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1.
Arthroscopy ; 34(4): 1072-1082, 2018 04.
Article in English | MEDLINE | ID: mdl-29305291

ABSTRACT

PURPOSE: Objective evaluation of the optimal graft tension angle to fully restore patellofemoral contact pressure in reconstruction of the medial patellofemoral ligament (MPFL) in comparison to the native knee. METHODS: Twelve cadaveric knee specimens were fixed in a custom-made fixation device. A sensitive pressure film (Tekscan) was fixed in the patellofemoral joint, and patellofemoral contact pressure was assessed during a dynamic flexion movement from 0° to 90°. The MPFL was cut and measurements were repeated. Reconstruction of the MPFL was performed with the gracilis tendon subsequently fixed in the femur at 15°, 30°, 45°, 60°, 75°, and 90° of knee flexion under controlled tension (2 N). The sequence of the flexion angles was alternated. Pressure measurements were repeated after every fixation of the graft. RESULTS: No significant differences were seen in the overall patellofemoral contact pressure compared to the native knee (P > .05). However, medial patellofemoral pressure showed a significant increased patellofemoral contact pressure after MPFL reconstruction at a knee flexion angle during graft fixation of 15° (P = .027), 45° (P = .050, P = .044), and 75° (P = .039). Moreover, proximal/distal patellofemoral contact pressure revealed a significantly reduced contact pressure at 15° (P = .003), 30° (P = .009), 45° (P = .025), 75° (P = .021), and 90° (P = .022) of flexion distal after MPFL reconstruction compared with the intact knee. Lateral patellofemoral contact pressure was significantly reduced in all performed reconstructions (P < .05). CONCLUSIONS: The flexion angle during graft fixation for MPFL reconstruction did not have a significant impact on the overall patellofemoral contact pressure. However, selective medial, proximal, distal, and lateral patellofemoral contact pressure was significantly altered for all reconstructions. Fixation of the MPFL graft at 60° of flexion was able to most closely restore patellofemoral contact pressure compared with the intact knee. CLINICAL RELEVANCE: Based on the findings of the present study, fixation of the graft in anatomic reconstruction of the MPFL should be considered in 60° of flexion under low tension (2 N) to most closely restore patellofemoral contact pressure compared with the native knee.


Subject(s)
Knee Injuries/surgery , Ligaments, Articular/surgery , Patellofemoral Joint/surgery , Tendons/transplantation , Biomechanical Phenomena/physiology , Cadaver , Femur/surgery , Gracilis Muscle , Humans , Knee Injuries/physiopathology , Knee Joint/pathology , Knee Joint/physiopathology , Knee Joint/surgery , Ligaments, Articular/injuries , Ligaments, Articular/physiopathology , Patellofemoral Joint/physiopathology , Pressure , Range of Motion, Articular
2.
J Cell Mol Med ; 21(11): 2748-2758, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28467017

ABSTRACT

Implantation of peripheral blood aspirates induced towards chondrogenic differentiation upon genetic modification in sites of articular cartilage injury may represent a powerful strategy to enhance cartilage repair. Such a single-step approach may be less invasive than procedures based on the use of isolated or concentrated MSCs, simplifying translational protocols in patients. In this study, we provide evidence showing the feasibility of overexpressing the mitogenic and pro-anabolic insulin-like growth factor I (IGF-I) in human peripheral blood aspirates via rAAV-mediated gene transfer, leading to enhanced proliferative and chondrogenic differentiation (proteoglycans, type-II collagen, SOX9) activities in the samples relative to control (reporter rAAV-lacZ) treatment over extended periods of time (at least 21 days, the longest time-point evaluated). Interestingly, IGF-I gene transfer also triggered hypertrophic, osteo- and adipogenic differentiation processes in the aspirates, suggesting that careful regulation of IGF-I expression may be necessary to contain these events in vivo. Still, the current results demonstrate the potential of targeting human peripheral blood aspirates via therapeutic rAAV transduction as a novel, convenient tool to treat articular cartilage injuries.


Subject(s)
Chondrocytes/metabolism , Chondrogenesis/genetics , Dependovirus/genetics , Insulin-Like Growth Factor I/genetics , Mesenchymal Stem Cells/metabolism , Biomarkers/metabolism , Cell Differentiation , Cell Proliferation , Cell- and Tissue-Based Therapy , Chondrocytes/cytology , Collagen Type II/genetics , Collagen Type II/metabolism , Dependovirus/metabolism , Gene Expression , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Humans , Insulin-Like Growth Factor I/metabolism , Lac Operon , Mesenchymal Stem Cells/cytology , Primary Cell Culture , Proteoglycans/genetics , Proteoglycans/metabolism , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism , Transduction, Genetic/methods , Transgenes
3.
Knee Surg Sports Traumatol Arthrosc ; 25(8): 2502-2510, 2017 Aug.
Article in English | MEDLINE | ID: mdl-26820966

