Knee osteoarthritis (KOA) is a multifactorial degenerative disorder of joints, affecting the world's population over the age of 65 and with a higher prevalence in females. KOA is responsible for many age associated joint problems such as stiffness and pain. Conventional methods for managing KOA such as nonsteroidal anti-inflammatory drugs (NSAID) may not improve pain or alter the disease progression and may have adverse side effects. Non-pharmacological management of OA is fundamental to management of functional limitations and provides effective symptom relief but has not shown that disease progression can be altered. Regenerative medicine is a relatively new approach which aims to induce cellular regeneration and promote self-healing through minimally invasive methods. The use of regenerative medicine slowed the progression of KOA and revealed significant improvements, yet further investigations are required to optimize the outcomes. Nutritional and metabolic aspects such as supplementations, vitamins and minerals were proven to have an impact on the progression of KOA. Genetic variations are rapidly inspected to identify any potential influence of these variations in the predisposition and diagnosis of KOA. Further supporting evidence suggests the potential influence of metabolic, nutritional and genetic aspects in optimizing the outcomes of regenerative medicine in the management of KOA.

BackgroundOsteoarthritis is a progressive multifactorial condition of the musculoskeletal system with major symptoms including pain, loss of function, damage of articular cartilage and other tissues in the affected area. Knee osteoarthritis imposes major individual and social burden, especially with the cost and complexity of surgical interventions. Mesenchymal stem/stromal cells have been indicated as a treatment for degenerative musculoskeletal conditions given their capacity to differentiate into tissues of the musculoskeletal system.MethodsA systematic search will be conducted in Medline, Embase, Cochrane Library, Scopus and relevant trial databases of English, Japanese, Korean, German, French, Italian, Spanish and Portuguese language papers published or in press to June 2018, with no restrictions on publication year applied. References will be screened and assessed for eligibility by two independent reviewers as per PRISMA guidelines. Cohort, cross-sectional or case controlled studies will be included for the analysis. Data extraction will be conducted using a predefined template and quality of evidence assessed. Statistical summaries and meta-analyses will be performed as necessary.DiscussionResults will be published in relevant peer-reviewed scientific journals and presented at national or international conferences by the investigators.Trial registrationThe protocol was registered on the PROSPERO international prospective register of systematic reviews prior to commencement, CRD42018091763.Electronic supplementary materialThe online version of this article (10.1186/s13018-019-1070-8) contains supplementary material, which is available to authorized users.

The purpose of this manuscript is to provide a current concept review for the rehabilitative management of knee osteoarthritis (KOA) following regenerative medicine intervention. A proposed comprehensive regenerative rehabilitative program has been created, based on a literature review of the current best practices of rehabilitative methods and non-operative management in KOA patients with an emphasis on the goals of regenerative medicine: to optimize self-healing and functional tissue recovery. Regenerative medicine promotes regeneration and joint restoration by using blood-based procedures such as platelet rich plasma, stem cell and cell-based or tissue engineering. Regenerative medicine procedures are variable and lack of standardization in product preparation, administration, and different treatment protocols. The lack of standardization imposes challenges in regenerative rehabilitation. Over the last decade, there is growing evidence in regenerative medicine and its uses in non-operative management of various pathologies. Advances in regenerative medicine technologies brings radical innovations to establish new and effective rehabilitation protocols promoting restoration of function through tissue regeneration and repair optimizing the standard of care, specifically in rehabilitation when combined with regenerative protocols for patients with KOA is the most common degenerative disease in the knee and can affect any synovial joint in the body. It is a leading cause of disability affecting the quality of lives of millions of people worldwide. Conventional methods of mild to moderate KOA are focused on shortterm symptomatic relief and do not promote joint homeostasis or regeneration of injured tissue. Regenerative medicine emphasizes a paradigm shift in patient-centered care promoting regeneration and joint restoration by using blood-based procedures such as platelet rich plasma, stem cell and cellbased or tissue engineering. The purpose of this current concept review is to outline a comprehensive post-regenerative rehabilitative program in the management of KOA based on the best available evidence. Our proposed regenerative rehabilitation program is intended to align the goals of regenerative medicine with the current, high-level evidence of non-operative management for KOA, to optimize selfhealing and functional tissue recovery.

Purpose This review aims to summarize the evidence for the role of mechanotherapies and rehabilitation in supporting the synergy between regeneration and repair after an orthobiologic intervention. Methods A selective literature search was performed using Web of Science, OVID, and PubMed to review research articles that discuss the effects of combining mechanotherapy with various forms of regenerative medicine. Results Various mechanotherapies can encourage the healing process for patients at different stages. Taping, bracing, cold water immersion, and extracorporeal shockwave therapy can be used throughout the duration of acute inflammatory response. The regulation of angiogenesis can be sustained with blood flow restriction and resistance training, whereas heat therapy and tissue loading during exercise are recommended in the remodeling phase. Conclusion Combining mechanotherapy with various forms of regenerative medicine has shown promise for improving treatment outcomes. However, further studies that reveal a greater volume of evidence are needed to support clinical decisions.