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Biomedical subjects

Andreas Weiler

Publications and source records attributed to Andreas Weiler.

30 records · Page 2Linked to original sources

The angiogenic peptide vascular endothelial growth factor (VEGF) is expressed during the remodeling of free tendon grafts in sheep.

BACKGROUND: Angiogenesis is important for the remodeling of autologous tendon grafts. A sheep model was used to examine the expression of the angiogenic peptide vascular endothelial growth factor (VEGF) in autologous tendon grafts after anterior cruciate ligament (ACL) reconstruction. METHODS: Merino sheep underwent ACL reconstruction with an autologous Achilles tendon split graft. VEGF and its receptors, the Fms-like tyrosine kinase receptor (FLT-1, VEGFR-1) and the kinase insert domain-containing receptor KDR (VEGFR-2/FLK-1) were detected immunohistochemically. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect which of the different VEGF splice forms are expressed during ACL remodeling. RESULTS: At 6 weeks, light microscopy showed zones with hypocellular necrotic graft tissue in the central part surrounded by hypercellular and hypervascularized reparative tissue invading the former graft tissue from the periphery. In contrast to the necrotic tissue, all cell types of the reparative tissue labeled strongly positive for VEGF. The VEGF receptors FLT-1 and KDR could be detected on endothelial cells of blood vessels. At 12 weeks, the complete graft diameter showed an increased vascular density (anti-factor VIII immunoreactivity), but zones of non-remodeled former graft tissue could not be found. Fusiform fibroblasts labeled strongly for VEGF. At 24 weeks, VEGF immunostaining decreased, and at 52 and 104 weeks, the grafts were largely VEGF-negative. RT-PCR supported the immunohistochemical results regarding VEGF expression and showed further that the splice variants VEGF(120 )and VEGF(164) are expressed during angiogenesis during the remodeling of tendons. CONCLUSION: We conclude that the angiogenic peptide VEGF plays a role in tendon graft remodeling.

Achilles Tendon↗

Arthroscopic evaluation of articular cartilage lesions in posterior-cruciate-ligament-deficient knees.

PURPOSE: The goal of this study was to gain more information on the likelihood of developing cartilage lesions in posterior cruciate ligament (PCL)-deficient knees. TYPE OF STUDY: Retrospective clinical study. METHODS: Standardized arthroscopy records of 181 patients with a nonsurgically treated acute or chronic PCL injury were analyzed with respect to cartilage degeneration. Subgroups with different duration of PCL insufficiency, the influence of isolated PCL or combined PCL/posterolateral instability, and the grade of posterior laxity was analyzed. RESULTS: PCL insufficiency significantly increased the risk of developing medial femoral condyle and patellar cartilage degeneration over time. Of patients whose PCL deficiency was present for more than 5 years, 77.8% showed degenerative cartilage lesions of the medial femoral condyle and 46.7% showed cartilage degeneration of the patella. After 1 year of PCL insufficiency, the number of medial femoral cartilage lesions increased threefold (13.6% v 39.1%). With the presence of combined PCL/posterolateral insufficiency the amount of medial femoral degeneration was significantly increased (36.6% v 60.6%). CONCLUSIONS: We found that PCL insufficiency is not a benign injury with respect to the development of degenerative articular cartilage lesions. The early and continuous increase in cartilage degeneration at the medial femoral condyle and the patella should be considered when discussing operative versus conservative treatment for a PCL-deficient knee. The rapid development of medial arthritis should also be considered during decision making, particularly in patients with combined PCL/posterolateral instability or those who underwent previous partial medial menisectomy.

Adolescent↗

Endoligamentous revascularization of an anterior cruciate ligament graft.

After replacement of the anterior cruciate ligament with a free tendon graft, the substitute initially is avascular and without a synovial surface. To ensure long-term survival, the graft must become revascularized. Despite numerous studies on the topic, there still is discussion regarding revascularization. The goal of the current study was to investigate the endoligamentous microcapillary revascularization of the free tendon graft after anterior cruciate ligament replacement with time. Thirty-six mature sheep had an anterior cruciate ligament reconstruction with an ipsilateral flexor tendon split graft. Midsubstance tissue samples were immunostained for von Willebrand factor (Factor VIII) at 6, 9, 12, 24, 52, and 104 weeks to detect the endothelial cells of capillaries. Cross sections of vessels were determined in three zones (subsynovial, intermediate, and center of the graft) and were evaluated by means of histomorphometry using a digital imaging analysis system. The observations showed that capillary vessels, which originate from the synovial envelope, invaded the avascular graft tissue from the surface toward the center zone. The highest level of vascular density was found after 6 weeks, reaching the vascular status of the native anterior cruciate ligament after 24 weeks. These findings are in contrast to the findings of previous studies in animals. The current study showed, for the first time, the kinetics of an endoligamentous revascularization of a free tendon graft at the capillary level. In the current model, the process of revascularization terminated earlier than previously described.