ABSTRACT

PURPOSE: To evaluate the knee kinematics of the intact, MPFL-ruptured and MPFL-reconstructed knee and, moreover, to compare dynamic patellofemoral contact pressure of the gracilis tendon and the fascia lata as an alternative graft option for reconstruction of the MPFL. METHODS: Eight paired human cadaveric knees were fixed in a custom-made fixation device. Patellofemoral contact pressure was assessed during a dynamic flexion movement at 15°-30°-45°-60°-75° and 90° using a pressure-sensitive film (Tekscan). The medial patellofemoral ligament was cut, and measurements were repeated. Finally, reconstruction of the MPFL was performed using the gracilis tendon (group I) or a fascia lata graft (group II). Tunnel localization was performed under fluoroscopic control. Grafts were fixed at 30° of flexion, and pressure measurements were repeated. RESULTS: Incision of the medial patellofemoral ligament significantly reduced patellofemoral contact pressure at 15°, 30° and 45° of knee flexion compared to the intact knee (p < 0.05), whereas reconstruction of the MPFL using either gracilis tendon of the fascia lata was able to restore pressure distributions at 15° and 30° of knee flexion. However, in the hamstring group, reconstruction of the MPFL revealed a significantly reduced contact pressure at 45° of flexion (p = 0.038) compared to the intact knee. In the fascia lata group, a significant reduction in patellofemoral contact pressure was observed after MPFL reconstruction at 45°, 60°, 75° and 90° of knee flexion (p < 0.05). CONCLUSIONS: Anatomic reconstruction of the MPFL with either a gracilis or a fascia lata graft showed comparable patellofemoral pressure distributions which were closely restored compared to the native knee. Therefore, the fascia lata has shown to be a viable alternative to the gracilis tendon for reconstruction of the MPFL. However, anatomic reconstruction of the MPFL may lead to persistently altered patellofemoral contact pressure during knee flexion compared to the native knee independent of the tested graft.


Subject(s)
Fascia Lata/transplantation , Gracilis Muscle/surgery , Ligaments, Articular/surgery , Patellofemoral Joint/surgery , Pressure , Range of Motion, Articular , Tendons/transplantation , Biomechanical Phenomena , Cadaver , Fluoroscopy , Hamstring Muscles , Humans , Knee Joint/physiopathology , Knee Joint/surgery , Ligaments, Articular/physiopathology , Patellofemoral Joint/physiopathology , Plastic Surgery Procedures
4.
Arch Orthop Trauma Surg ; 137(12): 1719-1724, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28942510

ABSTRACT

INTRODUCTION: The reliable diagnosis of partial-thickness tears of the rotator cuff is still elusive in clinical practise. Therefore, the purpose of the study was to determine the diagnostic accuracy of MR imaging and clinical tests for detecting partial-thickness tears of the rotator cuff as well as the combination of these parameters. MATERIALS AND METHODS: 334 consecutive shoulder arthroscopies for rotator cuff pathologies performed during the time period between 2010 and 2012 were analyzed retrospectively for the findings of common clinical signs for rotator cuff lesions and preoperative MR imaging. These were compared with the intraoperative arthroscopic findings as "gold standard". The reports of the MR imaging were evaluated with regard to the integrity of the rotator cuff. The Ellman Classification was used to define partial-thickness tears of the rotator cuff in accordance with the arthroscopic findings. Descriptive statistics, sensitivity, specificity, positive and negative predictive value were calculated. RESULTS: MR imaging showed 80 partial-thickness and 70 full-thickness tears of the rotator cuff. The arthroscopic examination confirmed 64 partial-thickness tears of which 52 needed debridement or refixation of the rotator cuff. Sensitivity for MR imaging to identify partial-thickness tears was 51.6%, specificity 77.2%, positive predictive value 41.3% and negative predictive value 83.7%. For the Jobe-test, sensitivity was 64.1%, specificity 43.2%, positive predictive value 25.9% and negative predictive value 79.5%. Sensitivity for the Impingement-sign was 76.7%, specificity 46.6%, positive predictive value 30.8% and negative predictive value 86.5%. For the combination of MR imaging, Jobe-test and Impingement-sign sensitivity was 46.9%, specificity 85.4%, positive predictive value 50% and negative predictive value 83.8%. CONCLUSIONS: The diagnostic accuracy of MR imaging and clinical tests (Jobe-test and Impingement-sign) alone is limited for detecting partial-thickness tears of the rotator cuff. Additionally, the combination of MR imaging and clinical tests does not improve diagnostic accuracy. LEVEL OF EVIDENCE: Level II, Diagnostic study.


