Cartilage and Bone Serum Biomarkers as Novel Tools for Monitoring Knee Osteochondritis Dissecans Treated with Osteochondral Scaffold

Abstract

Knee osteochondritis dissecans (OCD) is a focal disease of the joint characterized by modifications of bone and cartilage tissues. Biomimetic osteochondral scaffolds are used to restore these tissues. The aim of this prognostic prospective cohort study was to evaluate serum biomarkers of cartilage (fragments or propeptide of type II collagen: CTXII, C2C, and CPII) and bone (tartrate-resistant acid phosphatase (TRAP) 5b and osteocalcin (OC)) turnover during follow-up of patients treated with an osteochondral scaffold, to identify which were related to healing outcome and clinical score. We found that cartilage (CPII) and bone (OC) synthetic biomarkers were significantly increased during the first-year follow-up, while the respective degradative markers (CTXII, C2C, and TRAP5b) were not modulated. Only CTXII/CPII and C2C/CPII cartilage ratios were significantly modulated, evidencing a higher remodeling of cartilage compared to bone tissue. Cartilage and bone single biomarkers or ratios at one-year follow-up showed values close to or similar to those of healthy subjects. International Knee Documentation Committee (IKDC) score significantly increased from T0 to T2, while the Tegner score did not. Taking into consideration an IKDC score > 70 as clinical success, we found that all OCD cases with both CPII (> 300 pg/ml) and C2C/CPII (<0.35) presented IKDC scores of clinical success. OCD patients treated with an osteochondral scaffold showed an improvement at one-year follow-up, evidenced by both clinical and serum cartilage biomarkers. These data confirmed that cartilage and bone remodeling took place and showed that systemic biomarkers represent a sensitive tool for monitoring OCD patients during the follow-up.

Serum changes in pyridinoline, type II collagen cleavage neoepitope and osteocalcin in early stage male brucellosis patients

“…C2C has also been shown to correlate with knee degeneration in patients with symptomatic knee osteoarthritis 19 . Moreover, OC is one of the most abundant non-collagen bone proteins in the bone matrix and has been used as a biomarker for monitoring bone formation and bone turnover 20 , with its synthesis significantly increased during the remodeling processes 21 . In this study, the PYD, C2C, and OC serum levels were all statistically elevated in brucellosis individuals relative to the healthy controls, and their elevation indicates abnormal changes in the collagen metabolism in cartilage, bone formation, and bone turnover.…”

Serum changes of PYD, C2C and OC among male brucellosis patients at early period

“…OC is one of the most abundant noncollagen bone proteins in bone matrix, which has been used as a biochemical marker of bone formation and bone turnover [22]. The synthetic of OC signi cantly increased, suggesting the potentiality of bone tissues in the remodeling processes [23]. In this study, the serum levels of PYD, C2C and OC among male patients were higher than that of healthy control with a statistic signi cance,indicating that there were abnormal changes of collagen metabolism in bone and cartilage and abnormal changes of bone formation and bone turnover.…”

Multiphasic scaffolds for the repair of osteochondral defects: Outcomes of preclinical studies

“…Currently, four types of commercially available scaffolds have been reported in clinical studies published between 2015 and 2021 ( Table 4 ). These include MaioRegen® from Finceramica Italy [ [139] , [140] , [141] , [142] , [143] , [144] , [145] , [146] , [147] , [148] ], Trufit® from Smith & Nephew USA [ [149] , [150] , [151] , [152] , [153] , [154] ], Agili-C™ from CartiHeal Israel [ 155 , 156 ], and Chondrotissue® from BioTissue Switzerland [ 157 ]. The MaioRegen® is a tri-layer scaffold, while Trufit® and Agili-C™ are bi-layer scaffolds, and Chondrotissue® is a single layer scaffold.…”

“…Clinical studies using this scaffold have been reported since 2011, for the treatment of a variety of osteochondral lesions including most commonly the femoral condyles, tibial plateau, patella, and talus [ 158 ]. The more recent studies have investigated the use of MaioRegen® in a range of age groups, including juveniles [ 147 ], young adults [ 141 , 143 , 145 ], and middle-aged to elderly patients [ 139 , 140 , 142 , 144 , 146 , 148 ]. In juvenile knee osteochondritis dissecans (OCD), MaioRegen® achieved stable improvement over time with International Knee Documentation Committee (IKDC) subject score of 50.3 ± 17.4 at 1 year to 85.0 ± 9.3 at 6 years (higher score equates to better symptomatic and functional outcomes; maximum score 100), and Tegner score of 2.6 ± 1.4 pre-operation to 5.5 ± 2.0 at 6 years (higher score equates to better symptomatic and functional outcomes; maximum score 10) [ 147 ].…”

“…MOCART showed complete cartilage filling in 63.2% of lesions and complete graft integration in 47.4%, while subchondral bone appearance was considered normal in 42.1%. Gabusi et al (2018) [ 143 ] MaioRegen® Knee osteochondritis dissecans focal lesions 1.5–4 cm 2 14 patients Mean age 23.6 ± 8.6 years Time: 3 months, 1 year Evaluated serum biomarkers of cartilage (fragments or propeptide of type II collagen: CTXII, C2C, CPII) and bone (TRAP5b, OC) turnover. Cartilage (CPII) and bone (OC) synthetic biomarkers were significantly increased at 1 year, while degradative markers (CTXII, C2C, TRAP5b) were not modulated.…”