Introduction Treatment of musculoskeletal injuries is still demanding, because most of these tissues have low healing capability and are under different forces during healing and regeneration. Tissue engineering is one of the new approaches aimed to solve these difficulties. Simply, tissue engineering could be divided into three parts: scaffolds, healing promotive factors and stem cells. Healing promotive factors such as growth factors and a wide variety of glycosaminoglycans have major roles in the healing process of connective tissues; however, most of the tissue-engineered products are expensive and may not be available at the time of treatment. Synovial fluid is an available option, and it contains different healing promotive factors mainly glycosaminoglycans and lubricin. The major glycosaminoglycans that have been found in synovial fluid of different species are hyaluronic acid and chondroitin sulphate that have been shown to be effective in reducing peritendinous adhesion and inflammation. They also can modulate different stages of wound healing by motivating the healing cells to deposit more matrix and collagen fibres and have some antioxidant and protective effects, which promote efficient wound healing. This review has focused on the roles of these glycosaminoglycans on different musculoskeletal injuries in vitro, in vivo and in clinical situations. Due to the availability of hyaluronic acid and chondroitin sulphate in normal synovial fluid, it is reasonable to suggest the synovial fluid as a new treatment strategy in musculoskeletal medicine and surgery. Synovial fluid can be obtained from auto-, allo- and xenogeneic bases. The xenogeneicbased synovial fluid is more available than the other two forms. It is recommended to make some processing such as acellularization, sterilization and purification before application of the synovial fluid. Based on this evidence, it seems the exogenous synovial fluid could be considered as a popular therapeutic agent in the near future. The aim of this review was to discuss exogenous synovial fluid as a new option in tissue engineering. Conclusion Glycosaminoglycans such as hyaluronic acid and chondroitin sulphate make up the synovial fluid. Hyaluronic acid is beneficial in reducing peritendinous adhesion and signs of osteoarthrosis and in improving bone tunnel healing, tendon and bone regeneration. Exogenous synovial fluid looks to be a good method of providing glycosaminoglycans to the site of injury. We call on further studies to increase our understanding of synovial fluid and the effectiveness of its compounds in different injured tissues.