Showing papers by "Georg N. Duda published in 2012"
TL;DR: In this paper, the authors compared the gold standard autograft with biodegradable composite scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate combined with autologous bone marrow-derived mesenchymal stem cells (MSCs) or recombinant human bone morphogenetic protein 7 (rhBMP-7).
Abstract: The reconstruction of large defects (>10 mm) in humans usually relies on bone graft transplantation. Limiting factors include availability of graft material, comorbidity, and insufficient integration into the damaged bone. We compare the gold standard autograft with biodegradable composite scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate combined with autologous bone marrow-derived mesenchymal stem cells (MSCs) or recombinant human bone morphogenetic protein 7 (rhBMP-7). Critical-sized defects in sheep - a model closely resembling human bone formation and structure - were treated with autograft, rhBMP-7, or MSCs. Bridging was observed within 3 months for both the autograft and the rhBMP-7 treatment. After 12 months, biomechanical analysis and microcomputed tomography imaging showed significantly greater bone formation and superior strength for the biomaterial scaffolds loaded with rhBMP-7 compared to the autograft. Axial bone distribution was greater at the interfaces. With rhBMP-7, at 3 months, the radial bone distribution within the scaffolds was homogeneous. At 12 months, however, significantly more bone was found in the scaffold architecture, indicating bone remodeling. Scaffolds alone or with MSC inclusion did not induce levels of bone formation comparable to those of the autograft and rhBMP-7 groups. Applied clinically, this approach using rhBMP-7 could overcome autograft-associated limitations.
311 citations
TL;DR: This study suggests that there are unfavorable immune cells and factors participating in the initial healing phase and identifying beneficial aspects may lead to promising therapeutical approaches that might benefit further by eliminating the unfavorable factors.
Abstract: Bone healing commences with an inflammatory reaction which initiates the regenerative healing process leading in the end to reconstitution of bone An unbalanced immune reaction during this early bone healing phase is hypothesized to disturb the healing cascade in a way that delays bone healing and jeopardizes the successful healing outcome The immune cell composition and expression pattern of angiogenic factors were investigated in a sheep bone osteotomy model and compared to a mechanically-induced impaired/delayed bone healing group In the impaired/delayed healing group, significantly higher T cell percentages were present in the bone hematoma and the bone marrow adjacent to the osteotomy gap when compared to the normal healing group This was mirrored in the higher cytotoxic T cell percentage detected under delayed bone healing conditions indicating longer pro-inflammatory processes The highly activated periosteum adjourning the osteotomy gap showed lower expression of hematopoietic stem cell markers and angiogenic factors such as heme oxygenase and vascular endothelial growth factor This indicates a deferred revascularization of the injured area due to ongoing pro-inflammatory processes in the delayed healing group Results from this study suggest that there are unfavorable immune cells and factors participating in the initial healing phase In conclusion, identifying beneficial aspects may lead to promising therapeutical approaches that might benefit further by eliminating the unfavorable factors
218 citations
TL;DR: The current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing are reviewed.
213 citations
TL;DR: It is concluded that the effects of hypoxia are crucial for effective bone healing, which may potentially lead to the development of novel therapeutic approaches.
Abstract: Background
Bone fracture initiates a series of cellular and molecular events including the expression of hypoxia-inducible factor (HIF)-1. HIF-1 is known to facilitate recruitment and differentiation of multipotent human mesenchymal stromal cells (hMSC). Therefore, we analyzed the impact of hypoxia and HIF-1 on the competitive differentiation potential of hMSCs towards adipogenic and osteogenic lineages.
168 citations
TL;DR: Based on specific differences observed between the impact of chronological and in vitro MSC aging, it is concluded that both are distinct processes.