Subject(s)
Magnetic Resonance Imaging , Physical Examination , Rotator Cuff Injuries/diagnostic imaging , Rotator Cuff Injuries/diagnosis , Adult , Aged , Aged, 80 and over , Arthroscopy , Female , Humans , Male , Middle Aged , Retrospective Studies , Rotator Cuff/diagnostic imaging , Rotator Cuff Injuries/classification , Sensitivity and Specificity
5.
J Cutan Pathol ; 43(8): 711-6, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27106295

ABSTRACT

Painful subungual tumor masses in the toes usually emerge as glomus tumors or subungual exostoses. We present a patient with an aneurysmal bone cyst located subungually in whom the diagnosis was delayed due to inadequate diagnostic procedures, which led to marked destruction of the distal phalanx of the great toe of the right foot. After biopsy, the distal phalanx could not be preserved due to critical soft tissue involvement and the size of the process. Thus, we describe this rare entity to encourage clinicians to establish the diagnosis by biopsy of a tissue swelling of unclear origin and duration that does not resolve after a short time. Imaging examinations are useful in demonstrating periosteal involvement and extension of the lesion and can be helpful in the diagnostic algorithm. An interdisciplinary approach is a top priority to ensure optimal treatment.


Subject(s)
Bone Cysts, Aneurysmal/pathology , Nail Diseases/pathology , Adult , Humans , Male , Toes/pathology
6.
Knee Surg Sports Traumatol Arthrosc ; 24(7): 2174-80, 2016 Jul.
Article in English | MEDLINE | ID: mdl-25293677

ABSTRACT

PURPOSE: Biomechanical comparison of three different fixation techniques for a proximal biceps tenodesis. METHODS: Eighteen human cadaver specimens were used for the testing. A tenodesis of the proximal biceps tendon was performed using a double-loaded suture anchor (5.5-mm Corkscrew, Arthrex), a knotless anchor (5.5-mm SwiveLock, Arthrex) or a forked knotless anchor (8-mm SwiveLock, Arthrex). Reconstructions were cyclically loaded for 50 cycles from 10-60 to 10-100 N. Cyclic displacement and ultimate failure loads were determined, and mode of failure was evaluated. RESULTS: Cyclic displacement at 60 N revealed a mean of 3.3 ± 1.1 mm for the Corkscrew, 5.4 ± 1.4 mm for the 5.5-mm SwiveLock and 2.9 ± 1.6 mm for the 8-mm forked SwiveLock. At 100 N, 5.1 ± 2.2 mm were seen for the Corkscrew anchor, 8.7 ± 2.5 mm for the 5.5-mm SwiveLock and 4.8 ± 3.3 mm for the 8-mm forked SwiveLock anchor. Significant lower cyclic displacement was seen for the Corkscrew anchor (p < 0.020) as well as the 8-mm SwiveLock anchor (p < 0.023) compared to the 5.5-mm SwiveLock anchor at 60 N. An ultimate load to failure of 109 ± 27 N was found for the Corkscrew anchor, 125 ± 25 N were measured for the 5.5-mm SwiveLock anchor, and 175 ± 42 N were found for the 8-mm forked SwiveLock anchor. Significant differences were seen between the 8-mm SwiveLock compared to the 5.5-mm SwiveLock (p < 0.044) as well as the Corkscrew anchor (p < 0.009). No significant differences were seen between the Corkscrew and the 5.5-mm SwiveLock anchor. CONCLUSIONS: The new 8-mm forked SwiveLock anchor significantly enhances construct stability compared to a 5.5-mm double-loaded Corkscrew anchor as well as the 5.5-mm SwiveLock suture anchor. However, a restrictive postoperative rehabilitation seems to be important in all tested reconstructions in order to avoid early failure of the construct.


Subject(s)
Materials Testing , Suture Anchors , Suture Techniques , Tenodesis/instrumentation , Biomechanical Phenomena , Cadaver , Humans , Prosthesis Design , Shoulder/surgery , Tenodesis/methods
7.
Knee Surg Sports Traumatol Arthrosc ; 24(2): 447-55, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26818554

ABSTRACT

Tears of the superior labrum involving the biceps anchor are a common entity, especially in athletes, and may highly impair shoulder function. If conservative treatment fails, successful arthroscopic repair of symptomatic SLAP lesions has been described in the literature particularly for young athletes. However, the results in throwing athletes are less successful with a significant amount of patients who will not regain their pre-injury level of performance. The clinical results of SLAP repairs in middle-aged and older patients are mixed, with worse results and higher revision rates as compared to younger patients. In this population, tenotomy or tenodesis of the biceps tendon is a viable alternative to SLAP repairs in order to improve clinical outcomes. The present article introduces a treatment algorithm for SLAP lesions based upon the recent literature as well as the authors' clinical experience. The type of lesion, age of patient, concomitant lesions, and functional requirements, as well as sport activity level of the patient, need to be considered. Moreover, normal variations and degenerative changes in the SLAP complex have to be distinguished from "true" SLAP lesions in order to improve results and avoid overtreatment. The suggestion for a treatment algorithm includes: type I: conservative treatment or arthroscopic debridement, type II: SLAP repair or biceps tenotomy/tenodesis, type III: resection of the instable bucket-handle tear, type IV: SLAP repair (biceps tenotomy/tenodesis if >50 % of biceps tendon is affected), type V: Bankart repair and SLAP repair, type VI: resection of the flap and SLAP repair, and type VII: refixation of the anterosuperior labrum and SLAP repair.


