Pierre Hepp

Proximal humeral fractures: how stiff should an implant be? A comparative mechanical study with new implants in human specimens.

BackgroundThe objective of this study was to determine the in vitro characteristics of the clinically used and newly developed implants for the stabilization of proximal humeral fractures under static and cyclic loading. The goal was to optimize implant stiffness for fracture stabilization even in weak bone stock.MethodsIn a laboratory study using 35 fresh human humeri, the specimens were randomized into 5 groups, which included the clinically used humerus T-plate (HTP), the cross-screw osteosynthesis (CSO), the unreamed proximal humerus nail with spiral blade (UHN), the recently developed Synclaw Proximal Humerus Nail (Synclaw PHN) and the angle-stable Locking Compression Plate Proximal Humerus (LCP-PH). The implant stiffness was determined for three clinically relevant load cases: axial compression, torsion and varus bending. In addition, a cyclic varus-bending test was performed to determine the implant properties under cyclic loading.ResultsIn contrast to a rather elastic and minimally invasive implant(LCP-PH), the conventionally designed ones (Synclaw PHN, CSO, HTP, UHN) showed rather high stiffness values under static loading. In cyclic loading, a strong decrease in stiffness (p<0.05) was found for the rigid implants HTP and UHN. In comparison with the other implants, only the elastic implant (LCP-PH) showed a significantly lower load reduction in a weak bone stock (17±6.2%).ConclusionThe high initial stiffness of rigid implants led to an early loosening and failure of the implant-bone interface under cyclic loading. Implants with low stiffness and elastic characteristics, however, appear to minimize the peak stresses at the bone-implant interface, making them particularly suitable for fracture fixation in osteoporotic bone.

Where should implants be anchored in the humeral head

To determine histomorphometric and bone strength distribution of the proximal humerus, analyses were done on 24 freshly harvested human cadaveric humeri. Median ages of 46 and 69 years were recorded respectively for the male group (n = 11; minimum, 34 years; maximum, 76 years) and the female group (n = 13; minimum, 46 years; maximum, 90 years). The humeral head was sliced into four equal horizontal levels (Levels 1–4). Five regions of interest were defined in each cutting plane: anterior, posterior, lateral, medial, and central. Histomorphometric analyses evaluated structural parameters (tissue volume to bone volume ratio, trabecular thickness), connectivity (number of nodes, node to node length), and trabecular orientation (mean bone length). The peak values of histomorphometric parameters and bone strength were identified for the cranial section and decreased caudally. The medial and dorsal aspects of the proximal humeral head were found to be the areas of highest bone strength. The trabecular network formed a pattern that connected the center of the gleaned cavity. The structural and connectivity parameters, bone strength, and trabecular orientation showed region- and level-related characteristics. Knowledge of distribution, microstructure, and quality of bone in the humeral head allows the remaining bone stock to be used effectively, even in elderly patients, with a minimally invasive approach and maximum mechanical stability.

Repair of Chronic Osteochondral Defects Using Predifferentiated Mesenchymal Stem Cells in an Ovine Model

Background: The use of mesenchymal stem cells (MSCs) to treat osteochondral defects caused by sports injuries or disease is of particular interest. However, there is a lack of studies in large-animal models examining the benefits of chondrogenic predifferentiation in vitro for repair of chronic osteochondral defects. Hypothesis: Chondrogenic in vitro predifferentiation of autologous MSCs embedded in a collagen I hydrogel currently in clinical trial use for matrix-associated autologous chondrocyte transplantation facilitates the regeneration of a chronic osteochondral defect in an ovine stifle joint. Study Design: Controlled laboratory study. Methods: The optimal predifferentiation period of ovine MSCs within the type I collagen hydrogel in vitro was defined by assessment of several cellular and molecular biological parameters. For the animal study, osteochondral lesions (diameter 7 mm) were created at the medial femoral condyles of the hind legs in 10 merino sheep. To achieve a chronic defect model, implantation of the ovine MSCs/hydrogel constructs was not performed until 6 weeks after defect creation. The 40 defects were divided into 4 treatment groups: (1) chondrogenically predifferentiated ovine MSC/hydrogel constructs (preMSC-gels), (2) undifferentiated ovine MSC/hydrogel constructs (unMSC-gels), (3) cell-free collagen hydrogels (CF-gels), and (4) untreated controls (UCs). Evaluation followed after 6 months. Results: With regard to proteoglycan content, cell count, gel contraction, apoptosis, compressive properties, and progress of chondrogenic differentiation, a differentiation period of 14 days in vitro was considered optimal. After 6 months in vivo, the defects treated with preMSC-gels showed significantly better histologic scores with morphologic characteristics of hyaline cartilage such as columnarization and presence of collagen type II. Conclusion: Matrix-associated autologous chondrocyte transplantation with predifferentiated MSCs may be a promising approach for repair of focal, chronic osteochondral defects. Clinical Relevance: The results suggest an encouraging method for future treatment of focal osteochondral defects to prevent progression to osteoarthritis.

