Percutaneous vertebroplasty procedure is of major importance, given the significantly increasing aging population and the higher number of orthopedic procedures related to vertebral compression fractures. Vertebroplasty is a complex technique involving the injection of polymethylmethacrylate (PMMA) into the compressed vertebral body for mechanical stabilization of the fracture. Our understanding and ability to modify these mechanisms through alterations in cement material is rapidly evolving. However, the rate of cardiac complications secondary to PMMA injection and subsequent cement leakage has increased with time. The following review considers the main effects of PMMA bone cement on the heart, and the extent of influence of the materials on cardiac embolism. Clinically, cement leakage results in life‐threatening cardiac injury. The convolution of this outcome through an appropriate balance of complex material properties is highlighted via clinical case reports.

BACKGROUND: Microvasculature dysfunction is a common finding in pathologic remodeling of the heart and is thought to play an important role in the pathogenesis of hypertrophic cardiomyopathy (HCM), a disease caused by sarcomere gene mutations. We hypothesized that microvascular dysfunction in HCM was secondary to abnormal microvascular growth and could occur independent of ventricular hypertrophy. METHODS: We used multimodality imaging methods to track the temporality of microvascular dysfunction in HCM mouse models harboring mutations in the sarcomere genes Mybpc3 (cardiac myosin binding protein C3) or Myh6 (myosin heavy chain 6). We performed complementary molecular methods to assess protein quantity, interactions, and post-translational modifications to identify mechanisms regulating this response. We manipulated select molecular pathways in vivo using both genetic and pharmacological methods to validate these mechanisms. RESULTS: We found that microvascular dysfunction in our HCM models occurred secondary to reduced myocardial capillary growth during the early postnatal time period and could occur before the onset of myocardial hypertrophy. We discovered that the E3 ubiquitin protein ligase MDM2 (murine double minute 2) dynamically regulates the protein stability of both HIF1α (hypoxia-inducible factor 1 alpha) and HIF2α (hypoxia-inducible factor 2 alpha)/EPAS1 (endothelial PAS domain protein 1) through canonical and noncanonical mechanisms. The resulting HIF imbalance leads to reduced proangiogenic gene expression during a key period of myocardial capillary growth. Reducing MDM2 protein levels by genetic or pharmacological methods normalized HIF protein levels and prevented the development of microvascular dysfunction in both HCM models. CONCLUSIONS: Our results show that sarcomere mutations induce cardiomyocyte MDM2 signaling during the earliest stages of disease, and this leads to long-term changes in the myocardial microenvironment.

The cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are important regulators of cardiovascular physiology, with reduced natriuretic peptide (NP) activity linked to multiple human cardiovascular diseases. We hypothesized that deficiency of either ANP or BNP would lead to similar changes in left ventricular structure and function given their shared receptor affinities. We directly compared murine models deficient of ANP or BNP in the same genetic backgrounds (C57BL6/J) and environments. We evaluated control, ANP-deficient (Nppa−/−) or BNP-deficient (Nppb−/−) mice under unstressed conditions and multiple forms of pathological myocardial stress. Survival, myocardial structure, function and electrophysiology, tissue histology, and biochemical analyses were evaluated in the groups. In vitro validation of our findings was performed using human-derived induced pluripotent stem cell cardiomyocytes (iPS-CMs). In the unstressed state, both ANP- and BNP-deficient mice displayed mild ventricular hypertrophy which did not increase up to 1 year of life. NP-deficient mice exposed to acute myocardial stress secondary to thoracic aortic constriction (TAC) had similar pathological myocardial remodelling but a significant increase in sudden death. We discovered that the NP-deficient mice are more susceptible to stress-induced ventricular arrhythmias using both in vivo and ex vivo models. Mechanistically, deficiency of either ANP or BNP led to reduced myocardial cGMP levels and reduced phosphorylation of the cAMP response element-binding protein (CREB^S133) transcriptional regulator. Selective CREB inhibition sensitized wild-type hearts to stress-induced ventricular arrhythmias. ANP and BNP regulate cardiomyocyte CREB^S133 phosphorylation through a cGMP-dependent protein kinase 1 (PKG1) and p38 mitogen-activated protein kinase (p38 MAPK) signalling cascade. Our data show that ANP and BNP act in a non-redundant fashion to maintain myocardial cGMP levels to regulate cardiomyocyte p38 MAPK and CREB activity. Cardiac natriuretic peptide deficiency leads to a reduction in CREB signalling which sensitizes the heart to stress-induced ventricular arrhythmias.

Percutaneous vertebroplasty procedure is of major importance, given the significant increasing aging population and higher number of orthopedic procedures related to vertebral compression fractures. Vertebroplasty is a complex technique involving injection of polymethylmethacrylate (PMMA) into the compressed vertebral body for mechanical stabilization of the fracture. Our understanding and ability to modify these mechanisms through alterations in cement material is rapidly evolving. However, the rate of cardiac complications secondary to PMMA injection and subsequent cement leakage has increased with time. The following review considers the main features of PMMA bone cement on the heart, and the extent of influence of materials on cardiac embolism. Clinically, cement leakage results in life-threatening cardiac injury. The convolution of this outcome through an appropriate balance of complex material properties is highlighted via clinical case report.

Stenting is an alternative to endarterectomy for the treatment of carotid artery stenosis. However, stenting is associated with a higher risk of procedural stroke secondary to distal thromboembolism. Hybrid stents with a micromesh layer have been proposed to address this complication. We developed a micropatterned thin film nitinol (M-TFN) covered stent designed to prevent thromboembolism during carotid intervention. This innovation may obviate the need or work synergistically with embolic protection devices. The proposed double layered stent is low-profile, thromboresistant, and covered with a M-TFN that can be fabricated with fenestrations of varying geometries and sizes. The M-TFN was created in multiple geometries, dimensions, and porosities by sputter deposition. The efficiency of various M-TFN to capture embolic particles was evaluated in different atherosclerotic carotid stenotic conditions through in vitro tests. The covered stent prevented emboli dislodgement in the range of 70%–96% during 30 min duration tests. In vitro vascular cell growth study results showed that endothelial cell elongation, alignment and growth behaviour silhouettes significantly enhance, specifically on the diamond-shape M-TFN, with the dimensions of 145 µm × 20 µm and a porosity of 32%. Future studies will require in vivo testing. Our results demonstrate that M-TFN has a promising potential for carotid artery stenting.

We introduce a new tongue prosthetic assist device (TPAD), which shows the first prosthetic application for potential treatment of swallowing difficulty in dysphagia patients. The native tongue has a number of complex movements that are not feasible to mimic using a single mechanical prosthetic device. In order to overcome this challenge, our device has three key features, including (1) a superelastic nitinol structure that transfers the force produced by the jaws during chewing towards the palate, (2) angled composite tubes for guiding the nitinol strips smoothly during the motion, and (3) highly stretchable thin polymeric membrane as a covering sheet in order to secure the food and fluids on top of the TPAD for easy swallowing. A set of mechanical experiments has optimized the size and angle of the guiding tubes for the TPAD. The low-profile TPAD was successfully placed in a cadaver model and its mobility effectively provided a simplistic mimic of the native tongue elevation function by applying vertical chewing motions. This is the first demonstration of a new oral device powered by the jaw motions in order to create a bulge in the middle of the mouth mimicking native tongue behavior.