Subject(s)
Arm Injuries/surgery , Fibrocartilage/surgery , Shoulder Joint/surgery , Tendon Injuries/surgery , Adult , Algorithms , Arm Injuries/classification , Arm Injuries/diagnosis , Arthroscopy , Debridement , Fibrocartilage/injuries , Humans , Middle Aged , Reoperation , Shoulder Injuries , Shoulder Pain/etiology , Tendon Injuries/diagnosis
8.
Knee Surg Sports Traumatol Arthrosc ; 24(12): 3855-3862, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26318490

ABSTRACT

PURPOSE: Evaluation of the biomechanical performance of repairs of 25 % (Fox/Romeo II) and 50 % (Fox/Romeo III) full-thickness subscapularis tears using a single-suture anchor. METHODS: Six pairs of human cadaver specimens were used for the testing. Artificial subscapularis tears were created in order to simulate a 25 % (6) and a 50 % (6) full-thickness tear. The reconstructions were made with a double-loaded suture anchor (5.5-mm Bio-Corkscrew with two No. 2 Fiberwire) creating a double-mattress suture repair. Reconstructions were cyclically loaded from 10 to 60 N. The load was increased stepwise up to 100 and 180 N. Cyclic displacement (means + standard dev.) as well as load-to-failure was determined, and mode of failure was recorded. RESULTS: In the reconstructed shoulders at 60 N, a mean cyclic displacement of 3.2 ± 0.7 mm was found in the 25 % tear, 2.6 ± 0.6 mm in the 50 % tear. At 100 N, 5.1 ± 1.2 mm was seen in the 25 % tear and 4.3 ± 0.3 mm in the 50 % tear. At highest load of 180 N, 7.6 ± 2.2 mm was recorded in the 25 % tear, 6.5 ± 0.8 mm was found in the 50 % tear. Ultimate failure load was 486 ± 167 N in the 25 % tear and 455 ± 213 N in the 50 % tear. Statistically significant differences between the tested repairs were seen neither in cyclic displacement nor in ultimate failure loads (p > 0.05). Mode of failure revealed bone fractures and anchor pull-out as major cause in the 25 % group, whereas failure of the suture-tendon interface was the major cause of failure in the 50 % group. CONCLUSIONS: Subscapularis repair using a single double-loaded suture anchor revealed similar biomechanical performance in 25 % compared to 50 % full-thickness subscapularis tears. With increased tear size, however, an optimized suture-tendon interface seems to become more relevant in order to decrease failure rate of the repair. CLINICAL RELEVANCE: A single double-loaded suture anchor provides sufficient biomechanical strength even in Fox/Romeo grade III tears of the subscapularis tendon. However, a modified suture configuration is recommended, especially in grade III tears as the suture-tendon interface is the weakest point of the construct.


Subject(s)
Plastic Surgery Procedures/methods , Rotator Cuff Injuries/surgery , Suture Anchors , Suture Techniques , Weight-Bearing , Biomechanical Phenomena , Cadaver , Humans , Rotator Cuff/surgery , Sutures
9.
Arthroscopy ; 31(12): 2424-9.e3, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26248496

ABSTRACT

PURPOSE: To review the literature concerning surgical treatment options for chronic patellar tendinosis (jumper's knee), a common problem among athletes. When conservative treatment fails, surgical treatment is required. METHODS: Systematic review of the literature concerning the results of current surgical treatment options for chronic patellar tendinosis. All articles of studies with an evidence level ≥IV from January 2000 until February 2015 presenting the surgical outcome after arthroscopic as well as open treatment of chronic patellar tendinosis were included. The literature research of the PubMed database was performed using the following key words: "patellar" and "tendinitis," "tendonitis," "tendinosis" or "tendinopathy"; "inferior patellar pole"; "jumper's knee"; "surgical treatment" and "open" or "arthroscopic patellar tenotomy." RESULTS: A systematic review of the literature was performed especially to point out the effectiveness of arthroscopic treatment of chronic patellar tendinosis. The results revealed good clinical results for arthroscopic as well as open treatment of chronic patellar tendinosis that is refractory to conservative treatment in athletes. An average success rate of 87% was found for the open treatment group and of 91% for the arthroscopic treatment group. However, after open surgery, the mean time of return to the preinjury level of activity is 8 to 12 months, with a certain number of patients/athletes who cannot return to the preinjury level of activity. CONCLUSIONS: Minimally invasive, arthroscopically assisted or all-arthroscopic procedures may lead to a significantly faster return to sporting activities and may, therefore, be the preferred method of surgical treatment. LEVEL OF EVIDENCE: Level IV, systematic review of Level I-IV studies.