Matrix-Associated Implantation of Predifferentiated Mesenchymal Stem Cells Versus Articular Chondrocytes: In Vivo Results of Cartilage Repair After 1 Year

Background: The use of predifferentiated mesenchymal stem cells (MSC) leads to better histological results compared with undifferentiated MSC in sheep. This raises the need for a longer term follow-up study and comparison with a clinically established method. Hypothesis: We hypothesized that chondrogenic in vitro predifferentiation of autologous MSC embedded in a collagen I hydrogel leads to better structural repair of a chronic osteochondral defect in an ovine stifle joint after 1 year. We further hypothesized that resulting histological results would be comparable with those of chondrocyte-seeded matrix-associated autologous chondrocyte transplantation (MACT). Study Design: Controlled laboratory study. Methods: Predifferentiation period of ovine MSC within collagen gel in vitro was defined by assessment of several cellular and molecular biological parameters. For the animal study, 2 osteochondral lesions (7-mm diameter) were created at the medial femoral condyles of the hind legs in 9 sheep. Implantation of MSC gels was performed 6 weeks after defect creation. Thirty-six defects were divided into 4 treatment groups: (1) chondrogenically predifferentiated MSC gels (pre-MSC gels), (2) undifferentiated MSC gels (un-MSC gels), (3) MACT gels, and (4) untreated controls (UC). Histological, immunohistochemical, and radiological evaluations followed after 12 months. Results: After 12 months in vivo, pre-MSC gels showed significantly better histological outcome compared with un-MSC gels and UC. Compared with MACT gels, the overall scores were higher for O’Driscoll and International Cartilage Repair Society (ICRS). The repair tissue of the pre-MSC group showed immunohistochemical detection of interzonal collagen type II staining. Radiological evaluation supported superior bonding of pre-MSC gels to perilesional native cartilage. Compared with previous work by our group, no degradation of the repair tissue between 6 and 12 months in vivo, particularly in pre-MSC gels, was observed. Conclusion: Repair of chronic osteochondral defects with collagen hydrogels composed of chondrogenically predifferentiated MSC shows no signs of degradation after 1 year in vivo. In addition, pre-MSC gels lead to partially superior histological results compared with articular chondrocytes. Clinical Relevance: The results suggest an encouraging method for future treatment of focal osteochondral defects without donor site morbidity by harvesting articular chondrocytes.

Comparative anatomical measurements of osseous structures in the ovine and human knee

The ovine stifle has been increasingly used as a large animal model for the human knee. Still, comparative anatomical measurements of the knee in sheep and humans are missing. Thus, the purpose of this study was to describe and measure the osseous anatomy of the ovine stifle in comparison to the human knee. Twenty-four stifles of skeletal-mature merino-sheep and 24 human cadaver knees were obtained and distances between selected anatomical structures of the distal femur, the proximal tibia, and the patella were measured digitally and documented. Based on these, intercondylar ratio, tibial aspect ratio, patella aspect ratio and the cortical index were calculated. Regarding epicondylar width, lateral condylar width, medial condylar width and the tibial dimensions, the ovine stifle can be considered as a human knee scaled down by one third. However, sheep have a smaller trochlear width and a narrower femoral intercondylar notch than humans resulting in lower relative values for intercondylar width and intercondylar height. The distal femurs cortical index is the same in both species. In contrast, sheep have a massive bone stock below their tibial plateau and a proximal tibial shaft with remarkably thick cortical bone. The ovine stifle can be regarded as a useful model for the human knee. However, future studies should consider the differences in the femoral intercondylar notch width, the patellofemoral joints biomechanics and the proximal tibias cortical bone stock.

