Small changes in bone structure of female a7 nicotinic acetylcholine receptor knockout mice

BACKGROUND: Recently, analysis of bone from knockout mice identified muscarinic acetylcholine receptor subtype M3 (mAChR M3) and nicotinic acetylcholine receptor (nAChR) subunit a2 as positive regulator of bone mass accrual whereas of male mice deficient for a7-nAChR (a7KO) did not reveal impact in regulation of bone remodeling. Since female sex hormones are involved in fair coordination of osteoblast bone formation and osteoclast bone degradation we assigned the current study to analyze bone strength, composition and microarchitecture of female a7KO compared to their corresponding wild-type mice (a7WT). METHODS: Vertebrae and long bones of female 16-week-old a7KO (n = 10) and a7WT (n = 8) were extracted and analyzed by means of histological, radiological, biomechanical, cell- and molecular methods as well as time of flight secondary ion mass spectrometry (ToF-SIMS) and transmission electron microscopy (TEM). RESULTS: Bone of female a7KO revealed a significant increase in bending stiffness (p<0.05) and cortical thickness (p<0.05) compared to a7WT, whereas gene expression of osteoclast marker cathepsin K was declined. ToF-SIMS analysis detected a decrease in trabecular calcium content and an increase in C4H6N+ (p<0.05) and C4H8N+ (p<0.001) collagen fragments whereas a loss of osteoid was found by means of TEM. CONCLUSIONS: Our results on female a7KO bone identified differences in bone strength and composition. In addition, we could demonstrate that a7-nAChRs are involved in regulation of bone remodelling. In contrast to mAChR M3 and nAChR subunit a2 the a7-nAChR favours reduction of bone strength thereby showing similar effects as a7ß2-nAChR in male mice. nAChR are able to form heteropentameric receptors containing a- and ß-subunits as well as the subunits a7 can be arranged as homopentameric cation channel. The different effects of homopentameric and heteropentameric a7-nAChR on bone need to be analysed in future studies as well as gender effects of cholinergic receptors on bone homeostasis

Newly defined ATP-binding cassette subfamily B member 5 positive dermal mesenchymal stem cells promote healing of chronic iron-overload wounds via secretion of interleukin-1 receptor antagonist

In this study, we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP‐binding cassette subfamily B member 5 (ABCB5) for the therapy of nonhealing wounds. Local administration of dermal ABCB5+‐derived mesenchymal stem cells (MSCs) attenuated macrophage‐dominated inflammation and thereby accelerated healing of full‐thickness excisional wounds in the iron‐overload mouse model mimicking the nonhealing state of human venous leg ulcers. The observed beneficial effects were due to interleukin‐1 receptor antagonist (IL‐1RA) secreted by ABCB5+‐derived MSCs, which dampened inflammation and shifted the prevalence of unrestrained proinflammatory M1 macrophages toward repair promoting anti‐inflammatory M2 macrophages at the wound site. The beneficial anti‐inflammatory effect of IL‐1RA released from ABCB5+‐derived MSCs on human wound macrophages was conserved in humanized NOD‐scid IL2rγ null mice. In conclusion, human dermal ABCB5+ cells represent a novel, easily accessible, and marker‐enriched source of MSCs, which holds substantial promise to successfully treat chronic nonhealing wounds in humans

Experimental and Simulation-Based Investigation of Polycentric Motion of an Inherent Compliant Pneumatic Bending Actuator with Skewed Rotary Elastic Chambers

To offer a functionality that could not be found in traditional rigid robots, compliant actuators are in development worldwide for a variety of applications and especially for human–robot interaction. Pneumatic bending actuators are a special kind of such actuators. Due to the absence of fixed mechanical axes and their soft behavior, these actuators generally possess a polycentric motion ability. This can be very useful to provide an implicit self-alignment to human joint axes in exoskeleton-like rehabilitation devices. As a possible realization, a novel bending actuator (BA) was developed using patented pneumatic skewed rotary elastic chambers (sREC). To analyze the actuator self-alignment properties, knowledge about the motion of this bending actuator type, the so-called skewed rotary elastic chambers bending actuator (sRECBA), is of high interest and this paper presents experimental and simulation-based kinematic investigations. First, to describe actuator motion, the finite helical axes (FHA) of basic actuator elements are determined using a three-dimensional (3D) camera system. Afterwards, a simplified two-dimensional (2D) kinematic simulation model based on a four-bar linkage was developed and the motion was compared to the experimental data by calculating the instantaneous center of rotation (ICR). The equivalent kinematic model of the sRECBA was realized using a series of four-bar linkages and the resulting ICR was analyzed in simulation. Finally, the FHA of the sRECBA were determined and analyzed for three different specific motions. The results show that the actuator’s FHA adapt to different motions performed and it can be assumed that implicit self-alignment to the polycentric motion of the human joint axis will be provided