Subject(s)
Athletic Injuries/surgery , Patellar Ligament/surgery , Tendinopathy/surgery , Arthroscopy/methods , Chronic Disease , Humans , Tendinopathy/therapy
11.
Eur J Orthop Surg Traumatol ; 24(5): 707-14, 2014 Jul.
Article in English | MEDLINE | ID: mdl-23728442

ABSTRACT

BACKGROUND AND PURPOSE: The functional results and the complications following interlocking plate fixation of displaced proximal humerus fractures should be evaluated and compared with those following minimal invasive fixation techniques. PATIENTS AND METHODS: Fifty patients (30 women, 20 men, mean age 62.7 (18-91) years) were treated for a displaced proximal humerus fracture using an interlocking plate fixation (PHILOS®) between 2003 and 2004. The mean follow-up time was 12 (9-36) months. Functional and radiographic results (Constant-Murley and Neer scores) were analyzed and compared with an equivalent historical control group of 53 patients operated for the same fracture types using minimal invasive techniques (K-wires and/or cannulated screws) between 1995 and 1997. According to the OTA/AO classification, there were 15 type A, 18 type B, and 17 type C fractures in the plate fixation group, and 23, 25, and 5 of these types in the control group, respectively. RESULTS: The mean Neer score was 85.9, the mean Constant-Murley score 84, whereas 82.4 and 75.4 for the control group, respectively. Good and excellent results were seen in 78%, whereas in 70% in the control group. The results were dependent upon the fracture's type, sex, and patient's age. Complications were seen in 9 patients, whereas in 16 patients in the control group. INTERPRETATION: Using an interlocking plate, the indication of fixation of displaced proximal humerus fractures had been expanded to type C fractures. The implant failure rate can be reduced. The functional results achieved are better compared with those following minimal invasive techniques.


Subject(s)
Bone Plates , Fracture Fixation, Internal/instrumentation , Shoulder Fractures/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Bone Screws , Bone Wires , Case-Control Studies , Female , Fracture Fixation, Internal/methods , Humans , Male , Middle Aged , Postoperative Complications/etiology , Prospective Studies , Treatment Outcome , Young Adult
12.
Knee Surg Sports Traumatol Arthrosc ; 21(1): 161-9, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22729805

ABSTRACT

PURPOSE: High tibial osteotomy is an established method in the treatment for knee osteoarthritis. Infections are a rare but severe complication that might endanger the clinical, radiological and functional outcome and might require several surgical revisions. METHODS: A systematic literature review was performed through PubMed until November 2011. Search terms were "HTO" or "(high) tibial osteotomy", alone or in combination with "infection(s)", "infected" or "septic". Only articles focussing on the infection treatment or analysis of risk factors for emergence of infection after high tibial osteotomy were included. RESULTS: A total of 26 studies could be identified. Seven studies were published before and 19 in or after 2000. One study had a level of evidence II, five level of evidence III and 20 level of evidence IV. Superficial infections were found in 1-9% and deep infections in 0.5-4.7% of the cases. Pin tract infections occurred in 2-71% of the cases. One study reported on a secondary bacterial arthritis in 4.5% of the cases. An oblique skin incision, non-smokers and a one-day hospitalization were found to be risk factors for infection emergence. Depending on the type of infection, treatment consisted of oral or systemic antibiotic therapy, alone or in combination with surgical revision, debridement and hardware removal. In some cases, antibiotic-loaded cement beads were inserted for local antibiotic therapy. CONCLUSION: Infections after high tibial osteotomy are rare. Current data about infection rates, infection localization, risk factors for emergence of infection and treatment options allow not for a generalization of conclusions. A large multi-centre study is required to develop a diagnostic and therapeutic algorithm. LEVEL OF EVIDENCE: IV.


Subject(s)
Knee Joint/surgery , Osteoarthritis, Knee/surgery , Osteotomy/methods , Surgical Wound Infection , Tibia/surgery , Anti-Bacterial Agents/therapeutic use , Debridement , Device Removal , Humans , Osteotomy/instrumentation , Reoperation , Risk Factors , Surgical Wound Infection/etiology , Surgical Wound Infection/therapy
13.
Knee Surg Sports Traumatol Arthrosc ; 21(1): 39-48, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22898914

