Despite development of open and endovascular treatments of the iliac veins, there is no reported research on the biomechanical properties of human iliac veins. The specific requirements for devices and prosthesis for venous interventions are primarily empirical adaptations of devices developed for treating arteries. Although a lot of research has gone into developing devices, the receiving organ has not yet been studied in detail. Using the new methods and testing protocols described in this article we aim to investigate and determine the biomechanical properties of the common and external iliac veins in comparison to the common iliac artery, with the future goal of formulating a new mathematical model for the pelvic veins to facilitate in silico modeling. After consulting literature and experts in the field of biomechanics in search of suitable testing protocols, porcine samples were used to review, develop and confirm methods of conservation, biomechanical testing and histological investigation.Extension-inflation and planar biaxial extension testing for mechanical data, and histological and structural investigations were evaluated.The protocol is specifically tailored to the mechanical and structural investigation of human iliac veins and arteries, to allow comprehensive comparison of these vessels, for a better understanding and improvements in biomechanical modeling.Porcine tissue was used to show feasibility of the tests performed for ethical reasons and in anticipation of future research to evaluate the porcine model currently frequently used in endovascular research and training

In the current work, we investigate the mechanical and structural changes of the thoracic and abdominal aortas in response to high homocysteine and cholesterol conditions. Hyperhomocysteinemia, an elevated homocysteine level in the blood, has been recognized as an independent risk factor for atherosclerosis. Its relationship with aortic biomechanics and its influence on the macromolecular constituents of the aorta have been little studied. We therefore use a rabbit model of atherosclerosis, in which we combined balloon injury of the abdominal aorta, special diets, and intravenous homocysteine injections. Equibiaxial tensile tests, including (i) cyclic step-wise stress relaxation and (ii) continuous cyclic protocols, were carried out to characterize the inelastic behavior of the injured abdominal aorta and the intact thoracic aorta. Mechanical investigation was supplemented by multi-photon microscopy and histology. Our study reveals structural remodeling and changes in the mechanical properties in response to treatments. While a cholesterol-rich diet induced softening of both aortic segments, elevated homocysteine conditions led to intimal collagen deposition and stiffening of the abdominal aorta, even in the absence of hypercholesterolemia, suggesting an independent role of homocysteine in the initiation of atherosclerosis. Interestingly, in rabbits subjected to the combination of high homocysteine and cholesterol conditions, we observed no differences in the stress response compared to the control group, despite medial calcification. Finally, when comparing the two aortic regions, more pronounced inelastic phenomena were measured in the injured abdominal aorta, where atherosclerosis progressed most due to balloon injury, suggesting changes in tissue viscoelasticity as a potential indicator of wall remodeling. Statement of significance: The mechanical properties of the aorta are closely linked to its microstructure. In vascular diseases such as atherosclerosis, the aorta stiffens and remodeling of the aortic wall occurs. The role of the elevated homocysteine levels (hyperhomocysteinemia) in the development of atherosclerosis is not fully understood yet. In this study, we show the effects of treatments with elevated homocysteine and cholesterol conditions, as well as their combination, on the microstructure and passive mechanical properties of the abdominal and thoracic aortas in a rabbit model of atherosclerosis. Under high homocysteine conditions, we observed remodeling and disorganization of the aortic structure, aortic stiffening, and changes in rate-dependent mechanical properties. The results presented here may contribute to improved prevention and treatment of atherosclerosis.

Soft biomaterials strongly influence cellular behavior by transmitting mechanical cues via well-characterized mechanotransduction pathways. However, translating insights from simplified in vitro systems to complex in vivo responses remains a challenge. This review provides a framework for assessing the translational relevance of mechanobiological studies across different scales-from single cells and organoids to tissues and organs. First, we categorize soft biomaterials based on their architecture and mechanical features to establish consistent terminology. We then investigate how cells interpret the transmitted mechanical signals in advanced in vitro systems that simulate physiologically relevant mechanical environments. To discuss the translational potential, we present a scoring system and a comparative analysis demonstrating that physiological specificity, rather than experimental complexity, determines predictive value. Simple systems can yield highly translatable outcomes when mechanical cues mimic native conditions, while advanced models require careful validation to ensure their relevance. By integrating biomechanics, electrophysiology, and systems biology, we outline principles and validation strategies that enhance the predictive utility of mechanobiological findings and ultimately support the design of more effective biomaterials and tissue-engineered systems.

