Cartilage repair in the inflamed joint : considerations for biological augmentation towards tissue regeneration

Cartilage repair/regeneration procedures (e.g., microfracture, Autologous Chondrocyte Implantation -ACI-) typically result in a satisfactory outcome in selected patients. However, the vast majority of patients with chronic symptoms and, in general, a more diseased joint, do not benefit from these surgical techniques. The aims of this work were to i) review factors negatively influencing the joint environment; ii) review current adjuvant therapies that can be used to improve results of cartilage repair/regeneration procedures in patients with more diseased joints, iii) outline future lines of research and promising experimental approaches. Chronicity of symptoms and advancing patient age seem to be the most relevant factors negatively affecting clinical outcome of cartilage repair/regeneration. Preliminary experience with Hyaluronic Acid (HA), Platelet-Rich plasma (PRP), and Mesenchymal Stem Cells (MSC) has been positive but there is no strong evidence supporting the use of these products and this requires further assessment with high-quality, prospective clinical trials. The use of a Tissue Therapy strategy, based on more mature engineered tissues holds promise to tackle limitations of standard ACI procedures. Current research has highlighted the need for more targeted therapies, and i) induction of tolerance with Granulocyte-colony stimulating factor (G-CSF) or by preventing IL-6 downregulation; ii) combined IL-4 and IL-10 local release; iii) selective activation of the Prostaglandin E2 (PGE2) signaling seem the most promising innovative strategies. For older patients and for those with chronic symptoms, adjuvant therapies are needed in combination with microfracture and ACI.