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Assessment of structural cartilage damage is of high scientific and clinical interest. Optical Coherence Tomography (OCT) is a light-based cross-sectional imaging modality that allows the real-time assessment of articular cartilage at near-histological resolution. Algorithm routines for the detection, parameterization and quantification of sub-surface defects as assessed by OCT were implemented and validated in this study. Standard defects of 0.9 mm, 1.1 mm and 1.3 mm diameter were created in the sub-surface regions of macroscopically intact human articular cartilage samples (n = 60 defects of variable sizes in n = 20 samples). Subsequently, samples were scanned by 3D OCT and defect size, height, width and distance to the surface were determined based on the algorithm and related to manual measurements. Histology served as the standard-of-reference. Statistical analysis included one-way ANOVA’s and Tukey’s post-hoc test. All defects were correctly identified by the algorithm, while five structural tissue inhomogeneities were erroneously marked as defects (sensitivity 100%, specificity: 92.3%). Inter-modality analysis revealed no significant differences in terms of defect area, height or width within the different defect sizes, while the distance to the surface was significantly different. The comprehensive algorithm-based characterization of cartilage defects is consistent and reliable and allows their more objective evaluation. Given further research in this field, OCT and OCT-based quantitative measures may become clinically useful in the arthroscopic detection and evaluation of sub-surface cartilage defects.

Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate bone healing and is considered to increase blood flow. The aim of this study was to assess changes in micro-circulation of the foots’ soft tissue in response to LIPUS intervention. We hypothesised improved micro-circulation in response to LIPUS. Micro-circulation was assessed in 2 mm and 8 mm-deep skin of 50 healthy volunteers using non-invasive laser-doppler spectrophotometry (O2C-device). Measurements were performed before LIPUS-intervention (pre), directly after intervention (post) and 20, 40 and 60 minutes after LIPUS. All parameter of micro-circulation increased directly after LIPUS intervention at 8 mm depth. Participants with a low pre-intervention flow showed the largest changes (p

A bstract Response to loading of soft tissues as assessed by advanced magnetic resonance imaging (MRI) techniques is a promising approach to evaluate tissue functionality beyond (statically obtained) structural and compositional features. As cartilage and meniscus pathologies are closely intertwined in osteoarthritis (OA) and beyond, both tissues should ideally be studied to elucidate further the underlying mechanisms involved in load transmission and its failure leading to OA. Hence, we devised, constructed and validated a dedicated MRI-compatible pneumatic force-controlled loading device to study cartilage and meniscus functionality in a standardized and reproducible manner and in reference to alternative tissue evaluation methods. Mechanical reference measurements using digital force sensors confirmed the reproducible application of forces in the range of 0–76N. To demonstrate the device's utility in a basic research context, MRI measurements of human articular cartilage (obtained from the lateral femoral condyle, n = 5) and meniscus (obtained from lateral meniscus body, n = 5) were performed in the unloaded (δ0) and loaded configurations (δ1: [cartilage] 0.75 bar corresponding to 15.1 N, [meniscus] 2 bar corresponding to 37.1 N; δ2: [cartilage] 1.5 bar corresponding to 28.6 N, [meniscus] 4 bar corresponding to 69.1 N). Cartilage samples were directly indented, while meniscus samples were subject to torque-induced compression using a dedicated lever compression device. Morphological MR Imaging using Proton Density-weighted sequences and quantitative MR Imaging using T2 and T1ρ mapping were performed serially and at high resolution. For reference, samples underwent subsequent biomechanical and histological reference evaluation. In conclusion, the force-controlled loading device has been validated for the non-invasive response-to-loading assessment of human cartilage and meniscus samples by advanced MRI techniques. Hereby, both tissues may be functionally evaluated in combination, beyond mere static analysis and in reference to histological and biomechanical measures.

