Prevascularized silicon membranes for the enhancement of transport to implanted medical devices

Abstract

Recent advances in drug delivery and sensing devices for in situ applications are limited by the diffusion-limiting foreign body response of fibrous encapsulation. In this study, we fabricated pre-vascularized synthetic device ports to help mitigate this limitation. Membranes with rectilinear arrays of square pores with widths ranging from 40 to 200 μm were created using materials (50 μm thick double-sided polished silicon) and processes (photolithography and directed reactive ion etching) common in the manufacturing of microfabricated sensors. Vascular endothelial cells responded to membrane geometry by either forming vascular tubes that extended through the pore or completely filling membrane pores after four days in culture. Although tube formation began to predominate overgrowth around 75 μm and continued to increase at even larger pore sizes, tubes formed at these large pore sizes were not completely round and had relatively thin walls. Thus, the optimum range of pore size for pre-vascularization of these membranes was estimated to be 75 - 100 μm. This study lays the foundation for creating a pre-vascularized port that can be used to reduce fibrous encapsulation and thus enhance diffusion to implanted medical devices and sensors.

In Vivo Chemical Sensors: Role of Biocompatibility on Performance and Utility

“…Further compounding this issue, the fibrous capsule surrounding the implant is quite avascular, 120 preventing efficient glucose delivery to regions inside the collagen capsule. 121 Kumosa et al observed that oxygen levels in the tissue surrounding fully subcutaneous O 2 sensors also decrease over the first several weeks of implantation, 22,107 which may alter glucose sensor response further due to limited O 2 availability (the co-factor for GOx). Of note, the decreased oxygen levels are more likely due to inflammatory cell metabolism and poor vascularization than obstructed diffusion through the capsule.…”

“…Rather, the foreign body capsule increases the tortuosity of the glucose diffusion path from the vasculature to the sensor surface, creating a pronounced lag (on the order of 20–30 min) between glucose concentrations at the sensing surface and corresponding plasma levels. Further compounding this issue, the fibrous capsule surrounding the implant is quite avascular, preventing efficient glucose delivery to regions inside the collagen capsule . Kumosa et al observed that oxygen levels in the tissue surrounding fully subcutaneous O 2 sensors also decrease over the first several weeks of implantation, , which may alter glucose sensor response further due to limited O 2 availability (the cofactor for GOx).…”