Effects of polycaprolactone-based scaffolds on the blood-brain barrier and cerebral inflammation.

Severe pathoanatomical and mechanical injuries compromise patient recovery and survival following penetrating brain injury (PBI). The realization that the blood-brain barrier (BBB) plays a major role in dictating post-PBI events has led to rising interests in possible therapeutic interventions through the BBB. Recently, the choroid plexus has also been suggested as a potential therapeutic target. The use of biocompatible scaffolds for the delivery of therapeutic agents, but little is known about their interaction with cerebral tissue, which has important clinical implications. Therefore, the authors have sought to investigate the effect of polycaprolactone (PCL) and PCL/tricalcium phosphate (PCL/TCP) scaffolds on the maintenance of BBB phenotype posttraumatic brain injury. Cranial defects of 3 mm depth were created in Sprague Dawley rats, and PCL and PCL/TCP scaffolds were subsequently implanted in predetermined locations for a period of 1 week and 1 month. Higher endothelial barrier antigen (EBA) expressions from PCL-based scaffold groups (p>0.05) were found, suggesting slight advantages over the sham group (no scaffold implantation). PCL/TCP scaffold group also expressed EBA to a higher degree (p>0.05) than PCL scaffolds. Importantly, higher capillary count and area as early as 1 week postimplantation suggested lowered ischemia from the PCL/TCP scaffold group as compared with PCL and sham. Evaluation of interlukin-1ß expression suggested that the PCL and PCL/TCP scaffolds did not cause prolonged inflammation. BBB transport selectivity was evaluated by the expression of aquaporin-4 (AQP-4). Attenuated expression of AQP-4 in the PCL/TCP group (p<0.05) suggested that PCL/TCP scaffolds altered BBB selectivity to a lower degree as compared with sham and PCL groups, pointing to potential clinical implications in reducing cerebral edema. Taken together, the responses of PCL-based scaffolds with brain tissue suggested safety, and encourages further preclinical evaluation in PBI management with these scaffolds.

Brain tissue interaction with three-dimensional, honeycomb polycaprolactone-based scaffolds designed for cranial reconstruction following traumatic brain injury.

Following traumatic brain injury (TBI), resultant voids are unable to support injections of suspension treatments, leading to ineffective healing. Moreover, without a structure to support the large defect, the defect site suffers from mechanical instability, which may impair the healing process. Therefore, having a delivery vehicle that can temporarily fill and provide mechanical support to the defect site may alleviate the healing process. In this work, we reported for the first time, the inflammatory response of brain tissue with polycaprolactone (PCL) and PCL-tricalcium phosphate (TCP) scaffolds designed and fabricated for cranial reconstruction. After cranial defects were created in Sprague-Dawley rats, PCL and PCL-TCP scaffolds were implanted for a period of 1 week and 1 month. Following histology and immunofluorescence staining with the ionized calcium binding adaptor molecule-1 (IBA-1), glial fibrillary acidic protein (GFAP), nestin, and neuronal nuclei (NeuN), results indicated that IBA-1-positive activated microglia were observed across all groups, and declined significantly by 1 month (p<0.05). Interestingly, IBA-1-positive microglia were significantly fewer in the PCL-TCP group (p<0.05), suggesting a relatively milder inflammatory response. A decrease in the number of GFAP-positive cells among all groups over time (>29%) was also observed. Initially, astrocyte hypertrophy was observed proximal to the TBI site (55% in PCL and PCL-TCP groups, 75% in control groups), but it subsided by 1 month. Proximal to the TBI site, nestin immunoreactivity was intense during week 1, and which reduced by 1 month across all groups. NeuN-positive neurons were shrunken proximal to the TBI site (<0.9 mm), 32% smaller in the PCL-TCP group and 27% smaller in the PCL group. Based on above data indicating the comparatively milder, initial inflammatory response of brain tissue to PCL-TCP scaffolds, it is suggested that PCL-TCP scaffolds have notable clinical advantages as compared to PCL scaffolds.

External ventricular drain infections: successful implementation of strategies to reduce infection rate.

INTRODUCTION: External ventricular drain (EVD) infections can cause serious complications. We performed an audit of EVD infections within our neurosurgical unit. Through this study, we aimed to reduce the incidence of external ventricular drain-related infection, including ventriculities in neurosurgical patients. METHODS: We conducted an audit of the EVD infections in our institution observed over a one-and-a-half year period. This was conducted in three phases. A baseline EVD infection rate was determined for Phase I, from January to June 2007. We introduced the following measures to reduce EVD infection rate in Phase II, from July to December 2007: (1) For Neurosurgery doctors: performing proper surgical techniques to minimise intra-operative infections; educating junior doctors on proper CSF sampling from the EVD; and minimising the number of days the EVD is maintained in situ; (2) For Neurosurgery nurse clinicians: developing Standard Operating Procedures on nursing management of EVDs; conducting EVD care workshops for nurses working in neurosurgical wards; and competency skill checks on the management of EVDs for nurses working in the neurosurgical wards. Silver-coated EVDs were introduced in Phase III of the study from January to June 2008. RESULTS: The EVD infection rate decreased from a baseline of 6.1% to 3.8% in Phase II; a further reduction from 3.8% to 0% was achieved during Phase III. CONCLUSION: Good teamwork among doctors and nurses is essential for reducing EVD infection rate. We managed to reduce EVD infections substantially and would continue to strive to remain infection-free in the future.