A novel porous collagen scaffold around an implantable biosensor for improving biocompatibility. I. In vitro/in vivo stability of the scaffold and in vitro sensitivity of the glucose sensor with scaffold.

A new 3D porous and biostable collagen scaffold has been developed to improve the biocompatibility of implantable glucose sensors by minimizing tissue reactions while stimulating angiogenesis around the sensors. The novel collagen scaffold was crosslinked using nordihydroguaiaretic acid (NDGA) to enhance biostability. NDGA-treated collagen scaffolds were stable without physical deformation in the subcutaneous tissue of rats for 4 weeks. In contrast, glutaraldehyde (GA)-treated collagen scaffolds were extremely damaged following implantation. Both types of scaffolds (NDGA- and GA-crosslinked) were stable in vitro in the presence of collagenase with 70% retention of original weight after 4 weeks of incubation. The response current (i.e. sensitivity) of sensors with porous scaffolds was not significantly changed when compared with control sensors (no scaffold), while the response time (T(95%)) was slightly delayed after a glucose concentration increase from 5 to 15 mM. Above this range, the sensors coated with scaffolds had only a slightly lower sensitivity than the control sensors. These results indicate that we have developed a stable NDGA-crosslinked collagen scaffold for biosensors, and that the scaffold does not impair the function of our sensor. We plan to use this scaffold to enhance the function and lifetime of the implantable biosensors by providing a controlled local environment around the sensors with the help of various drugs and growth factors (dexamethasone, VEGF, PDGF).