Relationship between muscular and bony anatomy in native hips: a theoretical background for approach-specific implant positioning.

INTRODUCTION:: The aim of this study was to analyse the relationship between bony joint orientation and the distribution of hip musculature. METHODS:: The bone anatomy of the hip (femoral antetorsion (AT), acetabular anteversion (AV), and combined anteversion (AV/AT)) and the muscle volume of the gluteal muscles and the tensor fasciae latae were analysed bilaterally using computed tomography data of 49 patients. Muscle force direction (MFD) was determined for each muscle. The total MFD of the hip musculature was calculated and then correlated with the bony anatomy. RESULTS:: The mean AV, AT, and AV/AT were 21.9° ± 5.9°, 7.22° ± 7.4°, and 29.2° ± 9°, respectively. We found the following mean muscle volumes: gluteus maximus: 780 ± 227 cm3, gluteus medius: 322 ± 82 cm3, gluteus minimus: 85 ± 20 cm3, and tensor fasciae latae: 68 ± 22 cm3. The mean MFD was 18.92° ± 1.29°. We found a uniform distribution of the musculature that was not correlated with the bone anatomy. CONCLUSION:: This study highlights the variability in native acetabular and femoral anatomy and that bone hip anatomy does not correlate with the distribution of hip musculature. Although native acetabular anteversion matches the suggested targets for cup insertion, native combined anteversion is not related to current implant insertion targets. Understanding native muscular anatomy and the alterations that occur with different surgical approaches can serve as an explanatory model for THAs that has become unstable despite the components being implanted within the safe zone.

Outcome of short versus long interval in two-stage exchange for periprosthetic joint infection: a prospective cohort study.

INTRODUCTION: A two-stage exchange is the standard treatment approach for chronic periprosthetic joint infection (PJI). While a 6-8 week interval is commonly used before reimplantation, the optimal length of the prosthesis-free interval has not yet been determined. We evaluated the influence of a short (< 4 weeks) and long (≥ 4 weeks) interval on reinfection rate and functional outcome of hip and knee PJI. METHODS: In this prospective cohort, patients undergoing two-stage revision for PJI were assigned to prosthesis reimplantation after a short (< 4 weeks) or long (≥ 4 weeks) interval. All patients received standardized antimicrobial therapy, which consisted of antibiogram-adapted, non-biofilm-active antibiotics during the interval and an antimicrobial combination therapy with biofilm-active antibiotics after reimplantation. Follow-up was performed for infection, joint function, pain, need for care and quality of life. RESULTS: Thirty-eight patients undergoing two-stage revision for PJI (18 hips and 20 knees) were included. Short interval was used in 19 patients having a mean interval of 17.9 days (range 7-27 days), long interval in 19 patients having a mean interval of 63.0 days (range 28-204 days). At a mean follow-up of 39.5 months (range 32-48 months), 37 of 38 patients (97.4%) were infection-free. One failure occurred among patients with long interval and none among patients with short interval. Functional results (ROM, HHS, KSS, VAS) and quality of life (SF-36) were similar in both groups. Patients treated with long interval required cumulatively additional 204 inpatient days for nursing care compared to patients with short interval. CONCLUSIONS: This study suggests that two-stage exchange with short interval has a similar outcome than with long interval, when highly active antibiotic therapy is used. Patient inconvenience and care costs due to immobilization were lower when strategies with a short interval were used.

Long-term effects of intravenous iloprost therapy in patients with bone marrow oedema of the hip.

Bone marrow oedema (BMO) is a multifactorial condition. Various conservative treatment options include analgesic therapy, immobilisation of the affected joint and/or systemic intravenous iloprost or bisphosphonate therapy. Many studies confirm the positive effect of iloprost therapy in larger joints, e.g. the hip and knee joint, after short-term follow up. The objective of this study was to investigate that treatment with iloprost leads to positive long-term functional and radiological outcomes for BMO of the hip joint. Nineteen patients with BMO of the hip joint, ARCO stage 1-2, were included in this study. The Harris Hip Score, the SF-36, the WOMAC score and a visual analogue pain scale (VAS) were evaluated before and 29 ± 11 months after Ilomedin therapy. All patients underwent MRI for radiological follow-up monitoring three months after treatment. Significant improvements were found in the WOMAC Index and the VAS. In 79% of patients, follow-up MRI after three months showed complete regression of the oedema. Based on the positive results of our study, we support treatment with iloprost for BMO of the hip joint at ARCO stage 1-2.