Are polyaxially locked screws advantageous in the plate osteosynthesis of proximal humeral fractures in the elderly? A prospective randomized clinical observational study.

Objectives: To evaluate the results of plate osteosynthesis using either polyaxial or nonpolyaxially locked screw–plate systems in proximal humeral fractures in the elderly. Design: Prospective, randomized. Setting: Level I trauma center. Methods: Fifty-six patients (older than 60 years) with isolated, displaced three- and four-part fractures were included. Twenty-five patients (median age, 75.5 years) were randomized to a polyaxial locking screw plate (Group 1), whereas 31 patients (median age, 72 years) were treated with a locking screw plate (Group 2). Follow-up evaluations were performed 3, 6, and 12 months postoperatively using the Simple Shoulder Test, Disabilities of the Arm, Shoulder and Hand score, and Constant score as well as radiographs. The results and the complications were compared between both groups. Results: Forty-eight patients were available for follow-up (Group 1, 20 of 25; Group 2, 28 of 31). The Simple Shoulder Test, Disabilities of the Arm, Shoulder and Hand, and Constant score improved significantly from 3 to 12 months and did not differ between groups. Twelve months after the index procedure, the Simple Shoulder Test score was 8.6 ± 3.2 points in Group 1 and 9.7 ± 1.8 points in Group 2. The Disabilities of the Arm, Shoulder and Hand score was 17.8 ± 16.2 in Group 1 and 15.7 ± 11.8 in Group 2. The mean Constant score amounted to 73% ± 17% in Group 1 and 81% ± 13% in Group 2. There were six complications in Group 1 and eight in Group 2. Conclusions: Both the functional outcomes and the rate of complications after polyaxial locked plate osteosynthesis of proximal humeral fractures in elderly patients were comparable to those treated with nonpolyaxial implants. Despite the theoretical advantages of polyaxial locked plating in proximal humerus fractures, this study could not show a verifiable clinical advantage of these plates.

Straining of the intact and fractured proximal humerus under physiological-like loading.

Surgical treatment of proximal humeral fractures remains challenging in elderly patients, primarily due to insufficient implant fixation. Both bone quality and physiological-like loading conditions are commonly overlooked during pre-clinical in vitro evaluation. However, this knowledge is necessary in order to improve surgical treatment of the proximal humerus and the mechanical behavior of implants, particularly in patients with complex fractures and weak bone stock. We hypothesize that the bone quality has a high influence on the bone straining, independent of the arm position. The goal of this study was to determine the straining of the intact and fractured proximal humerus under physiological-like loading conditions. Furthermore, the impact of augmentation on tissue straining was evaluated. Two representative humeri were selected for this study, one osteoporotic and one reference quality, and scanned using both QCT and DEXA (average DEXA value=0.26 and 0.49 g/cm2 respectively). Subcaptial defects were generated, then stabilized with a plate prior to mechanical stiffness testing. From the QCT data, finite element models were generated and the in vitro stiffness tests analytically simulated. Under physiological-like loading conditions, the straining of the bone and implant were analyzed for 0 degrees, 90 degrees forward flexion, and 90 degrees abduction. Maximal strain values were found for the intact and fractured bone at 90 degrees abduction. This study demonstrates that the straining in a fractured bone of poor quality leads to considerably higher bone strains (up to +30%) than in a more healthy bone. Augmentation of a central void under physiological-like loading with commercial cement led to mechanical failure at the bone-cement interface. New concepts for the surgical treatment of complex fractures of the proximal humerus should take bone distribution into account and thereby allow effective treatment of fractures in osteoporotic patients. The ultimate salvage procedure of augmentation has mechanical limitations as long as current cement materials are used in osteoporotic patients.

Fracture-dislocations of the elbow joint--strategy for treatment and results.