Abstract: Mesenchymal stromal cells (MSCs) are of high relevance for the regeneration of mesenchymal tissues such as bone and cartilage. The promising role of MSCs in cell-based therapies and tissue engineering appears to be limited due to a decline of their regenerative potential with increasing donor age, their limited availability in human tissues and the need of in vitro expansion prior to treatment. We therefore aimed to determine to which degree in vitro aging and chronological aging may be similar processes or if in vitro culture-related changes at the cellular and molecular level are at least altered as a function of donor age. For that purpose we established MSCs cultures from young (yMSCs) and aged (aMSCs) rats that were cultured for more than 100 passages. These long-term MSCs cultures were non-tumorigenic and exhibited similar surface marker patterns as primary MSCs of passage 2. During in vitro expansion, but not during chronological aging, MSCs progressively lose their progenitor characteristics, e.g., complete loss of osteogenic differentiation potential, diminished adipogenic differentiation, altered cell morphology and increased susceptibility towards senescence. Transcriptome analysis revealed that long-term in vitro MSCs cultivation leads to down-regulation of genes involved in cell differentiation, focal adhesion organization, cytoskeleton turnover and mitochondria function. Accordingly, functional analysis demonstrated altered mitochondrial morphology, decreased antioxidant capacities and elevated ROS levels in long-term cultivated yMSCs as well as aMSCs. Notably, only the MSC migration potential and their antioxidative capacity were altered by in vitro as well as chronological aging. Based on specific differences observed between the impact of chronological and in vitro MSC aging we conclude that both are distinct processes.
148 citations
TL;DR: In this article, the effect of the scaffold architecture on cell organization, fibrous tissue, and mineralized tissue formation mechanisms in vivo has been investigated using an ovine, tibial, 30mm critical-sized defect as a model system.
Abstract: Critical-sized bone defect regeneration is a remaining clinical concern. Numerous scaffold-based strategies are currently being investigated to enable in vivo bone defect healing. However, a deeper understanding of how a scaffold influences the tissue formation process and how this compares to endogenous bone formation or to regular fracture healing is missing. It is hypothesized that the porous scaffold architecture can serve as a guiding substrate to enable the formation of a structured fibrous network as a prerequirement for later bone formation. An ovine, tibial, 30-mm critical-sized defect is used as a model system to better understand the effect of the scaffold architecture on cell organization, fibrous tissue, and mineralized tissue formation mechanisms in vivo. Tissue regeneration patterns within two geometrically distinct macroscopic regions of a specific scaffold design, the scaffold wall and the endosteal cavity, are compared with tissue formation in an empty defect (negative control) and with cortical bone (positive control). Histology, backscattered electron imaging, scanning small-angle X-ray scattering, and nanoindentation are used to assess the morphology of fibrous and mineralized tissue, to measure the average mineral particle thickness and the degree of alignment, and to map the local elastic indentation modulus. The scaffold proves to function as a guiding substrate to the tissue formation process. It enables the arrangement of a structured fibrous tissue across the entire defect, which acts as a secondary supporting network for cells. Mineralization can then initiate along the fibrous network, resulting in bone ingrowth into a critical-sized defect, although not in complete bridging of the defect. The fibrous network morphology, which in turn is guided by the scaffold architecture, influences the microstructure of the newly formed bone. These results allow a deeper understanding of the mode of mineral tissue formation and the way this is influenced by the scaffold architecture. © 2012 American Society for Bone and Mineral Research.
103 citations
TL;DR: Mechanical signals are integrated into the BMP signalling pathway by enhancing immediate early steps within the Smad pathway, independent of autocrine ligand secretion, which suggests a direct crosstalk of both mechanotransduction and B MP signalling, most likely at the level of the cell surface receptors.
Abstract: Efficient osteogenic differentiation is highly dependent on coordinated signals arising from growth factor signalling and mechanical forces. Bone morphogenetic proteins (BMPs) are secreted proteins that trigger Smad and non-Smad pathways and thereby influence transcriptional and non-transcriptional differentiation cues. Crosstalk at multiple levels allows for promotion or attenuation of signalling intensity and specificity. Similar to BMPs, mechanical stimulation enhances bone formation. However, the molecular mechanism by which mechanical forces crosstalk to biochemical signals is still unclear. Here, we use a three-dimensional bioreactor system to describe how mechanical forces are integrated into the BMP pathway. Time-dependent phosphorylation of Smad, mitogen-activated protein kinases and Akt in human fetal osteoblasts was investigated under loading and/or BMP2 stimulation conditions. The phosphorylation of R-Smads is increased both in intensity and duration under BMP2 stimulation with concurrent mechanical loading. Interestingly, the synergistic effect of both stimuli on immediate early Smad phosphorylation is reflected in the transcription of only a subset of BMP target genes, while others are differently affected. Together this results in a cooperative regulation of osteogenesis that is guided by both signalling pathways. Mechanical signals are integrated into the BMP signalling pathway by enhancing immediate early steps within the Smad pathway, independent of autocrine ligand secretion. This suggests a direct crosstalk of both mechanotransduction and BMP signalling, most likely at the level of the cell surface receptors. Furthermore, the crosstalk of both pathways over longer time periods might occur on several signalling levels.
