Conformation-regulated mechanosensory control via titin domains in cardiac muscle

The giant filamentous protein titin is ideally positioned in the muscle sarcomere to sense mechanical stimuli and transform them into biochemical signals, such as those triggering cardiac hypertrophy. In this review, we ponder the evidence for signaling hotspots along the titin filament involved in mechanosensory control mechanisms. On the way, we distinguish between stress and strain as triggers of mechanical signaling events at the cardiac sarcomere. Whereas the Z-disk and M-band regions of titin may be prominently involved in sensing mechanical stress, signaling hotspots within the elastic I-band titin segment may respond primarily to mechanical strain. Common to both stress and strain sensor elements is their regulation by conformational changes in protein domains

Bilayer Implants

OBJECTIVE: To compare the regenerative capacity of 2 distinct bilayer implants for the restoration of osteochondral defects in a preliminary sheep model. METHODS: Critical sized osteochondral defects were treated with a novel biomimetic poly-ε-caprolactone (PCL) implant (Treatment No. 2; n = 6) or a combination of Chondro-Gide and Orthoss (Treatment No. 1; n = 6). At 19 months postoperation, repair tissue (n = 5 each) was analyzed for histology and biochemistry. Electromechanical mappings (Arthro-BST) were performed ex vivo. RESULTS: Histological scores, electromechanical quantitative parameter values, dsDNA and sGAG contents measured at the repair sites were statistically lower than those obtained from the contralateral surfaces. Electromechanical mappings and higher dsDNA and sGAG/weight levels indicated better regeneration for Treatment No. 1. However, these differences were not significant. For both treatments, Arthro-BST revealed early signs of degeneration of the cartilage surrounding the repair site. The International Cartilage Repair Society II histological scores of the repair tissue were significantly higher for Treatment No. 1 (10.3 ± 0.38 SE) compared to Treatment No. 2 (8.7 ± 0.45 SE). The parameters cell morphology and vascularization scored highest whereas tidemark formation scored the lowest. CONCLUSION: There was cell infiltration and regeneration of bone and cartilage. However, repair was incomplete and fibrocartilaginous. There were no significant differences in the quality of regeneration between the treatments except in some histological scoring categories. The results from Arthro-BST measurements were comparable to traditional invasive/destructive methods of measuring quality of cartilage repair

Bone Marrow Concentrate Improves Early Cartilage Phase Maturation of a Scaffold Plug in the Knee

BACKGROUND Limited information exists on the clinical use of a synthetic osteochondral scaffold plug for cartilage restoration in the knee. PURPOSE/HYPOTHESIS The purpose of this study was to compare the early magnetic resonance imaging (MRI) appearance, including quantitative T2 values, between cartilage defects treated with a scaffold versus a scaffold with platelet-rich plasma (PRP) or bone marrow aspirate concentrate (BMAC). The hypothesis was that the addition of PRP or BMAC would result in an improved cartilage appearance. STUDY DESIGN Cohort study; Level of evidence, 3. METHODS Forty-six patients with full-thickness cartilage defects of the femur were surgically treated with a control scaffold (n = 11), scaffold with PRP (n = 23), or scaffold with BMAC (n = 12) and were followed prospectively. Patients underwent MRI with a qualitative assessment and quantitative T2 mapping at 12 months after surgery. An image assessment was performed retrospectively by a blinded musculoskeletal radiologist. The cartilage phase was measured by cartilage fill and quantitative T2 values on MRI. A comparison between groups after cartilage repair was performed. RESULTS The control scaffold group consisted of 8 male and 3 female patients (mean age, 38 years; mean body mass index [BMI], 25 kg/m(2)), the PRP group had 15 male and 8 female patients (mean age, 39 years; mean BMI, 26 kg/m(2)), and the BMAC group consisted of 8 male and 4 female patients (mean age, 36 years; mean BMI, 26 kg/m(2)). The PRP-treated (P = .002) and BMAC-treated (P = .03) scaffolds had superior cartilage fill compared with the control group. With quantitative methods, the PRP group demonstrated a mean T2 value (49.1 ms) that was similar to that of the control scaffold group (42.7 ms; P = .07), but the BMAC group demonstrated a mean T2 value (60.5 ms) closer to that of superficial hyaline cartilage (P = .01). The stratification of T2 values between the deep and superficial zones was not observed in any of the groups. CONCLUSION In this comparative study, patients treated with scaffold implantation augmented with BMAC had improved cartilage maturation with greater fill and mean T2 values closer to that of superficial native hyaline cartilage at 12 months. Further work will determine if this translates into improved clinical outcomes