Immunomodulatory placental-expanded, mesenchymal stromal cells improve muscle function following hip arthroplasty.

BACKGROUND: No regenerative approach has thus far been shown to be effective in skeletal muscle injuries, despite their high frequency and associated functional deficits. We sought to address surgical trauma-related muscle injuries using local intraoperative application of allogeneic placenta-derived, mesenchymal-like adherent cells (PLX-PAD), using hip arthroplasty as a standardized injury model, because of the high regenerative and immunomodulatory potency of this cell type. METHODS: Our pilot phase I/IIa study was prospective, randomized, double blind, and placebo-controlled. Twenty patients undergoing hip arthroplasty via a direct lateral approach received an injection of 3.0 × 108 (300 M, n = 6) or 1.5 × 108 (150 M, n = 7) PLX-PAD or a placebo (n = 7) into the injured gluteus medius muscles. RESULTS: We did not observe any relevant PLX-PAD-related adverse events at the 2-year follow-up. Improved gluteus medius strength was noted as early as Week 6 in the treatment-groups. Surprisingly, until Week 26, the low-dose group outperformed the high-dose group and reached significantly improved strength compared with placebo [150 M vs. placebo: P = 0.007 (baseline adjusted; 95% confidence interval 7.6, 43.9); preoperative baseline values mean ± SE: placebo: 24.4 ± 6.7 Nm, 150 M: 27.3 ± 5.6 Nm], mirrored by an increase in muscle volume [150 M vs. placebo: P = 0.004 (baseline adjusted; 95% confidence interval 6.0, 30.0); preoperative baseline values GM volume: placebo: 211.9 ± 15.3 cm3 , 150 M: 237.4 ± 27.2 cm3 ]. Histology indicated accelerated healing after cell therapy. Biomarker studies revealed that low-dose treatment reduced the surgery-related immunological stress reaction more than high-dose treatment (exemplarily: CD16+ NK cells: Day 1 P = 0.06 vs. placebo, P = 0.07 vs. 150 M; CD4+ T-cells: Day 1 P = 0.04 vs. placebo, P = 0.08 vs. 150 M). Signs of late-onset immune reactivity after high-dose treatment corresponded to reduced functional improvement. CONCLUSIONS: Allogeneic PLX-PAD therapy improved strength and volume of injured skeletal muscle with a reasonable safety profile. Outcomes could be positively correlated with the modulation of early postoperative stress-related immunological reactions.

Femoral head necrosis: A finite element analysis of common and novel surgical techniques.

BACKGROUND: Femoral head necrosis is a common cause of secondary osteoarthritis. At the early stages, treatment strategies are normally based on core decompression techniques, where the number, location and diameter of the drilling holes varies depending on the selected approach. The purpose of this study was to investigate the risk of femoral head, neck and subtrochanteric fracture following six different core decompression techniques. MATERIALS: Five common and a newly proposed techniques were analyzed in respect to their biomechanical consequences using finite element analysis. The geometry of a femur was reconstructed from computed-tomography images. Thereafter, the drilling configurations were simulated. The strains in the intact and drilled femurs were determined under physiological, patient-specific, muscle and joint contact forces. FINDINGS: The following results were observed: i) - an increase in collapse and fracture risk of the femur head by disease progression ii) - for a single hole approach at the subtrochanteric region, the fracture risk increases with the diameter iii) - the highest fracture risks occur for an 8mm single hole drilling at the subtrochanteric region and approaches with multiple drilling at various entry points iv) - the proposed novel approach resulted in the most physiological strains (closer to the experienced by the healthy bone). INTERPRETATION: Our results suggest that all common core decompression methods have a significant impact on the biomechanical competence of the proximal femur and impact its mechanical potential. Fracture risk increases with drilling diameter and multiple drilling with smaller diameter. We recommend the anterior approach due to its reduced soft tissue trauma and its biomechanical performance.

