Morphometric, Hemodynamic, and Biomechanical Factors Influencing Blood Flow and Oxygen Concentration in the Human Lamina Cribrosa.

Purpose: We developed a combined biomechanical and hemodynamic model of the human eye to estimate blood flow and oxygen concentration within the lamina cribrosa (LC) and rank the factors that influence LC oxygen concentration. Methods: We generated 5000 finite-element eye models with detailed microcapillary networks of the LC and computed the oxygen concentration of the lamina retinal ganglion cell axons. For each model, we varied the intraocular pressure (IOP) from 10 mm Hg to 55 mm Hg in 5-mm Hg increments, the cerebrospinal fluid pressure (13 ± 2 mm Hg), cup depth (0.2 ± 0.1 mm), scleral stiffness (±20% of the mean values), LC stiffness (0.41 ± 0.2 MPa), LC radius (1.2 ± 0.12 mm), average LC pore size (5400 ± 2400 µm2), the microcapillary arrangement (radial, isotropic, or circumferential), and perfusion pressure (50 ± 9 mm Hg). Blood flow was assumed to originate from the LC periphery and drain via the central retinal vein. Finally, we performed linear regressions to rank the influence of each factor on the LC tissue oxygen concentration. Results: LC radius and perfusion pressure were the most important factors in influencing the oxygen concentration of the LC. IOP was another important parameter, and eyes with higher IOP had higher compressive strain and slightly lower oxygen concentration. In general, superior-inferior regions of the LC had significantly lower oxygen concentration than the nasal-temporal regions, resulting in an hourglass pattern of oxygen deficiency. Conclusions: To the best of our knowledge, this study is the first to implement a comprehensive hemodynamical model of the eye that accounts for the biomechanical forces and morphological parameters of the LC. The results provide further insight into the possible relationship of biomechanical and vascular pathways leading to ischemia-induced optic neuropathy.

Design and evaluation of the crimping of a hooked self-expandable caval valve stent for the treatment of tricuspid regurgitation.

To design a hooked self-expandable caval valve stent and determine the best crimping scenario for its percutaneous implantation in the Superior and Inferior Vena Cava (SVC & IVC) for the treatment of tricuspid regurgitation (TR). A hooked, Nitinol based stent design was modeled using SOLIDWORKS and finite element analysis (FEA) was carried out using ABAQUS. The Nitinol material used in this study was modeled in ABAQUS as superelastic-plastic. Two cases were simulated. In case A, the stent model was crimped to 18 F by compressing the stent main body and then: (i) bending both the proximal and distal hooks; (ii) straightening the proximal hooks and bending the distal hooks. In case B, the stent model was crimped to 18 F by: (i) bending the proximal and distal hooks and then compressing the stent main body; (ii) straightening the proximal hooks and bending the distal hooks and then compressing the stent main body. The maximum strain after crimping was used to evaluate the best crimping scenario. Hook straightening produced strains of 10.7% and 10.96% as opposed to 12.6% and 13.0% produced by hook bending. From comparison of results of both cases simulated, it was found that straightening the hooks gave lower strain and thus was the best crimping procedure. The analysis performed in this paper may help understand the critical issue of crimpability of the new stent design. The best crimping scenario can be found based on finite element modeling and simulation. Identifying the best crimping way will also help the design team to optimize the delivery system that will eventually be used to deploy this caval valve stent.

Bioresorbable vascular scaffold radial expansion and conformation compared to a metallic platform: insights from in vitro expansion in a coronary artery lesion model.

AIMS: This study aimed to compare the acute expansion behaviour of a polymer-based bioresorbable scaffold and a second-generation metallic DES platform in a realistic coronary artery lesion model. Experimental mechanical data with conventional methods have so far shown little difference between metallic stents and currently available polymer-based bioresorbable scaffolds (BRS). Nevertheless, differences in acute results have been observed in clinical studies comparing BRS directly with metallic DES platforms. METHODS AND RESULTS: We examined the expansion behaviour of the bioresorbable vascular scaffold (3.0×18 mm Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) and a metallic DES (3.0×18 mm XIENCE Prime; Abbott Vascular) after expansion at 37°C using identical coronary artery stenosis models (in total 12 experiments were performed). Device expansion was compared during balloon inflation and after deflation using microscopy to allow assessment of plaque recoil. Minimal lumen diameter (MLD) and minimal lumen area (MLA) and stent eccentricity were quantified from optical coherence tomography (OCT) imaging at nominal diameter and after post-dilation at 18 atm. The MLA in the models with BVS deployed was 4.92±0.17 mm² while in the metallic DES it was 5.40±0.13 mm2 (p=0.02) at nominal pressure (NP), and 5.41±0.20 and 6.07±0.25 mm2 (p=0.02), respectively, after expansion at 18 atm. Stent eccentricity index at the MLA was 0.71±0.02 in BVS compared to 0.81±0.02 in the metal stent at NP (p=0.004), and 0.73±0.03 compared to 0.75±0.02 at 18 atm (p=0.39). CONCLUSIONS: Results obtained in this in vitro lesion model were comparable to the results in randomised clinical trials comparing BVS and XIENCE stents in vivo. Such models may be useful in future BRS developments to predict their acute response in vivo in eccentric lesions.

Nanoparticle-based delivery system for application of siRNA in vivo.

Small interfering RNAs (siRNAs) silence the expression of specific target genes by mediating RNA interference (RNAi) in mammalian cells. siRNAs have not only been widely used as a valuable tool for functional genomics research, but they also have demonstrated great potential in biomedical therapeutic applications for diseases caused by abnormal gene overexpression or mutation. One of the most important issues to overcome before full clinical application is the development of effective administration methods for siRNAs to the target tissue or cells in vivo, which is highly dependent on the delivery system. Currently, there are two major kinds of in vivo delivery systems: viral or nonviral. As one of the nonviral carrier systems, nanoparticles, combinations of liposomes and cationic polymer complexes, have exhibited improved in vivo stability, target specificity, and cell/tissue uptake and internalization of the encapsulated RNAi oligos, which result in more effective silencing with less cellular toxicity and immune stimulation. This review will discuss the latest advancements in nanoparticle-mediated RNAi delivery systems, including nano-materials, preparation, and characteristics. In conjunction, the clinical trial cases related to the nanoparticle-siRNA complexes will be highlighted. The safety issues of nanoparticles used in vivo will also be mentioned. Finally, this review will summarize the perspectives for future applications of nanoparticle-mediated RNAi delivery systems.

Current development of bioreactors for extracorporeal bioartificial liver (Review).

The research and development of extracorporeal bioartificial liver is gaining pace in recent years with the introduction of a myriad of optimally designed bioreactors with the ability to maintain long-term viability and liver-specific functions of hepatocytes. The design considerations for bioartificial liver are not trivial; it needs to consider factors such as the types of cell to be cultured in the bioreactor, the bioreactor configuration, the magnitude of fluid-induced shear stress, nutrients' supply, and wastes' removal, and other relevant issues before the bioreactor is ready for testing. This review discusses the exciting development of bioartificial liver devices, particularly the various types of cell used in current reactor designs, the state-of-the-art culturing and cryopreservation techniques, and the comparison among many today's bioreactor configurations. This review will also discuss in depth the importance of maintaining optimal mass transfer of nutrients and oxygen partial pressure in the bioreactor system. Finally, this review will discuss the commercially available bioreactors that are currently undergoing preclinical and clinical trials.