Optical Coherence Tomography (OCT) yields microscopic cross-sectional images of cartilage in real time and at high resolution. As yet, comprehensive grading of degenerative cartilage changes based on OCT has rarely been performed. This study investigated the potential of quantitative OCT using algorithm-based image parameters such as irregularity (OII – Optical Irregularity Index), homogeneity (OHI – Optical Homogeneity Index) and attenuation (OAI – Optical Attenuation Index) in the objective grading of cartilage degeneration. Therefore, OCT was used to image and assess 113 human osteochondral samples obtained from total knee replacements. Processing included the analysis of OII (by calculation of the standard deviation with regards to a fitted surface), of OHI (by edge detection of tissue signal changes) and of OAI (by analysis of relative imaging depth). Additionally, samples were subject to macroscopic (Outerbridge grading), biomechanical (elastic stiffness), qualitative OCT and histological evaluation (Modified Mankin grading). Significant correlations were found between all outcome measures. OII and OHI were effective in assessing cartilage surface, integrity and homogeneity, while OAI could discriminate between unmineralized and mineralized cartilage, respectively. Therefore, quantitative OCT holds potential as a diagnostic tool for more reliable, standardized and objective assessment of cartilage tissue properties. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1381–1388, 2014.

In severe shoulder instability, chronic glenoid bone deficiency is a challenge for arthroscopic shoulder surgeons. This paper presents a new all-arthroscopic technique of iliac crest bone graft transfer for those patients. Transportation through the rotator interval and repositioning into the glenoid defect is achieved by use of a tracking suture, while fixation of the graft is performed by biodegradable or titanium double-helix screws. Overall, the feasibility and reproducibility of this new reconstruction technique in recreating the bony and soft tissue anatomy of the antero-inferior glenoid could be demonstrated. So far, preliminary outcomes of 24 patients operated on using this technique are promising. Level of evidence Case series with no comparison group, Level IV.

The response to loading of human articular cartilage as assessed by magnetic resonance imaging (MRI) remains to be defined in relation to histology and biomechanics. Therefore, an MRI-compatible whole-knee joint loading device for the functional in situ assessment of cartilage was developed and validated in this study. A formalin-fixed human knee was scanned by computed tomography in its native configuration and digitally processed to create femoral and tibial bone models. The bone models were covered by artificial femoral and tibial articular cartilage layers in their native configuration using cartilage-mimicking polyvinyl siloxane. A standardized defect of 8 mm diameter was created within the artificial cartilage layer at the central medial femoral condyle, into which native cartilage samples of similar dimensions were placed. After describing its design and specifications, the comprehensive validation of the device was performed using a hydraulic force gauge and digital electronic pressure-sensitive sensors. Displacement-controlled quasi-static uniaxial loading to 2.5 mm $$(\delta _{2.5})$$ and 5.0 mm $$(\delta _{5.0})$$ of the mobile tibia versus the immobile femur resulted in forces of $$141 \pm 8$$ N $$(\delta _{2.5})$$ and $$906 \pm 38$$ N $$(\delta _{5.0})$$ (on the entire joint) and local pressures of $$0.680 \pm 0.088$$ MPa $$(\delta _{2.5})$$ and $$1.050 \pm 0.100$$ MPa $$(\delta _{5.0})$$ (at the site of the cartilage sample). Upon confirming the MRI compatibility of the set-up, the response to loading of macroscopically intact human articular cartilage samples ( $$n=5$$ ) was assessed on a clinical 3.0-T MR imaging system using clinical standard proton-density turbo-spin echo sequences and T2-weighted multi-spin echo sequences. Serial imaging was performed at the unloaded state $$(\delta _{0})$$ and at consecutive loading positions (i.e. at $$\delta _{2.5}$$ and $$\delta _{5.0})$$ . Biomechanical unconfined compression testing (Young’s modulus) and histological assessment (Mankin score) served as the standards of reference. All samples were histologically intact (Mankin score, $$1.8 \pm 1.3$$ ) and biomechanically reasonably homogeneous (Young’s modulus, $$0.42 \pm 0.14$$ MPa). They could be visualized in their entirety by MRI and significant decreases in sample height [ $$\delta _{0}$$ : $$2.86 \pm 0.25$$ mm; $$\delta _{2.5}$$ : $$2.56 \pm 0.25$$ mm; $$\delta _{5.0}$$ : $$2.02 \pm 0.16$$ mm; $$p