99 citations
TL;DR: The patellofemoral forces determined here provide evidence that peak forces across these joints reach values of around 3 BW during high flexion activities, also suggesting that the in vivo loading conditions at the knee can only be fully understood if the forces at the TF and the PF joints are considered together.
92 citations
01 Jan 2012
TL;DR: The scaffold proves to function as a guiding substrate to the tissue formation process and enables the arrangement of a structured fibrous tissue across the entire defect, which acts as a secondary supporting network for cells.
Abstract: Free to read
Critical-sized bone defect regeneration is a remaining clinical concern. Numerous scaffold-based strategies are currently being investigated to enable in vivo bone defect healing. However, a deeper understanding of how a scaffold influences the tissue formation process and how this compares to endogenous bone formation or to regular fracture healing is missing. It is hypothesized that the porous scaffold architecture can serve as a guiding substrate to enable the formation of a structured fibrous network as a prerequirement for later bone formation. An ovine, tibial, 30-mm critical-sized defect is used as a model system to better understand the effect of the scaffold architecture on cell organization, fibrous tissue, and mineralized tissue formation mechanisms in vivo. Tissue regeneration patterns within two geometrically distinct macroscopic regions of a specific scaffold design, the scaffold wall and the endosteal cavity, are compared with tissue formation in an empty defect (negative control) and with cortical bone (positive control). Histology, backscattered electron imaging, scanning small-angle X-ray scattering, and nanoindentation are used to assess the morphology of fibrous and mineralized tissue, to measure the average mineral particle thickness and the degree of alignment, and to map the local elastic indentation modulus. The scaffold proves to function as a guiding substrate to the tissue formation process. It enables the arrangement of a structured fibrous tissue across the entire defect, which acts as a secondary supporting network for cells. Mineralization can then initiate along the fibrous network, resulting in bone ingrowth into a critical-sized defect, although not in complete bridging of the defect. The fibrous network morphology, which in turn is guided by the scaffold architecture, influences the microstructure of the newly formed bone. These results allow a deeper understanding of the mode of mineral tissue formation and the way this is influenced by the scaffold architecture. Copyright © 2012 American Society for Bone and Mineral Research.
83 citations
TL;DR: Although recuperation seems to allow a certain recovery of iron storage, particularly in athletes with initially low ferritin levels, this retrieval was insufficient to fully normalise reduced iron levels, Therefore, iron status should be carefully monitored during the various training and competitive periods in elite athletes.
74 citations
01 Jan 2012
TL;DR: A polymer-based scaffold that can be loaded with cells and growth factors and inserted directly into a bone defect, with healing demonstrated in sheep after only 3 months, is designed and put to the test for evaluation of bone regeneration and load bearing in humans.
Abstract: The reconstruction of large defects (>10 mm) in humans usually relies on bone graft transplantation. Limiting factors include availability of graft material, comorbidity, and insufficient integration into the damaged bone. We compare the gold standard autograft with biodegradable composite scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate combined with autologous bone marrow-derived mesenchymal stem cells (MSCs) or recombinant human bone morphogenetic protein 7 (rhBMP-7). Critical-sized defects in sheep - a model closely resembling human bone formation and structure - were treated with autograft, rhBMP-7, or MSCs. Bridging was observed within 3 months for both the autograft and the rhBMP-7 treatment. After 12 months, biomechanical analysis and microcomputed tomography imaging showed significantly greater bone formation and superior strength for the biomaterial scaffolds loaded with rhBMP-7 compared to the autograft. Axial bone distribution was greater at the interfaces. With rhBMP-7, at 3 months, the radial bone distribution within the scaffolds was homogeneous. At 12 months, however, significantly more bone was found in the scaffold architecture, indicating bone remodeling. Scaffolds alone or with MSC inclusion did not induce levels of bone formation comparable to those of the autograft and rhBMP-7 groups. Applied clinically, this approach using rhBMP-7 could overcome autograft-associated limitations.
TL;DR: The Epionics SPINE system allows the practical and reliable dynamic assessment of lumbar spine shape and RoM, and may therefore provide a clinical solution for the evaluation of lower back pain as well as therapy monitoring.
