Lutz Dürselen

Musculo-skeletal loading conditions at the hip during walking and stair climbing

Musculo-skeletal loading plays an important role in the primary stability of joint replacements and in the biological processes involved in fracture healing. However, current knowledge of musculo-skeletal loading is still limited. In the past, a number of musculo-skeletal models have been developed to estimate loading conditions at the hip. So far, a cycle-to-cycle validation of predicted musculo-skeletal loading by in vivo measurements has not been possible. The aim of this study was to determine the musculo-skeletal loading conditions during walking and climbing stairs for a number of patients and compare these findings to in vivo data. Following total hip arthroplasty, four patients underwent gait analysis during walking and stair climbing. An instrumented femoral prosthesis enabled simultaneous measurement of in vivo hip contact forces. On the basis of CT and X-ray data, individual musculo-skeletal models of the lower extremity were developed for each patient. Muscle and joint contact forces were calculated using an optimization algorithm. The calculated peak hip contact forces both over- and under-estimated the measured forces. They differed by a mean of 12% during walking and 14% during stair climbing. For the first time, a cycle-to-cycle validation of predicted musculo-skeletal loading was possible for walking and climbing stairs in several patients. In all cases, the comparison of in vivo measured and calculated hip contact forces showed good agreement.Thus, the authors consider the presented approach as a useful means to determine valid conditions for the analysis of prosthesis loading, bone modeling or remodeling processes around implants and fracture stability following internal fixation.

The influence of muscle forces and external loads on cruciate ligament strain

We know it is important to avoid excessive strain on reconstructed ligaments, but we do not know how in dividual muscles affect cruciate ligament strain. To an swer this, we studied the effect of muscle forces and external loads on cruciate ligament strain. Nine cadav eric knee joints were tested in an apparatus that allowed unconstrained knee joint motion. Quadriceps, ham string, and gastrocnemius muscle forces were simu lated. Additionally, external loads were applied such as varus-internal or valgus-external rotation forces. Cru ciate ligament strain was recorded at different knee flex ion angles. Activation of the gastrocnemius muscle sig nificantly (P < 0.05) strained the posterior cruciate ligament at flexion angles larger than 40°. Quadriceps muscle activation significantly strained the anterior cruciate ligament when the knee was flexed 20° to 60° (P < 0.01) and reduced the strain on the posterior cruciate ligament in the same flexion range ( P< 0.05). Activation of the hamstring muscles strained the pos terior cruciate ligament when the knee was flexed 70° to 110° (P< 0.05). Combined varus and internal rotation forces significantly increased anterior cruciate ligament strain throughout the flexion range (P < 0.05). The re sults suggest that to minimize strain on the ligament after posterior cruciate ligament surgery, strong gas trocnemius muscle contractions should be avoided be yond 30° of knee flexion. The study also calls into ques tion the use of vigorous quadriceps exercises in the range of 20° to 60° of knee flexion after anterior cruciate ligament reconstruction.

TSG-6 Released from Intradermally Injected Mesenchymal Stem Cells Accelerates Wound Healing and Reduces Tissue Fibrosis in Murine Full-Thickness Skin Wounds

Proper activation of macrophages (Mφ) in the inflammatory phase of acute wound healing is essential for physiological tissue repair. However, there is a strong indication that robust Mφ inflammatory responses may be causal for the fibrotic response always accompanying adult wound healing. Using a complementary approach of in vitro and in vivo studies, we here addressed the question of whether mesenchymal stem cells (MSCs)-due to their anti-inflammatory properties-would control Mφ activation and tissue fibrosis in a murine model of full-thickness skin wounds. We have shown that the tumor necrosis factor-α (TNF-α)-stimulated protein 6 (TSG-6) released from MSCs in co-culture with activated Mφ or following injection into wound margins suppressed the release of TNF-α from activated Mφ and concomitantly induced a switch from a high to an anti-fibrotic low transforming growth factor-β1 (TGF-β1)/TGF-β3 ratio. This study provides insight into what we believe to be a previously undescribed multifaceted role of MSC-released TSG-6 in wound healing. MSC-released TSG-6 was identified to improve wound healing by limiting Mφ activation, inflammation, and fibrosis. TSG-6 and MSC-based therapies may thus qualify as promising strategies to enhance tissue repair and to prevent excessive tissue fibrosis.

