to form the smooth, articulating cartilage of the joint and prevents fibrocartilage formation. Interferometry and accelerometry measurements will be done to characterize the nano-mechanical cues that force the cells into differentiation in the bioreactor. Following these steps, we are going to characterize and identify the cells' phenotype in response to nanovibrations by using super-resolution confocal microscopy, qPCR, western analysis, RNA seq, and metabolomics. Then we are going to move to the encapsulation of the nanovibrated-chondrocytes into our novel hydrogel family. These synthetic, bioengineered, viscoelastic hydrogels belong to a family of polyethylene glycol (PEG)-based hydrogels where we will seek to manipulate the biophysical properties to match the stiffness of native cartilage. These hydrogels will be made of interpenetrated polymer networks (IPNS) that contain an elastic first network and the second network of a high molecular weight polymer that provides the viscous component. The second network will present peptide motifs (such as HAVDI) that are cadherin mimics; important for cartilage formation. Rheological measurements will be carried out to determine the elastic (G') and loss (G'') shear modulus of the material. The project aims to build a 3D delivery platform (tailored hydrogels) to support the nanovibrated-chondrocytes culture and prevent fibrocartilage formation as is the case with current carriers such as alginate gels or collagen membranes. Here we are presenting a highly interdisciplinary project that promises to manufacture a new technology system that focuses on bioengineered cell therapy. These biomaterials are promising as they are helping us to explore new methods to replace animal experimentation, and most importantly, create a deliverable injectable system that can be tuned to maximally support chondrogenesis and maintain mobility for people in need.