Knee osteoarthritis (OA) is a musculoskeletal disorder that may have a heavy impact on the patients’ quality of life. Available pharmacological treatments are effective only on a short-term basis, and their prolonged use has several adverse effects. The OA-affected joints exhibit a complex range of structural, tissue, cellular and biochemical changes. Inflammation mediators are expressed and in turn activate enzymes degrading the extracellular matrix (ECM) including collagen in the cartilage. Collagen is a fibrillar protein that may hierarchically auto-assemble in more complex fibers that are at the same time resistant and elastic, a feature observed both in cartilage, where collagen is the main constituent of the amorphous matrix, and in all specialized connective or supporting tissues, such as tendons, ligaments and bone. ChondroGrid is a medical device made of lyophilized low molecular weight hydrolyzed bovine collagen for intra- and peri-articular injection. Intra-articular collagen injection may be a safe adjuvant, yet evidence concerning its use is limited.