Primary tracheal tumors or peritracheal tumors (lung cancer, esophageal cancer, etc.) invading the trachea and causing airway obstruction have been considered as the terminal disease in thoracic surgery, mainly because there is no good clinical alternative to the trachea. You may find it strange that modern technology has successfully prepared replacements for large blood vessels, bones and joints, and even heart valves, and that a small trachea is just a ventilation tube that should be easy to use. The truth is that experimental and clinical research in tracheal surgery began as early as the 19th century, yet to this day there is no widely accepted and reliable clinical replacement for the trachea, and slow re-epithelialization and re-vascularization are technical challenges that need to be addressed. Since the tracheal lumen is connected to the outside world and is a bacterial environment, tracheal substitutes with good biocompatibility will become a breeding ground for bacterial growth while promoting the growth of normal tracheal tissue into regeneration. The bacterial growth will stimulate the proliferation of granulation tissue to block the lumen of the trachea on the one hand, and further invade the lung tissue to cause recurrent fatal pneumonia on the other. Intact epithelial tissue prevents bacterial invasion, controls granulation overgrowth, and aids in the drainage of sputum, preventing airway obstruction and reducing the incidence of pneumonia. Previous studies have shown that rapid revascularization is a prerequisite for rapid re-epithelialization of tracheal substitutes, and that normal tracheal tissue is dependent on the rich capillary network of the submucosa to ensure the renewal of metabolically active epithelial cells to maintain epithelial integrity. Anatomically, the tracheal blood supply is unique in that there are no thicker nutrient arteries and veins, but instead relies on tiny branches from the superior and inferior thyroid arteries and the aorta to form a chain of tissue segments lateral to the tracheal cricoid junction, which then enter the trachea in the form of subsegments to form a fine capillary network. The lateral tissue chain is easily disrupted during tracheal replacement surgery, and reconstruction of the blood supply to the tracheal replacement relies on the growth of the capillary network from normal tracheal tissue along the two anastomotic junctions, which has been shown to be very slow and limited in length (generally no more than 1 cm). In animal studies, even when a small section of the trachea was removed and reanastomosed immediately, the theoretically best tracheal replacement showed ischemic necrosis of its middle portion when the length exceeded 2 cm. For these reasons, clinical tracheal surgery is still based on partial resection of the affected trachea and end-to-end tracheal anastomosis. The extent of resection should not exceed 6 cm in adults and one-third of the total length of the trachea in children. Belsey, the originator of tracheal surgery, noted that “the solution of the tracheal substitute meant the end of the era of surgical pioneering”, successfully transcending the seemingly irreconcilable biological contradictions and greatly facilitating the development of similar exposed substitutes for the esophagus and urethra. The concept of tissue engineering has led to new ideas for the development of alternatives to the trachea. The basic approach is to inoculate the recipient autologous cells on a degradable scaffold material and construct an active tissue organ substitute after in vitro three-dimensional culture. As a multidisciplinary high-tech technology combining material science, molecular biology, cytology and engineering, the research of tissue engineering has gained rapid development in recent years, involving almost all surgical fields and representing the direction of medical development. In 2008, Dr. Macchiarini of Barcelona, Spain, reported the world’s first clinical application of “tissue-engineered trachea”, which caused a great sensation. The group used an allogeneic tracheal decellularized matrix as scaffolding material, inoculated with the patient’s own ciliated columnar epithelial cells and chondrocytes, cultured in an in vitro bioreactor, and successfully implanted a replacement 4 cm length of the patient’s left common bronchus. This experiment validated the feasibility of tissue-engineered trachea and demonstrated that tracheal decellularized matrix is the best tissue-engineered tracheal scaffold material in terms of biocompatibility and strength and flexibility. However, since the experimental group was unable to provide evidence of the role of in vitro inoculated cells in tracheal regeneration, it is controversial whether the procedure was a true tissue-engineered tracheal replacement or simply a decellularized tracheal graft, and if the latter is the case, it is foreseeable that its large-scale clinical application will encounter the same