The aim of this study is to characterize the mechanical properties of the human thoracic aorta after thoracic endovascular aortic repair (TEVAR). While patient-specific in silico models are becoming increasingly important for preoperative planning, their accuracy depends on reliable mechanical properties. However, the biomechanics of stented aortas remains poorly understood. To address this knowledge gap, the TEVAR-aorta interaction was first simulated under in vivo-like loading conditions using a custom-made mock circulation loop. After perfusion and stenting, tissue samples were obtained from thirteen healthy human thoracic aortas, and biaxial extension tests were performed under various stretch ratios to evaluate the effects of stent placement. Subsequently, a material model was employed to support in silico simulations of TEVAR-induced mechanical changes. Multi-photon imaging was used to assess the morphology of elastic lamellae in representative regions to provide structural insights, strengthening the mechanical findings. The results revealed region-specific mechanical alterations. The proximal (ascending) aorta exhibited a 32% decrease in the k2 parameter of the material model, while the distal region exhibited a 73% increase. This can lead to overstretching and rupture of the fibers proximally, while increased fiber recruitment occurs distally. Imaging showed that the elastic lamellae were 7.0% thinner proximally at the strut imprints, while they appeared 7.4% thicker distally. Although the changes in the obtained constitutive parameter did not result in statistically significant differences, they are consistent with these significant structural findings. Given the 159 biaxial specimens investigated, the observed mechanical differences are likely due to the intervention. This study improves stent graft design and patient-specific modeling by highlighting region-dependent alterations, thus supporting surgical planning and outcome prediction. Statement of Significance: Thoracic endovascular aortic repair (TEVAR) is a common interventional treatment for aortic diseases, yet its effects on the mechanical behavior of the human aorta remain poorly understood. Using ex vivo perfused human thoracic aortas, this study examined the effects of stent grafts on the structure and mechanics of the thoracic aortic wall. Combining mechanical testing, state-of-the-art imaging, and material modeling, region-specific changes in tissue behavior were identified. Overall, our findings demonstrate softening proximal to the heart (proximal/ascending aorta) and stiffening distally. These findings may help explain stent-tissue interaction and potentially influence surgical outcomes. The results can be used to improve stent design and support patient-specific computer simulations to assist surgeons in planning safer and more effective interventional procedures.

Hyperhomocysteinemia, an elevated level of homocysteine in the blood, is an independent risk factor for atherosclerosis and, more generally, cardiovascular disease. However, its relationship with aortic biomechanics has not been investigated yet. To better understand the influence of elevated homocysteine levels on aortic biomechanics, we propose an animal model in which hyperhomocysteinemia, hypercholesterolemia, and their combination were induced in rabbits by balloon injury of the abdominal aorta, special diets, and intravenous homocysteine injections. The effects of a diet deficient in B vitamins and choline, which are required for homocysteine degradation, a cholesterol-rich diet, their combination, and increased homocysteine concentration are investigated in relation to abdominal aortic biomechanics in rabbits. For this purpose, equibiaxial and non-equibiaxial extension tests were carried out, and the influence of risk factors on the stress-stretch relationship, mechanical anisotropy, and tissue inelasticity is discussed. The mechanical characterization of the tissue was supported by microstructural histological analyses. Our study reveals that deficiency of B vitamins and choline cause aortic stiffening even in the absence of hypercholesterolemia, suggesting a possible independent role in the development of atherosclerosis. Further increasing homocysteine concentration through intravenous injections in rabbits fed B vitamins and choline-deficient diet also results in a stiffer stress response and more pronounced inelastic phenomena with respect to the control group.