Animals↗

Unsaturated dodecahedranes--in quest of the C20H14 1,4,16-triene and C20H12 1,4,10(14),16-tetraene, and their cations and anions.

The highly pyramidal, highly strained 1,4,16-dodecahedratriene (4) and C20H12 1,4,10(14),16-dodecahedratetraene (5) are cage olefins with an intriguing "inner life". For 5 DFT calculations give information about the energetic and geometrical consequences of one-/two-electron oxidation and reduction. Attempts to prepare 4 and 5 through thermal retro[2+2]/[4+2]cycloaddition strategies proved unsuccessful. Still, the C20H14/C20H12 cage cations and anions are liberated upon electron impact or gas-discharge ionization of their thermally extremely stable tris-/tetrakisanthraceno-anellated derivatives. Mass-selection (photoelectron (PE) characterization) of the anions failed, however, due to the very small anion intensity, the preferential formation of hydrogen-poor ions, and minor cage disruption.

Journal Article↗

Alpha-smooth muscle actin is expressed by fibroblastic cells of the ovine anterior cruciate ligament and its free tendon graft during remodeling.

Contractile fibroblastic cells expressing the alpha-smooth muscle actin isoform, so-called myofibroblasts, have been identified to play a possible role during the healing of the medial collateral ligament by means of restoring the tissues in situ strain via extracellular matrix contraction. Recently, these cells have also been identified to be a normal part of the human anterior cruciate ligament. It has been hypothesized that myofibroblasts play a role in the wrinkling of the extracellular matrix. The goal of the present study was to identify myofibroblasts in the intact ovine anterior cruciate ligament and a free autologous tendon graft during remodeling after anterior cruciate ligament reconstruction. In 36 mature merino sheep the anterior cruciate ligament was replaced with an ipsilateral Achilles tendon split graft. Midsubstance tissue samples were immunostained for alpha-smooth muscle actin at 6, 9, 12, 24, 52, and 104 weeks. Myofibroblasts were identified in the intact ovine anterior cruciate ligament as well as in the Achilles tendon graft prior to implantation. During remodeling the first myofibroblasts were found at six weeks within newly formed fiber bundles. At 24, 52, and 104 weeks myofibroblast distribution and cell density were similar to those of the intact ovine anterior cruciate ligament. These findings indicate that alpha-smooth muscle actin containing fibroblastic cells are a regular part of the intact as well as the remodeled anterior cruciate ligament. There is evidence that myofibroblasts may be involved in maintaining tissue homeostasis in the mature ligament e.g., by means of crimp formation. The presence of these cells during the early remodeling may further indicate that alpha-smooth muscle actin containing fibroblastic cells are involved in the earliest stages of fiber bundle formation. The role and function of this special cell type for the anterior cruciate ligament needs to be further clarified.

Achilles Tendon↗

Biomechanical comparison of hamstring and patellar tendon graft anterior cruciate ligament reconstruction techniques: The impact of fixation level and fixation method under cyclic loading.

PURPOSE: To mechanically test different reconstruction techniques of the anterior cruciate ligament (ACL) under incremental cyclic loading and to evaluate the impact of the level and method of graft fixation on tensile properties of each technique. TYPE OF STUDY: In vitro biomechanical study. METHODS: Four hamstring and 1 patellar tendon reconstruction techniques were performed on 40 young to middle-aged human cadaveric knees (average age, 39 years). An anterior drawer with increasing loads of 20 N increments was applied at 30 degree of knee flexion. Anatomic, direct interference screw fixation was tested in 2 hamstring and in the patellar tendon groups. Nonanatomic (extracortical) graft anchorage was tested in the remaining 2 hamstring groups with indirect graft fixations on both sides and the combination of indirect tibial and direct femoral fixation. Structural properties were determined throughout the cyclic loading test. RESULTS: The more anatomic reconstruction techniques provided significantly higher structural properties and smaller loss of fixation compared with nonanatomic, extracortical fixation, with indirect repair on both fixation sites resulting in the lowest structural properties. The tibial fixation site was the weakest link in all of the anatomic reconstructions. Patellar tendon fixation with attached bone blocks in both bone tunnels significantly improved construct stiffness and decreased graft slippage. CONCLUSIONS: The results of this study suggest that anatomic fixation should be preferred for anchorage of hamstring tendons and linkage materials should be avoided. Direct soft-tissue fixation with interference screws still allows considerable graft slippage, which can be limited by using a bone block or application of a backup or hybrid fixation, especially on the tibial fixation site.