Inadequacy of Joint Aspiration for Detection of Persistent Periprosthetic Infection During Two-Stage Septic Revision Knee Surgery.

Despite the lack of validation, synovial aspiration remains a common practice during 2-stage septic revision total knee arthroplasty (TKA). The goal of this study was to investigate the diagnostic validity of synovial polymethylmethacrylate (PMMA) spacer aspiration of temporary knee arthrodesis to detect persistent periprosthetic joint infection before TKA reimplantation. This retrospective cohort study included 73 consecutive patients who underwent 2-stage septic revision TKA according to a standard protocol. After explantation surgery, including temporary arthrodesis with an intramedullary stabilized PMMA spacer, all patients had synovial aspiration 2 weeks before reimplantation to exclude persistent periprosthetic joint infection. Patients had a 2-week antibiotic holiday before aspiration. Sensitivity and specificity of the synovial PMMA spacer joint aspiration for the detection of periprosthetic joint infection were determined and referenced against intraoperative microbiologic and histologic samples obtained at second-stage surgery. Sensitivity of the synovial PMMA spacer aspiration was 21%. Because of poor diagnostic validity, synovial PMMA spacer aspiration cannot be recommended for routine exclusion of persistent periprosthetic joint infection before TKA reimplantation. Therefore, exclusion of persistent periprosthetic joint infection should be supplemented by other diagnostic methods, and it is not necessary to delay TKA reimplantation for PMMA spacer aspiration. [Orthopedics. 2017; 40(4):231-234.].

CD31+ Cells From Peripheral Blood Facilitate Bone Regeneration in Biologically Impaired Conditions Through Combined Effects on Immunomodulation and Angiogenesis.

Controlled revascularization and inflammation are key elements regulating endogenous regeneration after (bone) tissue trauma. Peripheral blood-derived cell subsets, such as regulatory T-helper cells and circulating (endothelial) progenitor cells, respectively, can support endogenous tissue healing, whereas effector T cells that are associated with an aged immune system can hinder bone regeneration. CD31 is expressed by diverse leukocytes and is well recognized as a marker of circulating endothelial (precursor) cells; however, CD31 is absent from the surface of differentiated effector T cells. Thus, we hypothesized that by separating the inhibitory fractions from the supportive fractions of circulating cells within the peripheral blood (PB) using the CD31 marker, bone regeneration in biologically compromised conditions, such as those observed in aged patients, could be improved. In support of our hypothesis, we detected an inverse correlation between CD31+ cells and effector T cells in the hematomas of human fracture patients, dependent on the age of the patient. Furthermore, we demonstrated the regenerative capacity of human PB-CD31+ cells in vitro. These findings were translated to a clinically relevant rat model of impaired bone healing. The transplantation of rat PB-CD31+ cells advanced bone tissue restoration in vivo and was associated with an early anti-inflammatory response, the stimulation of (re)vascularization, and reduced fibrosis. Interestingly, the depletion or enrichment of the highly abundant CD31+/14+ monocytes from the mixed CD31+ cell population diminished tissue regeneration at different levels, suggesting combined effects within the PB-CD31+ subsets. In summary, an intraoperative enrichment of PB-CD31+ cells might be a novel option to facilitate endogenous regeneration under biologically impaired situations by supporting immunomodulation and vascularization. © 2016 American Society for Bone and Mineral Research.

Temporary arthrodesis using fixator rods in two-stage revision of septic knee prothesis with severe bone and tissue defects.

