Nonoperative and Operative Soft-Tissue and Cartilage Regeneration and Orthopaedic Biologics of the Knee: An Orthoregeneration Network (ON) Foundation Review.

Orthoregeneration is defined as a solution for orthopedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include: drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electro-magnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the knee, including symptomatic osteoarthritis and chondral injuries, as well as injuries to tendon, meniscus, and ligament, including the anterior cruciate ligament. Promising and established treatment modalities include hyaluronic acid (HA) in liquid or scaffold form; platelet-rich plasma (PRP); bone marrow aspirate (BMA) comprising mesenchymal stromal cells (MSCs), hematopoietic stem cells, endothelial progenitor cells, and growth factors; connective tissue progenitor cells (CTPs) including adipose-derived mesenchymal stem cells (AD-MSCs) and tendon-derived stem cells (TDSCs); matrix cell-based therapy including autologous chondrocytes or allograft; vitamin D; and fibrin clot. Future investigations should standardize solution preparations, because inconsistent results reported may be due to heterogeneity of HA, PRP, BMAC, or MSC preparations and regimens, which may inhibit meaningful comparison between studies to determine the true efficacy and safety for each treatment.