Klueh Ulrike, Qiao Yi, Czajkowski Caroline, Ludzinska Izabela, Antar Omar, Kreutzer Donald L
Center for Molecular Tissue Engineering, University of Connecticut, School of Medicine, Farmington, CT, USA Department of Surgery, University of Connecticut, School of Medicine, Farmington, CT, USA
Center for Molecular Tissue Engineering, University of Connecticut, School of Medicine, Farmington, CT, USA Department of Surgery, University of Connecticut, School of Medicine, Farmington, CT, USA.
J Diabetes Sci Technol. 2015 Aug 25;9(5):957-65. doi: 10.1177/1932296815598776.
Implantable glucose sensors demonstrate a rapid decline in function that is likely due to biofouling of the sensor. Previous efforts directed at overcoming this issue has generally focused on the use of synthetic polymer coatings, with little apparent effect in vivo, clearly a novel approach is required. We believe that the key to extending sensor life span in vivo is the development of biocompatible basement membrane (BM) based bio-hydrogels as coatings for glucose sensors.
BM based bio-hydrogel sensor coatings were developed using purified BM preparations (ie, Cultrex from Trevigen Inc). Modified Abbott sensors were coated with Cultrex BM extracts. Sensor performance was evaluated for the impact of these coatings in vitro and in vivo in a continuous glucose monitoring (CGM) mouse model. In vivo sensor function was assessed over a 28-day time period expressed as mean absolute relative difference (MARD) values. Tissue reactivity of both Cultrex coated and uncoated glucose sensors was evaluated at 7, 14, 21 and 28 days post-sensor implantation with standard histological techniques.
The data demonstrate that Cultrex-based sensor coatings had no effect on glucose sensor function in vitro. In vivo glucose sensor performance was enhanced following BM coating as determined by MARD analysis, particularly in weeks 2 and 3. In vivo studies also demonstrated that Cultrex coatings significantly decreased sensor-induced tissue reactions at the sensor implantation sites.
Basement-membrane-based sensor coatings enhance glucose sensor function in vivo, by minimizing or preventing sensor-induced tissues reactions.
可植入式葡萄糖传感器功能迅速衰退,这可能是由于传感器生物污染所致。此前为克服这一问题所做的努力通常集中在使用合成聚合物涂层,但在体内几乎没有明显效果,显然需要一种新方法。我们认为,延长传感器在体内使用寿命的关键在于开发基于生物相容性基底膜(BM)的生物水凝胶作为葡萄糖传感器的涂层。
使用纯化的基底膜制剂(即来自Trevigen公司的Cultrex)开发基于基底膜的生物水凝胶传感器涂层。用Cultrex基底膜提取物涂覆改良后的雅培传感器。在连续葡萄糖监测(CGM)小鼠模型中,评估这些涂层在体外和体内对传感器性能的影响。在28天的时间内评估体内传感器功能,以平均绝对相对差异(MARD)值表示。在传感器植入后第7、14、21和28天,用标准组织学技术评估Cultrex涂层和未涂层葡萄糖传感器的组织反应性。
数据表明,基于Cultrex的传感器涂层在体外对葡萄糖传感器功能没有影响。通过MARD分析确定,基底膜涂层后体内葡萄糖传感器性能得到增强,尤其是在第2周和第3周。体内研究还表明,Cultrex涂层显著降低了传感器植入部位的传感器诱导组织反应。
基于基底膜的传感器涂层通过最小化或防止传感器诱导的组织反应,增强了体内葡萄糖传感器的功能。