Absorbable Implants↗

Tendon healing in a bone tunnel. Part I: Biomechanical results after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep.

PURPOSE: Interference fit fixation of soft-tissue grafts has recently raised strong interest because it allows for anatomic graft fixation that may increase knee stability and graft isometry. Although clinical data show promising results, no data exist on how tendon healing progresses using this fixation. The purpose of the present study was to investigate anterior cruciate ligament (ACL) reconstruction biomechanically using direct tendon-to-bone interference fit fixation with biodegradable interference screws in a sheep model. TYPE OF STUDY: Animal study. METHODS: Thirty-five mature sheep underwent ACL reconstruction with an autologous Achilles tendon split graft. Grafts were directly fixed with poly-(D,L-lactide) interference screws. Animals were euthanized after 6, 9, 12, 24, and 52 weeks and standard biomechanical evaluations were performed. RESULTS: All grafts at time zero failed by pullout from the bone tunnel, whereas grafts at 6 and 9 weeks failed intraligamentously at the screw insertion site. At 24 and 52 weeks, grafts failed by osteocartilaginous avulsion. At 24 weeks, interference screws were macroscopically degraded. At 6 and 9 weeks tensile stress was only 6.8% and 9.6%, respectively, of the graft tissue at time zero. At 52 weeks, tensile stress of the reconstruction equaled 63.8% and 47.3% of the Achilles tendon graft at time zero and the native ACL, respectively. A complete restitution of anterior-posterior drawer displacement was found at 52 weeks compared with the time-zero reconstruction. CONCLUSIONS: It was found that over the whole healing period the graft fixation proved not to be the weak link of the reconstruction and that direct interference fit fixation withstands loads without motion restriction in the present animal model. The weak link during the early healing stage was the graft at its tunnel entrance site, leading to a critical decrease in mechanical properties. This finding indicates that interference fit fixation of a soft-tissue graft may additionally alter the mechanical properties of the graft in the early remodeling stage because of a possible tissue compromise at the screw insertion site. Although mechanical properties of the graft tissue had not returned to normal at 1 year compared with those at time zero, knee stability had returned to normal at that time. There was no graft pullout after 24 weeks, indicating that screw degradation does not compromise graft fixation.

Absorbable Implants↗

Tendon healing in a bone tunnel. Part II: Histologic analysis after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep.

PURPOSE: Tendon-to-bone healing of soft-tissue grafts has been described to progress by the development of a fibrous interzone that undergoes a maturation process leading to the development of an indirect type of ligament insertion. Previous studies used extra-articular models or fixation far away from the joint line; thus, no data are available investigating tendon-to-bone healing of a soft-tissue graft fixed anatomically. Therefore, we studied the tendon-to-bone healing of the anatomic soft-tissue graft interference fit fixation in a model of anterior cruciate ligament (ACL) reconstruction in sheep. TYPE OF STUDY: Animal study. METHODS: Thirty-five mature sheep underwent ACL reconstruction with an autologous Achilles tendon split graft. Grafts were directly fixed with biodegradable poly-(D,L-lactide) interference screws. Animals were euthanized after 6, 9, 12, 24, and 52 weeks and histologic evaluations were performed. Undecalcified specimens were evaluated under normal and polarized light. Additionally, animals received a polychrome sequential labeling (tetracycline, xylenol orange, and calcein green) to determine bone growth per time under fluorescent light. RESULTS: Intratunnel histologic findings at 6 weeks showed a tendon-bone junction with only a partial fibrous interzone between the graft tissue and the surrounding bone. A mature intratunnel tendon-bone junction with a zone of fibrocartilage was found at 9 to 12 weeks. At the tunnel entrance site a wide regular ligamentous insertion site was seen in all specimens after 24 weeks. This insertion showed regular patterns such as the direct type of insertion of a normal ligament with a dense basophilic transition zone consisting of mineralized cartilage. CONCLUSIONS: A fibrous interzone between the graft tissue and the bone tunnel was only partially developed, which is in contrast to all previous studies in which nonanatomic fixation was used. Thus, it is reasonable to assume that the tendon-to-bone healing in the present study may progress partially by direct-contact healing without the development of a fibrous interzone. To our knowledge, this is the first report describing the development of a direct type of ligament insertion after ACL replacement with a soft-tissue graft. This is in contrast to previous studies reporting the development of an indirect type of insertion when using nonanatomic fixation far away from the joint line. Thus, histologic data strongly indicate that anatomic interference fit fixation is beneficial for tendon-to-bone incorporation by leading to the development of a direct type of ligament insertion.