Tissue decellularization has emerged as a technique to provide an acellular, non-immunogenic scaffold that preserves the morphological features of native tissue. To study the possible effects of decellularization, investigating the mechanical behavior and the protein composition is crucial. In this study, we performed extension-inflation tests on native and decellularized porcine vena cava and investigated their microstructure using multiphoton microscopy. The mechanical behavior of both groups showed typical pressure-stretch curves of vascular structures with viscoelastic and nonlinear features. Importantly, no significant differences were found at inflation of 10, 20 and 30 mmHg, although some variability was observed in the decellularized scaffolds. When analyzing the results of the vessel wall multiphoton microscopy investigations, it was found that collagen fibers were packed in tortuous bundles in the media, but scattered in the adventitia. The fibers were oriented around 72° from the circumferential direction for both groups and at the same time equally distributed out-of-plane. Moreover, the collagen fibers diameter for media and adventitia was around 4 µm. Tortuosity and straightness were the same in the adventitia; however, the situation was different in the media, where the fibers in native samples were straighter than in decellularized scaffolds. Our findings show the potential of our protocol to obtain venous scaffolds that could be used for vascular reconstruction, as their mechanical properties are largely comparable to those of their native counterparts. The detailed analysis of the microstructure also represents a first step towards better understanding the physiology of the vessels and replicating these conditions in silico. STATEMENT OF SIGNIFICANCE: Tissue engineering provides a scaffold as substrate for in vitro cells seeding. Decellularization completely removes immunogenic cellular components, preserving the organ ultrastructure. Consequently, decellularized scaffolds provide a natural microenvironment for cell repopulation and facilitate functional recovery in vitro. We have comprehensively characterized the decellularized porcine vena cava by comparing its mechanical properties and microstructural characteristics with its native counterpart. Extension-inflation testing is considered a method to mimic stresses and stretches in vivo. Since no significant differences were found between native and decellularized tissue, these scaffolds show some potential. Moreover, this study was expanded to include microstructural characterization of collagen fibers using multi-photon microscopy, making it the first of its kind dedicated to biomechanical and microstructural evaluation of decellularized veins.

This study investigates methodological variability across various expert laboratories worldwide, with regards to characterizing the mechanical properties of biological tissues. Two testing rounds were conducted on the specific use case of uniaxial tensile testing of porcine aorta. In the first round, 24 labs were invited to apply their established methods to assess inter-laboratory variability. This revealed significant methodological diversity and associated variability in the stress-stretch results, underscoring the necessity for a standardized approach. In the second round, a consensus protocol was collaboratively developed and adopted by 19 labs in an attempt to minimize variability. This involved standardized sample preparation and uniformity in testing protocol, including the use of a common cutting and thickness measurement tool. Despite protocol harmonization, significant variability persisted across labs, which could not be solely attributed to inherent biological differences in tissue samples. These results illustrate the challenges in unifying testing methods across different research settings, underlining the necessity for further refinement of testing practices. Enhancing consistency in biomechanical experiments is pivotal when comparing results across studies, as well as when using the resulting material properties for in silico simulations in medical research.

This study aims to assess the outcomes of therapeutic options for aortic arch pathologies by comparing thoracic endovascular aortic repair (TEVAR) with open arch replacement (OAR) using woven polyester grafts from a mechanical and biomechanical perspective, with emphasis on ex vivo perfused human thoracic aortas reproducing heart rate and stroke volume conditions. Eleven non-diseased thoracic aortas from human cadavers were divided into TEVAR (n = 5) and OAR (n = 6) and tested using a custom-built mock circulation loop. Pressure, diameter, and stroke volume were monitored during perfusion before and after the intervention. Samples undergoing TEVAR showed a higher ascending systolic pressure post-intervention than OAR (TEVAR: 137 +/- 9 mmHg vs OAR: 126 +/- 6 mmHg, p= 0.017). After the intervention, a significant discrepancy in the mean pressure differences between the ascending and descending aorta Delta P was observed (TEVAR: 9 +/- 3 mmHg vs OAR: 1 +/- 2 mmHg, p = 0.004). Input impedance at zero frequency, approximating Windkessel resistance, was higher for TEVAR than for OAR (TEVAR: 1.78 +/- 0.04 vs OAR: 1.66 +/- 0.03 mmHg s/ml, p = 0.004). A correlation was found between the resistance and the negative peak of the time-normalized wave intensity analysis (Kendall's coefficient tau = -0.35 and p = 0.023). Another correlation was observed between resistance and Delta P (tau = 0.51, p = 0.001). Looking at the replication of heart rate and stroke volume over the course of the study, the observed differences can largely be attributed to the type of intervention. The results suggest that TEVAR has adverse effects compared to OAR, particularly with regard to left ventricular afterload. Clinicians should consider the possibility of increased afterload and altered wave dynamics when deciding on TEVAR, particularly inpatients with pre-existing impaired cardiovascular conditions.

