Self-assembling peptide hydrogels for articular cartilage repair

Osteoarthritis affects millions of people globally, with damage to articular cartilage causing pain and altered mechanics during articulation. The treatment for late stage osteoarthritis is surgical intervention ultimately leading to total joint replacements. These treatments are not ideal for younger or more active patients so there is a clinical need for an early stage intervention treatment to reduce or stop the progression of osteoarthritis. It has been reported that there is a correlation between the loss of glycosaminoglycans (GAGs) from within osteoarthritic cartilage and the changes in biomechanics of the cartilage. It is hypothesized that the re-introduction of GAGs into early stage osteoarthritic cartilage through the use of permanent linkage and integration into a self-assembling peptide hydrogel matrix which could penetrate the cartilage tissue would potentially restore the resistance to deformation observed in osteoarthritic cartilage. Initially, synthetic self-assembling peptide-chondroitin sulfate (CS) conjugates were synthesized through utilizing copper-catalyzed click chemistry and subsequently characterized. The chosen peptide-CS conjugates were then incorporated into self-assembling peptide hydrogels and the morphologies and gel properties were investigated and evaluated in terms of the closest resemblance to the natural properties of the surrounding cartilage into which the hydrogels would be eventually injected. The best hydrogel candidates were then taken forward to be injected into a GAG depleted early stage osteoarthritic porcine cartilage model developed by Andres Barco (University of Leeds) where a severely GAG depleted state had been produced through a succession of surfactant and phosphate buffered saline washes. The hydrogels were doped with fluorescently labelled material which integrated into the hydrogel matrix, then injected into the cartilage tissue in a monomeric state. The hydrogels then self-assembled in situ and the deformation of the tissue was measured through creep indentation. The introduction of the peptide-CS conjugate showed significant restoration of resistance to deformation.