Permeability of subcutaneous tissues surrounding long-term implants to oxygen

Kumosa, L.; Routh, Timothy L.; Lin, Joe T.; Lucisano, Joseph Y.; Gough, David

doi:10.1016/j.biomaterials.2014.05.012

Cited by 26 publications

(31 citation statements)

References 23 publications

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“…The value used here was based on in vivo measures of oxygen diffusion using phosphorescence quenching microscopy (32). Although this estimate is considerably lower than Krogh's original estimate (33), it is within two-to threefold of many current estimates from various tissues-particularly those using in vivo methods (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). The diffusion constant was adjusted for temperature to 38°C in our analysis of endotherms and to 25°C for ectotherms, based on a reported Q10 of 1.1 (47).…”

Section: Methodsmentioning

confidence: 93%

Body mass scaling of passive oxygen diffusion in endotherms and ectotherms

Gillooly

Gómez

Mavrodiev

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The area and thickness of respiratory surfaces, and the constraints they impose on passive oxygen diffusion, have been linked to differences in oxygen consumption rates and/or aerobic activity levels in vertebrates. However, it remains unclear how respiratory surfaces and associated diffusion rates vary with body mass across vertebrates, particularly in relation to the body mass scaling of oxygen consumption rates. Here we address these issues by first quantifying the body mass dependence of respiratory surface area and respiratory barrier thickness for a diversity of endotherms (birds and mammals) and ectotherms (fishes, amphibians, and reptiles). Based on these findings, we then use Fick's law to predict the body mass scaling of oxygen diffusion for each group. Finally, we compare the predicted body mass dependence of oxygen diffusion to that of oxygen consumption in endotherms and ectotherms. We find that the slopes and intercepts of the relationships describing the body mass dependence of passive oxygen diffusion in these two groups are statistically indistinguishable from those describing the body mass dependence of oxygen consumption. Thus, the area and thickness of respiratory surfaces combine to match oxygen diffusion capacity to oxygen consumption rates in both air-and water-breathing vertebrates. In particular, the substantially lower oxygen consumption rates of ectotherms of a given body mass relative to those of endotherms correspond to differences in oxygen diffusion capacity. These results provide insights into the long-standing effort to understand the structural attributes of organisms that underlie the body mass scaling of oxygen consumption.allometry | metabolic theory | respiration rate | metabolism | oxygen consumption S ince the classic debates of Krogh and Bohr (1), the relationship of passive oxygen diffusion to oxygen consumption has remained the focus of considerable research (2). Still, we have much to learn about how oxygen diffusion across respiratory surfaces relates to whole-organism oxygen consumption (3). In particular, we have much to learn about how the structural constraints on oxygen diffusion capacity, namely the thickness and area of respiratory surfaces, relate to the body mass scaling of oxygen consumption in vertebrates-a pattern that reflects the scaling of species' energy use (3).Studies on the body mass dependence of oxygen diffusion have been undertaken over the last century in all major classes of vertebrates, typically using respiratory surface area as a metric of diffusion capacity (2, 3). Less commonly, studies have also considered potentially relevant changes in respiratory barrier thickness with mass (4). In many cases, these studies have concluded that the body mass scaling of oxygen diffusion relative to that of oxygen consumption differs between endotherms and ectotherms (3,5,6). This has led to very different conclusions regarding the structure and function of respiratory systems among classes of vertebrates, as explained below.Among endotherms, particularly...

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Section: Methodsmentioning

confidence: 93%

Body mass scaling of passive oxygen diffusion in endotherms and ectotherms

Gillooly

Gómez

Mavrodiev

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Such an increased affinity for oxygen is exacerbated by the decreased amount of oxygen present in wounded tissue. Gough et al have demonstrated that oxygen permeability within tissue surrounding an implant decreases over time before arriving at an asymptotic value, with the steepest drop coming in the first week [61,62]. Additionally, the concentration of unbound oxygen in tissue is much lower than that of glucose, meaning that oxygen limits the glucose oxidase reaction in the body [63,64].…”

Section: Discussionmentioning

confidence: 99%

Macrophage embedded fibrin gels: An in vitro platform for assessing inflammation effects on implantable glucose sensors

2014

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The erroneous and unpredictable behavior of percutaneous glucose sensors just days following implantation has limited their clinical utility for diabetes management. Recent research has implicated the presence of adherent inflammatory cells as the key mitigating factor limiting sensor functionality in this period of days post-implantation. Here we present a novel in vitro platform to mimic the cell-embedded provisional matrix that forms adjacent to the sensor immediately after implantation for the focused investigation of the effects of early stage tissue response on sensor function. This biomimetic surrogate is formed by imbibing fibrin-based gels with physiological densities of inflammatory RAW 264.7 macrophages. When surrounding functional sensors, macrophage-embedded fibrin gels contribute to sensor signal declines that are similar in both shape and magnitude to those observed in previous whole blood and small animal studies. Signal decline in the presence of gels is both metabolically-mediated and sensitive to cell type and activation. Computational modeling of the experimental setup is also presented to validate the design by showing that the cellular glucose uptake parameters necessary to achieve such experimental declines align well with literature values. Together, these data suggest this in vitro provisional matrix surrogate may serve as an effective screening tool for testing the biocompatibility of future glucose sensor designs.

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“…The oxygen concentration was adjusted using mass flow controllers (1179A, MKS Instruments, Inc., Andouver, MA, USA). Glucose challenges were performed by exposing the AnA hydrogels to varying physiologically relevant glucose concentrations (0–400 mg/dL in 10 mM TRIS with 10 mM CaCl 2 , 37 °C) at fixed oxygen concentrations (206.8 μM for ambient and 70 μM for interstitial oxygen concentration) [24]. The oxygen concentration was regulated by a vacuum degassing chamber (9000–1118, Systec) and vacuum pump (9000-1472, Systec).…”

Section: Methodsmentioning

confidence: 99%

“…These unique materials transduce chemical concentration into optical information (phosphorescence intensity or lifetime). While these materials were found to exhibit the desired response characteristics in benchtop testing, it was observed that the response often saturated at relatively low analyte concentrations when used in vivo; this undesired outcome has been attributed primarily to low tissue oxygen levels which have been found to be ≈3 times lower than air-equilibrated aqueous solutions [24,25]. These low oxygen concentrations disrupt the function of the bioresponsive material because they were designed and lab-proven based on a diffusion-reaction equilibrium expecting higher oxygen concentrations.…”

Section: Introductionmentioning

confidence: 99%

Composite Hydrogels with Engineered Microdomains for Optical Glucose Sensing at Low Oxygen Conditions

2017

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There is a growing need for advanced tools that enable frequent monitoring of biomarkers for precision medicine. In this work, we present a composite hydrogel-based system providing real-time optical bioanalyte monitoring. The responsive material, alginate-in-alginate (AnA), is comprised of an alginate hydrogel with embedded bioactive, nanofilm-coated phosphorescent microdomains; palladium tetracarboxyphenylporphyrin serves as an optical indicator, glucose oxidase as a model enzyme, and layer-by-layer deposited polyelectrolyte multilayers (PEMs) as the diffusion barrier. Glutaraldehyde crosslinking of the nanofilms resulted in a dramatic reduction in glucose diffusion (179%) while oxygen transport was not significantly affected. The responses of the AnA hydrogels to step changes of glucose at both ambient and physiological oxygen levels were evaluated, revealing controlled tuning of sensitivity and dynamic range. Stability, assessed by alternately exposing the responsive AnA hydrogels to extremely high and zero glucose concentrations, resulted in no significant difference in the response over 20 cycles. These AnA hydrogels represent an attractive approach to biosensing based on biocompatible materials that may be used as minimally-invasive, implantable devices capable of optical interrogation. The model glucose-responsive composite material studied in this work will serve as a template that can be translated for sensing additional analytes (e.g., lactate, urea, pyruvate, cholesterol) and can be used for monitoring other chronic conditions.

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Permeability of subcutaneous tissues surrounding long-term implants to oxygen

Cited by 26 publications

References 23 publications

Body mass scaling of passive oxygen diffusion in endotherms and ectotherms

Body mass scaling of passive oxygen diffusion in endotherms and ectotherms

Macrophage embedded fibrin gels: An in vitro platform for assessing inflammation effects on implantable glucose sensors

Composite Hydrogels with Engineered Microdomains for Optical Glucose Sensing at Low Oxygen Conditions

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