Alpha-2-Macroglobulin Concentrate as Orthobiologic in Osteoarthritis

In recent years, autologous concentrated alpha-2-macroglobulin (c-A2M) has emerged as a potential treatment for cartilage pathology as well as for nociceptive inflammatory arthritis due to its ability to trap and bait inflammatory mediators. It has been successfully used in the treatment of musculoskeletal pathology to reduce pain and improve mobility modulate cartilage degeneration. Following a whole blood density separation, similar to that used in preparing platelet-rich plasma (PRP), several high-molecular platelet-poor plasma (PPP) proteins can be concentrated by using simple ultrafiltration techniques, including the 725 kilo Dalton (kDa) A2M protein complex, known as a broad-spectrum proteinase inhibitor. As a component of PRP's anti-inflammatory properties, c-A2M has been shown to inhibit the activity of intra-articular inflammatory and degenerative proteases in animal experiments and in in vitro cell-based studies. Unfortunately, large clinical trials are lacking at this moment. This chapter is aimed at delineating the application of c-A2M as a novel non-surgical interventional orthobiologic strategy.