Biofouling of Polymer Hydrogel Materials and its Effect on Diffusion and Enzyme-Based Luminescent Glucose Sensor Functional Characteristics

Roberts, Jason; Park, Jaebum; Helton, Kristen; Wisniewski, Natalie A.; McShane, Michael J.

doi:10.1177/193229681200600605

Cited by 25 publications

(33 citation statements)

References 28 publications

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“…Hydrogels for injection were fabricated similarly as described previously 18 with a few changes (exchanging the green-excitable phenyl porphyrin with the red-excitable PdBP and a different hydrogel shape: 5 mm long strips with a ~750 µm × 750 µm square cross section; Figure 2). This shape was selected for ease of insertion through a needle, and was employed for both in vitro and in vivo sensor performance testing.…”

Section: Injectable Glucose Sensor Fabricationmentioning

confidence: 99%

“…18 Briefly, two reservoirs (one containing PBS and the other containing 400 mg/dL glucose in PBS) were connected to two separate pumps controlled by a LabVIEW program. Combined pump effluents flowed directly to the sample chamber housing the immobilized sensing strips.…”

Section: In Vitro Sensor Responsementioning

confidence: 99%

“…16 We hypothesize the upper limit of detection at 167 mg/dL is due to the diffusion of glucose and oxygen in this particular hydrogel matrix, because wider analytical ranges, but decreased sensitivity, have been reported in hydrogels with greater pHEMA content when using similar sensing chemistry. 18 Linear Stern-Volmer behavior indicates the dye is adequately accessible to oxygen at relevant physiological concentrations.…”

Section: In Vitro Performancementioning

confidence: 99%

“…[13][14][15] Demonstrations of potential hydrogel sensor formats over the years have included poly(ethylene glycol)-based microspheres and fibers [13][14][15] and includes a variety of hollow polymeric capsules and various nanocomposite particulate systems using other encapsulating materials. [16][17][18][19][20] Utilizing these unique properties of hydrogels in a fully implantable CGM may circumvent repetitive tissue trauma and infection associated with the percutaneous nature of traditional CGM devices in vivo. 9,21 Used in medical devices for decades, one of the most widely studied and well-characterized hydrogels for biomedical applications is poly (2-hydroxyethyl methacrylate) (pHEMA).…”

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confidence: 99%

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Preclinical Evaluation of Poly(HEMA-co-acrylamide) Hydrogels Encapsulating Glucose Oxidase and Palladium Benzoporphyrin as Fully Implantable Glucose Sensors

Unruh

Roberts

Nichols

et al. 2015

J Diabetes Sci Technol

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Background: Continuous glucose monitors (CGMs) require percutaneous wire probes to monitor glucose. Sensors based on luminescent hydrogels are being explored as fully implantable alternatives to traditional CGMs. Our previous work investigated hydrogel matrices functionalized with enzymes and oxygen-quenched phosphors, demonstrating sensitivity to glucose, range of response, and biofouling strongly depend on the matrix material. Here, we further investigate the effect of matrix composition on overall performance in vitro and in vivo. Methods: Sensors based on three hydrogels, a poly(2-hydroxyethyl methacrylate) (pHEMA) homopolymer and 2 poly(2-hydroxyethyl methacrylate-co-acrylamide) (pHEMA-co-AAm) copolymers, were compared. These were used to entrap glucose oxidase (GOx), catalase, and an oxygen-sensitive benzoporphyrin phosphor. All sensor formulations were evaluated for glucose response and stability at physiological temperatures. Selected sensors were then evaluated as implanted sensors in a porcine model challenged with glucose and insulin. The animal protocol used in this study was approved by an IACUC committee at Texas A&M University. Results: PHEMA-co-AAm copolymer hydrogels (75:25 HEMA:AAm) yielded the most even GOx and dye dispersion throughout the hydrogel matrix and best preserved GOx apparent activity. In response to in vitro glucose challenges, this formulation exhibited a dynamic range of 12-167 mg/dL, a sensitivity of 1.44 ± 0.46 µs/(mg/dL), and tracked closely with reference capillary blood glucose values in vivo. Conclusions: The hydrogel-based sensors exhibited excellent sensitivity and sufficiently rapid response to the glucose levels achieved in vivo, proving feasibility of these materials for use in real-time glucose tracking. Extending the dynamic range and assessing long-term effects in vivo are ongoing efforts.

