Biomimetic Trachea Regeneration Using a Modular Ring Strategy Based on Poly(Sebacoyl Diglyceride)/Polycaprolactone for Segmental Trachea Defect Repair

Abstract

The lack of a biomimetic tracheal substitute featured with cartilage ring/ vascularized connective tissue alternate structure (CVCAS) has significantly retarded a clinical breakthrough of tissue-engineered trachea in repairing extensive tracheal lesions. Herein, a novel modular strategy based on cartilage rings and biomaterial rings is used to generate a biomimetic trachea with CVCAS. Poly(sebacoyl diglyceride) and polycaprolactone (PCL) (PSeD/PCL) are blended to fabricate a porous scaffold with satisfactory mechanical properties, biodegradability, and biocompatibility. A cartilage ring is engineered in vitro using ring-shaped PSeD/PCL scaffold loaded with chondrocytes and cartilage tube is generated in vivo through the fusion of multiple modular cartilage rings. More importantly, biomimetic tracheas with CVCAS are successfully fabricated in vivo through alternately stacked cartilage rings and PSeD/PCL rings on a silicon tube. Notably, the engineered biomimetic trachea exhibits not only a bionic structure but also superior mechanical properties compared with the native rabbit trachea. Finally, segmental tracheal defects in rabbits are repaired by transplanting the biomimetic trachea with pedicled muscular flaps. The biomimetic trachea establishes stable blood supply and provided sufficient mechanical strength and biological function similar to those of native trachea. This work represents the first successful regeneration of biomimetic trachea with CVCAS and a promising approach for clinical application.

RETRACTED: Metallic Ions Encapsulated in Electrospun Nanofiber for Antibacterial and Angiogenesis Function to Promote Wound Repair

“…The macro-morphologies of the prepared membranes were photographed using a digital camera and a digital vacuum scanning electron microscope (SEM, JEOL JSM-5600LV, Japan). Samples were critical-point dried and then examined using the SEM ( Xu et al, 2020 ).…”

“…After 1 and 4 days of culture, the fibroblast viability on each membrane was evaluated using the Live and Dead Cell Viability Assay (Invitrogen, United States) following the manufacturer’s instructions, and the samples were examined using a confocal microscope (Nikon, Japan). The fibroblast viability was also measured using a cell counting kit-8 (CCK-8; Dojindo, Japan) following the manufacturer’s instructions, and the optical density (OD) was measured at 450 nm ( Xu et al, 2020 ).…”

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

“…Most literature recognizes the importance of tracheal lateral rigidity for normal respiration and ventilation, but they do not fully consider the tracheal longitudinal flexibility, which is needed to ensure the stability of the trachea during rotation, flexion, and extension of the neck ( Johnson et al, 2016 ; Xu et al, 2020a ). If a tracheal scaffold lacks the required longitudinal flexibility, the scaffold will become distorted, and the tracheal lumen will narrow during rotation, and the scaffold could tear during flexion and extension ( Xu et al, 2020b ). Hence, a new design mimicking the native tracheal anatomy could ensure the bionic function of a tracheal substitute ( Dikina et al, 2018 ).…”

Biological Evaluation of Acellular Cartilaginous and Dermal Matrixes as Tissue Engineering Scaffolds for Cartilage Regeneration

“…Extensively studies have demonstrated that the pore size and three-dimensional structure of scaffolds are crucial factors for cell proliferation, differentiation, and ECM production during cartilage regeneration ( Shi et al, 2017 ; Chen et al, 2020a ; Li et al, 2020 ; Xu et al, 2020b ). Although it is generally accepted that ACM is a good scaffold material because of its biomimetic cartilage-specific microenvironment, it is difficult to prepare ACM as a three-dimensional structure with a tunable pore size owing to its poor crosslinking property ( Xu et al, 2017 ; Li et al, 2019 ).…”