Disertační práce se zabývá experimentálním studiem viskosuplementů na bázi kyseliny hyaluronové, které se aplikují do synoviálních kloubů postižených osteoartrózou. Hlavní pozornost byla věnována objasnění vlivu koncentrace a molekulové hmotnosti kyseliny hyaluronové na tření v kontaktu kloubí chrupavky resp. změnám tření v kontaktu po smíchání osteoartritické synoviální kapaliny s exogenní kyselinou hyaluronovou. Důležitou součástí experimentů bylo rovněž studium reologických vlastností synoviální kapaliny a kyseliny hyaluronové. Výsledky ukázaly, že molekulová hmotnost kyseliny hyaluronové významně ovlivňuje viskozitu a viskoelastické vlastnosti roztoku. Výrazná závislost mezi reologickými vlastnostmi kyseliny hyaluronové a třením v kontaktu však nebyla pozorována. Přimíchání kyseliny hyaluronové do synoviální kapaliny způsobí výrazný pokles součinitele tření v kontaktu. Rozdíly mezi viskosuplementy obsahující kyselinu hyaluronovou s různou molekulovou hmotností ale nijak výrazné nejsou. Nicméně, výsledky poukazují na možné ovlivnění režimu mazání v důsledku vysoké molekulové hmotnosti kyseliny hyaluronové. Tyto původní výsledky rozšiřují pochopení mechanizmů, ke kterým dochází v kloubu bezprostředně do vstříknutí kyseliny hyaluronové a mohou být použity při dalším vývoji viskosuplementů či v klinické praxi.

Knee pain can alter lower-extremity neuromechanics and often results in functional disability. The relationship between lower-extremity neuromechanical alterations, due to anterior knee pain, and articular cartilage condition is unclear. The purpose of this study was to determine the independent effect of anterior knee pain during running on articular cartilage condition, as reflected by serum cartilage oligomeric matrix protein concentrations and muscle cocontraction duration. Seven men and five women completed a 30-min run in three different sessions: control (no infusion), sham (isotonic saline infusion), and pain (hypertonic saline infusion). Saline was infused into the right infrapatellar fat pad for the duration of the run. Subject-perceived pain was recorded every 3 min on a 100-mm visual analog scale. During the run, bilateral electromyography was recorded for five leg muscles, and heel and toe markers were used to track foot position. During the 30-min run of the pain session average subject-perceived pain was 27.8 (SD = 2.3 mm) and 19.7 (SD = 1.9) mm greater than during the control (0.0 mm) and sham (8.1 mm) session, respectively (p < 0.01). Knee pain while running did not result in changes in muscular cocontraction duration (p = 0.13). Blood samples were drawn prior to the run, immediately following the run, and 60 min following the run. Samples were analyzed using enzyme-linked immunosortbent assay to determine serum cartilage oligomeric matrix protein concentration. Average serum cartilage oligomeric matrix protein concentration was 14% greater at immediate post run (132.19 ± 158.61 ng/ml; Range = 22.61-290.81 ng/ml) relative to pre run (116.02 ± 118.87 ng/ml; Range = 19.81-234.89 ng/ml) (p < 0.01), and 18% less at 60 min post run (108.45 ± 171.78 ng/ml; Range = 20.84-280.23 ng/ml) relative to immediate post run (Figure 4; p < 0.01). Serum cartilage oligomeric matrix protein did not significantly differ between baseline and 60 min post-exercise (p = 0.29). There was not a difference in cartilage oligomeric matrix protein concentration between sessions. Knee pain while running does not cause an increase in serum cartilage oligomeric matrix protein concentration (p = 0.29). There are two important findings from this study. First, anterior knee pain during a 30 min running session does not appear to independently affect cartilage oligomeric matrix protein concentrations. This implies other factors, aside from anterior knee pain alone, influence articular cartilage degradation during movement that occurs while individuals are experiencing anterior knee pain. Second, the present experimental anterior knee pain model can be used to evaluate the independent effects of anterior knee pain over an extended duration while subjects perform a dynamic activity like running.

