Abstract
The rapid development of tissue engineering technology has provided new methods for tracheal replacement. However, none of the previously developed biomimetic tracheas exhibit both the anatomy (separated-ring structure) and mechanical behavior (radial rigidity and longitudinal flexibility) mimicking those of native trachea, which greatly restricts their clinical application. Herein, we proposed a biomimetic scaffold with a separated-ring structure: a polycaprolactone (PCL) scaffold with a ring-hollow alternating structure was three-dimensionally printed as a framework, and collagen sponge was embedded in the hollows amid the PCL rings by pouring followed by lyophilization. The biomimetic scaffold exhibited bionic radial rigidity based on compressive tests and longitudinal flexibility based on three-point bending tests. Furthermore, the biomimetic scaffold was recolonized by chondrocytes and developed tracheal cartilage in vitro. In vivo experiments showed substantial deposition of tracheal cartilage and formation of a biomimetic trachea mimicking the native trachea both structurally and mechanically. Finally, a long-segment tracheal replacement experiment in a rabbit model showed that the engineered biomimetic trachea elicited a satisfactory repair outcome. These results highlight the advantage of a biomimetic trachea with a separated-ring structure that mimics the native trachea both structurally and mechanically and demonstrates its promise in repairing long-segment tracheal defects.
Highlights
The trachea is a hollow organ that plays a vital role in respiration and indirect roles in swallowing and speech (Udelsman et al, 2018)
Mechanical testing results indicated that the biomimetic PCL scaffold exhibited better bending and extension properties in the longitudinal compared with the cylindrical PCL tube (Figure 1A and Supplementary Video 1)
The biomimetic PCL scaffold exhibited better longitudinal flexibility in the three-point bending test (Figure 1B), but it maintained similar radial rigidity compared with the cylindrical PCL tube (Figure 1C), and it returned to its original shape when the load was removed (Supplementary Video 2)
Summary
The trachea is a hollow organ that plays a vital role in respiration and indirect roles in swallowing and speech (Udelsman et al, 2018). In the case of long-segment tracheal defects (defects spanning 50% of the total tracheal length in adults or about 30% in children), it is almost impossible to reconstruct the defect using the gold-standard treatment of end-to-end anastomosis (Li et al, 2019). Investigating tracheal substitutes that can be implanted to reconstruct a continuous trachea are being developed (Best et al, 2018), such as cell-free prostheses, allografts, and autografts. Despite the broad range of Segment Tracheal Formation and Replacement tracheal substitutes available, each has its own inherent drawbacks (Dikina et al, 2018). Cell-free prostheses have met with limited success as they induce hemorrhaging and luminal stenosis and are prone to dislocation. While autografts are not susceptible to rejection, their shape and size are not ideal for tracheal replacement (Nomoto et al, 2013)
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