# Challenges for the Implantation of Symbiotic Nanostructured Medical Devices
## 4 Choices of Membranes for Symbiotic Implanted Medical Devices  
We illustrate this challenge by returning to the problem of an enzymatic biofuel cell. The membrane needs to have appropriate mechanical properties, have selective permeability to biological \"fuel\" molecules, and be easily constructed. Those requirements imply the usage of some form of a gel-like polymer. Recent examples include a composite material that comprised PDMS (polydimethylsiloxane) functionalized with a stable hydrogel layer of MPC (2-methoxyyl phosphorylcholine). This composite gel can potentially improve the long-term biocompatibility of a medical device, since the composite material is nontoxic to mammalian cells and strongly resists macrophage attachment and bacterial colonization [22; 23]. Additionally, a porous chitosan membrane coating, in combination with either PTFE (polytetrafluoroethylene) or Nafion (perfluorosulfonic acid) supporting polymers, was subcutaneously implanted in rats, and, after 100 days, it did not enhance the deposition of collagen but did promote angiogenesis [24]. In that context of utilizing an appropriate polymer membrane, we successfully implanted enzymatic biofuel cells and bioelectrodes that were enclosed using a chitosan membrane [25; 26; 27]. An important consideration for the design of the chitosan membrane is the environment of the bioelectrode. For example, an anode constructed using glucose oxidase releases gluconic acid, which induces a decrease in pH that can hydrolyze the chitosan. The fabrication of the chitosan membrane using cross-linking agents can help in stabilizing the membrane. Such a chitosan membrane allowed for the optimization of the bioelectrode coating. The thinness (10-15 \(\upmu\)m) and the hydrophilicity of the chitosan membrane allowed for the rapid wetting of the bioelectrode. This rapid wetting effectively resolved the hydration problems of bioelectrodes that were previously constructed using a cellulose acetate membrane [28; 29]. Though successful for implantations up to six months, those chitosan membranes may not provide the perfect solution for the challenge of biocompatibility. Nonetheless, if not perfectly suitable as a protective membrane for an implanted enzymatic biofuel cell, our recent results showed that chitosan provides an open structure that allows for the ingrowth and integration of cells. Cells were able to migrate into the chitosan structure within three days in culture, and they were able to adhere to the gel structure of the chitosan. These are properties of chitosan that can be exploited for future enzymatic biofuel cell systems that require integration and biocompatibility with tissues of the body. Indeed, a previous report indicated that treating the chitosan with cold atmospheric plasma could enhance the infiltration and ingrowth of mesenchymal stem cells for application in bone regeneration [30]. Such an exploitation of the capability of chitosan to form an open architecture to provide conditions for the infiltration and ingrowth of cells is a novel application compared to the usage of dense forms of chitosan as bioabsorbable implants for orthopedic applications [31]. We can further consider several directions in which the membrane can be improved in order to increase the lifetime, again using the example of improving the performance of the implanted enzymatic biofuel cell. The key direction is to fabricate a membrane that should remain stable when implanted for long periods. It is important to consider that even cross-linked chitosan is not the basis for a perfectly stable membrane when implanted, because 100% crosslinking cannot be guaranteed over the entirety of the membrane surface. For example, we observed that a biocathode can be implanted for up to six months in a rat. However, even if the chitosan membrane looks intact macroscopically and since it is difficult to ensure that there is 100% crosslinking in all regions, it is not possible to avoid the degradability 100% of the time for such long period of implantation [32].