for Implantable Glucose Sensors and Long-term Implantable
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
in vivo monitoring systems, which often fail due to the formation
of an avascular fibrous capsule that surrounds the device
and limits analyte exchange.
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.
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.
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.