PURPOSE: The present study describes a new temporary arthrodesis procedure, which aims for septic knee prosthesis replacement, in particular for larger bone and soft tissue defects. Our technique offers high stability and full weight-bearing capacity of the knee joint. METHODS: The study included 16 patients with major bone defects (AORI type IIb or greater) after receiving a radical debridement and a septic two-stage revision total knee arthroplasty. After removing the infected prosthesis and debridement, two AO fixator rods were positioned into the intramedullary space of the femur and tibia. Subsequently, both rods were joined tube-to-tube and adjusted in the center of the knee joint. Finally, the whole cavity of the knee joint was filled with PMMA. The number of previous surgeries, bacterial spectrum, risk factors for further infection and reinfection rates was recorded. Immediately after the temporary arthrodesis, radiographs of the knee with the enclosed spacers were taken in order to compare to previous radiographs and avoiding to miss possible spacer loosening. RESULTS: Nine of sixteen patients underwent more than two revision surgeries before receiving our new arthrodesis technique. No cases of spacer loosening were observed in all 16 patients; further, there were no peri-implant fractures, and four persistent infections were noted. CONCLUSIONS: Temporary arthrodesis using AO fixator rods offers a high stability without loosening. Its potential to replace conventional augmentation techniques should be taken into account, particularly in the case of larger bone and tissue defects. In clinical practice, the cemented spacer using AO fixator rods could be an alternative technique for temporary knee arthrodesis after septic debridement. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

Reproducibility of femoral offset following short stem and straight stem total hip arthroplasty.

Bone stock-preserving short stem prostheses have gained importance in total hip arthroplasty (THA) with the use of minimally invasive surgical procedures. Because of their metaphyseal fixation and their dependency on the calcar radius, it is unknown whether the femoral offset can be reproduced with the same accuracy following short stem vs standard stem THA. This study clarifies whether it is possible to restore the femoral offset using a short stem prosthesis (Fitmore; Zimmer, Warsaw, Indiana) compared with a conventional straight stem prosthesis (CLS; Zimmer) following minimally invasive implantation using an anterolateral approach. In a prospective, randomized, double-blinded study, 80 patients underwent THA using a short stem (SS group; n=40) or CLS implant (control group; n=40). Follow-up examinations were conducted 6 weeks postoperatively. Radiological and functional outcomes were measured. Subjective assessment of quality of life was evaluated using the Harris Hip Score (HHS), the Short Form 36-item health survey (SF-36), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pre- and postoperative comparison of the groups' change in offset showed no significant differences (SS group difference from pre- to postoperative, 6.1±6.5 mm; control group difference from pre- to postoperative, 6.5±7.1 mm; P=.93). Group comparison after 6 weeks revealed no significant differences in HHS, SF-36, or WOMAC. Based on these data, an equivalent reproducibility of the femoral offset was demonstrated following short stem and straight stem THA using a minimally invasive anterolateral approach. If the long-term results of short stems show a comparable survival, they represent a sensible alternative to standard stems.

The early phases of bone healing can be differentiated in a rat osteotomy model by focused transverse-transmission ultrasound.

Here we describe the use of a 5-MHz focused transmission system to image the bone repair region and to distinguish the early healing phases in a rat osteotomy (OT) model. Twelve-month-old female rats underwent a 2-mm OT. After 6 wk of consolidation, 2-D projection images of time-of-flight, speed of sound, and ultrasound attenuation were measured in vitro. The tissue types in the OT gap region were assessed by site-matched histology sections and micro-computed tomography (µCT). In the cases investigated, OT gap regions containing fibrous tissue (group A) were found to have similar properties compared with adjacent muscle tissue, whereas regions filled with cartilage and mineralized callus tissues (group B) differed significantly. Analysis of variance revealed that the healing group had a stronger effect on acoustic parameters (F < 35) than on µCT-based parameters (F < 22). This pilot study reports the feasibility of transverse transmission quantitative ultrasound in assessment of the onset of cartilage formation during callus formation.

CD133: enhancement of bone healing by local transplantation of peripheral blood cells in a biologically delayed rat osteotomy model.

