Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd U3092, Storrs, CT 06269, United States.
J Control Release. 2013 Aug 10;169(3):341-7. doi: 10.1016/j.jconrel.2012.12.028. Epub 2013 Jan 5.
Application of implantable glucose biosensors for "real-time" monitoring is reliant on controlling the negative tissue reaction at the sensor tissue interphase. A novel polymer coating consisting of poly(lactic-co-glycolic) acid (PLGA) microsphere dispersed in poly(vinyl alcohol) (PVA) hydrogels was evaluated in combination with dummy sensors as a "smart" drug eluting biocompatible coating for implantable biosensors to prevent the foreign body response, and thus enhance sensor performance in vivo. The polymeric microspheres slowly release tissue-modifying drugs at the implantation sites to control the inflammation and fibrous encapsulation, while the hydrogel allows rapid analyte diffusion to the sensing elements. Dummy sensors with identical dimensions to that of the functional glucose sensors (0.5×0.5×5mm) were coated with the PLGA/PVA composites using a mold fabrication process. Both normal and diabetic rats were used in the current study to investigate the effect of the diabetic state on tissue sensor interactions. It was evident that the PLGA/PVA hydrogel composite was able to form a uniform coating around the dummy sensor and stayed intact throughout the course of the study (one month). Tissue samples containing dummy sensors that were coated with dexamethasone free composites exhibited acute and chronic inflammation as well as fibrous encapsulation in both normal and diabetic rats. However, the diabetic rats exhibited decreased intensity and delayed onset of the foreign body response following implantation of drug free dummy sensors in comparison to those of normal rats. On the other hand, tissues containing dummy sensors that were coated with dexamethasone containing composites remained normal (i.e. similar to untreated tissues), with no inflammatory reaction or fibrous encapsulation occurring over the one-month period in both the normal and diabetic rats. The feasibility of utilizing PLGA microsphere/PVA hydrogel composites as coatings for implantable biosensors was demonstrated. This polymeric composite is an innovative approach to control the foreign body reaction at the tissue-device interface to prolong biosensor lifetime.
可植入葡萄糖生物传感器的“实时”监测应用依赖于控制传感器组织界面处的负组织反应。一种由聚（乳酸-共-乙醇酸）（PLGA）微球分散在聚乙烯醇（PVA）水凝胶中的新型聚合物涂层，作为一种“智能”药物洗脱生物相容性涂层，用于可植入生物传感器，以防止异物反应，从而提高生物传感器在体内的性能。聚合物微球在植入部位缓慢释放组织修饰药物，以控制炎症和纤维囊包，而水凝胶允许快速分析物扩散到传感元件。与功能葡萄糖传感器（0.5×0.5×5mm）具有相同尺寸的 dummy 传感器采用模具制造工艺涂覆 PLGA/PVA 复合材料。正常和糖尿病大鼠均用于本研究，以研究糖尿病状态对组织传感器相互作用的影响。显然，PLGA/PVA 水凝胶复合材料能够在 dummy 传感器周围形成均匀的涂层，并在整个研究过程（一个月）中保持完整。含有未涂敷地塞米松复合涂层的 dummy 传感器的组织样本在正常和糖尿病大鼠中均表现出急性和慢性炎症以及纤维囊包。然而，与正常大鼠相比，糖尿病大鼠在植入无药物 dummy 传感器后，异物反应的强度降低，且发病时间延迟。另一方面，涂有含地塞米松的 dummy 传感器的组织保持正常（即与未处理的组织相似），在正常和糖尿病大鼠中，在一个月的时间内没有发生炎症反应或纤维囊包。证明了将 PLGA 微球/PVA 水凝胶复合材料用作可植入生物传感器涂层的可行性。这种聚合物复合材料是一种控制组织-器件界面异物反应的创新方法，可延长生物传感器的使用寿命。