Absorbable Implants↗

Coincidence of recurrent arthritis and Behçet's disease following anterior cruciate ligament reconstruction.

Chronic recurrent inflammation with joint effusion following anterior cruciate ligament (ACL) reconstruction is common. We report an unusual case of a patient also suffering from undiagnosed Behçet's disease. The patient had chronic recurrent joint effusions of the knee 7 years after traumatic rupture of the ACL and autologous tendon reconstruction using a hamstring tendon autograft. Arthroscopic treatment of the notch impingement and therapy of the accompanying rheumatic disease relieved the patient of his ailment. On the one hand, this case report shows the necessity of including chronic rheumatoid joint disease in the differential diagnosis of a persistent impairment of joint homeostasis following ACL reconstruction, and on the other hand it shows the coincidence of Behçet's disease and recurrent joint inflammation in a patient following ACL surgery.

Adult↗

Ultrasound can predict regenerate stiffness in distraction osteogenesis.

Assessing the regenerate strength in distraction osteogenesis is crucial for clinical treatment. Several methods have been used to achieve this, including plain radiography, digital radiography, quantitative computed tomography, dual energy xray absorptiometry, and ultrasound. The aim of the current study was to investigate the use of ultrasound in monitoring regenerate formation and to correlate this to biomechanical testing results. An osteotomy was done on the tibia of 30 Yucatan micropigs and an Ilizarov-type half-ring external fixator was mounted. After a 5-day latency period, the tibias were distracted for 10 days and then left to consolidate for 10 days. Seven ultrasound examinations were done during Day 15 through Day 25. After sacrifice, the bone mineral density was measured using quantitative computed tomography. Maximum load and torsional stiffness were measured and correlated with ultrasound measurements and bone mineral density. The ultrasound penetration depth and the bone mineral density correlated closely with torsional stiffness. Ultrasound can be a noninvasive predictor of bone regenerate strength in the early phase of distraction osteogenesis, which may reduce the need for radiographs.

Animals↗

Fixed posterior subluxation in posterior cruciate ligament-deficient knees: diagnosis and treatment of a new clinical sign.

Among 248 patients seen for posterior cruciate ligament insufficiency, 109 (44%) had fixed posterior subluxation of the tibia, defined as a condition in which posterior sag could not be reduced to a neutral position, as evidenced by posterior tibial displacement of 3 mm or more on anterior stress radiographs at 200 N. The mean fixed posterior displacement was 6.23 mm (range, 3 to 20). The fixed posterior subluxation was divided into three grades: I, 3 to 5 mm (57.8%); II, 6 to 10 mm (33.9%); and III, more than 10 mm (8.3%). Comparison of the 109 study patients with the 139 control patients revealed a history of a failed posterior cruciate ligament operation or of a patellar tendon harvest, male sex, and a long history of posterior cruciate ligament insufficiency as significant risk factors for the development of a fixed posterior subluxation. After patients were treated with a posterior tibial support brace, the fixed posterior subluxation could be reduced to a mean of 2.58 +/- 5.22 mm within an average treatment period of 180 days. Fixed posterior subluxation can be detected in patients with posterior cruciate ligament deficiency by anterior and posterior stress radiographs and should be addressed before posterior cruciate ligament reconstruction to prevent early overloading of the graft.

Adolescent↗

A new device to detect early cartilage degeneration.

BACKGROUND: Currently available arthroscopic techniques do not allow the quantification of cartilage stiffness without direct mechanical indentation or penetration of the tissue. PURPOSE: A novel device, capable of quantifying cartilage stiffness during arthroscopy, is believed to detect degenerated cartilage. STUDY DESIGN: Controlled laboratory study. METHODS: The stiffness of biological materials was measured arthroscopically without contact between the instrument and the examined object. Object deformation was produced by a flow of sodium chloride and measured optically. Eight ovine femoral condyles and tibial plateaus were tested in a native and degenerated (0.1% trypsin solution) state. Cartilage stiffness was nondestructively determined by using the new device and by indentation methods. In addition, a standard probe was measured by 5 independent users. RESULTS: The trypsin caused cartilage degeneration and consequently stiffness reduction, measured at 30.8% by the new device and 33.0% by indentation. A good correlation (r = 0.69) between the new device and the standard indentation procedure was observed. Intraindividual and interindividual variability of the new device were low (<10%). CONCLUSIONS: The developed device has demonstrated the ability to quantify the mechanical quality of cartilage by means of mechanical stiffness measurements. CLINICAL RELEVANCE: The findings suggest that this device has the capability to detect cartilage degeneration at an early stage.

Animals↗