Sufficient angiogenesis is crucial during tissue regeneration and therefore also pivotal in bone defect healing. Recently, peripheral blood derived progenitor cells have been identified to have in addition to their angiogenic potential also osteogenic characteristics, leading to the hypothesis that bone regeneration could be stimulated by local administration of these cells. The aim of this study was to evaluate the angiogenic potential of locally administered progenitor cells to improve bone defect healing. Cells were separated from the peripheral blood of donor animals using the markers CD34 and CD133. Results of the in vitro experiments confirmed high angiogenic potential in the CD133(+) cell group. CD34(+) and CD133(+) cells were tested in an in vivo rat femoral defect model of delayed healing for their positive effect on the healing outcome. An increased callus formation and higher bone mineral density of callus tissue was found after the CD133(+) cell treatment compared to the group treated with CD34(+) cells and the control group without cells. Histological findings confirmed an increase in vessel formation and mineralization at day 42 in the osteotomy gap after CD133(+) cell transplantation. The higher angiogenic potential of CD133(+) cells from the in vitro experients therefore correlates with the in vivo data. This study demonstrates the suitability of angiogenic precursors to further bone healing and gives an indication that peripheral blood is a promising source for progenitor cells circumventing the problems associated with bone marrow extraction.

Effects of indigo carmine on human chondrocytes in vitro.

Joint infections following or accompanying superficious soft tissue infections are severe complication in orthopedic surgery. The use of intra-articular blue staining is a helpful method to visualize a fistula and to differentiate between superficial and intra-articular infections. Regarding this clinical implication data about the effects of indigo carmine, a frequently used blue staining substance, on cartilage is missing. The hypothesis of this study was that indigo carmine damages human chondrocytes in a time and concentration dependent manner. Human chondrocytes were isolated from donors with osteoarthritis who were treated with TKA. Cells were cultivated and treated with different concentrations of indigo carmine for 5 and 10 minutes. Morphologic damage was examined by light microscopy. Toxicity was quantified by counting vital cell number and lactate dehydrogenase (LDH) expression. Analysis by light microscopy showed defected cell structure and loss of cell number after treatment with 100% indigo carmine for 10 minutes. Treatment with 10% and 1% indigo carmine showed no significant cell defects and loss of cells. Counting vital cell number showed loss of vital cells after treatment with 100% and 10% indigo carmine for 10 minutes. LDH expression was significantly increased after treatment with 100% indigo carmine.Toxic effects were shown after treatment with indigo carmine. Therefore, it should be used in 1:100 dilution. This is both, sufficient for visualizing a fistula in a possible clinical application and could be protective for chondrocytes.

Use of Redon drains in primary total hip arthroplasty has no clinically relevant benefits.

Although no proven evidence exists for the use of drainage in primary total hip arthroplasty, such drainage is routinely used. This prospective, randomized study comprised 80 patients who underwent a non-cemented total hip arthroplasty using a minimally invasive anterolateral approach. Patients were divided into 2 groups of 40: group 1 underwent drainage treatment and group 2 underwent no drainage treatment. No selection of patients occurred by age, sex, or body mass index. Blood loss was not significantly different between groups 1 (mean blood loss, 0.9 L [range, 0.3-2.1 L]) and 2 (mean blood loss, 0.9 L [range, 0.3-2.4 L]) (P=.7). On postoperative day 1, patients who underwent drainage treatment reported significantly more pain at rest (P=.01) and under stress (P=.03). The same finding was observed on postoperative day 4 (at rest, P=.04; under stress, P=.02). The nonuse of drainage significantly reduced operative time by 72 seconds (P=.01). Patients without drainage treatment had significantly larger hematomas than patients with drainage (mean, 43.7 cm(2) [range, 0-343 cm(2)] vs mean, 40.1 cm(2) [range, 0-514 cm(2)], respectively) (P=.03). No clinically relevant benefits associated with the use of drainage were identified. The increased size of the hematoma was not reflected in patient comfort. The authors consider the use of drainage in primary total hip arthroplasty unnecessary.

Femur positioning in navigated total knee arthroplasty.