Impact of measurement errors on the determination of the linear modulus of human meniscal attachments

For the development of meniscal substitutes and related finite element models it is necessary to know the mechanical properties of the meniscus and its attachments. Measurement errors can falsify the determination of material properties. Therefore the impact of metrological and geometrical measurement errors on the determination of the linear modulus of human meniscal attachments was investigated. After total differentiation the error of the force (+0.10%), attachment deformation (−0.16%), and fibre length (+0.11%) measurements almost annulled each other. The error of the cross-sectional area determination ranged from 0.00%, gathered from histological slides, up to 14.22%, obtained from digital calliper measurements. Hence, total measurement error ranged from +0.05% to −14.17%, predominantly affected by the cross-sectional area determination error. Further investigations revealed that the entire cross-section was significantly larger compared to the load-carrying collagen fibre area. This overestimation of the cross-section area led to an underestimation of the linear modulus of up to −36.7%. Additionally, the cross-sections of the collagen-fibre area of the attachments significantly varied up to +90% along their longitudinal axis. The resultant ratio between the collagen fibre area and the histologically determined cross-sectional area ranged between 0.61 for the posterolateral and 0.69 for the posteromedial ligament. The linear modulus of human meniscal attachments can be significantly underestimated due to the use of different methods and locations of cross-sectional area determination. Hence, it is suggested to assess the load carrying collagen fibre area histologically, or, alternatively, to use the correction factors proposed in this study

Ligament balancing in TKA: Evaluation of a force-sensing device and the influence of patellar eversion and ligament release

Ligament balancing in total knee arthroplasty may have an important influence on joint stability and prosthesis lifetime. In order to provide quantitative information and assistance during ligament balancing, a device that intraoperatively measures knee joint forces and moments was developed. Its performance and surgical advantages were evaluated on six cadaver specimens mounted on a knee joint loading apparatus allowing unconstrained knee motion as well as compression and varus-valgus loading. Four different experiments were performed on each specimen. (1) Knee joints were axially loaded. Comparison between applied and measured compressive forces demonstrated the accuracy and reliability of in situ measurements (1.8N). (2) Assessment of knee stability based on condyle contact forces or varus-valgus moments were compared to the current surgical method (difference of varus-valgus loads causing condyle lift-off). The force-based approach was equivalent to the surgical method while the moment-based, which is considered optimal, showed a tendency of lateral imbalance. (3) To estimate the importance of keeping the patella in its anatomical position during imbalance assessment, the effect of patellar eversion on the mediolateral distribution of tibiofemoral contact forces was measured. One fourth of the contact force induced by the patellar load was shifted to the lateral compartment. (4) The effect of minor and major medial collateral ligament releases was biomechanically quantified. On average, the medial contact force was reduced by 20% and 46%, respectively. Large variation among specimens reflected the difficulty of ligament release and the need for intraoperative force monitoring. This series of experiments thus demonstrated the device's potential to improve ligament balancing and survivorship of total knee arthroplasty

Biomechanics of a cemented short stem: a comparative in vitro study regarding primary stability and maximum fracture load

Purpose!#!In total hip arthroplasty, uncemented short stems have been used more and more frequently in recent years. Especially for short and curved femoral implants, bone-preserving and soft tissue-sparing properties are postulated. However, indication is limited to sufficient bone quality. At present, there are no curved short stems available which are based on cemented fixation.!##!Methods!#!In this in vitro study, primary stability and maximum fracture load of a newly developed cemented short-stem implant was evaluated in comparison to an already well-established cemented conventional straight stem using six pairs of human cadaver femurs with minor bone quality. Primary stability, including reversible micromotion and irreversible migration, was assessed in a dynamic material-testing machine. Furthermore, a subsequent load-to-failure test revealed the periprosthetic fracture characteristics.!##!Results!#!Reversible and irreversible micromotions showed no statistical difference between the two investigated stems. All short stems fractured under maximum load according to Vancouver type B3, whereas 4 out of 6 conventional stems suffered a periprosthetic fracture according to Vancouver type C. Mean fracture load of the short stems was 3062 N versus 3160 N for the conventional stems (p = 0.84).!##!Conclusion!#!Primary stability of the cemented short stem was not negatively influenced compared to the cemented conventional stem and no significant difference in fracture load was observed. However, a clear difference in the fracture pattern has been identified