An anti-inflammatory gelatin hemostatic agent with biodegradable polyurethane nanoparticles for vulnerable brain tissue

Hemostasis plays a fundamental and critical role in all surgical procedures. However, the currently used topical hemostatic agents may at times undesirably induce inflammation, infection, and foreign body reaction and hamper the healing process. This may be serious in the central nervous system (CNS), especially for some neurosurgical diseases which have ongoing inflammation causing secondary brain injury. This study was aimed to develop a hemostatic agent with anti-inflammatory property by incorporating carboxyl-functionalized biodegradable polyurethane nanoparticles (PU NPs) and to evaluate its functionality using a rat neurosurgical model. PU NPs are specially-designed anti-inflammatory nanoparticles and absorbed by a commercially available hemostatic gelatin powder (Spongostan™). Then, the gelatin was implanted to the injured rat cortex and released anti-inflammatory PU NPs. The time to hemostasis, the cerebral edema formation, and the brain's immune responses were examined. The outcomes showed that PU NP-contained gelatin attenuated the brain edema, suppressed the gene expression levels of pro-inflammatory M1 biomarkers (e.g., IL-1β level to be about 25%), elevated the gene expression levels of anti-inflammatory M2 biomarkers (e.g., IL-10 level to be about 220%), and reduced the activation of inflammatory cells in the implanted site, compared with the conventional gelatin. Moreover, PU NP-contained gelatin increased the gene expression level of neurotrophic factor BDNF by nearly 3-folds. We concluded that the PU NP-contained hemostatic agents are anti-inflammatory with neuroprotective potential in vivo. This new hemostatic agent will be useful for surgery involving vulnerable tissue or organ (e.g., CNS) and also for diseases such as stroke, traumatic brain injury, and neurodegenerative diseases.