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Section: Injectable Glucose Sensor Fabricationmentioning

confidence: 99%

Section: In Vitro Sensor Responsementioning

confidence: 99%

Section: In Vitro Performancementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Preclinical Evaluation of Poly(HEMA-co-acrylamide) Hydrogels Encapsulating Glucose Oxidase and Palladium Benzoporphyrin as Fully Implantable Glucose Sensors

Unruh

Roberts

Nichols

et al. 2015

J Diabetes Sci Technol

Self Cite

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show abstract

“…19 Unless otherwise stated all chemicals were from Sigma-Aldrich and were used as received. A custom tetra-methacrylated porphyrin (TMAP) was made by functionalizing palladium(II) meso-Tetra(4-carboxyphenyl) porphine (Frontier Scientific) with 2-aminoethylmethacrylate in order to easily immobilize it in the sensor matrix (see Acknowledgements).…”

Section: Methodsmentioning

confidence: 99%

Enzymatic glucose sensor compensation for variations in ambient oxygen concentration

Collier

McShane

2013

SPIE Proceedings

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Due to the increasing prevalence of diabetes, research toward painless glucose sensing continues. Oxygen sensitive phosphors with glucose oxidase (GOx) can be used to determine glucose levels indirectly by monitoring oxygen consumption. This is an attractive combination because of its speed and specificity. Packaging these molecules together in “smart materials” for implantation will enable non-invasive glucose monitoring. As glucose levels increase, oxygen levels decrease; consequently, the luminescence intensity and lifetime of the phosphor increase. Although the response of the sensor is dependent on glucose concentration, the ambient oxygen concentration also plays a key role. This could lead to inaccurate glucose readings and increase the risk of hyper- or hypoglycemia. To mitigate this risk, the dependence of hydrogel glucose sensor response on oxygen levels was investigated and compensation methods explored. Sensors were calibrated at different oxygen concentrations using a single generic logistic equation, such that trends in oxygen-dependence were determined as varying parameters in the equation. Each parameter was found to be a function of oxygen concentration, such that the correct glucose calibration equation can be calculated if the oxygen level is known. Accuracy of compensation will be determined by developing an overall calibration, using both glucose and oxygen sensors in parallel, correcting for oxygen fluctuations in real time by intentionally varying oxygen, and calculating the error in actual and predicted glucose levels. While this method was developed for compensation of enzymatic glucose sensors, in principle it can also be implemented with other kinds of sensors utilizing oxidases.

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A review of gradient stiffness hydrogels used in tissue engineering and regenerative medicine

Xia

Liu

Yang

2017

J Biomedical Materials Res

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Substrate stiffness is known to impact characteristics including cell differentiation, proliferation, migration and apoptosis. Hydrogels are polymeric materials distinguished by high water content and diverse physical properties. Gradient stiffness hydrogels are designed by the need to develop biologically friendly materials as extracellular matrix (ECM) alternatives to replace the separated and narrow-ranged hydrogel substrates. Important new discoveries in cell behaviors have been realized with model gradient stiffness hydrogel systems from the two-dimensional (2D) to three-dimensional (3D) scale. Basic and clinical applications for gradient stiffness hydrogels in tissue engineering and regenerative medicine continue to drive the development of stiffness and structure varied hydrogels. Given the importance of gradient stiffness hydrogels in basic research and biomedical applications, there is a clear need for systems for gradient stiffness hydrogel design strategies and their applications. This review will highlight past work in the field of gradient stiffness hydrogels fabrication methods, mechanical property test, applications as well as areas for future study. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1799-1812, 2017.

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Biofouling of Polymer Hydrogel Materials and its Effect on Diffusion and Enzyme-Based Luminescent Glucose Sensor Functional Characteristics

Cited by 25 publications

References 28 publications

Preclinical Evaluation of Poly(HEMA-co-acrylamide) Hydrogels Encapsulating Glucose Oxidase and Palladium Benzoporphyrin as Fully Implantable Glucose Sensors

Preclinical Evaluation of Poly(HEMA-co-acrylamide) Hydrogels Encapsulating Glucose Oxidase and Palladium Benzoporphyrin as Fully Implantable Glucose Sensors

Enzymatic glucose sensor compensation for variations in ambient oxygen concentration

A review of gradient stiffness hydrogels used in tissue engineering and regenerative medicine

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