Abstract: The diagnosis of low back pain pathology is generally based upon invasive image-based assessment of structural pathology, but is limited in methods to evaluate function. The accurate and robust measurement of dynamic function may assist in the diagnosis and monitoring of therapy success. Epionics SPINE is an advanced strain-gauge measurement technology, based on the two sensor strips SpineDMS system, which allows the non-invasive assessment of lumbar and thoraco-lumbar motion for periods of up to 24 h. The aim of this study was to examine the reliability of Epionics SPINE and to collect and compare normative data for the characterisation of spinal motion in healthy subjects. Furthermore, the identification of parameters that influence lumbar range of motion (RoM) was targeted. Spinal shape was measured using Epionics SPINE in 30 asymptomatic volunteers during upright standing, as well as maximum flexion and extension, to check intra-rater reliability. Furthermore, back shape was assessed throughout repeated maximum flexion and extension movements in 429 asymptomatic volunteers in order to collect normative data of the lordosis angle and RoM in different gender and age classes. The lordosis angle during standing in the healthy collective measured with Epionics SPINE was 32.4° ± 9.7°. Relative to this standing position, the average maximum flexion angle was 50.8° ± 10.9° and the average extension angle 25.0° ± 11.5°. Comparisons with X-ray and Spinal Mouse data demonstrated good agreement in static positions. Age played a larger role than gender in influencing lumbar posture and RoM. The Epionics SPINE system allows the practical and reliable dynamic assessment of lumbar spine shape and RoM, and may therefore provide a clinical solution for the evaluation of lower back pain as well as therapy monitoring.
TL;DR: It is concluded that the mechanical environment of the cell after remodeling is depending on mechanical loading rather than on initial scaffold stiffness, which suggests that from initially distinct mechanical starting conditions (scaffold stiffness), the construct's mechanical properties converge over time.
Abstract: Fibroblasts as many other cells are known to form, contract, and remodel the extracellular matrix (ECM). The presented study aims to gain an insight into how mechanical boundary conditions affect the production of ECM components, their remodeling, and the feedback of the altered mechanical cell environment on these processes. The influence of cyclic mechanical loading (f=1 Hz, 10% axial compression) and scaffold stiffness (E=1.2 and 8.5 kPa) on the mechanical properties of fibroblast-seeded scaffold constructs were investigated in an in vitro approach over 14 days of culture. To do so, a newly developed bioreactor system was employed. While mechanical loading resulted in a clear upregulation of procollagen-I and fibronectin production, scaffold stiffness showed to primarily influence matrix metalloproteinase-1 (MMP-1) secretion and cell-induced scaffold contraction. Higher stiffness of the collagen scaffolds resulted in an up to twofold higher production of collagen-degrading MMP-1. The changes of mechani...
TL;DR: It was found that the formation of the hard callus could be reproduced in silico for a wide range of threshold values, however, the bridging of the fracture gap by cartilage on the periosteal side was observed only for a rather specific choice of the threshold values for tissue differentiation.
Abstract: During secondary bone healing, different tissue types are formed within the fracture callus depending on the local mechanical and biological environment. Our aim was to understand the temporal succession of these tissue patterns for a normal bone healing progression by means of a basic mechanobiological model. The experimental data stemmed from an extensive, previously published animal experiment on sheep with a 3 mm tibial osteotomy. Using recent experimental data, the development of the hard callus was modelled as a porous material with increasing stiffness and decreasing porosity. A basic phenomenological model was employed with a small number of simulation parameters, which allowed comprehensive parameter studies. The model distinguished between the formation of new bone via endochondral and intramembranous ossification. To evaluate the outcome of the computer simulations, the tissue images of the simulations were compared with experimentally derived tissue images for a normal healing progression in sheep. Parameter studies of the threshold values for the regulation of tissue formation were performed, and the source of the biological stimulation (comprising e.g. stem cells) was varied. It was found that the formation of the hard callus could be reproduced in silico for a wide range of threshold values. However, the bridging of the fracture gap by cartilage on the periosteal side was observed only (i) for a rather specific choice of the threshold values for tissue differentiation and (ii) when assuming a strong source of biological stimulation at the periosteum.
TL;DR: Current available methods for local drug delivery and their limitations in therapy are described and a new set of design and performance requirements for intra-operatively customized implant coatings for controlled drug delivery is proposed.
TL;DR: This study will answer the question of whether patients with synovia with poor lubricating properties may be at risk for thermally induced bone necrosis and subsequent implant failure and deliver the different friction properties of various implant materials.