problems as other alternatives. In fact, slow revascularization is also a technical difficulty that hinders the large-scale clinical application of tissue-engineered organs. Traditional tissue engineering techniques are divided into two separate steps: in vitro cell-scaffold material three-dimensional culture and in vivo implantation and compatible regeneration of the tissue-engineered substitute with normal tissue. Since the current technology is unable to build the capillary network structure in normal tissues inside the tissue-engineered organ, the entire substitute is mostly immersed in the culture medium during the in vitro culture process, and the inoculated seed cells rely on the infiltration of nutrients in the culture medium to obtain nutrients. When implanted in vivo, the tissue-engineered substitutes rely on a slow recanalization process derived from the surrounding normal tissue for final nutritional support because they do not have a vascular system that can be directly sutured to the recipient’s circulatory system, which will directly lead to massive necrosis of the seed cells inside the three-dimensional structure of the substitutes due to the ischemic phase they face, poisoning the local regenerative microenvironment. The slow recanalization makes the concept of tissue-engineered active tissue substitutes difficult to implement in clinical practice, leading the scientific community to question the underlying principles and methods. Some research groups have proposed the concept of in situ tissue engineering in an attempt to promote the proliferation and differentiation of in situ stem cells and achieve tissue reconstruction by relying on the self-induced effects of scaffold materials, which is considered a compromise of last resort. Tissue regeneration requires a relatively closed microenvironment and a sufficient amount of active seed cells, and there are limits to in situ regeneration without relying on seed cells. To address these challenges, we propose the concept of an “in vivo bioreactor”, the basic design principle of which is to use a portable pump system to create a continuous nutrient infusion inside the implanted tissue engineering substitute, thus combining the absolutely separate in vitro cell-scaffold material culture and in vivo substitute synthesis processes of traditional tissue engineering technology. The system integrates the absolutely separated in vitro cell-scaffold material culture and the in vivo substitution process in traditional tissue engineering technology. In preliminary pre-experiments, we have validated three major advantages of this design. First, in a conventional bioreactor design, the cell-scaffold material complex is immersed in a nutrient solution, and the seed cells in the central part rely on nutrient infiltration for nutritional support. In contrast, in the “in vivo bioreactor” design concept, the nutrient solution simulates blood flow inside the substitute, and the laminar and osmotic pressures generated by the movement increase the thickness of the supportable tissue from 100 microns to 300 microns in a static culture of a conventional bioreactor. Secondly, seed cells can be added to the perfusion solution for continuous cell inoculation in the application. In acute surgery, the scaffold material can be implanted first, and appropriate tissue can be taken for seed cell isolation and in vitro expansion, and then inoculated into the tissue engineering substitute through the “in vivo bioreactor” periodically, thus avoiding the patient’s long-term waiting and achieving temporary functional replacement in one phase, and gradually enhancing the perfection. The third advantage is that various growth factors can be added to the perfusion solution, and the local cytokine expression can be controlled by regulating the concentration of growth factors in the perfusion solution, and the precise ratio of multiple cytokines can be combined. In this design we treat the patient himself as a bioreactor for the regeneration process of his tissue engineered tissues and organs, maximizing the use and thus enhancing the local regenerative microenvironment. In order to regulate the clinical application of tissue engineering technology in China, in June 2009, the Health Planning Commission issued the “Notice of the General Office of the Ministry of Health on the Announcement of the First List of Class III Medical Technologies Allowed for Clinical Application” (Health Office of Medical Affairs [2009] No. 84), listing tissue engineering tissue transplantation as a Class III medical technology for regulation. Regulation. The specific requirements are divided into two major parts: seed cells and stent materials. For seed cells, a clinical application level cell therapy laboratory needs to be established. For stent materials, our homogeneous and heterogeneous (porcine) tracheal decellularization matrix products have been shaped and completed pre-clinical testing by the State Drug Administration.