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The development of tracheal tissue engineering (TTE) has seen a rapid growth in recent years. The purpose of this study was to investigate the global status, trends, and hotspots of TTE research based on bibliometrics and visualization analysis. Publications related to TTE were retrieved and included in the Web of Science Core Collection. VOSviewer and CiteSpace were used to generate knowledge maps. Six hundred fifty-five publications were identified, and the quantity of the annual publications worldwide was on the increase. International collaboration is a widespread reality. The United States led the world in the field of trachea tissue engineering, whereas University College London was the institution with the greatest contribution. In addition, Biomaterials had a great influence in this field, attracting the largest number of papers. Moreover, the topics of TTE research largely concentrated on the biomechanical scaffold preparation, the vascularization and epithelialization of scaffold, the tracheal cartilage regeneration, and the tissue-engineered tracheal transplantation. And the research on the application of decellularization and 3D printing for the construction of a tissue-engineered trachea was likely to receive more widespread attention in the future. Impact statement In recent years, tracheal tissue engineering (TTE) has experienced rapid growth. In this study, we investigated the worldwide status and trends of TTE research, and revealed the countries, institutions, journals, and authors that had made significant contributions to the field of TTE. Moreover, the possible research hotspots in the future were predicted. According to our research, researchers can gain a better understanding of the trends in this field, and stay informed of the most current research by tracking key journals, institutions, and authors.

Transplantation of tissue-engineered trachea is an effective treatment for long-segment tracheal injury. This technology avoids problems associated with a lack of donor resources and immune rejection, generating an artificial trachea with good biocompatibility. To our knowledge, a systematic summary of basic and clinical research on tissue-engineered trachea in the last 20 years has not been conducted. Here, we analyzed the development trends of tissue-engineered trachea research by bibliometric means and outlined the future perspectives in this field. The Web of Science portal was selected as the data source. CiteSpace, VOSviewer, and the Bibliometric Online Analysis Platform were used to analyze the number of publications, journals, countries, institutions, authors, and keywords from 475 screened studies. Between 2000 and 2023, the number of published studies on tissue-engineered trachea has been increasing. Biomaterials published the largest number of papers. The United States and China have made the largest contributions to this field. University College London published the highest number of studies, and the most productive researcher was an Italian scholar, Paolo Macchiarini. However, close collaborations between various researchers and institutions from different countries were generally lacking. Despite this, keyword analysis showed that manufacturing methods for tracheal stents, hydrogel materials, and 3D bioprinting technology are current popular research topics. Our bibliometric study will help scientists in this field gain an in-depth understanding of the current research progress and development trends to guide their future work, and researchers in related fields will benefit from the introduction to transplantation methods of tissue-engineered trachea.

Long segment trachea defects are repaired by tracheal substitution, while decellularized technology has been effectively employed to prepare tissue engineering trachea (TET). However, its clinical application is restricted by the long preparation cycle, while poor vascularization is associated with the transplantation failure. In the present study, we used sodium lauryl ether sulfate (SLES) to develop a novel rapid decellularized tracheal preparation method, then constructed a TET with revascularization functions. Summarily, we decellularized rabbit trachea using various SLES concentrations. Results from histological analysis, immunohistochemical and DAPI staining, as well as DNA quantitative assay, revealed that 1-0.1% (v/v) SLES treatment not only entirely removed cellular components to reduce its immunogenicity, but also retained the tracheal matrix's gross structure. SEM images, safranine O-fast green staining, total collagen content assay and collagen II immunofluorescence revealed that low SLES concentrations preserved the bioactive components of the decellularized tracheal matrix. Next, we performed cytobiocompatible and cytotoxin assays to verify biocompatibility of the decellularized tracheal matrix, and is confirmed by the omentum transplantation of rats. Results from omentum transplantation revealed that the decellularized tracheal matrix had low immunogenicity and excellent biocompatibility. Its revascularization capacity was confirmed by histologic appearance and CD31 immunofluorescence. Based on these findings, we selected 0.1% (v/v) as the optimal SLES concentration for preparing a decellularized tracheal matrix. Next, we seeded allogeneic bone marrow stem cells (BMSC) onto the matrix to construct TET patches. In vivo tracheal defect reconstruction confirmed the biocompatibility and revascularization capacity of this novel TET, and the formation of a vascular network around the patch promoted submucosa and mucosa regeneration without significant stenosis, 4 weeks post-surgery. In conclusion, we used SLES to successfully develop a novel decellularized approach for the preparation of TET, which has low immunogenic and inflammatory responses, as well as excellent biocompatibility, and revascularization ability in vivo without additional exogenous cytokines.

