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Successful tracheal regeneration using biofabricated autologous analogues without artificial supports.

ABSTRACT: Tracheas have a tubular structure consisting of cartilage rings continuously joined by a connective tissue membrane comprising a capillary network for tissue survival. Several tissue engineering efforts have been devoted to the design of scaffolds to produce complex structures. In this study, we successfully fabricated an artificial materials-free autologous tracheal analogue with engraftment ability by combining in vitro cell self-aggregation technique and in-body tissue architecture. The cartilage rings prepared by aggregating chondrocytes on designated culture grooves that induce cell self-aggregation were alternately connected to the connective tissues to form tubular tracheal analogues by subcutaneous embedding as in-body tissue architecture. The tracheal analogues allogeneically implanted into the rat trachea matured into native-like tracheal tissue by covering of luminal surfaces by the ciliated epithelium with mucus-producing goblet cells within eight months after implantation, while maintaining their structural integrity. Such autologous tracheal analogues would provide a foundation for further clinical research on the application of tissue-engineered tracheas to ensure their long-term functionality.

SUBMITTER: Hiwatashi S

PROVIDER: S-EPMC9700768 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Successful tracheal regeneration using biofabricated autologous analogues without artificial supports.

Hiwatashi Shohei S Iwai Ryosuke R Nakayama Yasuhide Y Moriwaki Takeshi T Okuyama Hiroomi H

Scientific reports 20221124 1

Tracheas have a tubular structure consisting of cartilage rings continuously joined by a connective tissue membrane comprising a capillary network for tissue survival. Several tissue engineering efforts have been devoted to the design of scaffolds to produce complex structures. In this study, we successfully fabricated an artificial materials-free autologous tracheal analogue with engraftment ability by combining in vitro cell self-aggregation technique and in-body tissue architecture. The carti ...[more]

PMID: 36434016

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Project description:BackgroundSince the esophagus has no redundancy, congenital and acquired esophageal diseases often require esophageal substitution, with complicated surgery and intestinal or gastric transposition. Peri-and-post-operative complications are frequent, with major problems related to the food transit and reflux. During the last years tissue engineering products became an interesting therapeutic alternative for esophageal replacement, since they could mimic the organ structure and potentially help to restore the native functions and physiology. The use of acellular matrices pre-seeded with cells showed promising results for esophageal replacement approaches, but cell homing and adhesion to the scaffold remain an important issue and were investigated.MethodsA porcine esophageal substitute constituted of a decellularized scaffold seeded with autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) was developed. In order to improve cell seeding and distribution throughout the scaffolds, they were micro-perforated by Quantum Molecular Resonance (QMR) technology (Telea Electronic Engineering).ResultsThe treatment created a microporous network and cells were able to colonize both outer and inner layers of the scaffolds. Non seeded (NSS) and BM-MSCs seeded scaffolds (SS) were implanted on the thoracic esophagus of 4 and 8 pigs respectively, substituting only the muscle layer in a mucosal sparing technique. After 3 months from surgery, we observed an esophageal substenosis in 2/4 NSS pigs and in 6/8 SS pigs and a non-practicable stricture in 1/4 NSS pigs and 2/8 SS pigs. All the animals exhibited a normal weight increase, except one case in the SS group. Actin and desmin staining of the post-implant scaffolds evidenced the regeneration of a muscular layer from one anastomosis to another in the SS group but not in the NSS one.ConclusionsA muscle esophageal substitute starting from a porcine scaffold was developed and it was fully repopulated by BM-MSCs after seeding. The substitute was able to recapitulate in shape and function the original esophageal muscle layer.

Project description:BackgroundTracheal necrosis, which is rare because the trachea has rich in blood supply, can be a serious condition. Herein, we report the case of extensive tracheal necrosis that developed after right apical segmentectomy for a metastatic lung tumor of esophageal cancer.Case presentationA 74-year-old man who had undergone thoracoscopic subtotal esophagectomy and gastric tube reconstruction via the posterior sternal route for esophageal adenocarcinoma 2 years previously was referred to our department with an enlarging nodal lesion in the right upper lung lobe. Computed tomography revealed a 30-mm tumor in the right apical segment with no lymph node enhancement, suggesting primary lung cancer or a metastatic lung tumor. The patient underwent right apical segmentectomy. The upper lobe was adherent to the chest wall and mediastinal fat from the apex of the lung to the dorsal side, with particularly strong adhesion at the esophagectomy site. After dissecting the adhesions, right apical segmentectomy was performed via complete video-assisted thoracic surgery. The patient was discharged on the 9th day after surgery without any complications. Pathologic findings revealed a metastatic lung tumor originating from the patient's esophageal cancer. On the 26th day after surgery, the patient returned with dyspnea and increased sputum. Computed tomography images revealed that the posterior wall of the trachea was missing an area of 16 × 42 mm and was connected to the dead space after the right apical segmentectomy, with no effusion. We diagnosed extensive tracheal necrosis. Considering that the patient's status was very well despite the extensive tracheal necrosis, we chose conservative treatment. After receiving 12 days of intravenous antibiotic treatment, his symptoms improved, and he was discharged on day 26 after admission.ConclusionsRight upper lung lobe resection after esophagectomy has a risk of tracheal necrosis. Conservative treatment is one approach to manage massive tracheal necrosis in patients with stable respiratory conditions.

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Successful tracheal regeneration using biofabricated autologous analogues without artificial supports.

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Successful tracheal regeneration using biofabricated autologous analogues without artificial supports.

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