Effects of Polycaprolactone-Based Scaffolds on the Blood–Brain Barrier and Cerebral Inflammation

Abstract

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-1β 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.

Bridges of biomaterials promote nigrostriatal pathway regeneration

“…PCL had already been shown to be permissive to neural growth. In vitro, neural cells grow over the surface of 2D films made of PCL and show a normal electrophysiologic activity . PCL has seldom been used in vivo in the CNS.…”

Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats

“…According the investigations of neurogenic potential and neurons, it was demonstrated that PCL did not evoke an undesirable inflammatory response [ 69 ]. Moreover, PCL-based scaffolds did not cause further changes to the vascular supply in and around the defect region [ 70 ]. In our study, we could also observe a high tolerance of PCL devices by host tissues.…”

Hypertonic saline infusion suppresses apoptosis of hippocampal cells in a rat model of cardiopulmonary resuscitation

“…Coronal paraffin wax brain tissue sections were obtained as previously described 21 . In order to measure the apoptosis of hippocampal neurons, In Situ Cell Death Detection Kit (Roche, Switzerland) was used according to the manufacturer’s instructions.…”

“…Apoptosis of hippocampal neurons after resuscitation was detected by terminal deoxynucleotidyl transferase-mediated uridine 59-triphosphate-biotin nick end labeling (Tunel) assay. Coronal paraffin wax brain tissue sections were obtained as previously described 21 . In order to measure the apoptosis of hippocampal neurons, In Situ Cell Death Detection Kit (Roche, Switzerland) was used according to the manufacturer’s instructions.…”