Abstract: When walking long distances, hip prostheses heat up due to friction. The influence of articulating materials and lubricating properties of synovia on the final temperatures, as well as any potential biological consequences, are unknown. Such knowledge is essential for optimizing implant materials, identifying patients who are possibly at risk of implant loosening, and proving the concepts of current joint simulators. An instrumented hip implant with telemetric data transfer was developed to measure the implant temperatures in vivo. A clinical study with 100 patients is planned to measure the implant temperatures for different combinations of head and cup materials during walking. This study will answer the question of whether patients with synovia with poor lubricating properties may be at risk for thermally induced bone necrosis and subsequent implant failure. The study will also deliver the different friction properties of various implant materials and prove the significance of wear simulator tests. A clinically successful titanium hip endoprosthesis was modified to house the electronics inside its hollow neck. The electronics are powered by an external induction coil fixed around the joint. A temperature sensor inside the implant triggers a timer circuit, which produces an inductive pulse train with temperature-dependent intervals. This signal is detected by a giant magnetoresistive sensor fixed near the external energy coil. The implant temperature is measured with an accuracy of 0.1°C in a range between 20°C and 58°C and at a sampling rate of 2-10 Hz. This rate could be considerably increased for measuring other data, such as implant strain or vibration. The employed technique of transmitting data from inside of a closed titanium implant by low frequency magnetic pulses eliminates the need to use an electrical feedthrough and an antenna outside of the implant. It enables the design of mechanically safe and simple instrumented implants.
TL;DR: In this paper, the authors investigated the role of bone defect size in the early phase of critical sized bone defect healing, and found that bone defect sizes are correlated with inter-fragmentary tissue strains within the bone defect area.
Abstract: This study addresses the hypothesis that callus formation, patterning, and mineralisation are impaired during the early phase of critical sized bone defect healing, and may relate to inter-fragmentary tissue strains within the bone defect area Twenty four 12 week old Sprague Dawley rats were used for this study They were divided into two groups defined by the femur bone defect size: (i) 1 mm resulting in normal healing (NH), and (ii) a large sized 5 mm defect resulting in critical healing (CH) Callus formation, patterning, and mineralisation kinetics in both groups were examined in the periosteal and osteotomy gap regions using a novel longitudinal study setup Finite element analyses on µCT generated tomograms were used to determine inter-fragmentary tissue strain patterns and compared to callus formation and patterning over the course of time Using a novel longitudinal study technique with µCT, in vivo tracking and computer simulation approaches, this study demonstrates that: (i) periosteal bone formation and patterning are significantly influenced by bone defect size as early as 2 weeks; (ii) osteotomy gap callus formation and patterning are influenced by bone defect size, and adapt towards a non-union in critical cases by deviating into a medullary formation route as early as 2 weeks after osteotomy; (iii) the new bone formation in the osteotomy gap enclosing the medullary cavity in the CH group is highly mineralised; (iv) inter-fragmentary strain patterns predicted during the very early soft callus tissue phase (less than 2 weeks) are concurrent with callus formation and patterning at later stages In conclusion, bone defect size influences early onset of critical healing patterns
TL;DR: Characterising the angular velocity of lordosis throughout the thoracolumbar spine according to age and gender is characterised to serve as normative data for comparison to patients with spinal pathology or after surgical treatment.
Abstract: The importance of functional parameters for evaluating the severity of low back pain is gaining clinical recognition, with evidence suggesting that the angular velocity of lordosis is critical for identification of musculoskeletal deficits. However, there is a lack of data regarding the range of functional kinematics (RoKs), particularly which include the changing shape and curvature of the spine. We address this deficit by characterising the angular velocity of lordosis throughout the thoracolumbar spine according to age and gender. The velocity of lumbar back shape changes was measured using Epionics SPINE during maximum flexion and extension activities in 429 asymptomatic volunteers. The difference between maximum positive and negative velocities represented the RoKs. The mean RoKs for flexion decreased with age; 114°/s (20–35 years), 100°/s (36–50 years) and 83°/s (51–75 years). For extension, the corresponding mean RoKs were 73°/s, 57°/s and 47°/s. ANCOVA analyses revealed that age and gender had the largest influence on the RoKs (p<0.05). The Epionics SPINE system allows the rapid assessment of functional kinematics in the lumbar spine. The results of this study now serve as normative data for comparison to patients with spinal pathology or after surgical treatment.