The construction of ideal tissue engineering trachea has always been a difficult problem in trachea transplantation surgery. The biological characteristics of decellularized matrix prepared by detergent-enzymatic (DEM) and 3D printing biomimetic scaffold (PTS) in vivo and in vitro were compared. In order to comprehensively evaluate its performance, we tested morphological and biomechanical characteristics of the native tracheas(Group A), DEM(Group B), and PTS(Group C). The above groups were co-cultured with bone marrow mesenchymal stem cells (BMSCs), after which cell attachment and proliferation on the scaffolds were detected. Allogeneic implantation experiments were performed to assess the in vivo biocompatibility of the studied scaffolds. Moreover, an in-situ experiment of the tracheal repair was conducted to compare the survival of every group. The biomechanical properties of PTS were significantly better than those of other scaffolds (P < .05). And they retained their structural integrity in the host compared with the other scaffolds (P < .05). Besides, significantly milder immune-rejection reactions were observed in Group C than those in Group A (P < .05). In situ experiments showed that Group C significantly a good postoperative condition compared with the other scaffold groups (P < .05). Fiberoptic bronchoscopy analysis of PTS showed a better condition in the lumen. In conclusion, PTS has excellent biomechanical properties. Although the PTS group showed lower biocompatibility than the decellularized group, it exhibited better cell attachment and proliferation. In situ transplantation results showed that PTS could be an ideal source of tissue engineering material for tracheal repair., (© 2022 Wiley Periodicals LLC.)

Tissue engineering technology provides effective alternative treatments for tracheal reconstruction. The formation of a functional microvascular network is essential to support cell metabolism and ensure the long-term survival of grafts. However, given the lack of an identifiable vascular pedicle of the trachea that could be anastomosed to the blood vessels directly in the recipient's neck, successful tracheal transplantation faces significant challenges in rebuilding the adequate blood supply of the graft. Herein, we describe a one-step method to construct microvascularization of tissue-engineered trachea in orthotopic transplantation. Forty rabbit tracheae were decellularized using a vacuum-assisted decellularization (VAD) method. Histological appearance and immunohistochemical (IHC) analysis demonstrated efficient removal of cellular components and nuclear material from natural tissue, which was also confirmed by 4'-6-diamidino-2-phenylindole(DAPI) staining and DNA quantitative analysis, thus significantly reducing the antigenicity. Scanning electron microscopy (SEM), immunofluorescence (IF) analysis, GAG and collagen quantitative analysis showed that the hierarchical structures, composition and integrity of the extracellular matrix (ECM) were protected. IF analysis also demonstrated that basic fibroblast growth factor (b-FGF) was preserved during the decellularization process, and also exerted biocompatibility and proangiogenic properties by the chick chorioallantoic membrane(CAM) assay. Xenotransplantation assays indicated that the VAD tracheal matrix would no longer induced inflammatory reactions implanted in the body for 4 weeks after treated by VAD more than 16 h. Furthermore, we seeded the matrix with bone marrow-derived endothelial cells (BMECs) in vitro and performed in vivo tracheal patch repair assays to prove the biocompatibility and neovascularization of VAD-treated tracheal matrix, and the formation of a vascular network around the patch promoted the crawling of surrounding ciliated epithelial cells to the surface of the graft. We conclude that this natural VAD tracheal matrix is non-immunogenic and no inflammatory reactions in vivo transplantation. Seeding with BMECs on the grafts and then performing orthotopic transplantation can effectively promote the microvascularization and accelerate the native epithelium cells crawling to the lumen of the tracheal graft., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To shorten the preparation time of rabbit decellularized tracheal matrix through a modified detergent-enzymatic method with higher concentration of DNase (50 kU/mL), providing an experimental and theoretical basis for clinical decellularization technology., Methods: The control group was a natural trachea, and the experimental group was a tracheal matrix subjected to two and four decellularization cycles. The performance of each group of samples was evaluated by histology and immunohistochemical staining, scanning electron microscopy, biomechanical property testing, inoculation and cytotoxicity tests, and allograft experiments., Results: The results showed that the nuclei of the nonchondral areas of the tracheal stroma were essentially completely removed and MHC-I and MHC-II antigens were removed after two decellularization cycles. Histological staining and scanning electron microscopy showed that the extracellular matrix was retained and the basement membrane was intact. Cell inoculation and proliferation tests confirmed that the acellular tracheal matrix had good biocompatibility, and the proliferation capacity of bone mesenchymal stem cells on the matrix was increased in the experimental group compared with the control group ( p  < 0.05). Histological staining and CD68 molecular marker analysis after the allograft experiment showed that the inflammatory response of the acellular tracheal matrix was weak and the infiltration of surrounding macrophages was reduced., Conclusion: A modified detergent-enzymatic method with an increased DNase (50 kU/mL) concentration requires only two cycles (4 days) to obtain a decellularized rabbit tracheal matrix with a short preparation time, good biocompatibility, suitable mechanical properties, and reduced preparation cost.

