Reinforced Electrospun Polycaprolactone Nanofibers for Tracheal Repair in an In Vivo Ovine Model

Abstract

Tracheal stenosis caused by congenital anomalies, tumors, trauma, or intubation-related damage can cause severe breathing issues, diminishing the quality of life, and potentially becoming fatal. Current treatment methods include laryngotracheal reconstruction or slide tracheoplasty. Laryngotracheal reconstruction utilizes rib cartilage harvested from the patient, requiring a second surgical site. Slide tracheoplasty involves a complex surgical procedure to splay open the trachea and reconnect both segments to widen the lumen. A clear need exists for new and innovative approaches that can be easily adopted by surgeons, and to avoid harvesting autologous tissue from the patient. This study evaluated the use of an electrospun patch, consisting of randomly layered polycaprolactone (PCL) nanofibers enveloping 3D-printed PCL rings, to create a mechanically robust, suturable, air-tight, and bioresorbable graft for the treatment of tracheal defects. The study design incorporated two distinct uses of PCL: electrospun fibers to promote tissue integration, while remaining air-tight when wet, and 3D-printed rings to hold the airway open and provide external support and protection during the healing process. Electrospun, reinforced tracheal patches were evaluated in an ovine model, in which all sheep survived for 10 weeks, although an overgrowth of fibrous tissue surrounding the patch was observed to significantly narrow the airway. Minimal tissue integration of the surrounding tissue and the electrospun fibers suggested the need for further improvement. Potential areas for further improvement include a faster degradation rate, agents to increase cellular adhesion, and/or an antibacterial coating to reduce the initial bacterial load.

3D Printed Biomimetic PCL Scaffold as Framework Interspersed With Collagen for Long Segment Tracheal Replacement

“…Finally, we investigated the feasibility of using the proposed biomimetic trachea to repair long-segment tracheal defects in an animal model to provide direct evidence of its potential for future clinical application. Although some authors demonstrating anatomically correct tracheal scaffolds, they didn’t achieved the repair of long-segment tracheal defects ( Best et al, 2018 ; Townsend et al, 2018 ). Our results demonstrated that the biomimetic trachea could enable the survival and normal function in rabbits with artificial defects for at least 8 weeks post-surgery.…”

“…Polycaprolactone (PCL), which is approved by the United States Food and Drug Administration (FDA) for internal use in the human body, is the most widely used 3D-printable biomaterial ( Li et al, 2020 ). PCL has excellent biocompatibility and suitable mechanical properties for use in 3D-printing of a tracheal scaffold ( Gao et al, 2017 ; Townsend et al, 2018 ). Recently, Ke et al (2019) 3D-printed a patient-matched tracheal ring using PCL and human mesenchymal stem cell-laden hydrogels, however, a troublesome procedure is still needed to incorporate those single rings into an integrated tracheal tube.…”

Evaluation of Acellular Bilayer Silk Fibroin Grafts for Onlay Tracheoplasty in a Rat Defect Model

“…This outcome was observed by other researchers following reconstruction of tracheal defects with acellular biomaterials derived from natural or synthetic polymers. 14,15,18,19 This default wound-healing program most likely reflects a lack of inductive chondrogenic stimuli present during the tissue-remodeling process. Indeed, Igai and colleagues demonstrated that targeted release of basic fibroblastic growth factor from drug-loaded gelatin sponges facilitated cartilage regeneration in canine tracheal defects, in contrast to unloaded scaffold controls.…”

3D-bioprinted tracheal reconstruction: an overview

“…Townsend et al,used 15x25mm PCL implants in sheep. The animals had to be euthanized prior to the end of the study due to respiratory distress secondary to tracheal narrowing at the reconstruction site (Townsend et al, 2018). On the other hand, Rehmani et al reconstructed a 40 × 16 mm defect in 7 pigs with a PCL implant covered with an extracellular matrix and found that 5 pigs had well-sized tracheal lumen with minimal stenosis and granulation tissue after 3 months (Rehmani et al, 2017).…”

“…They are simple to manage, extensively available, and cost-effective for interventional studies (Park et al, 2018a). Nevertheless, dog, sheep, and pig models might be better to reproduce the size of teenagers with adult sized tracheas, but these large animals are difficult to manage post-operatively and are more expensive (Zopf et al, 2014;Townsend et al, 2018;Rehmani et al, 2017).…”