Modeling of subcutaneous adipose tissue (SAT) plays an important role in forensic biomechanics as blunt force trauma represents one of the most common types of injury. To better understand the involved injury mechanisms, a material model is needed that can (i) represent realistic behavior for combined loading scenarios and (ii) consider the microstructure of the SAT. Therefore, a SAT model was developed that consists of two parts for the strain-energy function - a neo-Hookean part representing the adipocytes and a part representing the surrounding reinforced basement membrane, which is modeled via three circular fiber families oriented in the three main planes, resulting in isotropic model behavior. To verify the performance of the model, the analytical and numerical model solution were compared with experimental data under biaxial tension at different stretch ratios (1:1, 1:0.5, 0.5:1) and under simple shear using an objective evaluation method. The material parameters were evaluated by fitting to the data under equibiaxial tension. For the numerical analysis, the model was implemented as a user-defined material in LS-DYNA to simulate the respective experimental setups. The analytical fitting of the model was robust. Using the resulting material parameters, both the analytical and numerical simulation results were able to represent the experimental data under biaxial tension as well as under simple shear quite well. Since the fitting was only performed with data under equibiaxial tension, these findings suggest that the model assumptions are reasonable. Therefore, the model could help to further investigate the injury mechanisms in blunt impacts.

Computational fluid dynamics (CFD) simulations have been introduced to enable individualized risk prognosis for patients with unruptured cerebral aneurysms. The present contribution provides an overview of the biomechanical and physiological principles of aneurysm formation and rupture. It describes the computational steps of the CFD and the evaluated parameters. The clinical value of CFD is then discussed based on a recent literature review. Finally, we discuss current methodological limitations and possible future developments to overcome the actual drawbacks of CFD.

Atherosclerosis, the leading cause of cardiovascular disease, cannot be sufficiently explained by established risk factors, including cholesterol. Elevated plasma homocysteine (Hcy) is an independent risk factor for atherosclerosis and is closely linked to cardiovascular mortality. However, its role in atherosclerosis has not been fully clarified yet. We have previously shown that rabbits fed a diet deficient in B vitamins and choline (VCDD), which are required for Hcy degradation, exhibit an accumulation of macrophages and lipids in the aorta, aortic stiffening and disorganization of aortic collagen in the absence of hypercholesterolemia, and an aggravation of atherosclerosis in its presence. In the current study, plasma Hcy levels were increased by intravenous injections of Hcy into balloon-injured rabbits fed VCDD (VCDD+Hcy) in the absence of hypercholesterolemia. While this treatment did not lead to thickening of aortic wall, intravenous injections of Hcy into rabbits fed VCDD led to massive accumulation of VLDL-triglycerides as well as significant impairment of vascular reactivity of the aorta compared to VCDD alone. In the aorta intravenous Hcy injections into VCDD-fed rabbits led to fragmentation of aortic elastin, accumulation of elastin-specific electron-dense inclusions, collagen disorganization, lipid degradation, and autophagolysosome formation. Furthermore, rabbits from the VCDD+Hcy group exhibited a massive decrease of total protein methylated arginine in blood cells and decreased creatine in blood cells, serum and liver compared to rabbits from the VCDD group. Altogether, we conclude that Hcy contributes to atherogenic transformation of the aorta not only in the presence but also in the absence of hypercholesterolemia.