Objective: To study the different concentrations of Triton X-100 and nuclease needed to remove cells from the tracheal matrix of rabbits and analyse their biocompatibility and cellular compatibility., Methods: Fifty tracheas were harvested from donor New Zealand rabbits. Thirty tracheas were randomly divided into five groups (n = 6 each). The tracheas in group A were untreated and served as a control group, and those in groups B, C, D and E were treated with different concentrations of Triton X-100 (1%, 2%, 3% and 4%), respectively. The tracheas of the five groups were assessed by histological observation, scanning electron microscopy and mechanical evaluation. The remaining 20 donor tracheas, which were divided into a control group and an optimally decellularized group, were used for xenogeneic transplantation and cell seeding., Results: Many epithelial cells and cartilage cells were observed in the tracheas of group A. There were fewer cartilage cells in the tracheas of groups C, D and E than in the tracheas of groups A and B under histological observation. In scanning electron microscopy, there were many ciliated epithelial cells in the tracheas of group A; in groups B and C, the ciliated epithelial cells disappeared, but the basement membrane was intact. The basement membranes were broken in the tracheas of groups D and E. Implanted decellularized tracheas showed good biocompatibility. Bone marrow mesenchymal stem cells grown in the decellularized tracheal matrix grew well., Conclusion: Decellularized tracheal matrix obtained from rabbits by 2% Triton X-100 may be suitable for the construction of tissue-engineered trachea because of its favourable morphological and biomechanical properties as well as its biocompatibility and cellular compatibly.

To establish the procedures of genipin-linked scaffold for in situ tracheal reconstruction in a rabbit model, and to demonstrate whether stem cells can be further differentiated in the bioreactor in vivo. It will further provide an experimental and theoretical foundation for clinical application. Previously, in vitro evaluation proved the detergent–enzymatic method effectively removed stromal epithelial cells, and the number of nuclei was reduced significantly (p < 0.05). The content of type II collagen was not statistically reduced (p > 0.05). Plasmids with green fluorescence protein were transfected into 293T cells, and these cells subsequently synthesized lentivirus with green fluorescence protein that could infect other cells. After in vivo experiments, macroscopic specimen observation and hematoxylin and eosin staining comparison showed that the genipin cross-linked decellularized scaffold had low immunological rejection. Blood routine proved the progenitor cells (such as mononuclear cells) can be mobilized from the bone marrow by the growth factors, to allow their circulation into the peripheral blood. The immunohistochemistry of Type II collagen after surgery showed the expression level of bone marrow mesenchymal stem cells transplantated group was statistically higher than the autologous transplantated group (p < 0.05). The fluorescences of Bone marrow mononuclear cells (BMNCs) were traced after the specimens harvested. It successfully demonstrated that the procedures combining stem cells with the genipin cross-linked decellularized scaffold could apply to in situ airway construction. Compared to bone marrow mesenchymal stem cells, BMNCs can also be used to achieve chondrocyte differentiation; this procedure will avoid in vitro cell culture, shortening the time and economic costs.

The influences of pore sizes and surface modifications on biomechanical properties and biocompatibility (BC) of porous tracheal scaffolds (PTSs) fabricated by polycaprolactone (PCL) using 3D printing technology. The porous grafts were surface-modified through hydrolysis, amination, and nanocrystallization treatment. The surface properties of the modified grafts were characterized by energy dispersive spectroscopy (EDS) and scanning electron microscopy (SEM). The materials were cocultured with bone marrow mesenchymal stem cells (BMSCs). The effect of different pore sizes and surface modifications on the cell proliferation behavior was evaluated by the cell counting kit-8 (CCK-8). Compared to native tracheas, the PTS has good biomechanical properties. A pore diameter of 200 μm is the optimum for cell adhesion, and the surface modifications successfully improved the cytotropism of the PTS. Allogeneic implantation confirmed that it largely retains its structural integrity in the host, and the immune rejection reaction of the PTS decreased significantly after the acute phase. Nano-silicon dioxide (NSD)-modified PTS is a promising material for tissue engineering tracheal reconstruction. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 360-370, 2019., (© 2018 Wiley Periodicals, Inc.)

