Subchondral bone scan uptake correlates with articular cartilage degeneration in osteoarthritic knees.

AIM: The aim of this study was to analyze subchondral bone scan uptake in osteoarthritic knees with reference to subchondral bone microstructure and articular cartilage histology. METHODS: This cross-sectional, laboratory study evaluated 123 human distal femoral condyle specimens of 67 patients after joint replacement surgery. All patients were preoperatively examined with bone scan of the knee joint. Specimens were evaluated for cartilage histology and micro-computed tomography analysis of subchondral bone. Data between bone scan, histology and micro-computed tomography were statistically analyzed using either coefficient of correlation, Student's t-test or one-way analysis of variance with Tukey post hoc test. RESULTS: Bone scan grading and histological articular cartilage degeneration scores showed significant correlation (r = 0.812, P < 0.001). Both bone scan positive and histologically confirmed osteoarthritis samples showed increase in subchondral trabecular bone volume and thickness, reflected in micro-computed tomography. Overall, positive predictive value (%) of bone scan for osteoarthritic cartilage lesions was 91.9%, and the sensitivity and specificity were 88.3% and 60%, respectively. Histology showed that bone scan has both a high positive predictive and a low negative predictive value for detection of osteoarthritic cartilage lesions. CONCLUSION: Bone scan uptake correlated with articular cartilage degeneration in osteoarthritic knees. Bone scan may be a useful diagnostic tool that reflects pathologic changes of cartilage in osteoarthritis.

Extracellular Matrix (ECM) Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-ß3 in Articular Cartilage Repair.

Recombinant human transforming growth factor beta-3 (rhTGF-ß3) is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-ß3 using a multilayered extracellular matrix (ECM) membrane. We hypothesize that the sustained release of rhTGF-ß3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS) are investigated using rhTGF-ß3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs) using western blot and circular dichroism (CD) analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-ß3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-ß3-loaded EMLDS ((+) rhTGF-ß3 EMLDS) in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair.

Histomorphochemical comparison of microfracture as a first-line and a salvage procedure: is microfracture still a viable option for knee cartilage repair in a salvage situation?

Microfracture is considered as the first-line procedure for knee cartilage repair, but the results of microfracture seem less predictable and rather controversial in a salvage situation. Thus, the purpose of the study was to histomorphochemically compare microfracture as a salvage procedure with microfracture as a first-line procedure in a rabbit model. We hypothesized that microfracture in a salvage situation would result in histomorphochemically inferior cartilage repair compared to microfracture as a first-line procedure, and the inferiority would be attributed to less migration of reparable marrow cells to the defect due to destruction of microarchitecture of the subchondral bone. Thirty-six New Zealand white rabbits were divided into three groups: (i) untreated full-thickness chondral defect, (ii) single microfracture treatment (first microfracture group), and (iii) repeated microfracture in 8 weeks after the first procedure (second microfracture group). In each group, rabbits were sacrificed at the end of 8 weeks, and osteochondral specimens at the repair sites were obtained for histomorphochemical analysis. Results showed that microfracture as a salvage procedure resulted in overall inferior cartilage repair histomorphochemically compared with microfracture as a first-line procedure, which correlated with deteriorative changes in the quality of underlying subchondral bone rather than intrinsic incapability to recruit the reparative cells in the defect area. In conclusion, although a comparable number of reparable cells and a mechanically weakened subchondral bone are anticipated, more study is necessary to clearly determine when a microfracture should be performed in a situation.

Effect of different bone marrow stimulation techniques (BSTs) on MSCs mobilization.

The therapeutic effect of bone marrow stimulation techniques (BSTs) is mainly attributed to the role of mesenchymal stem cells (MSCs) from the bone marrow. However, no studies have directly shown the amount of MSCs drained by BSTs. This study hypothesized that differences in the opening of subchondral bone affect the number of MSCs drained from the bone marrow. We purposed that as the exposed area and hole size of BSTs vary, the number of MSCs drained out was measured. Three groups of different BSTs were designed that have variations in the sizes of total exposed area and individual holes. Three different BSTs using a curette, 1.5- and 0.8-mm awls were carried out on the full-thickness femoral cartilage defect of young rabbits. After BST, the number of MSCs in the blood clot was measured by CFU-Fs assay. As the size of the total exposed area increased, so did the number of MSCs obtained. The number of MSCs drained from bone marrow may vary depending on different BSTs and this could affect therapeutic efficacy of cartilage defect. As current microfracture (MF) method cannot drain the most MSCs clinically, more improved surgery technique is needed.