Prevascularized Tracheal Scaffolds Using the Platysma Flap for Enhanced Tracheal Regeneration

Abstract

Objectives: One of the greatest hurdles in tracheal tissue engineering is insufficient vascularization, which leads to delayed mucosal regeneration, inflammation, and restenosis. This study investigated whether a prevascularized segmental tracheal substitute using platysma can enhance tracheal mucosal regeneration.Methods: Three-dimensional (3D) printed scaffolds with (group M) or without (group S) Matrigel coating were implanted under the feeding vessels of the platysma in New Zealand White rabbits (n = 3) to induce vascularization. After 1 or 2 weeks, tracheal defects were created and vascularized scaffolds with feeders of the platysma were transplanted as rotational flaps. As controls, scaffolds with or without Matrigel coating was transplanted into a tracheal defect without prevascularization. Airway patency and epithelization were examined using a rigid bronchoscope every 2 weeks. Surviving animals were euthanized at 24 weeks, and microcomputed tomography and histological evaluation were performed.Results: Animals with 2 weeks of prevascularization showed longer survival than animals with 0 or 1 weeks of prevascularization regardless of the Matrigel coating. Wider airway patency was observed in group M than group S. Group M showed migration of epithelium over the scaffold from 4 weeks after transplantation and complete coverage with epithelium at 12 weeks, whereas group S showed migration of the epithelium from 14 weeks and incomplete coverage with epithelium even at 24 weeks.Conclusion: This two-step method, utilizing the platysma as an in vivo bioreactor, may be a promising approach to achieve long-term survival and enhanced luminal patency. Matrigel coating on the scaffold had a synergistic effect on epithelial regeneration.

Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering

“…In the AV-loop method, an arteriovenous shunt is surgically incorporated into the scaffold in order to prevascularize the construct ( Wu et al, 2017 ; Weigand et al, 2018 ). Another in vivo strategy is implantation of the scaffold in a highly vascular pouch or flap in the body of the host ( Lee et al, 2021 ). After the prevascularization of the scaffold, the final scaffold can be implanted in the defected tissue.…”

Biomimetic in situ tracheal microvascularization for segmental tracheal reconstruction in one‐step

“…Many studies have attempted to promote tissue‐engineered tracheal revascularization, but there is still no consensus on how to construct microvascular grafts reasonably and effectively. Currently, there are three main strategies for vascularized construction of tracheal grafts: (1) heterotopic wrapping method, in which orthotopic transplantation is performed after the microvascularization of the grafts is completed in ectopic embedding in muscle flaps, 23 , 56 , 57 , 58 , 59 forearm fascia, 6 , 60 or omentum 61 , 62 over several weeks; (2) promotion of angiogenesis using decellularized trachea that retains vascular growth factors 15 , 16 ; (3) 3D printing of microvascularized grafts using bioinks mixed with ECs and vascular growth factors. 63 Although the above methods play a certain role in the microvascularization of tracheal grafts, they still have the following shortcomings: the ectopic wrapping method may require a secondary surgery, which is more traumatic; the decellularized trachea can easily soften and collapse after surgery, which requires repeated implantation of endotracheal stents; and the 3D bioprinted microvascularized tissue has weak biomechanical properties that cannot match the performance requirements of long‐segment tracheal grafts.…”

Skin-on-a-Chip Technology: Microengineering Physiologically Relevant In Vitro Skin Models

“…The importance of vascularization, in particular for implanted skin grafts, pressured the development of innovative approaches to recreate in vivo-like vasculature. One popular strategy to generate vascularization in skin grafts relies on the host vessels’ ability to invade the implanted engineered tissue [ 52 ]. Alternative approaches to induce vasculogenesis in vitro include cell seeding onto scaffolds or hydrogels, cell sheeting engineering and cell encapsulation [ 53 ].…”