Objective: To investigate the biocompatibility and immunogenicity of the tracheal matrix decellularized by sodium perchlorate (NaClO 4 )., Methods: Bone marrow mesenchymal stem cells (BMSCs) were divided from 2-month-old New Zealand white rabbits. The trachea of 6-month-old New Zealand white rabbits were trimmed to a length of 1.5 cm and randomly divided into control group (group A 1 , n =5, just stripped the loose connective tissue outside the trachea) and experimental group (group B 1 , n =5, decellularized by improved NaClO 4 immersion method). The cytotoxicity of the scaffold leaching solution was detected by MTT assay, and the major histocompatibility complex (MHC) expression was detected by immunohistochemical method. The 4th generation of BMSCs were seeded onto the scaffold of 2 groups, and the cell activity around the material was observed by inverted microscope after Giemsa staining at 48 hours, while the cells states on the scaffold were observed at 7 and 14 days after culturing by scanning electron microscope. Another 10 6-month-old New Zealand white rabbits were randomly divided into control group (group A 2 , n =5) and experimental group (group B 2 , n =5), which implanted the native trachea and decellularized tracheal matrix into the subcutaneous sac of the back neck, respectively. The serum immunoglobulin IgM and IgG contents were analysed at 5, 10, 15, 20, 25, and 30 days after operation, and HE staining observation was performed at 30 days after operation., Results: MTT assay showed that the proliferation activity of BMSCs cultured in the leach liquor of group B 1 was well, showing no significant difference when compared with group A 1 and negative control group with pure culture medium ( P >0.05). The immunohistochemical staining showed that the decellularized process could significantly reducing the antigenicity of matrix materials. Giemsa staining showed that BMSCs grew well around the two tracheal matrixs (groups A 1 and B 1 ) in vitro . Scanning electron microscope observation showed that the cells were attached to the outer wall of the tracheal material in group A 1 , which present a flat, round, oval shaped, tightly arranged cells and cluster distribution; and in group B 1 , the cells formed a single lamellar sheet cover the outer wall of the tracheal material, whose morphology was similar to that in group A 1 , and the growth trend was better. In vivo experimental results showed that the rejection of group B 2 was lower than that of group A 2 . The contens of IgM and IgG in group A 2 were significantly higher than those in group B 2 at each time point after operation ( P <0.05). HE staining showed no signs of rejection, macrophagocyte, or lymphocyte infiltration occurred, and the collagen fibers maintained their integrity in group B 2 ., Conclusion: The decellularized matrix treated by NaClO 4 has a fine biocompatibility, while its immunogenicity decreased, and it is suitable for the scaffold material for constructing of tissue engineered trachea.

The goals of our study were to evaluate the biomechanical properties and cellular biocompatibility of 3D printed tracheal graft fabricated by polycaprolactone (PCL). Compared with native tracheal patch, there was a significant increase in maximum stress and elastic modulus for 3DP tracheal graft (p < 0.05). BMSCs were co-cultured under four different conditions to investigate cytotoxicity of the graft: (1) co-cultured with normal culture medium, as blank control; (2) co-cultured with perfluoropropylene, as negative control; (3) co-cultured with 3DP tracheal graft; and (4) co-cultured with polyvinyl chloride, as positive control. Moreover, the results of SRB assay showed that compared with blank and negative control group, there was no significant difference in the cell proliferation of 3DP tracheal graft group for 21 days (p > 0.05). These results revealed that 3DP tracheal graft in our study has favorable cellular biocompatibility and biomechanical properties, and, therefore, will be a promising alternative for tissue-engineered trachea.

Decellularization techniques have been widely used as an alternative strategy for organ reconstruction. This study investigated the mechanical, pro-angiogenic and in vivo biocompatibility properties of decellularized airway matrices cross-linked with genipin. New Zealand rabbit tracheae were decellularized and cross-linked with genipin, a naturally derived agent. The results demonstrated that, a significant (p < 0.05) increase in the secant modulus was computed for the cross-linked tracheae, compared to the decellularized samples. Angiogenic assays demonstrated that decellularized tracheal scaffolds and cross-linked tracheae treated with 1% genipin induce strong in vivo angiogenic responses (CAM analysis). Seven, 15 and 30 days after implantation, decreased (p < 0.01) inflammatory reactions were observed in the xenograft models for the genipin cross-linked tracheae matrices compared with control tracheae, and no increase in the IgM or IgG content was observed in rats. In conclusion, treatment with genipin improves the mechanical properties of decellularized airway matrices without altering the pro-angiogenic properties or eliciting an in vivo inflammatory response.

