No abstract

Osteoarthritis (OA) is a degenerative joint disorder commonly encountered in clinical practice, and is the leading cause of disability in elderly people. Due to the poor self-healing capacity of articular cartilage and lack of specific diagnostic biomarkers, OA is a challenging disease with limited treatment options. Traditional pharmacologic therapies such as acetaminophen, non-steroidal anti-inflammatory drugs, and opioids are effective in relieving pain but are incapable of reversing cartilage damage and are frequently associated with adverse events. Current research focuses on the development of new OA drugs (such as sprifermin/recombinant human fibroblast growth factor-18, tanezumab/monoclonal antibody against β-nerve growth factor), which aims for more effectiveness and less incidence of adverse effects than the traditional ones. Furthermore, regenerative therapies (such as autologous chondrocyte implantation (ACI), new generation of matrix-induced ACI, cell-free scaffolds, induced pluripotent stem cells (iPS cells or iPSCs), and endogenous cell homing) are also emerging as promising alternatives as they have potential to enhance cartilage repair, and ultimately restore healthy tissue. However, despite currently available therapies and research advances, there remain unmet medical needs in the treatment of OA. This review highlights current research progress on pharmacologic and regenerative therapies for OA including key advances and potential limitations.

Driven by market demand, many biological and synthetic scaffolds have been developed during the last 15 years. Both positive and negative results have been reported in clinical applications for tendon and ligament repair. To obtain data for this review, multiple electronic databases were used (e.g., Pubmed and ScienceDirect), as well as the US FDA website and the reference lists from clinical trials, review articles and company reports, in order to identify studies relating to the use of these commercial scaffolds for tendon and ligament repair. The commercial names of each scaffold and the keywords 'tendon' and 'ligament' were used as the search terms. Initially, 378 articles were identified. Of these, 47 were clinical studies and the others were reviews, editorials, commentaries, animal studies or related to applications other than tendons and ligaments. The outcomes were reviewed in 47 reports (six on Restore, eight on Graftjacket, four on Zimmer, one on TissueMend, five on Gore-Tex, six on Lars, 18 on Leeds-Keio and one study used both Restore and Graftjacket). The advantages, disadvantages and future perspectives regarding the use of commercial scaffolds for tendon and ligament treatment are discussed. Both biological and synthetic scaffolds can cause adverse events such as noninfectious effusion and synovitis, which result in the failure of surgery. Future improvements should focus on both mechanical properties and biocompatibility. Nanoscaffold manufactured using electrospinning technology may provide great improvement in future practice.

Porcine small intestinal submucosa (SIS) has been recommended as a cell-free, biocompatible biomaterial for the repair of rotator cuff tendon tear. However, we have observed noninfectious edema and severe pain in patients who have undergone SIS implantation for tendon repair. The aim of this study was to conduct an independent assessment of the safety and efficacy of Restore SIS membrane. The Restore orthobiologic implant was examined by histology and the nested PCR technique using porcine immunoreceptor DAP12 gene to examine if SIS membrane contained porcine cells or DNA, respectively. The material was also implanted into mice and rabbits for the evaluation of biological reaction and inflammatory response. Restore SIS was found to contain multiple layers of porcine cells. Chloroacetate esterase staining showed that some of these cells were mast cells. Nested PCR of the DAP12 gene demonstrated that Restore SIS contained porcine DNA material. Subcutaneous implantation of Restore SIS membrane in mice, and in rabbits for rotator cuff tendon repair, showed that the membrane caused an inflammatory reaction characterized by massive lymphocyte infiltration. In conclusion, Restore SIS is not an acellular collagenous matrix, and contains porcine DNA. Our results contradict the current view that Restore SIS is a cell-free biomaterial, and that no inflammatory response is elicited by its implantation. We suggest that further studies should be conducted to evaluate the clinical safety and efficacy of SIS implant biomaterials.