ABSTRACT

PURPOSE: To evaluate whether medial open wedge high tibial osteotomy (HTO) results in structural and biochemical changes in the lateral meniscus in adult sheep. METHODS: Three experimental groups with biplanar osteotomies of the right proximal tibiae were tested: (a) closing wedge HTO resulting in 4.5° of tibial varus, (b) open wedge HTO resulting in 4.5° of tibial valgus (standard correction) and (c) open wedge HTO resulting in 9.5° of valgus (overcorrection), each of which was compared to the contralateral knees with normal limb axes. After 6 months, the lateral menisci were macroscopically and microscopically evaluated. The proteoglycan and DNA contents of the red-red and white-white zones of the anterior, middle and posterior third were determined. RESULTS: Semiquantitative macroscopic and microscopic grading revealed no structural differences between groups. The red-red zone of the middle third of the lateral menisci of animals that underwent overcorrection exhibited a significant 0.7-fold decrease in mean DNA contents compared with the control knee without HTO (P = 0.012). Comparative estimation of the DNA and proteoglycan contents and proteoglycan/DNA ratios of all other parts and zones of the lateral menisci did not reveal significant differences between groups. CONCLUSION: Open wedge HTO does not lead to significant macroscopic and microscopic structural changes in the lateral meniscus after 6 months in vivo. Overcorrection significantly decreases the proliferative activity of the cells in the red-red zone of the middle third in the sheep model.


Subject(s)
Menisci, Tibial/pathology , Osteotomy/adverse effects , Tibia/surgery , Animals , Biomarkers/metabolism , Bone Malalignment/etiology , Bone Malalignment/metabolism , Bone Malalignment/pathology , DNA/metabolism , Menisci, Tibial/metabolism , Osteotomy/methods , Proteoglycans/metabolism , Sheep
14.
Mol Med ; 18: 346-58, 2012 May 09.
Article in English | MEDLINE | ID: mdl-22160392

ABSTRACT

Administration of therapeutic genes to human osteoarthritic (OA) cartilage is a potential approach to generate effective, durable treatments against this slow, progressive disorder. Here, we tested the ability of recombinant adeno-associated virus (rAAV)-mediated overexpression of human insulinlike growth factor (hIGF)-I to reproduce an original surface in human OA cartilage in light of the pleiotropic activities of the factor. We examined the proliferative, survival and anabolic effects of the rAAV-hIGF-I treatment in primary human normal and OA chondrocytes in vitro and in explant cultures in situ compared with control (reporter) vector delivery. Efficient, prolonged IGF-I secretion via rAAV stimulated the biological activities of OA chondrocytes in all the systems evaluated over extended periods of time, especially in situ, where it allowed for the long-term reconstruction of OA cartilage (at least for 90 d). Remarkably, production of high, stable amounts of IGF-I in OA cartilage using rAAV advantageously modulated the expression of central effectors of the IGF-I axis by downregulating IGF-I inhibitors (IGF binding protein [IGFBP]-3 and IGFBP4) while up-regulating key potentiators (IGFBP5, the IGF-I receptor and downstream mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 [MAPK/ERK-1/2] and phosphatidylinisitol-3/Akt [PI3K/Akt] signal transduction pathways), probably explaining the enhanced responsiveness of OA cartilage to IGF-I treatment. These findings show the benefits of directly providing an IGF-I sequence to articular cartilage via rAAV for the future treatment of human osteoarthritis.


Subject(s)
Cartilage/metabolism , Chondrocytes/metabolism , Dependovirus/genetics , Insulin-Like Growth Factor I/metabolism , Osteoarthritis/metabolism , Aged , Cell Proliferation , Genetic Vectors , Humans , Insulin-Like Growth Factor Binding Proteins/metabolism , Mitogen-Activated Protein Kinases/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Receptor, IGF Type 1/metabolism , Recombination, Genetic
15.
J Gene Med ; 14(7): 501-11, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22711470

ABSTRACT

BACKGROUND: Genetic modification of mesenchymal stem cells (MSCs) comprises a promising tool to generate cell- and gene-based platforms for regenerative approaches of articular cartilage repair. In the present study, we systematically screened a panel of 15 nonviral compounds for their ability to promote safe, efficient and durable gene expression in human bone marrow-derived MSCs (hMSCS) without impeding their commitment towards chondrogenic differentiation. METHODS: Primary hMSCs were transfected with plasmid vectors carrying sequences for the Photinus pyralis luciferase Escherichia coli ß-galactosidase, or human insulin-like growth factor I via 15 nonviral formulations. Transgene expression and transfection efficiencies were monitored for each component in parallel with the effects on cell viability and cytotoxicity. Upon optimization, the most promising reagent was then evaluated for a possible influence on the chondrogenic potential of hMSCs. RESULTS: Among all formulations tested, GeneJammer® gave the best results for transgene expression and transfection efficacy (25-14% from days 2-21 in monolayer cultures and 35% in 21-day aggregate cultures), allowing for high levels of viability (92-94%) and modest cytotoxicity (< 12%). Most notably, the application of this reagent did not affect the potential of the cells for chondrogenic differentiation when maintained in long-term (21 days) three-dimensional (aggregate) cultures. CONCLUSIONS: The data indicate that safe, efficient transgene expression can be achieved in hMSCs over time using the nonviral GeneJammer® compound, showing promise for future therapeutic settings aiming to treat human articular cartilage disorders.


