Sarrafian, Tiffany L.

Importance Rectovaginal fistulas (RVFs) are challenging to treat, often requiring multiple surgical interventions. Research into novel therapies is limited by the lack of a sizeable and representative animal model. Given the similarities in porcine and human vaginal and rectal tissue, pigs are an ideal species for translation to human patients. Objective The objective of this study was to develop a feasible and reproducible RVF model in pigs. Study Design Six female pigs underwent RVF creation and were divided into 3 groups according to the following methods: (1) placement of 1-inch disc magnets across the rectovaginal septum, (2) a 1-inch round defect created using electrocautery and placement of a 1-inch stainless-steel gauge stent, (3) a 1-inch round defect using electrocautery without subsequent stenting. Fistulas were evaluated at 6 weeks with measurements and photographic documentation. The animals were euthanized between 12 and 14 weeks. The primary outcome of this study was fistula patency. Secondary outcomes were fistula dimension and histologic appearance of the fistula tract. Results All pigs did well with no infection or complications related to fistula creation. Both surgical methods reliably resulted in a patent fistula at 14 weeks: cautery alone and cautery with gauge stenting. Only 1 patent fistula in the magnet group was noted at the time of euthanasia. All patent fistulas showed histologic evidence of complete epithelialization of the fistula tract. Conclusions This study demonstrates 3 safe and feasible methods for RVF creation in pigs, with 2 methods showing increased reliability.

Current clinically used electronic implants, including cardiac pacing leads for epicardial monitoring and stimulation of the heart, rely on surgical suturing or direct insertion of electrodes to the heart tissue. These approaches can cause tissue trauma during the implantation and retrieval of the pacing leads, with the potential for bleeding, tissue damage, and device failure. Here, we report a bioadhesive pacing lead that can directly interface with cardiac tissue through physical and covalent interactions to support minimally invasive adhesive implantation and gentle on-demand removal of the device with a detachment solution. We developed 3D-printable bioadhesive materials for customized fabrication of the device by graft-polymerizing polyacrylic acid on hydrophilic polyurethane and mixing with poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) to obtain electrical conductivity. The bioadhesive construct exhibited mechanical properties similar to cardiac tissue and strong tissue adhesion, supporting stable electrical interfacing. Infusion of a detachment solution to cleave physical and covalent cross-links between the adhesive interface and the tissue allowed retrieval of the bioadhesive pacing leads in rat and porcine models without apparent tissue damage. Continuous and reliable cardiac monitoring and pacing of rodent and porcine hearts were demonstrated for 2 weeks with consistent capture threshold and sensing amplitude, in contrast to a commercially available alternative. Pacing and continuous telemetric monitoring were achieved in a porcine model. These findings may offer a promising platform for adhesive bioelectronic devices for cardiac monitoring and treatment.

Surgical sealing and repair of injured and resected gastrointestinal (GI) organs are critical requirements for successful treatment and tissue healing. Despite being the standard of care, hand-sewn closure of GI defects using sutures faces limitations and challenges. In this work, we introduce an off-the-shelf bioadhesive GI patch capable of atraumatic, rapid, robust, and sutureless repair of GI defects. The GI patch integrates a nonadhesive top layer and a dry, bioadhesive bottom layer, resulting in a thin, flexible, transparent, and ready-to-use patch with tissue-matching mechanical properties. The rapid, robust, and sutureless sealing capability of the GI patch is systematically characterized using ex vivo porcine GI organ models. In vitro and in vivo rat models are used to evaluate the biocompatibility and degradability of the GI patch in comparison to commercially available tissue adhesives (Coseal and Histoacryl). To validate the GI patch’s efficacy, we demonstrate successful sutureless in vivo sealing and healing of GI defects in rat colon, stomach, and small intestine as well as in porcine colon injury models. The proposed GI patch provides a promising alternative to suture for repair of GI defects and offers potential clinical opportunities for the repair of other organs.

The diaphragm muscle (DIAm) is the primary inspiratory muscle responsible for force generation across a range of ventilatory and higher force airway clearance behaviors throughout life. Our laboratory has previously reported DIAm sarcopenia, the age‐related atrophy and weakening of skeletal muscle, in multiple rodent models. Interestingly, in Fischer 344 rats, there is an increase in body mass from 6 to 24 months of age, which is greater in females (~140%) than in males (~110%), suggesting potential sex‐related differences in the manifestation of sarcopenia. Transdiaphragmatic pressure (Pdi) measurements provide information about force generation in vivo across a range of motor behaviors. The purpose of this study was to evaluate if there are sex‐related differences in DIAm sarcopenia, and if such differences translate to a functional impact on Pdi generation. We hypothesized that because of differences in weight gain, DIAm sarcopenia is more pronounced in male vs. female Fischer 344 rats, and that there is a greater impact of sarcopenia on maximum Pdi generated by bilateral phrenic nerve stimulation (Pdi max ). Since Pdi generated across a range of ventilatory motor behaviors only requires <50% Pdi max , we also hypothesize that sarcopenia does not impair Pdi generation during ventilatory behaviors. Compared to 6‐month old rats, DIAm sarcopenia was apparent in ‐ 24‐month old rats of both sexes with a 30% reduction in maximum specific force. There was also a ~20% decrease in the cross‐sectional area of type IIx and/or IIb fibers with age, and this reduction was more pronounced in male rats. Thus, these mixed results do not entirely support our hypothesis of more pronounced DIAm sarcopenia in male rats. However, DIAm sarcopenia was associated with a ~30% decrease in Pdi max that was comparable between male and female rats. Importantly, the Pdi generated during ventilatory behaviors was unaffected by DIAm sarcopenia, even during more forceful ventilatory efforts induced by complete oropharyngeal airway occlusion. Although ventilatory behaviors are preserved with aging, a reduction in Pdi max indicates an impaired ability of the DIAm to generate higher force expulsive airway clearance behaviors necessary for maintaining airway patency. Support or Funding Information NIH R01‐AG044615 and T32‐HL105355 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .