Brain Tissue Interaction with Three-Dimensional, Honeycomb Polycaprolactone-Based Scaffolds Designed for Cranial Reconstruction Following Traumatic Brain Injury

Abstract

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 PCLtricalcium 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.

Influence of internal pore architecture on biological and mechanical properties of three‐dimensional fiber deposited scaffolds for bone regeneration

“…Polymeric scaffolds have several advantages over metal or ceramic scaffolds. Currently used polymers, especially PCL, are slowly biodegradable, can be shaped freely with FDM technology, and are less brittle than ceramics …”

“…In literature, orientations of 60° and 45° are the most commonly used . For bone tissue engineering, scaffolds must provide sufficient initial mechanical strength and stiffness to substitute for the loss of mechanical function of the diseased, damaged, or missing tissue .…”

“…Currently used polymers, especially PCL, are slowly biodegradable, can be shaped freely with FDM technology, and are less brittle than ceramics. [36][37][38][39] In this study, the influence of pore shape on the mechanical and biological properties of 3D fiber deposited PCL scaffolds has been investigated. Bone tissue was also studied as a reference to show how 3D scaffolds can mimic a natural tissue.…”

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

“…Our previous findings [22] demonstrated that cerebral inflammation was not further aggravated in PCL and PCL/TCP groups. The attenuated expression of IL-1β was an expected outcome, as it is known from previous studies that its expression does not persist more than a few days.…”

“…[22] Apart from their potential use as biomolecule delivery vehicles, bioactive scaffolds may also be used to assist in the regeneration of the cranium [23,24], which is important for preventing neurological deterioration and significant depression after PBI. [25,26] For this purpose, we have developed PCL/tricalcium phosphate (PCL/TCP) scaffolds that are capable of promoting bone regeneration.…”