Purpose To determine if multiparametric magnetic resonance (MR) imaging mapping can be used to quantify the response to loading of histologically intact human knee cartilage. Materials and Methods Institutional review board approval and written informed consent were obtained. Twenty macroscopically intact cartilage-bone samples were obtained from the central lateral femoral condyles in 11 patients undergoing total knee replacement. A clinical 3.0-T MR imaging system was used to generate T1, T1ρ, T2, and T2* maps with inversion recovery, spin-lock multiple gradient-echo, multiple spin-echo, and multiple gradient-echo sequences. Serial mapping was performed at three defined strain levels (strain 0 [δ0], 0%; strain 1 [δ1/2], 19.8% ± 4.6 [standard deviation]; strain 2 [δ1], 39.5% ± 9.3) by using displacement-controlled static indentation loading. The entire sample and specific cartilage zones (superficial zone [SZ], transitional zone [TZ], and deep zone [DZ]) and regions (subpistonal area [SPA] and peripistonal area [PPA]) were defined as regions of interest. Upon log transformation, repeated measures analysis of variance was used to detect groupwise regional and zonal differences. Load-induced relative changes were determined and analyzed by using paired Student t test and Spearman correlation. Biomechanical testing (unconfined compression) and histologic assessment (Mankin score) served as the reference standard. Results All samples were histologically intact. Strain-related decreases were found at the SZ and TZ for T1 and T2*; for T1ρ, increases were seen in all zones; and for T2, increases were seen at the SZ and PPA only. Significant parameter changes in the entire sample depth of SPA versus PPA were found for δ1/2 (T1ρ, 14% ± 12 vs 6% ± 9) and δ1 (T1, -4% ± 5 vs -1% ± 3; T1ρ, 13% ± 12 vs 7% ± 7; T2*, -9% ± 12 vs -2% ± 8). SPA versus PPA changes were significant at the SZ and TZ (T1), TZ and DZ (T1ρ), and SZ (T2*). No significant correlations were found between relative changes and biomechanical or histologic parameters. Conclusion Serial multiparametric MR imaging mapping can be used to evaluate cartilage beyond mere static analysis and may provide the basis for more refined graduation strategies of cartilage degeneration. © RSNA, 2016 Online supplemental material is available for this article.

Background Although there are many studies discussing the etiological and pathological factors leading to both, acute and chronic tendon injuries, the pathophysiology of tendon injuries is still not clearly understood. Although most lesions are uncomplicated, treatment is long and unsatisfactory due to the poor vascularity of tendon tissue. Platelet mediator concentrate (PMC) contains many growth factors derived from platelets, which can promote wound healing. In this study we investigate the effects of PMC on tenocyte proliferation and differentiation in order to provide an experimental basis for tissue regeneration strategies and to develop new treatment concepts. Methods Using enzyme linked immunosorbent assay (ELISA) we were able to quantify the several growth factors and cytokines found in PMC. Tenocytes were isolated both from human and from mouse Achilles tendons and stimulated with PMC. CyQuant® and Cell Titer Blue® assays were carried out to analyze tendon growth and viability at different concentrations of PMC. Real time RT-PCR was used to analyze tenocyte gene expression with or without PMC treatment. Immunohistochemistry was carried out to detect the tenocyte-specific antibody tenomodulin (TNMD) and scleraxis (SCX). Results We were able to detect numerous mediators such as platelet derived growth factor BB (PDGF-BB), interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF-α), transforming growth factor beta 1 (TGF-ß1), and bone morphogenetic proteins 2, 4 and 7 (BMP-4, BMP-2, BMP-7) in PMC. It was possible to show a positive effect of PMC on human tendon cell growth and viability in a dose-dependent manner. Furthermore, PMC treatment led to induction of gene expression of scleraxis (SCX), type I collagen A 1 (Col1A1) and TNMD by tenocytes. Conclusions We suggest that the use of autologous PMC may be a suitable addition to conventional tendon therapy that is capable of increasing and optimizing tendon healing and reducing the risk of recurrence.