TL;DR: Neither increased external rotation of the limb nor restriction of internal rotation during walking could be established and both surgical approaches seem to be equally applicable approaches with good to very good functional results.
Abstract: Minimally invasive total hip arthroplasty has been successfully introduced in the past decade. Nevertheless, standard approaches such as the direct lateral approach are still commonly used in orthopaedic surgery due to easy handling, good intra-operative overview and low complication rates. However, a frequent occurrence of fatty atrophy within the anterior third of the gluteus medius muscle has been demonstrated when using the modified direct-lateral approach (mDL), which may be associated with a reduction in function, limitation of internal leg rotation, gait disorders and pain. The question addressed in this study is whether mDL-approach leads to unfavourable changes in foot progression angle (FPA), gait and to more postoperative pain compared with a minimally invasive anterolateral approach (ALMI). Thirty patients with primary osteoarthritis of the hip were recruited for this study. All subjects received an uncemented THA (Alloclassic®-Zweymuller stem, Allofit® Cup, FA Zimmer®), 15 through an ALMI-approach and 15 via the mDL-approach. Gait analyses were performed both preoperatively and 3 months after surgery to measure FPA, step length, stance duration, cadence and walking speed. Additionally, the Harris-Hip Score, pain according to the visual analogue scale and the Trendelenburg sign were evaluated. No influence of the surgical approach could be observed on the gait patterns or FPA. Furthermore, neither increased external rotation of the limb nor restriction of internal rotation during walking could be established. Pain and Harris-Hip Score did not differ significantly between the two groups. In comparison with an ALMI approach, the mDL approach did not lead to a change in FPA postoperatively. No detrimental effect could be found on the gait pattern or pain after surgery. Based on these measurements, the minimally invasive anterolateral approach did not appear to provide functional benefits in outcome over the mDL approach. Consequently, both surgical approaches seem to be equally applicable approaches with good to very good functional results.
TL;DR: It is believed that transplanted MSCs residing in the interstitial compartment evolve their regenerative capabilities through paracrine pathways, similar results could be obtained with respect to functional muscle regeneration.
Abstract: Mesenchymal stem cell (MSC) therapy is a promising approach for regaining muscle function after trauma. Prior to clinical application, the ideal time of transplantation has to be determined. We investigated the effects of immediate and delayed transplantation. Sprague-Dawley rats received a crush trauma to the left soleus muscle. Treatment groups were transplanted locally with 2 × 10(6) autologous MSCs, either immediately or 7 days after trauma. Saline was used as sham therapy. Contraction force tests and histological analyses were performed 4 weeks after injury. GFP-labelled MSCs were followed after transplantation. The traumatized soleus muscles of the sham group displayed a reduction of twitch forces to 36 ± 17% and of tetanic forces to 29 ± 11% of the non-injured right control side, respectively. Delayed MSC transplantation resulted in a significant improvement of contraction maxima in both stimulation modes (twitch, p = 0.011; tetany, p = 0.014). Immediate transplantation showed a significant increase in twitch forces to 59 ± 17% (p = 0.043). There was no significant difference in contraction forces between muscles treated by immediate and delayed cell transplantation. We were able to identify MSCs in the interstitium of the injured muscles up to 4 weeks after transplantation. Despite the fundamental differences of the local environment, which MSCs encounter after transplantation, similar results could be obtained with respect to functional muscle regeneration. We believe that transplanted MSCs residing in the interstitial compartment evolve their regenerative capabilities through paracrine pathways. Our data suggest a large time window of the therapeutical measures.
TL;DR: Evidence is provided that subject specific loading conditions and physiological boundary constraints are essential for explaining inter-patient variations in bone adaptation patterns and improved knowledge of the rules governing the adaptation of bone following THA helps towards understanding the interplay between mechanics and biology.
Abstract: Bone adaptation after total hip arthroplasty is associated with the change in internal load environment, and can result in compromised bone stock, which presents a considerable challenge should a revision procedure be required. Under the assumption of a generic mechano-regulatory algorithm for governing bone adaptation, the aim of this study was to understand the contribution of subject specific loading conditions towards explaining the local periprosthetic remodelling variations in patients.
