The effect of nitric oxide surface flux on the foreign body response to subcutaneous implants

Abstract

Although the release of nitric oxide (NO) from biomaterials has been shown to reduce the foreign body response (FBR), the optimal NO release kinetics and doses remain unknown. Herein, polyurethane-coated wire substrates with varying NO release properties were implanted into porcine subcutaneous tissue for 3, 7, 21 and 42 d. Histological analysis revealed that materials with short NO release durations (i.e., 24 h) were insufficient to reduce the collagen capsule thickness at 3 and 6 weeks, whereas implants with longer release durations (i.e., 3 and 14 d) and greater NO payloads significantly reduced the collagen encapsulation at both 3 and 6 weeks. The acute inflammatory response was mitigated most notably by systems with the longest duration and greatest dose of NO release, supporting the notion that these properties are most critical in circumventing the FBR for subcutaneous biomedical applications (e.g., glucose sensors).

Antifouling Super Water Absorbent Supramolecular Polymer Hydrogel as an Artificial Vitreous Body

“…The major reason for the failure of the implantable biodevice is the occurrence of biofouling, which has been recognized to elicit the rejection reaction and notorious fibrosis 31, 32, 33. While biofouling usually starts with the nonspecific adsorption of proteins to the implanted biomaterial surface 34, 35, 36, 37.…”

Characterization of porous, dexamethasone-releasing polyurethane coatings for glucose sensors

“…During this time, the sensor is presented with an unstable microenvironment characterized by immune cell infiltration, inflammation, and formation of a granulation tissue. Strategies for improving in vivo sensor performance development of new biomaterials and localized drug delivery for resisting biofouling, attenuating inflammation, and increasing vascularization of the foreign body capsule (17, 25, 26, 29). …”

“…Attenuation of inflammation contends that the benefits of minimizing the deleterious effects of acute inflammation on sensor function outweigh the potential advantages of engineering the tissue response. One strategy for the attenuation of acute inflammation involves the local release of anti-inflammatory mediators such as nitric oxide, non-steroidal anti-inflammatory drugs, and glucocorticoids (17-19). …”

Microfabricated microporous membranes reduce the host immune response and prolong the functional lifetime of a closed-loop insulin delivery implant in a type 1 diabetic rat model

“…Innovative strategies have thus been extensively explored to overcome the foreign body response (FBR) whilst simultaneously enabling efficient mass transport to and from these devices; both of which are vital to prolonging implant lifetime and viability in the clinic, and technologically challenging to achieve [22]. Active strategies to mitigate the FBR rely on the sustained local release of anti-inflammatory agents (e.g., dexamethasone [23e25] or nitric oxide (NO) [26]) or pro-angiogenic mediators (e.g., vascular endothelial growth factor (VEGF) [27]) from the implant surface. The continuous release of dexamethasone or NO has been shown to reduce inflammatory cell recruitment and minimize fibrous capsule formation around implants; however it is difficult to provide a steady supply of these agents throughout a device's lifetime [26].…”

“…Active strategies to mitigate the FBR rely on the sustained local release of anti-inflammatory agents (e.g., dexamethasone [23e25] or nitric oxide (NO) [26]) or pro-angiogenic mediators (e.g., vascular endothelial growth factor (VEGF) [27]) from the implant surface. The continuous release of dexamethasone or NO has been shown to reduce inflammatory cell recruitment and minimize fibrous capsule formation around implants; however it is difficult to provide a steady supply of these agents throughout a device's lifetime [26]. Other coatings such as sirolimus or paclitaxel coatings are also conceivable, and are already used in interventional cardiology as so called drug eluting stents.…”