Carbonic anhydrase immobilized on hollow fiber membranes using glutaraldehyde activated chitosan for artificial lung applications

Kimmel, Jeremy D.; Arazawa, David T.; Ye, Sang‐Ho; Shankarraman, Venkat; Wagner, William R.; Federspiel, William J.

doi:10.1007/s10856-013-5006-2

Cited by 33 publications

(31 citation statements)

References 37 publications

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“…Immobilized enzymes may aid in CO 2 removal for artificial lungs. 7,8 In neural devices, immobilized proteins, anti-inflammatory peptides, and antioxidants may decrease the FBR and increase tissue integration in the peripheral 9 and central nervous system. 10,11 …”

Section: Introductionmentioning

confidence: 99%

Enhancing surface immobilization of bioactive moleculesviaa silica nanoparticle based coating

2018

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Surface modification is of significant interest in biomaterials, biosensors, and device biocompatibility. Immobilization of bioactive or biomimetic molecules is a common method of disguising a foreign body as host tissue to decrease the foreign body response (FBR) and/or increase device–tissue integration. For example, in neural interfacing devices, immobilization of L1, a neuron-specific adhesion molecule, has been shown to increase neuron adhesion and reduce inflammatory gliosis on and around the implants. However, the activity of modified surfaces is limited by the relatively low concentration of the immobilized component, in part due to the low surface area of flat surfaces available for modification. In this work, we demonstrate a novel method for increasing the device surface area by attaching a layer of thiolated silica nanoparticles (TNPs). This coating method results in an almost two-fold increase in the immobilized L1 protein. L1 immobilized nanotextured surfaces showed a 100% increase in neurite outgrowth than smooth L1 immobilized surfaces without increasing the adhesion of astrocytes in vitro. The increased bioactivity observed in the cell assay was determined to be mainly due to the higher protein surface density, not the increase in surface roughness. In addition, we tested immobilization of a superoxide dismutase mimic (SODm) on smooth and roughened substrates. The SODm immobilized rough surfaces demonstrated an increase of 145% in superoxide scavenging activity compared to chemically matched smooth surfaces. These results not only show promise in improving biomimetic coating for neural implants, but may also improve surface immobilization efficacy in other fields such as catalysts, protein purification, sensors, and tissue engineering devices.

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Section: Introductionmentioning

confidence: 99%

Enhancing surface immobilization of bioactive moleculesviaa silica nanoparticle based coating

2018

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“…Previous work by our group to chemically increase trans-HFM CO 2 pressure utilized bioactive CA-HFMs for a 31–37% improvement in blood CO 2 removal efficiency [27], [28]. In this work, the addition of SO 2 to an oxygen sweep gas increased CO 2 removal of unmodified PMP HFMs up to 17%, and for bioactive CA-PMP HFMs up to 109% (Figure 2).…”

Section: Discussionmentioning

confidence: 67%

“…The fluid flow rate through the model oxygenator was set to 45 mL/min. The sweep gas flow rate was adjusted to maintain a constant CO 2 concentration in the sweep gas exiting the model oxygenator at approximately 3000 ppm to avoid sweep gas flow limitation of gas exchange [28]. The sweep gas flow rate for PMP HFMs ranged from 0.90 L/min (O 2 ) to 1.02 L/min (O 2 + 2.2% SO 2 ), while CA-PMP ranged from 1.35 L/min (O 2 ) to 2.20 L/min (O 2 + 2.2% SO 2 ).…”

Section: Methodsmentioning

confidence: 99%

“…We reported development of CA immobilized bioactive HFMs which converts bicarbonate to CO 2 directly at the HFM surface, restoring the trans-HFM CO 2 gradient as it is depleted in the diffusional boundary layer, and increasing CO 2 removal rates from blood by 36% in model gas exchange devices [27]–[29]. The main impediment to CO 2 removal by bioactive HFMs is diffusional boundary layer resistance which restricts transport of CO 2 and bicarbonate from the bulk fluid to the HFM surface, not the CA catalyzed conversion of bicarbonate to CO 2 [28]. Further improvements in the trans-HFM CO 2 gradient and exploitation of CA coating activity could be realized through blood acidification, chemically shifting equilibrium from bicarbonate to CO 2 .…”

