title: Cartilage Repair in the Inflamed Joint: Considerations for Biological Augmentation Toward Tissue Regeneration.
abstract: Cartilage repair/regeneration procedures (e.g., microfracture, autologous chondrocyte implantation [ACI]) typically result in a satisfactory outcome in selected patients. However, the vast majority of patients with chronic symptoms and, in general, a more diseased joint, do not benefit from these surgical techniques. The aims of this work were to (1) review factors negatively influencing the joint environment; (2) review current adjuvant therapies that can be used to improve results of cartilage repair/regeneration procedures in patients with more diseased joints, (3) outline future lines of research and promising experimental approaches. Chronicity of symptoms and advancing patient age appear to be the most relevant factors negatively affecting clinical outcome of cartilage repair/regeneration. Preliminary experience with hyaluronic acid, platelet-rich plasma, and mesenchymal stem cell has been positive but there is no strong evidence supporting the use of these products and this requires further assessment with high-quality, prospective clinical trials. The use of a Tissue Therapy strategy, based on more mature engineered tissues, holds promise to tackle limitations of standard ACI procedures. Current research has highlighted the need for more targeted therapies, and (1) induction of tolerance with granulocyte colony-stimulating factor (G-CSF) or by preventing IL-6 downregulation; (2) combined IL-4 and IL-10 local release; and (3) selective activation of the prostaglandin E2 (PGE2) signaling appear to be the most promising innovative strategies. For older patients and for those with chronic symptoms, adjuvant therapies are needed in combination with microfracture and ACI.
authors.affiliation: 1 IRCCS Istituto Ortopedico Galeazzi , Milan, Italy .
authors.forename: Celeste
authors.initials: C
authors.lastname: Scotti
authors.affiliation: 2 Orthopedic Arthroscopic Surgery International (O.A.S.I.) Bioresearch Foundation , Gobbi Onlus, Milan, Italy .
authors.forename: Alberto
authors.initials: A
authors.lastname: Gobbi
authors.affiliation: 2 Orthopedic Arthroscopic Surgery International (O.A.S.I.) Bioresearch Foundation , Gobbi Onlus, Milan, Italy .
authors.forename: Georgios
authors.initials: G
authors.lastname: Karnatzikos
authors.affiliation: 3 Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel , Basel, Switzerland .
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.affiliation: 4 Department of Orthopedics, Osaka University Graduate School of Medicine , Osaka, Japan .
authors.forename: Kazunori
authors.initials: K
authors.lastname: Shimomura
authors.affiliation: 5 COAST Surgery Center, University of California , San Diego, California.
authors.forename: John G
authors.initials: JG
authors.lastname: Lane
authors.affiliation: 1 IRCCS Istituto Ortopedico Galeazzi , Milan, Italy .|6 Department of Biomedical Sciences for Health, University of Milan , Milan, Italy .
authors.forename: Giuseppe Michele
authors.initials: GM
authors.lastname: Peretti
authors.affiliation: 7 Institute for Medical Science in Sports, Osaka Health Science University , Osaka, Japan .|8 Center for Advanced Medical Engineering and Informatics, Osaka University , Osaka, Japan .
authors.forename: Norimasa
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007596:Joints / Q000473:pathology*; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods*; D014945:Wound Healing