Impact of the Vascular System and CGM

血管系统和 CGM 的影响

• 批准号: 8642863
• 负责人: DON KREUTZER
• 金额: $ 179.7万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8642863
• 关键词: Agonist; Angiogenic Factor; Basement membrane; Biological; Blood Vessels; Cell surface; Cells; Communities; Cornea; Data; Development; Devices; Diabetes Mellitus; Diabetic mouse; Drainage procedure; Drug Delivery Systems; Edema; Evolution; Excision; Family; Fibronectins; Fibrosis; Foreign Bodies; Foreign-Body Reaction; Glucose; Goals; Growth Factor; Healed; Individual; Inflammation; Inflammatory; Injury; Laboratories; Lasers; Lead; Liquid substance; Literature; Lymphangiogenesis; Lymphatic Endothelial Cells; Malignant Neoplasms; Mediator of activation protein; Membrane; Microsurgery; Modeling; Mus; Natural regeneration; Nutrient; Oxygen; Pathway interactions; Performance; Perfusion; Play; Reaction; Recombinants; Research; Role; SKI gene; Site; Skin; Source; Study models; Surgical sutures; Swelling; Technology; Testing; Time; TimeLine; Tissues; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor B; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor D; Vascular Endothelial Growth Factor Receptor; Vascular Endothelial Growth Factors; Vascular System; Vascularization; angiogenesis; base; biomaterial compatibility; cytokine; density; diabetic; extracellular; gene therapy; glucose monitor; glucose sensor; healing; human disease; implantation; in vivo; inhibitor/antagonist; injured; interstitial; lymphatic vessel; member; neovascularization; public health relevance; receptor; repaired; response; sensor; vessel regression; wound healing

The concept that increasing blood vessel (BV) density and proximity to glucose sensors increases real time interstitial glucose levels and sensor function in vivo is accepted, despite limited experimental data to support that concept. Currently there is no previous data or even conjecture in the literature on the role of lymphatic vessels (LV) or the combinations of BV & LV in enhancing sensor function in vivo. Likewise nothing is known about the mediators and mechanisms involved in the formation and function of these vascular networks at sensor implantation sites. Recent gene therapy studies in our laboratories have demonstrated that 1) VEGF-A based local gene therapy increases vascular networks (blood vessels and lymphatic vessels) at sites of glucose sensor implantation; and 2) this local increase of vascular networks enhances and extends glucose sensor function in vivo from 7 days to greater than 28 days post sensor implantation. This exciting data provides "proof of concept" that increasing vascular networks at sites of glucose sensor implantation enhances performance of continuous glucose monitoring (CGM). Among the key questions that this data leads to is: 1) what are the key cells, mediators and mechanism(s) that control vascular networks (blood vessels (BV) and lymphatic vessels (LV)) at sites of sensor implantation; 2) how do they control CGM; 3) are BV, LV or the combination of vascular networks critical to enhancing and extending CGM in vivo; 4) what is the role of inflammation and fibrosis in controlling vascular networks at sensor implantation sites, and 5) can bio- enhanced extracellular matricies (ECM) be developed to control vascular network formation and enhance and extend CGM for both transcutaneous and totally implantable glucose sensors? The 3 major research goals for this application are: 1) develop and validate ECM based sensor coatings with drug delivery capability to control inflammation, fibrosis and promote vascular network formation in normal and diabetic mice; 2) determine the impact of BV, LV and BV+LV on tissue reactions and CGM in normal and diabetic mice; 3) characterize the cells, mediators and pathways that control angiogenesis, lymphangiogenesis using traditional and laser capture microsurgery technology and tissue from sensor implantation sites and correlate with CGM diabetic status.

增加血管（BV）密度和与葡萄糖传感器的接近度会增加真实的间质时间， 尽管支持该概念的实验数据有限，但体内葡萄糖水平和传感器功能是可以接受的。 目前，在文献中没有关于淋巴管（LV）或淋巴结的作用的先前数据，甚至没有推测。 BV和LV的组合在体内增强传感器功能。同样，对调解人也一无所知， 传感器植入部位的血管网络的形成和功能所涉及的机制。新近基因 我们实验室的治疗研究已经证明：1）基于VEGF-A的局部基因治疗增加了血管生成， 葡萄糖传感器植入部位的血管网络（血管和淋巴管）;以及2）这种局部增加 血管网络增强并延长体内葡萄糖传感器功能，从传感器植入后7天延长至28天以上 置入这一令人兴奋的数据提供了“概念证明”，即在葡萄糖传感器部位增加血管网络 植入增强了连续葡萄糖监测（CGM）的性能。 这些数据引出的关键问题包括：1）控制细胞增殖的关键细胞、介质和机制是什么？ 传感器植入部位的血管网络（血管（BV）和淋巴管（LV））; 2）它们如何控制 CGM; 3）BV、LV或血管网络的组合对增强和延长体内CGM至关重要; 4）什么 是炎症和纤维化在控制传感器植入部位的血管网络中的作用，以及5）可以生物- 增强的细胞外基质（ECM）被开发来控制血管网络的形成，并增强和扩展 经皮和完全植入式葡萄糖传感器的CGM？ 该应用的3个主要研究目标是：1）开发和验证基于ECM的传感器涂层， 药物递送能力，以控制炎症、纤维化并促进正常和 2）测定BV、LV和BV+LV对正常和糖尿病小鼠的组织反应和CGM的影响; 小鼠; 3）表征控制血管生成、淋巴管生成的细胞、介质和途径， 传统和激光捕获显微外科技术和传感器植入部位的组织，并与 CGM糖尿病状态。

项目成果

Basement Membrane-Based Glucose Sensor Coatings Enhance Continuous Glucose Monitoring in Vivo.

基底膜葡萄糖传感器涂层增强体内连续血糖监测。

• DOI: 10.1177/1932296815598776
• 发表时间: 2015
• 期刊: Journal of diabetes science and technology
• 影响因子: 5
• 作者: Klueh,Ulrike;Qiao,Yi;Czajkowski,Caroline;Ludzinska,Izabela;Antar,Omar;Kreutzer,DonaldL
• 通讯作者: Kreutzer,DonaldL

Crosslinked basement membrane-based coatings enhance glucose sensor function and continuous glucose monitoring in vivo.

基于交联基底膜的涂层增强了葡萄糖传感器功能和体内连续葡萄糖监测。

• DOI: 10.1002/jbm.a.36206
• 发表时间: 2018
• 期刊: Journal of biomedical materials research. Part A
• 作者: Klueh,Ulrike;Ludzinska,Izabela;Czajkowski,Caroline;Qiao,Yi;Kreutzer,DonaldL
• 通讯作者: Kreutzer,DonaldL