CT scans of 3 consecutive THA patients were obtained and used for the construction of subject specific finite element models using verified musculoskeletal loading and physiological boundary conditions. Using either strain energy density or equivalent strain as mechano-transduction signals, predictions of bone adaptation were compared to DEXA derived BMD changes from 7 days to 12 months post-implantation. Individual changes in BMD of up to 33.6% were observed within the 12 month follow-up period, together with considerable inter-patient variability of up to 26%. Estimates of bone adaptation using equivalent strain and balanced loading conditions led to the best agreement with in vivo measured BMD, with RMS errors of only 3.9%, 7.3% and 7.3% for the individual subjects, compared to errors of over 10% when the loading conditions were simplified.
This study provides evidence that subject specific loading conditions and physiological boundary constraints are essential for explaining inter-patient variations in bone adaptation patterns. This improved knowledge of the rules governing the adaptation of bone following THA helps towards understanding the interplay between mechanics and biology for better identifying patients at risk of excessive or problematic periprosthetic bone atrophy.
TL;DR: It is shown that the defective fracture healing in Nf1(Prx1) mice is characterized by diminished cartilaginous callus formation and a thickening of the periosteal bone, paralleled by fibrous tissue accumulation within the fracture site.
TL;DR: This study provides a framework for the design of effective implants with open pore structures to ensure mechanical stability as well as promote mechanical stimulation and encourage in vivo osseointegration.
Abstract: Large segmental bone defects remain a clinical challenge. Titanium lattice-structured implants in combination with laser sintering technology promises to be an alternative to bone grafting in the treatment of critical sized bone defects. Laser sintering allows the rapid manufacturing of patient specific 3D-structured scaffolds with highly interconnected macroporous networks and tunable mechanical properties. Unknown remains to what degree the mechanical properties of these implants could be tuned, without leading to mechanical failure but still providing adequate mechanical stimuli for tissue ingrowth. The aim of this study was to evaluate various implant designs for their mechanical potential towards (a) optimized safety against stress failure and (b) optimal intrastructural straining for bone ingrowth. Finite element analyses of several lattice-structured configurations were performed. Results illustrated a strong influence of the configuration on the load carrying capacity of the constructs. The likelihood of mechanical failure was predicted to be highly dependent on structure configuration with little influence of implant porosity. Increasing porosity did not result in an increase in the implant intrastructural straining in all configurations; however, the lattice configuration was the determinant factor for implant load transfer capacity. This study provides a framework for the design of effective implants with open pore structures to ensure mechanical stability as well as promote mechanical stimulation and encourage in vivo osseointegration. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
TL;DR: The outcome of skeletal muscle regeneration after injury can be improved in animals of both sexes with MSC transplantation, independent of treatment.
TL;DR: The present study demonstrated an effect of systemically administered MSCs in the treatment of skeletal muscle injuries, which seems to present an alternative to a local administration.
Abstract: Skeletal muscle trauma leads to severe functional deficits, which cannot be addressed by current treatment options. Our group could show the efficacy of local transplantation of mesenchymal stroma cells (MSCs) for the treatment of injured muscles. While local application of MSCs has proven to be effective, we hypothesized that a selective intra-arterial transplantation would lead to a better distribution of the cells and so improved physiological recovery of muscle function.
TL;DR: BMP-2 is overexpressed and its concentrations are consequently higher in patients suffering from arthrofibrosis after TKA, compared with the control group with referred pain.
Abstract: Because of the multiple possible aetiologies of painful total knee arthroplasty (TKA), the diagnosis and treatment of such patients are challenging. In a considerable number of patients, an intraarticular pathology is present, although not verifiable with clinical and diagnostic imaging techniques as in cases of primary arthrofibrosis. In these patients, the differentiation between intra- and extraarticular causes of pain remains difficult. Until now, little attention has been paid to changes of the synovial fluid and tissue in these knees. The objective of this study was to analyse the changes of the synovial environment in patients suffering from arthrofibrosis after TKA in comparison with knees with referred pain suffering from hip arthritis. The changes of the synovial environment probably provide additional diagnostic information to verify an intraarticular pathology. The synovial fluid of 10 consecutive knees in 10 patients presenting with a primary arthrofibrosis after TKA without signs of infection, instability, malalignment, or loosening was analysed and compared to the synovial fluid of 10 knees with referred pain serving as controls. The BMP-2 concentration was measured in the synovial fluid, and the presence of cytokines leading to an overexpression of BMP-2 was detected by measuring the change of BMP-2 expression in a synoviocyte cell line following exposing to the synovial fluid of the patients. The concentration of BMP-2 in the synovial fluid was significantly higher in arthrofibrotic TKA knees (24.3 ± 6.9 pg/mL), compared with the control group 5.9 ± 4.8 pg/mL (P < 0.001). Corresponding to this finding, BMP-2 expression in synoviocytes was upregulated 11.5-fold (P < 0.05) by synovial fluid of patients suffering from arthrofibrosis after TKA, compared with the control group with referred pain. BMP-2 is overexpressed and its concentrations are consequently higher in patients suffering from arthrofibrosis after TKA. The synovial BMP-2 concentration may be a potential marker for differentiating between intra- and extraarticular causes of pain. II.
