The performance of indwelling medical devices that depend on an interface with soft tissue is plagued by complex, unpredictable foreign body responses. Such devices—including breast implants, biosensors, and drug delivery devices—are often subject to a collection of biological host responses, including fibrosis, which can impair device functionality. This work describes a milliscale dynamic soft reservoir (DSR) that actively modulates the biomechanics of the biotic-abiotic interface by altering strain, fluid flow, and cellular activity in the peri-implant tissue. We performed cyclical actuation of the DSR in a preclinical rodent model. Evaluation of the resulting host response showed a significant reduction in fibrous capsule thickness (P = 0.0005) in the actuated DSR compared with non-actuated controls, whereas the collagen density and orientation were not changed. We also show a significant reduction in myofibroblasts (P = 0.0036) in the actuated group and propose that actuation-mediated strain reduces differentiation and proliferation of myofibroblasts and therefore extracellular matrix production. Computational models quantified the effect of actuation on the reservoir and surrounding fluid. By adding a porous membrane and a therapy reservoir to the DSR, we demonstrate that, with actuation, we could (i) increase transport of a therapy analog and (ii) enhance pharmacokinetics and time to functional effect of an inotropic agent. The dynamic reservoirs presented here may act as a versatile tool to further understand, and ultimately to ameliorate, the host response to implantable biomaterials.

Ischemic stroke is the leading cause of disabilities worldwide. MicroRNA-377 (miR-377) plays important roles in ischemic injury. The present study focused on the mechanisms of miR-377 in protecting ischemic brain injury in rats. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in rats. Primary rat microglial cells and brain microvascular endothelial cells (BMECs) were exposed to oxygen-glucose deprivation (OGD). The concentrations of cytokines (TNF-α, IL-1β, IL-6, IFN-γ, TGF-β, MMP2, COX2, and iNOS) in the culture medium were measured by specific ELISA. Tube formation assay was for the in vitro study of angiogenesis. Luciferase reporter assay was performed to confirm whether VEGF and EGR2 were direct targets of miR-377. The MCAO rats were intracerebroventricular (ICV) injection of miR-377 inhibitor to assess its protective effects in vivo. MiR-377 levels were decreased in the rat brain tissues at 1, 3, and 7 d after MCAO. Both microglia cells and BMECs under OGD showed markedly lower expression levels of miR-377 while higher expression levels of EGR2 and VEGF compared to those under normoxia conditions. Knockdown of miR-377 inhibited microglial activation and the release of pro-inflammatory cytokines after OGD. Suppression of miR-377 promoted the capillary-like tube formation and cell proliferation and migration of BMECs. The anti-inflammation effect of EGR2 and the angiogenesis effect of VEGF were regulated by miR-377 after OGD. Inhibition of miR-377 decreased cerebral infarct volume and suppressed cerebral inflammation but promoted angiogenesis in MCAO rats. Knockdown of miR-377 lessened the ischemic brain injury through promoting angiogenesis and suppressing cerebral inflammation. J. Cell. Biochem. 119: 327-337, 2018. © 2017 Wiley Periodicals, Inc.

Symptomatic internal carotid artery (ICA) occlusion with hemodynamic impairment remains a dismal disease when untreated. In this prospective, single-center, controlled study, we investigated the feasibility, safety, and long-term outcome of stenting by endovascular recanalization for patients with chronic ICA occlusion. Forty patients with symptomatic chronically occluded ICA were assigned to receive endovascular recanalization (group A, n = 18) or conservative management (group B, n = 22). The primary end point was 100% complete recanalization of the primary occlusion at 60 minutes, and secondary end points were improvement in neurologic function and cognitive function. Patients in the 2 groups were comparable in demographic and baseline characteristics. Successful recanalization was achieved in 88.9% (16 of 18) of patients with the restoration of Thrombolysis in Myocardial Ischemia/Thrombolysis in Cerebral Ischemia 2 or 3 flow. There was no procedural or new cerebral ischemic event. Improvement in brain perfusion was observed in 12 (12 of 18, 75%) patients on single-photon emission computed tomography. Improvement in neurologic function defined as a reduction of ≥4 points on the National Institutes of Health Stroke Scale (NIHSS) at 6 months was observed in group A (baseline, 6.83 ± 3.01 vs 6 months, 2.61 ± 1.20; P < .01) and group B (baseline, 6.05 ± 2.75 vs 6 months, 4.77 ± 1.69; P < .05). A significant difference in NIHSS scores was noted between group A and B at 1, 3, and 6 months (P < .05 or .001). Improvement in cognitive function defined as an increase of ≥8 on the Montreal Cognitive Assessment (MoCA) was observed in group A at 3 and 6 months (baseline, 14.67 ± 3.56 vs 3 months, 24.17 ± 3.55 and 6 months, 24.72 ± 2.85; P < .01). Significant improvement in MoCA was also observed in group B (P < .01). Furthermore, a significant difference in MoCA scores was noted between group A and B at 1, 3, and 6 months (P < .05 or .001). Endovascular recanalization is feasible and safe for patients with symptomatic chronic carotid artery occlusion. Successful carotid artery stenting can improve neurological function and global cognitive function than nonrevascularization.

No abstract

The complex motion of the beating heart is accomplished by the spatial arrangement of contracting cardiomyocytes with varying orientation across the transmural layers, which is difficult to imitate in organic or synthetic models. High-fidelity testing of intracardiac devices requires anthropomorphic, dynamic cardiac models that represent this complex motion while maintaining the intricate anatomical structures inside the heart. In this work, we introduce a biorobotic hybrid heart that preserves organic intracardiac structures and mimics cardiac motion by replicating the cardiac myofiber architecture of the left ventricle. The heart model is composed of organic endocardial tissue from a preserved explanted heart with intact intracardiac structures and an active synthetic myocardium that drives the motion of the heart. Inspired by the helical ventricular myocardial band theory, we used diffusion tensor magnetic resonance imaging and tractography of an unraveled organic myocardial band to guide the design of individual soft robotic actuators in a synthetic myocardial band. The active soft tissue mimic was adhered to the organic endocardial tissue in a helical fashion using a custom-designed adhesive to form a flexible, conformable, and watertight organosynthetic interface. The resulting biorobotic hybrid heart simulates the contractile motion of the native heart, compared with in vivo and in silico heart models. In summary, we demonstrate a unique approach fabricating a biomimetic heart model with faithful representation of cardiac motion and endocardial tissue anatomy. These innovations represent important advances toward the unmet need for a high-fidelity in vitro cardiac simulator for preclinical testing of intracardiac devices.