Hybrid fixation has been proposed to improve outcomes of anterior cruciate ligament (ACL) reconstructions. This study evaluated midterm outcomes after transfemoral graft fixation using either a conventional or a modified technique using additional bone plug augmentation (BPA) of the femoral tunnel aperture.Seventy-one consecutive patients undergoing ACL reconstruction using a quadrupled hamstring autograft with transfemoral graft fixation and tibial interference screw fixation were included. Of these, 56 patients could be followed up 61 months (range 52-69 months) after ACL reconstruction both clinically and by magnetic resonance imaging (group A, conventional technique, n = 34; group B, modified technique, n = 22). Anteroposterior (AP) laxity measurements and International Knee Documentation Committee (IKDC), Lysholm and Tegner activity scoring were performed, while imaging included assessment of bone tunnel diameters, graft condition and graft filling at the femoral bone tunnel aperture.Patients with additional BPA had a significantly higher degree of graft filling at the femoral bone tunnel aperture (p = .0135) and 'healthier' grafts (p = .0495). They also tended to display less AP laxity difference in terms of mean differences and total patient numbers. Lysholm, IKDC and Tegner activity index scores and bone tunnel diameters were not significantly different.Additional BPA is an easy-to-perform, cheap and safe manoeuvre, which has the capacity to improve morphological and clinical outcomes at five year follow-up. However, femoral tunnel widening is unaffected by additional BPA.

Biodegradable transfemoral graft fixation devices used in anterior cruciate ligament (ACL) reconstruction have recently been reported to precociously lose structural integrity. This study investigated outcomes after ACL reconstruction using hamstring grafts and biodegradable transfemoral fixation at 5-year follow-up. The condition of both graft and fixation device was evaluated by magnetic resonance imaging (MRI) and related to clinical outcomes. In total, 85 patients on whom index ACL reconstructive surgery by means of a quadrupled semitendinosus–gracilis graft and biodegradable transfemoral fixation was performed were included in the study. Fifty-nine patients could be assessed by clinical and MRI examinations at a mean follow-up of 61 months (range, 52–69 months). Completely intact pins were found in 17 patients (29%), intact pins with delicate areas of resorption in 8 patients (14%), pin deformation in 5 patients (8%), pin fracture in 22 patients (37%) and pin migration in 3 patients (5%). In 40 patients (68%), pins had undergone degradation at the graft suspension point. Hamstring graft integrity and signal intensity scores were found to be significantly higher in patients with deformed, broken or dislocated pins as compared to patients with fully or mainly intact pins. Clinically, the mean side-to-side difference in anterior-posterior-laxity was 1.1 ± 1.6 mm, while Lysholm, IKDC and Tegner scores were 89 ± 11, 84 ± 14 and 4 (1–9). No statistically significant correlation was found between pin condition and clinical outcomes. Biodegradable fixation pins lose structural integrity in a way that suggests continuous loading of the pin/graft construct, thereby questioning osseous incorporation of the graft. This situation is clinically relevant in terms of improved graft condition. Retrospective case series, Level III.

To evaluate the diagnostic performance of T1, T1ρ, T2, T2*, and UTE-T2* (ultrashort-echo time-enhanced T2*) mapping in the refined graduation of human meniscus degeneration with histology serving as standard-of-reference. This IRB-approved intra-individual comparative ex vivo study was performed on 24 lateral meniscus body samples obtained from 24 patients undergoing total knee replacement. Samples were assessed on a 3.0-T MRI scanner using inversion-recovery (T1), spin-lock multi-gradient-echo (T1ρ), multi-spin-echo (T2) and multi-gradient-echo (T2* and UTE-T2*) sequences to determine relaxation times of quantitative MRI (qMRI) parameters. Relaxation times were calculated on the respective maps, averaged to the entire meniscus and to its zones. Histologically, samples were analyzed on a four-point score according to Williams (0-III). QMRI results and Williams (sub)scores were correlated using Spearman’s ρ, while Williams grade-dependent differences were assessed using Kruskal–Wallis and Dunn’s tests. Sensitivities and specificities in the detection of intact (Williams grade [WG]-0) and severely degenerate meniscus (WG-II-III) were calculated. Except for T2*, significant increases in qMRI parameters with increasing Williams grades were observed. T1, T1ρ, T2, and UTE-T2* exhibited high sensitivity and variable specificity rates. Significant marked-to-strong correlations were observed for these parameters with each other, with histological WGs and the subscores tissue integrity and cellularity. QMRI mapping holds promise in the objective evaluation of human meniscus. Although sufficient discriminatory power of T1, T1ρ, T2, and UTE-T2* was only demonstrated for the histological extremes, these data may aid in the future MRI-based parameterization and quantification of human meniscus degeneration.

