Biomaterials and the Central Nervous System: Neurosurgical Applications of Materials Science - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 136

when PMM began to degrade [2]. Interestingly, many other biodegradable
polymers do demonstrate tolerable long-term intracranial biocompatibility,
highlighting that each new material's stability must be assessed individually
before considering CNS implantation.
Understanding a material's biocompatibility requires an intimate under-
standing of the brain's immune system and inflammatory cascade. Within 24
hours of the tissue damage that is expected with the implantation of any device,
microglia enter the damaged tissue site and begin the process of phagocyto-
sis of dead cells [2-4]. Several groups have demonstrated that these microglia
then secrete neurotrophic factors, such as brain-derived neurotrophic factor
(BDNF) or glial cell line-derived neurotrophic factor (GDNF) [3, 4] that may
exert some neuroprotective role. In the days following, astrocytes arrive at
the injured site; they have also been shown to release neurotrophic factors [5,
6]. With activated macrophages/microglia, a release of certain chemical fac-
tors such as the chemokine monocyte chemotactic protein (MCP-1) and the
pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) is seen [7].
TNFα, in turn, has demonstrable neurotoxic activity, suggesting that released
inflammatory factors may reduce neuronal viability surrounding the site of an
implanted device [7-11]. Certainly the limitation of many implanted intracra-
nial devices may be the failure of the device to evade the host's immune system
over the long term. Some have even stated that the major clinical limitation
of brain-machine-interface (BMI) technology is the inability to consistently
record from a single neuron over time as a result of the brain's robust foreign
body response to implanted electrodes [11, 12].
Though identifying materials suitable for intracranial implantation may
appear daunting, many materials have been used historically with great suc-
cess for varied clinical CNS applications. Applications of biomaterials cur-
rently in use include shunt systems used to treat hydrocephalus, intracranial
drug-delivery vehicles, hydrogel scaffolds for CNS repair, microelectrodes
for deep brain stimulation, and vehicles for delivery of neural stem cells [1].
In the following text, we will explore the various biomaterials in use in the
CNS at the experimental and clinical levels. We will explore their relative
safety, limitations, and strengths and, in turn, will identify the ideal char-
acteristics of materials that may be used safely in the neurosurgical theater.
Cerebrospinal Fluid Shunt Systems
One of the most common clinical entities encountered in neurosurgery is
that of hydrocephalus, a condition characterized by excessive accumulation
of cerebrospinal fluid (CSF) due to either excessive production or inadequate
clearance. The most common treatment for hydrocephalus is placement
of a shunt system that diverts excess CSF from the cerebral ventricles or