Finite element modeling has become one of the main tools necessary for understanding cardiovascular homeostasis and lesion progression. The accuracy of such simulations significantly depends on the precision of material parameters, which are obtained via the mechanical characterization process, i.e., experimental testing and material parameter estimation using the optimization process. The process of mounting specimens on the machine often introduces slight preloading to avoid sagging and to ensure perpendicular orientation with respect to the loading axes. As such, the reference configuration proposes non-zero forces at zero-state displacements. This error further extends to the material parameters’ estimation where initial loading is usually manually annulled. In this work, we have developed a new computational procedure that includes prestretches during mechanical characterization. The verification of the procedure was performed on the series of simulated virtual planar biaxial experiments using the Gasser–Ogden–Holzapfel material model where the exact material parameters could be set and compared to the obtained ones. Furthermore, we have applied our procedure to the data gathered from biaxial experiments on aortic tissue and compared it with the results obtained through standard optimization procedure. The analysis has shown a significant difference between the material parameters obtained. The rate of error increases with the prestretches and decreases with an increase in maximal experimental stretches.

The brain is arguably the most complex human organ and modelling its mechanical behaviour has challenged researchers for decades. There is still a lack of understanding on how this multiphase tissue responds to mechanical loading and how material parameters can be reliably calibrated. While previous viscoelastic models with two relaxation times have successfully captured the response of brain tissue, the Theory of Porous Media provides a continuum mechanical framework to explore the underlying physical mechanisms, including interactions between solid matrix and free-flowing interstitial fluid. Following our previously published experimental testing protocol, here we perform finite element simulations of cyclic compression-tension loading and compression-relaxation experiments on human brain white and gray matter specimens. The solid volumetric stress proves to be a crucial factor for the overall biphasic tissue behaviour as it strongly interferes with porous effects controlled by the permeability. An inverse parameter identification reveals that poroelasticity alone is insufficient to capture the time-dependent material behaviour, but a poro-viscoelastic formulation captures the response of brain tissue well. We provide valuable insights into the individual contributions of viscous and porous effects. However, due to the strong coupling between porous, viscous, and volumetric effects, additional experiments are required to reliably determine all material parameters.

Cardiovascular diseases are the leading cause of death worldwide and include, among others, critical conditions of the aortic wall. Importantly, such critical conditions require effective diagnosis and treatment, which are not yet accurate enough. However, they could be significantly strengthened with predictive material models of the aortic wall. In particular, such predictive models could support surgical decisions, preoperative planning, and estimation of postoperative tissue remodeling. However, developing a predictive model requires experimental data showing both structural parameters and mechanical behavior. Such experimental data can be obtained using multimodal experiments. This review therefore discusses the current approaches to multimodal experiments. Importantly, the strength of the aortic wall is determined primarily by its passive components, i.e., mainly collagen, elastin, and proteoglycans. Therefore, this review focuses on multimodal experiments that relate the passive mechanical behavior of the human aortic wall to the structure and organization of its passive components. In particular, the multimodal experiments are classified according to the expected results. Multiple examples are provided for each experimental class and summarized with highlighted advantages and disadvantages of the method. Finally, future directions of multimodal experiments are envisioned and evaluated.