Finite element modeling of soft tissues: Material models, tissue interaction and challenges

BACKGROUND Musculoskeletal soft tissues, such as articular cartilage, ligaments, knee meniscus and intervertebral disk, have a complex structure, which provides elasticity and capability to support and distribute the body loads. Soft tissues describe an inhomogeneous and multiphasic structure, and exhibit a nonlinear, time-dependent behavior. Their mechanical response is governed by a substance composed of protein fiber-rich and proteoglycan-rich extracellular matrix and interstitial fluid. Protein fibers (e.g. collagen) give the tissue direction dependent stiffness and strength. To investigate these complex biological systems, the use of mathematical tools is well established, alone or in combination with experimental in vitro and in vivo tests. However, the development of these models poses many challenges due to the complex structure and mechanical response of soft tissues. METHODS Non-systematic literature review. FINDINGS This paper provides a summary of different modeling strategies with associated material properties, contact interactions between articulating tissues, validation and sensitivity of soft tissues with special focus on knee joint soft tissues and intervertebral disk. Furthermore, it reviews and discusses some salient clinical findings of reported finite element simulations. INTERPRETATION Model studies extensively contributed to the understanding of functional biomechanics of soft tissues. Models can be effectively used to elucidate clinically relevant questions. However, users should be aware of the complexity of such tissues and of the capabilities and limitations of these approaches to adequately simulate a specific in vivo or in vitro phenomenon.

Primary stability and strain distribution of cementless hip stems as a function of implant design

BACKGROUND Short stem prostheses have been developed to preserve the femoral bone stock. The purpose of this study was to evaluate the stress-shielding effect in the proximal femur as well as the micromotion between bone and implant as a measure of primary stability for a new short stem in comparison to a clinically successful short stem and a straight stem. METHODS Using paired fresh human femurs, stress shielding was examined by using tri-axial strain gage rosettes. The strain distribution of the proximal femur was measured before and after implantation of three cementless prostheses of different design concepts and stem lengths. Furthermore, interface motion and rotational stability were investigated under dynamic loading (100-1600 N) after 100,000 load cycles using inductive miniature displacement transducers. FINDINGS A reduction of longitudinal cortical strains in the proximal femur was displayed for all three implants. The reduction was less pronounced for the shorter stem implants, however. Interface motion was below the critical threshold of 150 μm at almost all measuring points for all three stems, with a tendency for greater rotational stability in the shorter stem implants. INTERPRETATION The new short stem prosthesis displayed reduced stress shielding and comparable primary stability to an established short stem and a conventional shaft design. Shortening the stem did not negatively influence primary stability. The clinical implications of these findings remain to be proven.

Fabrication, mechanical and in vivo performance of polycaprolactone/tricalcium phosphate composite scaffolds.

This paper explores the use of selective laser sintering (SLS) for the generation of bone tissue engineering scaffolds from polycaprolactone (PCL) and PCL/tricalcium phosphate (TCP). Different scaffold designs are generated, and assessed from the point of view of manufacturability, porosity and mechanical performance. Large scaffold specimens are produced, with a preferred design, and are assessed through an in vivo study of the critical size bone defect in sheep tibia with subsequent microscopic, histological and mechanical evaluation. Further explorations are performed to generate scaffolds with increasing TCP content. Scaffold fabrication from PCL and PCL/TCP mixtures with up to 50 mass% TCP is shown to be possible. With increasing macroporosity the stiffness of the scaffolds is seen to drop; however, the stiffness can be increased by minor geometrical changes, such as the addition of a cage around the scaffold. In the animal study the selected scaffold for implantation did not perform as well as the TCP control in terms of new bone formation and the resulting mechanical performance of the defect area. A possible cause for this is presented.

Comparative animal study of three ligament prostheses for the replacement of the anterior cruciate and medial collateral ligament

Three different ligament prostheses (Leeds-Keio, Gore-Tex and a prototype of Aramid) were implanted in sheep knee joints replacing the anterior cruciate ligament and the medial collateral ligament. After 1 yr the knees were explanted and their biomechanical properties were assessed by a drawer test and tensile tests of the implants. Additionally the ligament replacements, the synovial membrane and the lymph nodes were inspected histologically. For each type of prosthesis partial or total ruptures occurred. None of the operated joints regained normal stability and stiffness. Anterior knee stability was best for the Gore-Tex treated group and worst for those joints that received a Leeds-Keio implant. The stiffness and rupture strength were highest for the Gore-Tex prostheses. Histologically the strongest intra-articular inflammatory response was observed in the Gore-Tex treated joints. Inside the drill tunnels the severest foreign body reaction was found for the Aramid prostheses. Gore-Tex fibres often showed good bony integration. Wear particles formed from all prostheses and caused small granulomas and mild synovities. The results suggest that none of the tested materials represent an ideal solution for ligament replacement. Relatively good stability does not guarantee good biocompatibility and vice versa. This suggests that ligament prostheses should be applied only in salvage cases.