Objective To evaluate the usefulness of quantitative parameters obtained by optical coherence tomography (OCT) and magnetic resonance imaging (MRI) in the comprehensive assessment of human articular cartilage degeneration. Materials and methods Human osteochondral samples of variable degeneration (n = 45) were obtained from total knee replacements and assessed by MRI sequences measuring T1, T1r, T2 and T2* relaxivity and by OCT-based quantification of irregularity (OII, optical irregularity index), homogeneity (OHI, optical homogeneity index]) and attenuation (OAI, optical attenuation index]). Samples were also assessed macroscopically (Outerbridge classification) and histologically (Mankin classification) as grade-0 (Mankin scores 0-4)/grade-I (scores 5-8)/grade-II (scores 9-10)/grade-III (score 11-14). After data normalisation, differences between Mankin grades and correlations between imaging parameters were assessed using ANOVA and Tukey's post-hoc test and Spearman's correlation coefficients, respectively. Sensitivities and specificities in the detection of Mankin grade-0 were calculated. Results Significant degeneration-related increases were found for T2 and OII and decreases for OAI, while T1, T1r, T2* or OHI did not reveal significant changes in relation to degeneration. A number of significant correlations between imaging parameters and histological (sub)scores were found, in particular for T2 and OII. Sensitivities and specificities in the detection of Mankin grade-0 were highest for OHI/T1 and OII/T1r, respectively. Conclusion Quantitative OCT and MRI techniques seem to complement each other in the comprehensive assessment of cartilage degeneration. Sufficiently large structural and compositional changes in the extracellular matrix may thus be parameterized and quantified, while the detection of early degeneration remains challenging.

Optical Coherence Tomography (OCT) is an imaging technique that allows the surface and subsurface evaluation of semitransparent tissues by generating microscopic cross-sectional images in real time, to millimetre depths and at micrometre resolutions. As the differentiation of cartilage degeneration remains diagnostically challenging to standard imaging modalities, an OCT- and MRI-compatible indentation device for the assessment of cartilage functional properties was developed and validated in the present study. After describing the system design and performing its comprehensive validation, macroscopically intact human cartilage samples (n=5) were indented under control of displacement (delta 1=202 mu m; delta 2=405 mu m; delta 3=607 mu m; delta 4=810 mu m) and simultaneous OCT imaging through a transparent indenter piston in direct contact with the sample; thus, 3-D OCT datasets from surface and subsurface areas were obtained. OCT-based evaluation of loading-induced changes included qualitative assessment of image morphology and signal characteristics. For inter-method cross referencing, the device's compatibility with MRI as well as qualitative morphology changes under analogous indentation loading conditions were evaluated by a series of T2 weighted gradient echo sequences. Cartilage thickness measurements were performed using the needle-probe technique prior to OCT and MRI imaging, and subsequently referenced to sample thickness as determined by MRI and histology. Dynamic indentation testing was performed to determine Young's modulus for biomechanical reference purposes. Distinct differences in sample thickness as well as corresponding strains were found; however, no significant differences in cartilage thickness were found between the used techniques. Qualitative assessment of OCT and MRI images revealed either distinct or absent sample-specific patterns of morphological changes in relation to indentation loading. For OCT, the tissue area underneath the indenter piston could be qualitatively assessed and displayed in multiple reconstructions, while for MRI, T2 signal characteristics indicated the presence of water and related tissue pressurisation within the sample. In conclusion, the present indentation device has been developed, constructed and validated for qualitative assessment of human cartilage and its response to loading by OCT and MRI. Thereby, it may provide the basis for future quantitative approaches that measure loading-induced deformations within the tissue to generate maps of local tissue properties as well as investigate their relation to degeneration.