The ascending thoracic aortic aneurysm (ATAA) is a permanent dilatation of the vessel with a high risk of adverse events, and shows heterogeneous properties. To investigate regional differences in the biomechanical properties of ATAAs, tissue samples were collected from 10 patients with tricuspid aortic valve phenotype and specimens from minor, anterior, major, and posterior regions were subjected to multi-ratio planar biaxial extension tests and second-harmonic generation (SHG) imaging. Using the data, parameters of a microstructure-motivated constitutive model were obtained considering fiber dispersion. SHG imaging showed disruptions in the organization of the layers. Structural and material parameters did not differ significantly between regions. The non-symmetric fiber dispersion model proposed by Holzapfel et al. [25] was used to fit the data. The mean angle of collagen fibers was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. The experimental data collected in this study contribute to the biomechanical data available in the literature on human ATAAs. Region-specific parameters for the constitutive models are fundamental to improve the current risk stratification strategies, which are mainly based on aortic size. Such investigations can facilitate the development of more advanced finite element models capable of capturing the regional heterogeneity of pathological tissues. Statement of Significance Tissue samples of human ascending thoracic aortic aneurysms (ATAA) were collected. Samples from four regions underwent multi-ratio planar biaxial extension tests and second-harmonic generation imaging. Region-specific parameters of a microstructure-motivated model considering fiber dispersion were obtained. Structural and material parameters did not differ significantly between regions, however, the mean fiber angle was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. This study provides a unique set of mechanical and structural data, supporting the microstructural influence on the tissue response. It may facilitate the development of better finite element models capable of capturing the regional tissue heterogeneity.(c) 2023 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Biomechanics plays an important role in the diagnosis and treatment of pathological conditions of the heart. Computational models are paving the way for personalized therapeutic treatment but they rely on accurate constitutive equations for predicting their biomechanical behavior. Even so, viscoelasticity remains under-explored in computational modeling despite experimental observations. To facilitate the viscoelastic modeling of cardiovascular soft tissues, we previously developed a fractional viscoelastic modeling approach, which extends existing hyperelastic models. This has comparable computational costs to the conventional hyperelastic model and only requires two additional material parameters for the viscoelastic response. This approach was demonstrated to be able to accurately capture the viscoelastic response of the human myocardium. However, the numerical properties of this fractional viscoelastic approach have not yet been examined. In this work, we present its implementation in Finite Element Analysis, examine its numerical properties in uniaxial extension and 2D inflation test examples, and examine its physiological implication in a computational model of an idealized left ventricle in a fully idealized circulatory system. Optimal convergence properties were observed and the importance of viscoelasticity during passive filling, ventricular motion, and regional fiber strain and stresses were explained.

Esophageal biomechanical studies are being performed to understand structural changes resulting from stretches during repair of esophageal atresias as well as to obtain biomechanical values for tissue-engineered esophagus. The present study offers insights into ultrastructural changes after stretching of the ovine esophagus using uniaxial stretch tests. In vitro uniaxial stretching was performed on esophagi ( n = 16) obtained from the abattoir within 4–6 h of 1-month-old lambs. Esophagi were divided into 4 groups (4 esophagi/group): control, Group1 (G1), Group2 (G2), Group3 (G3) stretched to 20%, 30% and 40% of their original length respectively. Force and lengthening were measured with 5 cycles performed on every specimen. Transmission electron microscopic (TEM) studies were performed on the 4 groups. During observational TEM study of the control group there were no significant differences in muscle cell structure or extracellular matrix. In all stretched groups varying degrees of alterations were identified. The degree of damage correlated linearly with the increasing level of stretch. Distance between the cells showed significant difference between the groups (control (μ = 0.41 μm, SD = 0.26), G1 (μ = 1.36 μm, SD = 1.21), G2 (μ = 2.8 μm, SD = 1.83), and G3 (μ = 3.01 μm, SD = 2.06). The diameter of the cells (control μ = 19.87 μm, SD = 3.81; G1 μ = 20.38 μm, SD = 4.45; G2 μ = 21.7 μm, SD = 6.58; G3 μ = 24.48 μm, SD = 6.69) and the distance between myofibrils (control μ = 0.23 μm, SD = 0.08; G1 μ = 0.27 μm, SD = 0.08; G2 μ = 0.4 μm, SD = 0.15; G3 μ = 0.61 μm, SD = 0.2) were significantly different as well ( p < 0.05 was considered to be significant). Esophageal stretching > 30% alters the regular intracellular and extracellular structure of the esophageal muscle and leads to disruption of intra- and extracellular bonds. These findings could provide valuable insights into alterations in the microscopic structure of the esophagus in esophageal atresias repaired under tension as well as the basis for mechanical characterization for tissue engineering of the esophagus.

