It is estimated that about 0.5% of the world’s population will require an articular cartilage (AC) intervention at some point in their life. Current treatment options for chondral lesions are only marginally successful, and if left untreated, lead to osteoarthritic (OA) joint disease, one of the major sources of disability world-wide. Many of the common surgical approaches to treat cartilage lesions such as microfracture (MF), are dependent on the efficient migration of cells from the underlying subchondral bone (SB) to ensure successful regeneration of the tissue. However, the extent of cell migration and hence the clinical outcome, is highly variable. To overcome this critical limitation, a scaffold is proposed which uses two key mechanisms to induce stem cell migration. Firstly, the scaffold is composed of granular hydrogels, whose void space naturally facilitates the endogenous migration of mesenchymal stem cells (MSCs). Secondly, some microgels are modified with sulfate groups, to allow the retention of positively charged growth factors (GFs) (e.g. TGFB3 and PDGF-BB). Therefore, hyaluronic acid (HA) was triple-modified with methacrylate groups, transglutaminase (TG)-sensitive peptides and sulfate groups to produce AptoGEL, a new and exciting material with key properties needed for chondral regeneration. We believe this advanced, yet biocompatible material, provides an ideal 3D environment for promoting cell migration and differentiation leading to a fully functional chondral repair.
In conclusion, in this project we were able to transform bulk hydrogels where the cells cannot penetrate into a granular system with cell guidance capabilities. The results demonstrated that our strategy can be easily extrapolated to other tissues and, the most important, the whole system can retain different GFs cocktails depending on the need.
