Nonoperative and Operative Soft-Tissue and Cartilage Regeneration and Orthopaedic Biologics of the Foot and Ankle: An Orthoregeneration Network Foundation Review

Orthoregeneration is defined as a solution for orthopaedic 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 electromagnetic 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 foot and ankle (including acute traumatic injuries and fractures, tumor, infection, osteochondral lesions, arthritis, and tendinopathy) and procedures, including osteotomy or fusion. Promising and established treatment modalities include 1) bone-based therapies (such as cancellous or cortical autograft from the iliac crest, proximal tibia, and/or calcaneus, fresh-frozen or freeze-dried cortical or cancellous allograft, including demineralized bone matrix putty or powder combined with growth factors, and synthetic bone graft substitutes, such as calcium sulfate, calcium phosphate, tricalcium phosphate, bioactive glasses (often in combination with bone marrow aspirate), and polymers; proteins such as bone morphogenic proteins; and platelet-derived growth factors; 2) cartilage-based therapies such as debridement, bone marrow stimulation (such as microfracture or drilling), scaffold-based techniques (such as autologous chondrocyte implantation [ACI] and matrix-induced ACI, autologous matrix-induced chondrogenesis, matrix-associated stem cell transplantation, particulated juvenile cartilage allograft transplantation, and minced local cartilage cells mixed with fibrin and platelet rich plasma [PRP]); and 3) blood, cell-based, and injectable therapies such as PRP, platelet-poor plasma biomatrix loaded with mesenchymal stromal cells, concentrated bone marrow aspirate, hyaluronic acid, and stem or stromal cell therapy, including mesenchymal stem cell allografts, and adipose tissue-derived stem cells, and micronized adipose tissue injections. Level of Evidence: Level V, expert opinion.