Background Matrix metalloproteinase 12 (MMP12) is a macrophage-secreted protein that is massively upregulated as a pro-inflammatory factor in metabolic and vascular tissues of mice and humans suffering from cardiometabolic diseases (CMDs). However, the molecular mechanisms explaining the contributions of MMP12 to CMDs are still unclear. Methods We investigated the impact of MMP12 deficiency on CMDs in a mouse model that mimics human disease by simultaneously developing adipose tissue inflammation, insulin resistance, and atherosclerosis. To this end, we generated and characterized low-density lipoprotein receptor (Ldlr)/Mmp12-double knockout (DKO) mice fed a high-fat sucrose- and cholesterol-enriched diet for 16–20 weeks. Results DKO mice showed lower cholesterol and plasma glucose concentrations and improved insulin sensitivity compared with LdlrKO mice. Untargeted proteomic analyses of epididymal white adipose tissue revealed that inflammation- and fibrosis-related pathways were downregulated in DKO mice. In addition, genetic deletion of MMP12 led to alterations in immune cell composition and a reduction in plasma monocyte chemoattractant protein-1 in peripheral blood which indicated decreased low-grade systemic inflammation. Aortic en face analyses and staining of aortic valve sections demonstrated reduced atherosclerotic plaque size and collagen content, which was paralleled by an improved relaxation pattern and endothelial function of the aortic rings and more elastic aortic sections in DKO compared to LdlrKO mice. Shotgun proteomics revealed upregulation of anti-inflammatory and atheroprotective markers in the aortas of DKO mice, further supporting our data. In humans, MMP12 serum concentrations were only weakly associated with clinical and laboratory indicators of CMDs. Conclusion We conclude that the genetic deletion of MMP12 ameliorates obesity-induced low-grade inflammation, white adipose tissue dysfunction, biomechanical properties of the aorta, and the development of atherosclerosis. Therefore, therapeutic strategies targeting MMP12 may represent a promising approach to combat CMDs.

Abstract Background Suture anchors (SAs) made of human allogenic mineralized cortical bone matrix are among the newest developments in orthopaedic and trauma surgery. Biomechanical properties of an allogenic mineralized suture anchor (AMSA) are not investigated until now. The primary objective was the biomechanical investigation of AMSA and comparing it to a metallic suture anchor (MSA) and a bioabsorbable suture anchor (BSA) placed at the greater tuberosity of the humeral head of cadaver humeri. Additionally, we assessed the biomechanical properties of the SAs with bone microarchitecture parameters. Methods First, bone microarchitecture of 12 fresh frozen human cadaver humeri from six donors was analyzed by high-resolution peripheral quantitative computed tomography. In total, 18 AMSAs, 9 MSAs, and 9 BSAs were implanted at a 60° angle. All three SA systems were systematically implanted alternating in three positions within the greater tuberosity (position 1: anterior, position 2: central, position 3: posterior) with a distance of 15 mm to each other. Biomechanical load to failure was measured in a uniaxial direction at 135°. Results Mean age of all specimens was 53.6 ± 9.1 years. For all bone microarchitecture measurements, linear regression slope estimates were negative which implies decreasing values with increasing age of specimens. Positioning of all three SA systems at the greater tuberosity was equally distributed (p = 0.827). Mean load to failure rates were higher for AMSA compared to MSA and BSA without reaching statistical significance between the groups (p = 0.427). Anchor displacement was comparable for all three SA systems, while there were significant differences regarding failure mode between all three SA systems (p < 0.001). Maximum load to failure was reached in all cases for AMSA, in 44.4% for MSA, and in 55.6% for BSA. Suture tear was observed in 55.6% for MSA and in 22.2% for BSA. Anchor breakage was solely seen for BSA (22.2%). No correlations were observed between bone microarchitecture parameters and load to failure rates of all three suture anchor systems. Conclusions The AMSA showed promising biomechanical properties for initial fixation strength for RCR. Since reduced BMD is an important issue for patients with chronic rotator cuff lesions, the AMSA is an interesting alternative to MSA and BSA. Also, the AMSA could improve healing of the enthesis.