Gas permeable membranes are a vital component of extracorporeal membrane oxygenation systems. Over more than half a century, membrane fabrication and packaging technology have progressed to enable safer and longer duration use of respiratory life support. Current research efforts seek to improve membrane efficiency and hemocompatibility, with the aim of producing smaller and more robust systems for ambulatory use. This review explores past and present innovations in oxygenator technology, suggesting possible applications of state-of-the-art membrane fabrication methods to address shortcomings of earlier concepts.
An implantablehemofilter for the treatment of kidney failure depends critically on the transport characteristics of the membrane and the biocompatibility of the membrane, cartridge, and blood conduits. A novel membrane with slit-shaped pores optimizes the trade-off between permeability and selectivity, enabling implanted therapy. Sustained (3–8) day function of an implanted parallel-plate hemofilter with minimal anticoagulation was achieved by considering biocompatibility at the subnanometer scale of chemical interactions and the millimeter scale of blood fluid dynamics. A total of 400 nm-thick polysilicon flat sheet membranes with 5–8 nm 2 micron slit-shaped pores were surface-modified with polyethylene glycol. Hemofilter cartridge geometries were refined based on computational fluid dynamics predictions of blood flow. In an uncontrolled pilot study, silicon filters were implanted in six class A dogs. Cartridges were connected to the cardiovascular system by anastamoses to the aorta and inferior vena cava and filtrate was drained to collection pouches positioned in the peritoneum. Pain medicine and acetylsalicylic acid were administered twice daily until the hemofilters were harvested on postoperative days 3 (n = 2), 4 (n = 2), 5 (n = 1), and 8 (n = 1). No hemofilters were thrombosed. Animals treated for 5 and 8 days had microscopic fractures in the silicon nanopore membranes and 20–50 ml of transudative (albumin sieving coefficient 0.5 – 0.7) fluid in the collection pouches at the time of explant. Shorter experimental durations (3–4 days) resulted in filtration volumes similar to predictions based on mean arterial pressures and membrane hydraulic permeability and (∼ 0.2 – 0.3), similar to preimplantation measurements. In conclusion, a detailed mechanistic and materials science attention to blood–material interactions allows implanted hemofilters to resist thrombosis. Additional testing is needed to determine optimal membrane characteristics and identify limiting factors in long-term implantation.
Mechanical loading is known to alter tendon structure, but its cellular mechanisms are unclear. This study aimed to determine the effect of mechanical loading on tendon cells in vivo. C57BL/6J female mice were used in a treadmill running study. The treadmill running protocol consisted of treadmill training for 1 week, followed by sustained moderate running at 13 m/min for 50 min/day, 5 days/week, for 3 weeks. Immunohistochemical staining of tendon sections of mice after treadmill running revealed that numerous cells in the tendon section expressed a-SMA, whereas in the tendon sections of control mice, only a few cells exhibited weak a-SMA signals. Furthermore, mouse patellar tendon cells (MPTCs) derived from treadmill running mice were generally larger in culture, proliferated faster, expressed a higher level of a-SMA, and formed more abundant stress fibers compared to MPTCs from control mice. In addition, MPTCs from treadmill running mice generated larger traction forces (169 AE 66.1 Pa) than those from control mice (102 AE 34.2 Pa). Finally, cells from treadmill running mice produced higher levels of total collagen (516.4 AE 92.7 mg/10,000 cells) than their counterparts (303.9 AE 34.8 mg/10,000 cells). Thus, mechanical loading via treadmill running increased the presence of myofibroblasts in mouse patellar tendons. As myofibroblasts are activated fibroblasts, their presence in the tendon following treadmill running indicates that they actively repair and remodel tendon tissue under strenuous mechanical loading, leading to known changes in tendon structure. Keywords: treadmill running; tendon cell; myofibroblast; a-SMA; collagen; cell traction force Tendons, which consist of collagen, elastin, proteoglycans, and cells, transmit muscular forces to bones. Tendons alter their structure in response to mechanical loading.1 For example, exercise enhances both their structural and mechanical properties.2 Exercise also increases the collagen level, collagen fibril size, and fibril density.2-4 These ultra-structural morphological changes are manifested through improvement in mechanical properties, such as increased ultimate tensile strength of normal tendons following swimming and running. 5,6 However, the cellular mechanisms responsible for such effects are unclear. One possibility is that, as a result of chronic mechanical loading, a new type of cell becomes present in tendons and is responsible for structural changes. We suspected that the new cells might be myofibroblasts, because mechanical loading of tendon cells in vitro induces differentiation of tendon cells into myofibroblasts. 7 Myofibroblasts are characterized by a-smooth muscle actin (a-SMA) expression, the formation of a-SMA-containing stress fibers, and the generation of large traction forces that are required for wound closure and extracellular matrix (ECM) remodeling. 8 The purpose of our study was to test the hypothesis that chronic mechanical loading induces the presence of myofibroblasts in tendons. We applied mechanical loading to mouse pa...
Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart or lung function during cardiopulmonary failure until organ recovery or replacement. Currently, the need for high levels of systemic anticoagulation and the risk for bleeding are main drawbacks of ECMO that can be addressed with a redesigned ECMO system. Our lab has developed an approach using microelectromechanical systems (MEMS) fabrication techniques to create novel gas exchange membranes consisting of a rigid silicon micropore membrane (SμM) support structure bonded to a thin film of gas-permeable polydimethylsiloxane (PDMS). This study details the fabrication process to create silicon membranes with highly uniform micropores that have a high level of pattern fidelity. The oxygen transport across these membranes was tested in a simple water-based bench-top set-up as well in a porcine in vivo model. It was determined that the mass transfer coefficient for the system using SµM-PDMS membranes was 3.03 ± 0.42 mL O min m cm Hg with pure water and 1.71 ± 1.03 mL O min m cm Hg with blood. An analytic model to predict gas transport was developed using data from the bench-top experiments and validated with in vivo testing. This was a proof of concept study showing adequate oxygen transport across a parallel plate SµM-PDMS membrane when used as a membrane oxygenator. This work establishes the tools and the equipoise to develop future generations of silicon micropore membrane oxygenators.
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