Polarization-sensitive optical coherence tomography (PS-OCT) is a light-based, high-resolution, real-time, noninvasive, and nondestructive imaging modality yielding quasimicroscopic cross-sectional images of cartilage. As yet, comprehensive parameterization and quantification of birefringence and tissue properties have not been performed on human cartilage. PS-OCT and algorithm-based image analysis were used to objectively grade human cartilage degeneration in terms of surface irregularity, tissue homogeneity, signal attenuation, as well as birefringence coefficient and band width, height, depth, and number. Degeneration-dependent changes were noted for the former three parameters exclusively, thereby questioning the diagnostic value of PS-OCT in the assessment of human cartilage degeneration.

Early diagnosis and treatment of cartilage degeneration is of high clinical interest. Loss of surface integrity is considered one of the earliest and most reliable signs of degeneration, but cannot currently be evaluated objectively. Optical Coherence Tomography (OCT) is an arthroscopically available light-based non-destructive real-time imaging technology that allows imaging at micrometre resolutions to millimetre depths. As OCT-based surface evaluation standards remain to be defined, the present study investigated the diagnostic potential of 3D surface profile parameters in the comprehensive evaluation of cartilage degeneration. To this end, 45 cartilage samples of different degenerative grades were obtained from total knee replacements (2 males, 10 females; mean age 63.8 years), cut to standard size and imaged using a spectral-domain OCT device (Thorlabs, Germany). 3D OCT datasets of 8 × 8, 4 × 4 and 1 × 1 mm (width × length) were obtained and pre-processed (image adjustments, morphological filtering). Subsequent automated surface identification algorithms were used to obtain the 3D primary profiles, which were then filtered and processed using established algorithms employing ISO standards. The 3D surface profile thus obtained was used to calculate a set of 21 3D surface profile parameters, i.e. height (e.g. Sa), functional (e.g. Sk), hybrid (e.g. Sdq) and segmentation-related parameters (e.g. Spd). Samples underwent reference histological assessment according to the Degenerative Joint Disease classification. Statistical analyses included calculation of Spearman's rho and assessment of inter-group differences using the Kruskal Wallis test. Overall, the majority of 3D surface profile parameters revealed significant degeneration-dependent differences and correlations with the exception of severe end-stage degeneration and were of distinct diagnostic value in the assessment of surface integrity. None of the 3D surface profile parameters investigated were capable of reliably differentiating healthy from early-degenerative cartilage, while scan area sizes considerably affected parameter values. In conclusion, cartilage surface integrity may be adequately assessed by 3D surface profile parameters, which should be used in combination for the comprehensive and thorough evaluation and overall improved diagnostic performance. OCT- and image-based surface assessment could become a valuable adjunct tool to standard arthroscopy.

Biomedical optics express 6(7), 2398-2411 (2015). doi:10.1364/BOE.6.002398, Published by Optical Society of America (OSA), PubMed Central, Washington, DC

Background Abrasion arthroplasty (AAP) is a procedure by which intrinsic cartilage healing is believed to be stimulated. Although clinically accepted for degenerative and traumatic cartilage lesions scientific evidence at a molecular level that proves the effect of AAP is scarce. Method Mononuclear cells were extracted from postoperative joint effusions 21.5 h post AAP and simple debridement of cartilage lesions. Luminex, ELISA and FACS experiments were performed. Immunohistochemical stainings of cell cultures for cartilage markers were used to confirm the findings. Results Postoperative joint effusions after AAP showed increased contents of Mononuclear cells compared to Arthroscopic Chondroplasty (ACP). BMP-4 and IGF were increased in AAP as complared to ACP. Mononuclear cells isolated after AAP express the MSC markers CD 73, CD 105, CD 90, CD 44 and are CD34 negative. Chondrogenic differentiation was demonstrated by positive staining for Sox9, collagen II, proteoglycan, chondroitin-4-sulfate. Conclusion Our results support the clinical application of AAP as a procedure that enhances cartilage repair as an alternative to far more complex procedures that have gained popularity. Furthermore the data presented supports clinical investigations that recommend not to use suction drainage as by this procedure a considerable amount of the regeneratory potential of postoperative joint effusions might be extracted.