Navigated total knee arthroplasty (TKA) results in better restoration of neutral mechanical axis than does the conventional technique. Nevertheless, coronal malalignment has not been eliminated. It is yet unknown whether errors in implant positioning occur more on the femoral side, more on the tibial side, or equally on both sides. The hypothesis of this study was that a predominance of coronal component malalignment exists on the tibial side in navigated tibia-first TKA.Fifty-seven consecutive navigated (OrthoPilot; B. Braun Aesculap, Tuttlingen, Germany) TKAs were included in this retrospective study. Pre- and postoperative digital whole-leg standing radiographs were analyzed. Coronal alignment was measured for the whole leg pre- and postoperatively. Lateral distal femur angle and medial proximal tibia angle were analyzed on the preoperative radiographs. On the postoperative radiographs, coronal alignment of the femoral and tibial components were measured separately in reference to the tibial and femoral mechanical axis. The coronal alignment improved from 8.2° ± 3.7° preoperatively to 1.1° ± 1.2° postoperatively, with 5 (8%) outliers outside the 3° window. The femoral component was malaligned (0.6° ± 0.6°), whereas the tibial component showed a significantly higher deviation from the mechanical axis of 1.0° ± 1.1° (P=.009). The femoral component was positioned more precisely than the tibial component. The latter influences gap management in the tibia-first technique and may thereby have a relevant effect on joint stability. Accuracy of the surgical technique and differences in the mathematical algorithm for the determination of landmarks are possible reasons for the difference in precision between the femoral and tibial component positioning.

In situ tele-thermographic measurements during PMMA spacer augmentation in temporary arthrodesis after periprosthetic knee joint infection.

Poly-Methylmethacrylate (PMMA) is widely-used in orthopaedic surgery in revision arthroplasty or as a spacer in temporary arthrodesis of periprostehtic knee joint infection during a two stage procedure. The intra-operative temperature behaviour, however, has not yet been quantified. It is known that high temperature induce thermally necrosis of surrounding bone tissue during polymerisation process. The aim was to evaluate the PMMA surface temperature during polymerisation phase in situ. We hypothesized, that temperature measured in vivo could become critical in terms of the induction of thermal bone necrosis during the polymerisation phase of PMMA. The PMMA surface was measured tele-thermographically in situ during knee arthroplasty revision surgery. Infrared pictures were analyzed for temperature peaks and changes. Measurements yielded maximum PMMA-surface-temperatures ranging from 101 to 110 degrees and a two-minute-plateau of > 100°. Hot PMMA during the polymerisation phase could potentially induce tissue (bone) necrosis. Therefore temperature of PMMA of more than 70 degrees should be avoided. Cooling of the PMMA is highly recommendable.

Intra-Arterial MSC Transplantation Restores Functional Capacity After Skeletal Muscle Trauma.

INTRODUCTION: 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. MATERIALS AND METHODOLOGY: 18 female Sprague Dawley rats received an open crush trauma of the left soleus muscle. Autologous MSC were transduced using dsCOP-GFP and 2.5 x 10(6)cells were transplanted into the femoral artery of 9 animals one week after trauma. Control animals (n=9) received a saline injection. Cell tracking, analysis of tissue fibrosis and muscle force measurements were performed after 3 weeks. RESULTS: Systemic MSC-therapy improved the muscle force significantly compared to control (fast twitch: 82.4%, tetany: 61.6%, p = 0.02). The histological analysis showed no differences in the quantity of fibrotic tissue. Histological examination revealed no cells in the traumatized muscle tissue 21 days after transplantation. CONCLUSIONS: The present study demonstrated an effect of systemically administered MSCs in the treatment of skeletal muscle injuries. For possible future therapeutic approaches a systemic application of MSCs seems to present an alternative to a local administration. Such systemic treatment would be preferable since it allows functional improvement and possible cellular concentration at injury sites that are not easily accessible.

Histogram feature-based classification improves differentiability of early bone healing stages from micro-computed tomographic data.