Subject(s)
Cell Differentiation/genetics , Chondrogenesis/drug effects , Mesenchymal Stem Cells/physiology , Polyamines/pharmacology , Tissue Engineering/methods , Transfection/methods , Cartilage, Articular/metabolism , Cell Aggregation/drug effects , Cell Aggregation/genetics , Cell Culture Techniques , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Gene Expression , Genetic Vectors , Humans , Mesenchymal Stem Cells/drug effects , Plasmids , Transgenes/genetics
16.
Arthroscopy ; 28(2): 178-87, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22112611

ABSTRACT

PURPOSE: To compare the biomechanical properties and footprint coverage of a single-row (SR) repair using a modified suture configuration versus a double-row (DR) suture-bridge repair in small to medium and medium to large rotator cuff tears. METHODS: We created 25- and 35-mm artificial defects in the rotator cuff of 24 human cadaveric shoulders. The reconstructions were performed as either an SR repair with triple-loaded suture anchors (2 to 3 anchors) and a modified suture configuration or a modified suture-bridge DR repair (4 to 6 anchors). Reconstructions were cyclically loaded from 10 to 60 N. The load was increased stepwise up to 100, 180, and 250 N. Cyclic displacement and load to failure were determined. Furthermore, footprint widths were quantified. RESULTS: In the 25-mm rupture, ultimate load to failure was 533 ± 107 N for the SR repair and 681 ± 250 N for the DR technique (P ≥ .21). In the 35-mm tear, ultimate load to failure was 792 ± 122 N for the SR reconstruction and 891 ± 174 N for the DR reconstruction (P ≥ .28). There were no statistically significant differences for both tested rupture sizes. Cyclic displacement showed no significant differences between the tested configurations at 60 N (P = .563), 100 N (P = .171), 180 N (P = .211), and 250 N (P = .478) for the 25-mm tear. For the 35-mm tear, cyclic displacement showed significantly lower gap formation for the SR reconstruction at 180 N (P = .037) and 250 N (P = .020). No significant differences were found at 60 N (P = .296) and 100 N (P = .077). A significantly greater footprint width (P = .028) was seen for the DR repair (16.2 mm) compared with the SR repair (13.8 mm). However, both reconstructions were able to achieve complete footprint coverage compared with the initial footprint. CONCLUSIONS: The tested SR repair using a modified suture configuration was similar in load to failure and cyclic displacement to the DR suture-bridge technique independent of the tested initial sizes of the rupture. The tested DR repair consistently restored a larger footprint than the SR method. However, both constructs achieved complete footprint coverage. CLINICAL RELEVANCE: SR repairs with modified suture configurations might combine the biomechanical advantages and increased footprint coverage that are described for DR repairs without increasing the overall costs of the reconstruction.


Subject(s)
Rotator Cuff/surgery , Suture Anchors , Suture Techniques , Biomechanical Phenomena , Cadaver , Humans , Rotator Cuff Injuries
17.
Knee Surg Sports Traumatol Arthrosc ; 20(8): 1456-62, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22105975

ABSTRACT

PURPOSE: The literature data on patellar height following unicompartmental knee arthroplasty (UKA) are scarce. METHODS: A total of 41 knee joints in 37 patients after UKA were prospectively evaluated for patellar height by using the Insall-Salvati and modified Insall-Salvati ratio. Patellar height was measured preoperatively, postoperatively, at 6, 12 weeks, and, at 1 year postoperatively. Patients were categorized according to age, gender, operated side, and rehabilitation program. RESULTS: Regarding all the patients, the Insall-Salvati ratio demonstrated a significant decrease only for the time period "postoperatively-1 year postoperatively", whereas the modified Insall-Salvati ratio showed a significant decrease only for the period "preoperatively-postoperatively". The Insall-Salvati ratio showed a significant decrease in the patellar height of men and left knees, whereas the modified Insall-Salvati ratio revealed a significant decrease in patients older than 65 years and those who followed a specific rehabilitation program. CONCLUSIONS: The decrease in the patellar height after UKA occurs within the first postoperative year. Women, right knees, patients younger than 65 years and those who do not follow a specific rehabilitation program are less prone to decrease in the patellar height; ratio-specific differences are evident for each subgroup. LEVEL OF EVIDENCE: Diagnostic study, Level III.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Knee Joint/surgery , Osteoarthritis, Knee/surgery , Patella/anatomy & histology , Age Factors , Aged , Female , Humans , Knee Joint/anatomy & histology , Knee Joint/diagnostic imaging , Male , Middle Aged , Osteoarthritis, Knee/pathology , Patella/diagnostic imaging , Patella/surgery , Postoperative Period , Prospective Studies , Radiography
18.
Knee Surg Sports Traumatol Arthrosc ; 20(11): 2315-24, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22222614