Although glucocorticoids are often used as an adjunct to epinephrine to treat anaphylactic shock, glucocorticoids can also be a rare cause of anaphylactic shock. Only through the administration of a challenge dose of different glucocorticoids and different substrates that glucocorticoids are delivered in can the determination be made about which glucocorticoid or accompanying solvent may be the culprit which caused the anaphylactic reaction. These challenge tests should only be performed in a controlled environment as repeat anaphylaxis is a risk, especially if the patient has a history of glucocorticoid-induced anaphylaxis.

Osteoarthritis (OA) is a degenerative condition of cartilage and is the leading cost of disability in the United States. Motion analysis experiments in combination with knee-joint finite element (FE) analysis may be used to identify exercises that maintain knee-joint osteochondral (OC) loading at safe levels for patients at high-risk for knee OA, individuals with modest OC defects, or patients rehabilitating after surgical interventions. Therefore, a detailed total knee-joint FE model was developed by modifying open-source knee-joint geometries in order to predict OC tissue stress and strain during the stance phase of gait. The model was partially validated for predicting the timing and locations of maximum contact parameters (contact pressure, contact area, and principal Green-Lagrangian strain), but over-estimated contact parameters compared with both published in vivo studies and other FE analyses of the stance phase of gait. This suggests that the model geometry and kinematic boundary conditions utilized in this FE model are appropriate, but limitations in the material properties used, as well as potentially the loading boundary conditions represent primary areas for improvement.

Introduction: Articular cartilage (AC) is a low friction load bearing material found in synovial joints. The natural repair of damaged tissue is difficult and often requires surgical intervention. With large defects it becomes necessary to match the original tissue geometry. We hypothesized that localized collagen (COL) and/or proteoglycan (PG) remodeling occurs during AC spherical reshaping. The objective of this study was to determine the presence, magnitude and depth dependence of COL and PG remodeling that accompanies AC reshaping. Methods: Full thickness AC blocks (7x7 mm2 surface area) were harvested from the ridges of the patellofemoral groove of immature (1-3 week old) bovine knees. The top 0-1 mm with intact articular surface was sliced off with a vibrating microtome. A 6 mm diameter disk was punched out of the slice and the most anterior edge was notched to mark directionality. The final sample was a 1 mm thick, 6 mm diameter disk with a notch on the most anterior edge. Samples were either not treated (day 0; D0) or allowed to free swell overnight in 20% FBS. Then cultured samples were placed in culture with 20% FBS in either free swelling (FS), static bending with the articular surface concave (concave) or in static bending with the articular surface convex (convex). Wet-weight and opening angle were measured before and 2 hours after removal from culture. Following culture, samples were cut in half in the anterior posterior direction. One half of each sample was frozen and later analyzed for PG, COL and cell content. The other half was fixed for 24-48 hours in 4% paraformaldehyde; samples were then transferred to 20% Hexabrix for 24 hours before imaging by micro-computed tomography (μCT) to assess PG distribution. Following μCT, samples were again placed in 4% paraformaldehyde for 24-48 hours and then prepared for qPLM to assess collagen orientation (α), parallelism index (PI), and area fraction of non-birefringent tissue (AFNBR). Variations were assessed by ANOVA with post hoc tests for significant ANOVA (pResults: Four days of spherical bending significantly changed (pDiscussion: Spherical bending reshapes AC into a cup shape. Trends of decreasing α standard deviation (αSD) with depth in concave samples and increasing αSD with depth in convex samples indicate that COL matrix disorganization is associated with regions of compressive strain. Consequently, further evaluation on the disorganization of the collagen network should be studied to elucidate mechanisms of cartilage reshaping.