TL;DR: It is shown that the in situ fracture haematoma is essential for bone regeneration and using BMP as a positive control the presented experimental setup can serve to evaluate innovative therapeutical concepts in long bone application.
Abstract: Critical or delayed bone healing in rat osteotomy (OT) models is mostly achieved through large defects or instability. We aimed to design a rat OT model for impaired bone healing based on age, gender and parity. The outcome should be controllable through variations of the haematoma in the OT including a bone morphogenetic protein (BMP) 2 guided positive control. Using external fi xation to stabilise femoral a 2 mm double OT in 12 month old, female Sprague Dawley rats after a minimum of 3 litters healing was characterised following in situ haematoma formation (ISH-group)), transplantation of a BMP charged autologous blood clot (BMP-group) and the artifi cial blood clot only (ABC-group) into the OT-gap. In vivo micro-computer tomography (μCT) scans were performed after 2, 4 and 6 weeks. After 6 weeks specimens underwent histological analyses. In μCT examinations and histological analyses no bony bridging was observed in all but one animal in the ISHgroup. In the BMP group complete bridging was achieved in all animals. The ABC-group showed less mineralised tissue formation and smaller bridging scores during the course of healing than the ISH-group. In this pilot study we introduce a model for impaired bone healing taking the major biological risk factors into account. We could show that the in situ fracture haematoma is essential for bone regeneration. Using BMP as a positive control the presented experimental setup can serve to evaluate innovative therapeutical concepts in long bone application.
TL;DR: Osteochondral defect healing starts with subchondral bone plate restoration, however, after 6 months, incomplete or irregular sub chondralBone plate restoration and subsequent failure of osteochondral defects closure is common.
Abstract: Purpose
It is unknown what causes donor site morbidity following the osteochondral autograft transfer procedure or how donor sites heal. Contact pressure and edge loading at donor sites may play a role in the healing process. It was hypothesized that an artificially created osteochondral defect in a weightbearing area of an ovine femoral condyle will cause osseous bridging of the defect from the upper edges, resulting in incomplete and irregular repair of the subchondral bone plate.
TL;DR: An artificial lymph node (ALN)-bioreactor culture system combining a miniaturized perfusion bioreactor with a 3D matrix-based cell culture of immune competent cells forming micro-organoids might be an excellent tool to investigate the mechanisms of MSC-mediated immune modulation during simulated in vivo conditions.
Abstract: IntroductionMesenchymal stromal cells (MSC), known for their high immune modulatory capacity are promising tools for several cell-based therapies. To better mimic the in vivo situation of MSC inter...
TL;DR: The preliminary results confirm that ultrasound navigation is a highly accurate tool that allows a reproducible registration of the APP and thereby enables accurate and precise intraoperative determination of the acetabular cup orientation also in patients with increased BMI.
Abstract: This feasibility study investigated the accuracy of anterior pelvic reference plane (APP) registration and acetabular cup orientation in two cadavers with different BMIs. Five observers each registered the APP five times in the 2 cadavers (BMIs: 32 kg/m² and 25 kg/m²) using an ultrasound-based navigation system. By comparison against the CT-derived reference landmarks, the errors in determining the individual landmarks defining the APP, as well as the resulting errors in the orientation of the APP and the acetabular cup orientation were determined. Across all measurements obtained with the ultrasound navigation system, the errors in rotation and version in determining the APP were 0.5° ± 1.0° and −0.4° ± 2.0°, respectively. The cup abduction and anteversion errors determined from all measurements of the five investigators for both cadavers together were −0.1° ± 1.0° and −0.4° ± 2.7°, respectively. The data further demonstrated a high reproducibility of the measurements for the resulting cup adduction and anteversion angle. Our preliminary results confirm that ultrasound navigation is a highly accurate tool that allows a reproducible registration of the APP and thereby enables accurate and precise intraoperative determination of the acetabular cup orientation also in patients with increased BMI.