Optical Coherence Tomography (OCT) is an evolving imaging technology allowing non-destructive imaging of cartilage tissue at near-histological resolution. This study investigated the diagnostic value of real time 3-D OCT in comparison to conventional 2-D OCT in the comprehensive grading of human cartilage degeneration. Fifty-three human osteochondral samples were obtained from eight total knee arthroplasties. OCT imaging was performed by either obtaining a single two-dimensional cross-sectional image (2-D OCT) or by collecting 100 consecutive parallel 2-D OCT images to generate a volumetric data set of 8 × 8 mm (3-D OCT). OCT images were assessed qualitatively according to a modified version of the DJD classification and quantitatively by algorithm-based evaluation of surface irregularity, tissue homogeneity, and signal attenuation. Samples were graded according to the Outerbridge classification and statistically analyzed by one-way ANOVA, Kruskal Wallis and Tukey's or Dunn's post-hoc tests. Overall, the generation of 3-D volumetric datasets and their multiple reconstructions such as rendering, surface topography, parametric, and cross-sectional views proved to be of potential diagnostic value. With increasing distance to the mid-sagittal plane and increasing degeneration, score deviations increased, too. In conclusion, 3-D imaging of cartilage with image analysis algorithms adds considerable potential diagnostic value to conventional OCT diagnostics.

Optical Coherence Tomography (OCT) yields microscopic cross-sectional images of cartilage in real time and at high resolution. As yet, comprehensive grading of degenerative cartilage changes based on OCT has rarely been performed. This study investigated the potential of quantitative OCT using algorithm-based image parameters such as irregularity (OII - Optical Irregularity Index), homogeneity (OHI - Optical Homogeneity Index) and attenuation (OAI - Optical Attenuation Index) in the objective grading of cartilage degeneration. Therefore, OCT was used to image and assess 113 human osteochondral samples obtained from total knee replacements. Processing included the analysis of OII (by calculation of the standard deviation with regards to a fitted surface), of OHI (by edge detection of tissue signal changes) and of OAI (by analysis of relative imaging depth). Additionally, samples were subject to macroscopic (Outerbridge grading), biomechanical (elastic stiffness), qualitative OCT and histological evaluation (Modified Mankin grading). Significant correlations were found between all outcome measures. OII and OHI were effective in assessing cartilage surface, integrity and homogeneity, while OAI could discriminate between unmineralized and mineralized cartilage, respectively. Therefore, quantitative OCT holds potential as a diagnostic tool for more reliable, standardized and objective assessment of cartilage tissue properties.

Purpose This study investigated the potential of cyclic compressive loading in the generation of in vitro engineered cartilaginous tissue with the aim of contributing to a better understanding of mechanical preconditioning and its possible role in further optimizing existing matrix-associated cartilage replacement procedures. Methods Human chondrocytes were harvested from 12 osteoarthritic knee joints and seeded into a type I collagen (col-I) hydrogel at low density (2 × 10(5) cells/ml gel). The cell-seeded hydrogel was condensed and cultivated under continuous cyclic compressive loading (frequency: 0.3 Hz; strain: 10%) for 14 days under standardized conditions. After retrieval, specimens were subject to staining, histomorphometric evaluation, gene expression analysis and biomechanical testing. Results Cellular morphology was altered by both stimulation and control conditions as was staining for collagen II (col-II). Gene expression measurements revealed a significant increase for col-II under either cultivation condition. No significant differences in col-I, aggrecan and MMP-13 gene expression profiles were found. The col-II/col-I mRNA ratio significantly increased under stimulation, whereas the biomechanical properties deteriorated under either cultivation method. Conclusions Although the effects observed are small, mechanical preconditioning has demonstrated its potential to modulate biological properties of collagen hydrogels seeded with human chondrocytes.