ABSTRACT

PURPOSE: To examine the entire repair tissue resulting from marrow-stimulation techniques in patients with early osteoarthritis. METHODS: The repair tissue and adjacent articular cartilage after failed marrow-stimulation techniques (microfracture and Pridie drilling) of 5 patients (47-65 years old) with cartilage defects and radiographic early osteoarthritis (Kellgren-Lawrence grading 1 and 2) was removed during total joint arthroplasty (mean time until analysis: 8.8 months), analysed by histology, polarized light microscopy, immunohistochemistry, biochemistry and by histological score systems. RESULTS: Macroscopic cartilage repair assessment revealed ICRS grades of II (nearly normal) and III (abnormal). Cartilage defects were mostly completely filled with a fibrocartilaginous tissue that had small and large fissures. Cartilage-specific stains of the repair tissue were more intense than the surrounding native cartilage but reduced compared with normal articular cartilage. The subchondral bone was incompletely restored. A new tidemark was absent. The repair tissue always showed positive immunoreactivity for types II and X collagen, and was sometimes positive for type I collagen. Proteoglycan contents of the repair tissue were generally higher than of the surrounding cartilage. The repair tissue was always more cellular than the adjacent articular cartilage. Histological scoring of the repair tissue revealed a mean Sellers score of 17.6 ± 3.0 and an ICRS grading of 7-9. CONCLUSION: Failed marrow stimulation of articular cartilage defects in patients with early osteoarthritis is characterized by fibrocartilaginous repair. The balance of cell number to extracellular matrix is shifted towards an increased cell number in this tissue. Articular cartilage repair did not reach the quality of normal hyaline articular cartilage. LEVEL OF EVIDENCE: IV.


Subject(s)
Arthroplasty, Subchondral , Cartilage, Articular/pathology , Osteoarthritis, Knee/surgery , Wound Healing , Aged , Arthroplasty, Replacement, Knee , Cartilage, Articular/metabolism , Cartilage, Articular/surgery , Cell Count , Chondrocytes/pathology , Collagen/metabolism , Female , Fibrocartilage/pathology , Humans , Immunohistochemistry , Male , Microscopy , Middle Aged , Osteoarthritis, Knee/pathology , Proteoglycans/metabolism , Treatment Failure
19.
Sarcoma ; 2012: 347417, 2012.
Article in English | MEDLINE | ID: mdl-22645415

ABSTRACT

Treatment of chondrosarcoma remains a major challenge in orthopaedic oncology. Gene transfer strategies based on recombinant adenoassociated viral (rAAV) vectors may provide powerful tools to develop new, efficient therapeutic options against these tumors. In the present study, we tested the hypothesis that rAAV is adapted for a stable and safe delivery of foreign sequences in human chondrosarcoma tissue by transducing primary human chondrosarcoma cells in vitro and in situ with different reporter genes (E. coli lacZ, firefly luc, Discosoma sp. RFP). The effects of rAAV administration upon cell survival and metabolic activities were also evaluated to monitor possibly detrimental effects of the gene transfer method. Remarkably, we provide evidence that efficient and prolonged expression of transgene sequences via rAAV can be safely achieved in all the systems investigated, demonstrating the potential of the approach of direct application of therapeutic gene vectors as a means to treat chondrosarcoma.

20.
J Gene Med ; 13(4): 230-42, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21449036

ABSTRACT

BACKGROUND: Genetically modified chondrocytes embedded in alginate improve cartilage repair in experimental models, and alginates are clinically used for articular chondrocyte transplantation. In the present study, we tested the hypothesis that the alginate system allows for sustained transgene expression in cartilage defects in a preclinical large animal model in vivo. METHODS: Primary cultures of ovine articular chondrocytes were transfected with the Photinus pyralis luc or the Escherichia coli lacZ genes in monolayer culture in vitro using eight different nonviral compounds. Optimally transfected chondrocytes were encapsulated in spheres composed of nonbiomedical or biomedical grade alginates for evaluation of luciferase expression, cell numbers and viabilities in vitro. Transfected chondrocytes encapsulated in spheres comprised of the different alginates were then implanted into osteochondral defects in the knee joints of sheep to examine the profiles of transgene expression in vivo. RESULTS: Ovine articular chondrocytes were efficiently transfected with FuGENE 6. Transgene expression was detectable after encapsulation in the alginates over 21 days in vitro. Transplantation of genetically modified chondrocytes to cartilage defects in vivo resulted in maximal transgene expression on day 1 after transfection, with a decrease by day 21, the longest time point evaluated. Remarkably, the reduction in luciferase activity was less pronounced when biomedical grade alginates were employed, compared to nonbiomedical grade alginates, suggesting that such alginates might be better suited to support elevated transgene expression after transplantation of genetically modified chondrocytes. CONCLUSIONS: This approach may be of value to study the effects of potential therapeutic genes upon cartilage repair in a clinically relevant setting.


Subject(s)
Alginates/chemistry , Cartilage, Articular/cytology , Cartilage, Articular/injuries , Cell Transplantation/methods , Chondrocytes/transplantation , Genetic Therapy/methods , Analysis of Variance , Animals , Female , Plasmids/genetics , Sheep , Transfection
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