OBJECTIVE: Contrast between not fully mineralized tissues is weak and limits conventional computed tomography (CT). An automated grayscale histogram-based analysis features could improve the sensitivity to tissue alterations during early bone healing. MATERIALS AND METHODS: Tissue formation in a rat osteotomy model was analyzed using in vivo micro-CT and classified histologically (mineralized, cartilage, and connective tissues). A conventional threshold-based method including manual contouring was compared to a novel moment-based method: after removing the background peak, the histograms of each slice were characterized by their moments and analyzed as a function of the position along the long bone axis. RESULTS: The threshold-based method could differentiate between the mineralized and connective tissue (R = 0.73). The moment-based approach yielded a clear distinction between all 3 groups with a classification accuracy up to R = 0.93. CONCLUSIONS: The moment-based evaluation outperforms the conventional threshold-based CT analysis in sensitivity to the healing stage, user independence, and time consumption.

Immediate and delayed transplantation of mesenchymal stem cells improve muscle force after skeletal muscle injury in rats.

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.

Mesenchymal stem cell therapy following muscle trauma leads to improved muscular regeneration in both male and female rats.

BACKGROUND: Mesenchymal stem cell (MSC) therapy has the potential to enhance muscular regeneration. In previous publications, our group was able to show a dose-response relationship in female animals between the amount of transplanted cells and muscle force. The impact of sex on the regeneration of musculoskeletal injuries following MSC transplantation remains unclear. OBJECTIVE: We investigated histologic and biomechanical regeneration parameters in rats after autologous transplantation of MSCs. Our hypothesis was that female rats have greater muscle regeneration potential than male rats after autologous MSC transplantation. METHODS: Thirty-six Sprague-Dawley rats received an open crush trauma of the left soleus muscle. One week after trauma, 2.5 × 10(6) autologous MSCs, harvested from tibial biopsies, were transplanted locally (female, n = 9; male, n = 9). Control animals received saline solution (female, n = 9; male, n = 9). Histologic analysis and biomechanical evaluation by in vivo muscle force measurement were performed 3 weeks after transplantation. RESULTS: MSC therapy improved the force of the injured soleus in male rats significantly (twitch: treated, 0.76 [0.51-1.15]; twitch: untreated, 0.45 [0.32-0.73] [P = 0.01]; tetany: treated, 0.63 [0.4-1.21], tetany: untreated, 0.34 [0.16-0.48] [P = 0.04]). Force measurements in females also revealed significant improvements (twitch: treated, 0.71 [0.38-0.96]; twitch: untreated, 0.36 [0.18-0.63] [P = 0.005]; tetany: treated, 0.53 [0.21-0.68]; tetany: untreated, 0.27 [0.11-0.47] [P = 0.01]). The intersexual comparison of fast twitch and tetanic contraction forces revealed no significance (twitch, P = 0.55; tetany, P = 0.19). The histologic analysis showed no differences in the amount of fibrotic tissue (male, P = 0.9; female, P = 0.14) and the size of muscle area (male, P = 0.2; female, P = 0.56) following treatment. Male animals showed higher values for muscle area (P = 0.011) and less fibrosis (P = 0.028), independent of treatment. CONCLUSION: The outcome of skeletal muscle regeneration after injury can be improved in animals of both sexes with MSC transplantation.

Femoral Offset (3D) in Patients without Osteoarthritis - Index Values from 200 Hip Joints.

INTRODUCTION: Femoral offset (FO) is a crucial parameter for hip joint biomechanics. Reference values for FO are particularly important when joint geometry has to be reconstructed during surgical interventions. Such reference values are scarce in literature and have mainly been obtained from osteoarthritis (OA) patients. The aim of this study was to conduct a patient-specific study of FO without osteoarthritis and to create a dataset of FO index values. MATERIALS AND METHODOLOGY: One hundred (49 female, 51 male; mean age: 59 (18 - 83) years) pelvic computed tomography (CT) scans were analyzed to determine FO in each patient. Bilateral symmetry and correlation between demographic data and FO were analyzed. RESULTS: The mean FO ± SD was different for male (4.36 ± 0.56 cm) and female patients (3.95 ± 0.35 cm) (p <.0001). No Side differences of FO were observed in male and female patients. Significant correlation between height and FO was only observed in male patients. CONCLUSION: The values obtained in this study can be used as index values for the restoration and evaluation of hip geometry. For men, FO can be approximated using the correlation between FO and height.