Guillermo Ameer, Sc.D.

Biomaterials for Implantable Glucose Sensors and Long-term Implantable Devices

The design of biomaterials must take into account the function of the device in which the biomaterial will eventually be incorporated. For example, a well integrated vascular network is important for the bioartificial pancreas, as the presence of blood vessels within 100-200 µm of pancreatic islets is important to glucose control and tissue homeostasis. The vascular density surrounding islet cells after transplantation has been shown to be below normal levels, leading to cell hypoxia. Cells encapsulated within an immunoisolation membrane may also become necrotic due to the lack of nutrient delivery and waste removal. Neovascularization is also important to the function of implantable biosensors and other
in vivo monitoring systems, which often fail due to the formation of an avascular fibrous capsule that surrounds the device and limits analyte exchange.

To address the problem of neovascularization, researchers have focused on the use of growth factors and other signaling molecules. Despite significant work in the field, the multifunctional nature of growth factors and the lack of understanding of the spatial and temporal synergy between different growth factors have hindered their implementation in clinical applications. In an attempt to better understand tissue-material interactions and avoid the use of exogenous growth factors, researchers have investigated the role of device microarchitecture in the vascularization process. Several studies have found that porosity and pore size are important factors controlling the amount of vessel growth within and surrounding non-degradable polymers. These studies have found that a 60µm pore size is ideal for promoting vascularization. However, the effects of the changing microarchitecture of degradable polymer membranes have not been investigated.

This presentation will discuss the effects polymer degradation kinetics and changes in membrane microarchitecture on neovascularization within the adjacent fibrous capsule. The overall objective was to determine whether degradable membranes with a specific initial microarchitecture can allow for the formation of mature vasculature in vivo, without the addition of growth factors or endothelial cell seeding. Assessment of neovascularization around degradable polymers is relevant to the field of tissue engineering and the short-term monitoring of analytes such glucose. The resorption of the material is expected to eliminate the chronic foreign body response typically associated with materials used as permanent implants.

Regarding long-term implantable devices, sometimes the biomaterial can be designed to modulate initial cellular processes, thereby improving the long-term function of the device. An example is the surface modification of currently-used vascular grafts with a citric acid-based biodegradable elastomer to reduce the incidence of clotting (a typical cause for device short-term failure) and eliminate tissue overgrowth at the graft-artery connection site (a typical cause for device long-term failure). In this case the role of the elastomer is to facilitate the regeneration of a functional endothelium while minimizing platelet attachment and subsequent clotting processes. This surface modification paradigm could potentially be applied to other permanent implants where the successful function of the implant depends on the prevention of unwanted cellular or tissue responses.