Effect of partial meniscectomy at the medial posterior horn on tibiofemoral contact mechanics and meniscal hoop strains in human knees.

We examined the influence of partial meniscectomy of 10 mm width on 10 human cadaveric knee joints, as it is performed during the treatment of radial tears in the posterior horn of the medial meniscus, on maximum contact pressure, contact area (CA), and meniscal hoop strain in the lateral and medial knee compartments. In case of 0° and 30° flexion angle, 20% and 50% partial meniscectomy did not influence maximum contact pressure and area. Only in case of 60° knee flexion, 50% partial resection increased medial maximum contact pressure and decreased the medial CA statistically significant. However, 100% partial resection increased maximum contact pressure and decreased CA significantly in the meniscectomized medial knee compartment in all tested knee positions. No significant differences were noted for meniscal hoop strain. From a biomechanical point of view, our in vitro study suggests that the medial joint compartment is not in danger of accelerated cartilage degeneration up to a resection limit of 20% meniscal depth and 10 mm width. Contact mechanics are likely to be more sensitive to partial meniscectomy at higher flexion angles, which has to be further investigated.

Processed xenogenic cartilage as innovative biomatrix for cartilage tissue engineering: effects on chondrocyte differentiation and function

One key point in the development of new bioimplant matrices for the reconstruction and replacement of cartilage defects is to provide an adequate microenvironment to ensure chondrocyte migration and de novo synthesis of cartilage‐specific extracellular matrix (ECM). A recently developed decellularization and sterilization process maintains the three‐dimensional (3D) collagen structure of native septal cartilage while increasing matrix porosity, which is considered to be crucial for cartilage tissue engineering. Human primary nasal septal chondrocytes were amplified in monolayer culture and 3D‐cultured on processed porcine nasal septal cartilage scaffolds. The influence of chondrogenic growth factors on neosynthesis of ECM proteins was examined at the protein and gene expression levels. Seeding experiments demonstrated that processed xenogenic cartilage matrices provide excellent environmental properties for human nasal septal chondrocytes with respect to cell adhesion, migration into the matrix and neosynthesis of cartilage‐specific ECM proteins, such as collagen type II and aggrecan. Matrix biomechanical stability indicated that the constructs retrieve full stability and function during 3D culture for up to 42 days, proportional to collagen type II and GAG production. Thus, processed xenogenic cartilage offers a suitable environment for human nasal chondrocytes and has promising potential for cartilage tissue engineering in the head and neck region. Copyright

A new metaphyseal bone defect model in osteoporotic rats to study biomaterials for the enhancement of bone healing in osteoporotic fractures

The intention of this study was to establish a new critical size animal model that represents clinically relevant situations with osteoporotic bone status and internally fixated metaphyseal defect fractures in which biomaterials for the enhancement of fracture healing in osteoporotic fracture defects can be studied. Twenty-eight rats were ovariectomized (OVX) and treated with a calcium-, phosphorus-, vitamin D3-, soy- and phytoestrogen-free diet. After 3months Dual-energy X-ray absorptiometry measurements showed statistically significant reductions in bone mineral density of the spine of -25.9% and of the femur of -21.3% of the OVX rats compared with controls, confirming osteoporosis in the OVX rats. The OVX rats then underwent either 3 or 5mm wedge-shaped osteotomy of the distal metaphyseal area of the femur that was internally stabilized with a T-shaped mini-plate. After 42days biomechanical testing yielded completely unstable conditions in the 5mm defect femora (bending stiffness 0Nmm(-2)) and a bending stiffness of 12,500Nmm(-2) in the 3mm defects, which showed the beginning of fracture consolidation. Micro-computed tomography showed statistically significant more new bone formation in the 3mm defects (4.83±0.37mm(2)), with bridging of the initial fracture defect area, compared with the 5mm defects (2.68±0.34mm(2)), in which no bridging of the initial defect was found. These results were confirmed by histology. In conclusion, the 5mm defect can be considered as a critical size defect model in which biomaterials can be tested.