Yes / Articular cartilage is a vascular tissue with limited repair capabilities, leaving an afflicted person in extreme pain. The tissue experiences numerous forces throughout its lifetime. This study focuses on development of a novel hydrogel composed of chitosan and β-glycerophosphate for articular cartilage repair. The aim of this study was to investigate the mechanical properties and swelling behaviour of a novel hydrogel composed of chitosan and β-glycerophosphate for cartilage repair. The mechanical properties were measured for compression forces. Mach-1 mechanical testing system was used to obtain storage and loss modulus for each hydrogel sample to achieve viscoelastic properties of fabricated hydrogels. Two swelling tests were carried out to compare water retaining capabilities of the samples. The hydrogel samples were made of five different concentrations of β-glycerophosphate cross-linked with chitosan. Each sample with different β-glycerophosphate concentration underwent sinusoidal compression forces at three different frequencies -0.1Hz, 0.316Hz and 1Hz. The result of mechanical testing was obtained as storage and loss modulus. Storage modulus represents the elastic component and loss modulus represents the viscosity of the samples. The results obtained for 1Hz were of interest because the knee experiences frequency of 1Hz during walking.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24830号 / 医博第4998号 / 新制||医||1067(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 後藤, 慎平, 教授 河本, 宏, 教授 羽賀, 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background: Fresh osteochondral allograft (OCA) transplantation represents a biologic restoration technique as an alternative treatment option for larger osteochondral lesions of the talus (OLT). The purpose of this study was to evaluate midterm outcomes after OCA transplantation for the treatment of OLT. Methods: Nineteen patients (20 ankles) received partial unipolar OCA transplant for symptomatic OLT between January 1998 and October 2014. The mean age was 34.7 years, and 53% were male. The average graft size was 3.8 cm2. All patients had a minimum follow-up of 2 years. Outcomes included the American Academy of Orthopaedic Surgeons Foot and Ankle Module (AAOS-FAM), the Olerud-Molander Ankle Score (OMAS), and pain and satisfaction questionnaires. Failure of OCA was defined as conversion to arthrodesis or revision OCA transplantation. Results: Five of 20 ankles (25%) required further surgery, of which 3 (5%) were considered OCA failures (2 arthrodesis and 1 OCA revision). The mean time to failure was 3.5 (range, 0.9 to 6.7) years. Survivorship was 88.7% at 5 years and 81.3% at 10 years. The median follow-up of the 17 patients with grafts in situ was 9.7 years. The mean OMAS improved significantly from 40 points preoperatively to 71 points postoperatively (P < .05; range, 5 to 55). The mean postoperative AAOS-FAM core score was 81.5 ± 15 (range, 40.5 to 96.6). Fifteen of 17 patients responded to follow-up questions regarding their ankle; 14 patients reported less pain and better function, and 13 patients were satisfied with the results of the procedure. Conclusion: Our study of midterm results after OCA transplantations showed that this procedure was a reasonable treatment option for large OLT. Level of Evidence: Level IV, case series.

In search of better scaffolding materials for in vitro culture of chondrocytes, the combination of chitosan (similar to glycosoaminoglycans) and gelatin (denatured collagen) was tested due to its resemblance to cartilage extra-cellular matrix (ECM). Porous scaffolds were fabricated from chitosan gelatin blends (1:1, 2:1, and 3:1). The response of chondrocytes to them was evaluated from the amount of sulphated GAG and collagen type 2 secreted after 3 and 5 weeks. The effect due to static (transwell inserts) and dynamic (rotating bioreactor) culture methods was analyzed. Results indicate that 1:1 chitosan gelatin blends showed the best chondro-conductive potential. The rotating bioreactor facilitated better cell distribution across scaffold but did not show higher ECM secretion compared to transwell culture after 3 weeks. Gelatin leeched out by dissolution in culture media and left an open and interconnected chitosan network. Chitosan gelatin scaffolds show a potential for use in cartilage tissue engineering applications

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