Oxygen sensitivity and biocompatibility of an implantable paramagnetic probe for repeated measurements of tissue oxygenation

Meenakshisundaram, Guruguhan; Eteshola, Edward; Pandian, Ramasamy P.; Bratasz, Anna; Selvendiran, Karuppaiyah; Lee, Stephen C.; Krishna, Murali C.; Swartz, Harold M.; Kuppusamy, Periannan

doi:10.1007/s10544-009-9298-4

Cited by 44 publications

(43 citation statements)

References 32 publications

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“…EPR Oximetry. EPR oxymetry was performed as described previously (37). Oxygen-sensing probe octa-n-butoxynaphthalocyanine (LiNc-BuO) particles were implanted in each animal at two locations: in the center of the flap and outside the flap (control), along the same craniocaudal plane.…”

Section: Methodsmentioning

confidence: 99%

Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds

Biswas¹,

Roy²,

Banerjee³

et al. 2010

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

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249

199

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Ischemia complicates wound closure. Here, we are unique in presenting a murine ischemic wound model that is based on bipedicle flap approach. Using this model of ischemic wounds we have sought to elucidate how microRNAs may be implicated in limiting wound reepithelialization under hypoxia, a major component of ischemia. Ischemia, evaluated by laser Doppler as well as hyperspectral imaging, limited blood flow and lowered tissue oxygen saturation. EPR oximetry demonstrated that the ischemic wound tissue had pO 2 <10 mm Hg. Ischemic wounds suffered from compromised macrophage recruitment and delayed wound epithelialization. Specifically, epithelial proliferation, as determined by Ki67 staining, was compromised. In vivo imaging showed massive hypoxia inducible factor-1α (HIF-1α) stabilization in ischemic wounds, where HIF-1α induced miR-210 expression that, in turn, silenced its target E2F3, which was markedly down-regulated in the wound-edge tissue of ischemic wounds. E2F3 was recognized as a key facilitator of cell proliferation. In keratinocytes, knock-down of E2F3 limited cell proliferation. Forced stabilization of HIF-1α using Ad-VP16-HIF-1α under normoxic conditions upregulated miR-210 expression, down-regulated E2F3, and limited cell proliferation. Studies using cellular delivery of miR-210 antagomir and mimic demonstrated a key role of miR-210 in limiting keratinocyte proliferation. In summary, these results are unique in presenting evidence demonstrating that the hypoxia component of ischemia may limit wound re-epithelialization by stabilizing HIF-1α, which induces miR-210 expression, resulting in the down-regulation of the cell-cycle regulatory protein E2F3.skin | tissue repair | wound healing

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Section: Methodsmentioning

confidence: 99%

Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds

Biswas¹,

Roy²,

Banerjee³

et al. 2010

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

Self Cite

249

199

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“…We have used PDMS to encapsulate LiNc-BuO and developed the implants in the form of thin films (OxyChip). The efficacy and safety of OxyChip have been well characterized in animal models [17, 18]. We have taken steps to obtain investigational device exemption (IDE) status from FDA for testing the OxyChips in human subjects.…”

Section: Probes For Clinical Epr Oximetrymentioning

confidence: 99%

Advances in Probes and Methods for Clinical EPR Oximetry

Swartz¹,

Hou

Khan

et al. 2014

Advances in Experimental Medicine and Biology

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EPR oximetry, which enables reliable, accurate, and repeated measurements of the partial pressure of oxygen in tissues, provides a unique opportunity to investigate the role of oxygen in the pathogenesis and treatment of several diseases including cancer, stroke, and heart failure. Building on significant advances in the in vivo application of EPR oximetry for small animal models of disease, we are developing suitable probes and instrumentation required for use in human subjects. Our laboratory has established the feasibility of clinical EPR oximetry in cancer patients using India ink, the only material presently approved for clinical use. We now are developing the next generation of probes, which are both superior in terms of oxygen sensitivity and biocompatibility including an excellent safety profile for use in humans. Further advances include the development of implantable oxygen sensors linked to an external coupling loop for measurements of deep-tissue oxygenations at any depth, overcoming the current limitation of 10 mm. This paper presents an overview of recent developments in our ability to make meaningful measurements of oxygen partial pressures in human subjects under clinical settings.

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“…One oxygen-sensitive material we are currently studying for use with EPR oximetry is a paramagnetic microcrystal composed of lithium octa-n-butoxynaphthalocyanine (LiNc–BuO) contained within an oxygen-permeable silicone polymer [11]. This has shown promise in sensitivity and function during oxygen measurements in a currently ongoing Food and Drug Administration (FDA) Phase 1 Trial of Safety/Efficacy [12].…”

Section: Introductionmentioning

confidence: 99%

Development of the Implantable Resonator System for Clinical EPR Oximetry

Caston

Schreiber

Hou

et al. 2017

Cell Biochem Biophys

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Hypoxic tumors are more resistant to radiotherapy and chemotherapy, which decreases the efficacy of these common forms of treatment. We have been developing implantable paramagnetic particulates to measure oxygen in vivo using electron paramagnetic resonance. Once implanted, oxygen can be measured repeatedly and non-invasively in superficial tissues (<3 cm deep), using an electron paramagnetic resonance spectrometer and an external surface-loop resonator. To significantly extend the clinical applications of electron paramagnetic resonance oximetry, we developed an implantable resonator system to obtain measurements at deeper sites. This system has been used to successfully obtain oxygen measurements in animal studies for several years. We report here on recent developments needed to meet the regulatory requirements to make this technology available for clinical use. radio frequency heating is discussed and magnetic resonance compatibility testing of the device has been carried out by a Good Laboratory Practice-certified laboratory. The geometry of the implantable resonator has been modified to meet our focused goal of verifying safety and efficacy for the proposed use of intracranial measurements and also for future use in tissue sites other than the brain. We have encapsulated the device within a smooth cylindrical-shaped silicone elastomer to prevent tissues from adhering to the device and to limit perturbation of tissue during implantation and removal. We have modified the configuration for simultaneously measuring oxygen at multiple sites by developing a linear array of oxygen sensing probes, which each provide independent measurements. If positive results are obtained in additional studies which evaluate bio-compatibility and chemical characterization, we believe the implantable resonator will be at a suitable stage for initial testing in human subjects.

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Oxygen sensitivity and biocompatibility of an implantable paramagnetic probe for repeated measurements of tissue oxygenation

Cited by 44 publications

References 32 publications

Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds

Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds

Advances in Probes and Methods for Clinical EPR Oximetry

Development of the Implantable Resonator System for Clinical EPR Oximetry

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