Optical Coherence Tomography (OCT) as emerging clinical diagnostic imaging technology for dermatology and other semitransparent tissues has shown high potential in monitoring and evaluating the inner structure of articular cartilages. Since novel therapies for the limitation of cartilage degeneration in early stages of osteoarthritis are available, the early minimal invasive diagnosis of cartilage degradation is clinically essential for further treatment options. With the advancing performance and thus diagnostic opportunities of 3D-OCT devices, we carried out a systematic study by monitoring arthrotic alterations of porcine osteochondral explants that are mechanically induced under traumatic impaction. As for in-vitro tomographic imaging we utilized two OCT devices, a Thorlabs FD-OCT device with 92KHz A-scan rate and 1310nm as central wavelength and a self-developed FD-OCT device at 840nm central wavelength. This allows the comparison in image contrast and optical penetration of cartilage tissue between these two spectral bandwidths. Further we analyzed human biopsies of articular cartilages with various degrees of osteoarthritis. The 2D and 3D OCT tomograms are characterized qualitatively regarding the inner tissue structure and quantitatively regarding the tissue absorption parameters. Therefore, we are developing image processing algorithms for the automated monitoring of cartilage tissue. A scoring system for 3D-monitoring allows the characterization of the probe volume regarding the morphological structure and tissue compactness by processing the C - scan data.

This study evaluated the incidence, amount, morphology and clinical significance of bone tunnel widening (TW) at a mean 5-year period after anterior cruciate ligament reconstruction (ACLR) with a transtibial drilling technique. Fifty-nine patients undergoing primary ACLR using quadrupled hamstring autografts, biodegradable transfemoral pins for femoral-sided and 2-mm oversized interference screws for tibial-sided graft fixation were followed up at a mean 61 months postoperatively. Patients were examined clinically and by MRI. Tunnel cross-sectional areas (CSA) were related to drill diameters, which were significantly correlated with radiographic tunnel sizes. Tunnel morphologies were assessed and their positions determined using an anatomical coordinate system. CSA had more than doubled in all segments measured (p

Cartilage repair strategies increasingly focus on the in vitro development of cartilaginous tissues that mimic the biological and mechanical properties of native articular cartilage. However, current approaches still face problems in the reproducible and standardized generation of cartilaginous tissues that are both biomechanically adequate for joint integration and biochemically rich in extracellular matrix constituents. In this regard, the present study investigated whether long-term continuous compressive loading would enhance the mechanical and biological properties of such tissues. Human chondrocytes were harvested from 8 knee joints (n=8) of patients having undergone total knee replacement and seeded into a collagen type I hydrogel at low density of 2×10(5)cells/ml gel. Cell-seeded hydrogels were cut to disks and subjected to mechanical stimulation for 28 days with 10% continuous cyclic compressive loading at a frequency of 0.3 Hz. Histological and histomorphometric evaluation revealed long-term mechanical stimulation to significantly increase collagen type II and proteoglycan staining homogenously throughout the samples as compared to unstimulated controls. Gene expression analyses revealed a significant increase in collagen type II, collagen type I and MMP-13 gene expression under stimulation conditions, while aggrecan gene expression was decreased and no significant changes were observed in the collagen type II/collagen type I mRNA ratio. Mechanical propertywise, the average value of elastic stiffness increased in the stimulated samples. In conclusion, long-term mechanical preconditioning of human chondrocytes seeded in collagen type I hydrogels considerably improves biological and biomechanical properties of the constructs, corroborating the clinical potential of mechanical stimulation in matrix-associated autologous chondrocyte transplantation (MACT) procedures.

For the development of articular cartilage replacement material, it is essential to study the dependence between mechanical stimulation and cell activity in cellular specimens. Bioreactor cultivation is widely used for this purpose, however, it is hardly possible to obtain a quantitative relationship between collagen type II production and applied loading history. For this reason, a bioreactor system is developed, measuring applied forces and number of loading cycles by means of a load cell and a forked light barrier, respectively. Parallel to the experimental study, a numerical model by means of the finite element method is proposed to simulate the evolution of material properties during cyclic stimulation. In this way, a numerical model can be developed for arbitrary deformation cases.

The aim of the paper is to investigate the remodeling phenomenon of a cell-seeded material (collagen type-I) due to collagen type-II newly synthesized by the cells. For the experiments, a cell-seeded condensed collagen gel is mechanically stimulated in a bioreactor for four weeks. The remodeled stiffness of the cell-seeded gel is measured by a compression test and is explained with an evolution law. (© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)