Viscosupplementation for treatment of osteoarthritis: from initial discovery to current status and results

Viscosupplementation is a therapeutic modality based on the replacement of synovial fluid or exudates with an elastoviscous hyaluronan solution. The first clinical trials were carried out on race horses with painful osteoarthritis of traumatic origin. In the early 1970s, the clinical trials were extended to painful osteoarthritis in humans. Analgesic effects lasting longer than the residence time of the injected hyaluronan in joints were reported both in horses and humans. The hyaluronan used was a noninflammatory fraction of the molecule with an average molecular weight of 2-3 million at a 1% concentration. The analgesic effect of this elastoviscous hyaluronan solution was demonstrated in behavioral animal pain models. Later it was shown that the elastoviscous properties of hyaluronan solutions are the determining factors in reducing pain-elicited nerve activity in both normal and inflamed cat and rat joints. It also was demonstrated in animal arthritis models that elastoviscous hyaluronan solutions promote the healing of traumatic intra-articular wounds. From the mid-1980s, several hyaluronan preparations of greatly varying average molecular weight but with the same concentration were introduced as viscosupplementation-based therapeutic agents. The elastoviscous properties of these solutions varied also, because of the greatly varying average molecular weights (0.5-6.0 million), imitating the rheological properties of either healthy or pathological synovial fluid. Currently, viscosupplementation products available worldwide vary greatly in their elastoviscous properties, and their dosage is not standardized in terms of frequency of injections required or in regard to the removal of exudates before injection. The question of which patient at what stage of the disease responds best with long-lasting pain relief to the many therapeutic products marketed with greatly varying elastoviscous properties has not yet been answered. At the same time, viscosupplementation was introduced, the same highly elastoviscous hyaluronan solutions also were applied in ophthalmic surgery as viscosurgical tools to protect sensitive tissues in the eye during surgery and to be used as soft instruments for tissue manipulation. Modified hyaluronan products (gels) also were introduced for augmentation of the intercellular matrix in tissues (viscoaugmentation) and for separating tissues to prevent adhesions and excessive scar formation (viscoseparation). Hyaluronan and its derivatives (gels) also have been used for drug delivery. The therapeutic use of highly elastoviscous solutions and gels of hyaluronan and its derivatives to build intercellular matrices for supplementation, regeneration, and developing new tissues introduced the concept of matrix engineering into medical practice.