Tracheal stenosis can become a fatal condition, and current treatments include augmentation of the airway with autologous tissue. A tissue-engineered approach would not require a donor source, while providing an implant that meets both surgeons' and patients' needs. A fibrous, polymeric scaffold organized in gradient bilayers of polycaprolactone (PCL) and poly-lactic-co-glycolic acid (PLGA) with 3D printed structural ring supports, inspired by the native trachea rings, could meet this need. The purpose of the current study was to characterize the tracheal scaffolds with mechanical testing models to determine the design most suitable for maintaining a patent airway. Degradation over 12 weeks revealed that scaffolds with the 3D printed rings had superior properties in tensile and radial compression, with at least a three fold improvement and 8.5-fold improvement, respectively, relative to the other scaffold groups. The ringed scaffolds produced tensile moduli, radial compressive forces, and burst pressures similar to or exceeding physiological forces and native tissue data. Scaffolds with a thicker PCL component had better suture retention and tube flattening recovery properties, with the monolayer of PCL (PCL-only group) exhibiting a 2.3-fold increase in suture retention strength (SRS). Tracheal scaffolds with ring reinforcements have improved mechanical properties, while the fibrous component increased porosity and cell infiltration potential. These scaffolds may be used to treat various trachea defects (patch or circumferential) and have the potential to be employed in other tissue engineering applications.

Experiencing early life stress can result in maladjusted stress response via dysregulation of the hypothalamic-pituitary-adrenal axis and serves as a risk factor for developing chronic pelvic pain disorders. We investigated whether neonatal maternal separation (NMS) would increase susceptibility to experimental colitis or exposure to acute or chronic stress. Male mice underwent NMS from postnatal day 1–21 and as adults were assessed for open field behavior, hindpaw sensitivity, and visceromotor response (VMR) to colorectal distension (CRD). VMR was also measured before and after treatment with intracolonic trinitrobenzene sulfonic acid (TNBS) or exposure to acute or chronic water avoidance stress (WAS). Myeloperoxidase (MPO) activity, proinflammatory gene and corticotropin-releasing factor (CRF) receptor expression were measured in distal colon. Baseline VMR was not affected by NMS, but undergoing CRD increased anxiety-like behaviors and mechanical hindpaw sensitivity of NMS mice. Treatment with TNBS dose-dependently decreased body weight and survival only in NMS mice. Following TNBS treatment, IL-6 and artemin mRNA levels were decreased in the distal colon of NMS mice, despite increased MPO activity. A single WAS exposure increased VMR during CRD in NMS mice and increased IL-6 mRNA and CRF2 protein levels in the distal colon of naïve mice, whereas CRF2 protein levels were heightened in NMS colon both at baseline and post-WAS exposure. Taken together, these results suggest that NMS in mice disrupts inflammatory- and stress-induced gene expression in the colon, potentially contributing towards an exaggerated response to specific stressors later in life.