Abstract Between January 1993 and December 1996, 41 patients with fracture dislocation of the elbow joint were treated in our department. In 28 patients (median age 46 years, range 15–77 years; 16 male, 12 female), a clinical and radiological follow-up was obtained after median 34 months (range 12–59 months). In addition to the humero-ulnar dislocation, isolated fractures were present in 13 patients and combined fractures in 15 (all with involvement of the radial head). Primary neurological deficits were found in 7 and open fractures in 3 patients. In 7 patients, primary definitive surgical therapy was carried out by open reduction and internal fixation. A two-step surgical management (initial closed reduction and immobilization, 5 patients with external fixator, 7 with plaster; secondary open surgical procedure) was performed in 12 and conservative treatment in 9 patients. According to the Leipzig Elbow Score, taking subjective, clinical and radiological criteria into consideration, 4 patients achieved ‘excellent’ and 5 patients a ‘good’ result. Ten patients were scored ‘moderate’ and 9 ‘poor’. The rate of secondary complications necessitating revision was 36%. Poor results were primarily caused by extensive initial soft-tissue damage, delayed definitive surgical therapy, and ectopic heterotopic ossification. In contrast, fracture localization and degree of arthrosis were not of significant importance for the final outcome. In fracture dislocations, the goal is a primary definitive surgical treatment aiming for early postoperative physiotherapy.

Mesenchymal Stem Cells in Cartilage Repair: State of the Art and Methods to monitor Cell Growth, Differentiation and Cartilage Regeneration

Degenerative joint diseases caused by rheumatism, joint dysplasia or traumata are particularly widespread in countries with high life expectation. Although there is no absolutely convincing cure available so far, hyaline cartilage and bone defects resulting from joint destruction can be treated today by appropriate transplantations. Recently, procedures were developed based on autologous chondrocytes from intact joint areas. The chondrocytes are expanded in cell culture and subsequently transplanted into the defect areas of the affected joints. However, these autologous chondrocytes are characterized by low expansion capacity and the synthesis of extracellular matrix of poor functionality and quality. An alternative approach is the use of adult mesenchymal stem cells (MSCs). These cells effectively expand in 2D culture and have the potential to differentiate into various cell types, including chondrocytes. Furthermore, they have the ability to synthesize extracellular matrix with properties mimicking closely the healthy hyaline joint cartilage. Beside a more general survey of the architecture of hyaline cartilage, its composition and the pathological processes of joint diseases, we will describe here which advances were achieved recently regarding the development of closed, aseptic bioreactors for the production of autologous grafts for cartilage regeneration based on MSCs. Additionally, a novel mathematical model will be presented that supports the understanding of the growth and differentiation of MSCs. It will be particularly emphasized that such models are helpful to explain the well-known fact that MSCs exhibit improved growth properties under reduced oxygen pressure and limited supply with nutrients. Finally, it will be comprehensively shown how different analytical methods can be used to characterize MSCs on different levels. Besides discussing methods for non-invasive monitoring and tracking of the cells and the determination of their elastic properties, mass spectrometric methods to evaluate the lipid compositions of cells will be highlighted.

The autologous osteochondral transplantation of the knee: clinical results, radiographic findings and histological aspects.

Introduction: The osteochondral transplantation (OCT) is a well accepted treatment option for focal cartilage lesions in the knee joint, whereas the fate of the transplanted cartilage is still unclear and the clinical outcome is variable. The purpose of this study was to evaluate the histological character of autologous transplanted cartilage and to correlate technical aspects and the patients’ history with the clinical outcome. Material and Methods: The OCT was performed in 27 patients (median age of 32 (22–43) years) with a focal chondral lesion at the medial femoral condyle. We investigated the clinical outcome after a median follow-up of 13.5 (5–28) months using the Lysholm-score and the integration of the transplanted plugs using an MRI-scoring system. Biopsy specimens from representative patients (n=8) were evaluated with histological staining and immunohistochemistry. Results: The median Lysholm-score was 80 (range 45–98). The wide range of the Lysholm-score in clinical outcome did not show significant differences in: follow-up, concomitant injuries, defect size or genesis. The MRI analysis revealed in all cases a regular osseous integration of the subchondral bone, but a failed chondral integration. The congruency of the plugs to the joint surface was often incorrect, however a correlation between the MRI-score and the clinical outcome could not be shown. Histology of the transplanted cartilage revealed small changes in immunohistochemistry after a relatively short-term follow-up, whereas the cartilage has still the typical hyaline character. Often, the surrounding cartilage consists of fibrous and granulation tissue. Conclusion: The congruency of the joint surface can not be restored to the original status, particularly in larger defects with irregular shapes. However, we did not find any aspects which affected the function of the knee joint following OCT. It can be assumed that remaining lesions at the surrounding cartilage could maintain the inflammatory process and therefore maintain the pain and a low knee function. Further investigations are needed to specify the effects of the OCT on the transplanted cartilage and its influence on the later clinical outcome.