Section: Introductionmentioning

confidence: 99%

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Acidic sweep gas with carbonic anhydrase coated hollow fiber membranes synergistically accelerates CO2 removal from blood

et al. 2015

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The use of extracorporeal carbon dioxide removal (ECCO2R) is well established as a therapy for patients suffering from acute respiratory failure. Development of next generation low blood flow (< 500 mL/min) ECCO2R devices necessitates more efficient gas exchange devices. Since over 90% of blood CO2 is transported as bicarbonate (HCO3−), we previously reported development of a carbonic anhydrase (CA) immobilized bioactive hollow fiber membrane (HFM) which significantly accelerates CO2 removal from blood in model gas exchange devices by converting bicarbonate to CO2 directly at the HFM surface. This present study tested the hypothesis that dilute sulfur dioxide (SO2) in oxygen sweep gas could further increase CO2 removal by creating an acidic microenvironment within the diffusional boundary layer adjacent to the HFM surface, facilitating dehydration of bicarbonate to CO2. CA was covalently immobilized onto poly (methyl pentene) (PMP) HFMs through glutaraldehyde activated chitosan spacers, potted in model gas exchange devices (0.0151m2) and tested for CO2 removal rate with oxygen (O2) sweep gas and a 2.2% SO2 in oxygen sweep gas mixture. Using pure O2 sweep gas, CA-PMP increased CO2 removal by 31% (258 mL/min/m2) compared to PMP (197 mL/min/m2) (P < 0.05). Using 2.2% SO2 acidic sweep gas increased PMP CO2 removal by 17% (230 mL/min/m2) compared to pure oxygen sweep gas control (P < 0.05); device outlet blood pH was 7.38 units. When employing both CA-PMP and 2.2% SO2 sweep gas, CO2 removal increased by 109% (411 mL/min/m2) (P < 0.05); device outlet blood pH was 7.35 units. Dilute acidic sweep gas increases CO2 removal, and when used in combination with bioactive CA-HFMs has a synergistic effect to more than double CO2 removal while maintaining physiologic pH. Through these technologies the next generation of intravascular and paracorporeal respiratory assist devices can remove more CO2 with smaller blood contacting surface areas.

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“…During ECCO 2 R using hollow fiber membranes, the CO 2 held as bicarbonate must be converted to dissolved CO 2 before it can be removed. This conversion limiting CO 2 removal rates was demonstrated in a study using hollow fibers immobilized with carbonic anhydrase, to catalyze the conversion of bicarbonate to dissolved CO 2 , resulting in a 37% enhancement of the CO 2 removal rate [27, 28]. Respiratory hemodialysis, by directly removing bicarbonate, is not limited by the conversion of bicarbonate to dissolved CO 2 permitting lower blood flow rates yet still able to attain therapeutic results.…”

Section: Discussionmentioning

confidence: 99%

Extracorporeal CO2 removal by hemodialysis: in vitro model and feasibility

May

Sen

Cove

et al. 2017

ICMx

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BackgroundCritically ill patients with acute respiratory distress syndrome and acute exacerbations of chronic obstructive pulmonary disease often develop hypercapnia and require mechanical ventilation. Extracorporeal carbon dioxide removal can manage hypercarbia by removing carbon dioxide directly from the bloodstream. Respiratory hemodialysis uses traditional hemodialysis to remove CO2 from the blood, mainly as bicarbonate. In this study, Stewart’s approach to acid-base chemistry was used to create a dialysate that would maintain blood pH while removing CO2 as well as determine the blood and dialysate flow rates necessary to remove clinically relevant CO2 volumes.MethodsBench studies were performed using a scaled down respiratory hemodialyzer in bovine or porcine blood. The scaling factor for the bench top experiments was 22.5. In vitro dialysate flow rates ranged from 2.2 to 24 mL/min (49.5–540 mL/min scaled up) and blood flow rates were set at 11 and 18.7 mL/min (248–421 mL/min scaled up). Blood inlet CO2 concentrations were set at 50 and 100 mmHg.ResultsResults are reported as scaled up values. The CO2 removal rate was highest at intermittent hemodialysis blood and dialysate flow rates. At an inlet pCO2 of 50 mmHg, the CO2 removal rate increased from 62.6 ± 4.8 to 77.7 ± 3 mL/min when the blood flow rate increased from 248 to 421 mL/min. At an inlet pCO2 of 100 mmHg, the device was able to remove up to 117.8 ± 3.8 mL/min of CO2. None of the test conditions caused the blood pH to decrease, and increases were ≤0.08.ConclusionsWhen the bench top data is scaled up, the system removes a therapeutic amount of CO2 standard intermittent hemodialysis flow rates. The zero bicarbonate dialysate did not cause acidosis in the post-dialyzer blood. These results demonstrate that, with further development, respiratory hemodialysis can be a minimally invasive extracorporeal carbon dioxide removal treatment option.

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Carbonic anhydrase immobilized on hollow fiber membranes using glutaraldehyde activated chitosan for artificial lung applications

Cited by 33 publications

References 37 publications

Enhancing surface immobilization of bioactive moleculesviaa silica nanoparticle based coating

Enhancing surface immobilization of bioactive moleculesviaa silica nanoparticle based coating

Acidic sweep gas with carbonic anhydrase coated hollow fiber membranes synergistically accelerates CO2 removal from blood

Extracorporeal CO2 removal by hemodialysis: in vitro model and feasibility

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