Objective: To summarize the recent research situation and progress of decellularized matrix in tissue engineered trachea transplantation and to forecast the possible perspects., Methods: Recent original articles about study and application for decellularized matrix in tissue engineered trachea were reviewed. The application and study of different decellularized matrices involved in animals or patients with tracheal lesions were elaborated., Results: Decellularized matrices researched and applied in tissue engineered trachea include jejunum, urinary bladder, aorta, and trachea., Conclusion: Decellularized urinary bladder matrix and jejunal matrix appears to be efficacious method for the patch repair of partial circumferential tracheal defects. The application of decellularized aortic matrix may need more study, and decellularized tracheal matrix has a bright future in long tracheal defects.

According to the numerous experimental studies but limited clinical applications, the tracheal replacement is still far to be applied maturely. This should be attribute to the poor biocompatibility of the substitute and insufficient vascularization, even with added prosthetic migration and dislocation, epithelial ischemia and necrosis, as well as local infections, and so on. Here we present a review in the attempts to summarize the progress and prospective advances in tracheal substitute.

To prepare an NCECS/nHA composite for tissue-engineered trachea and investigate its biomechanical and biocompatibile properties. Biomechanical tests were performed on dry and wet NCECS/nHA composite specimens prepared in vitro. The cell adhesion rate on each composite surface after 2, 6, and 12 hours of culture was calculated, and cell proliferation activity was measured using an MTT assay. NCECS/nHA composites exhibited satisfactory tensile strength and Young's modulus values. The adhesion rate of rabbit tracheal chondrocytes on NCECS/nHA surfaces reached 88.4% after 12 hours of culture. NCECS/nHA composites are promising scaffold materials for tissue-engineered trachea owing to satisfactory biocompatible and biomechanical properties.

Objective: To review the research of the artificial tracheal prosthesis in the past decade so as to provide theoretical references for the development of the artificial tracheal prosthesis., Methods: The literature about the artificial tracheal prosthesis was extensively reviewed and analyzed., Results: Many new materials are used for the research of artificial tracheal prosthesis which have excellent biocompatibility and stability of the structural characteristics. And many complications such as migration, obstruction, and infection have been resolved, but so far none of the new materials has been used for clinical treatment successfully., Conclusion: The choice of the materials for artificial tracheal prosthesis is the key to succeed. Biodegradable polymer materials with its unique biological properties become the new direction of the tracheal prosthesis research.

Objective: Tracheal reconstruction continues to pose a significant challenge in thoracic surgery. The study objective was to develop a novel method to eliminate the antigenicity of tracheal allografts by using vitrified cryopreservation and present the experimental results after cervical tracheal replacement in rabbits., Methods: Fifteen New Zealand rabbits, irrespective of gender, weighing 2.5 to 3.0 kg, were randomly divided into 3 groups: (A), the experimental group (n = 5), tracheal allotransplantation after 4 weeks of vitrified cryopreservation; (B), the negative control group (n = 5), fresh tracheal autotransplantation; and (C), the positive control group (n = 5), fresh tracheal segments implanted as allografts. The patency of implanted grafts, lymphocytic infiltrate, cartilage scores, and ink perfusion to evaluate revascularization were used to investigate the impact of vitrified cryopreservation on the antigenicity of tracheal grafts and vascular regeneration., Results: Rabbits in groups A and B all had uneventful postoperative courses with patent lumens and structural integrity, with obvious vascular regeneration and less lymphocytic infiltrate. Although in excellent condition, animals were sacrificed after a short-term follow-up of 4 weeks for further examination as scheduled. In group C, massive lymphocytic infiltrate and inflammatory cells without noticeable revascularization were observed, and rabbits died within 2 weeks after surgery for airway stenosis or severe obstruction., Conclusion: The antigenicity of tracheal allografts was significantly decreased by using the vitrified cryopreservation method, which would be a novel alternative method to store donor trachea to make tracheal banking possible.

This is a study to evaluate the biomechanical properties of porcine trachea; the intention is to provide experimental methods as well as evidence for further studies on human trachea and artificial trachea. In the current study, the biomechanical indices such as bending stiffness, radial pedestal and stress-straining, bursting strength, and residual stress were adopted. The findings were as follows: there is residual stress in the trachea; when the 50mm trachea is compressed 50%, the force of radial pedestal is about 10N; the force of break from cricoid to eminence is from 180mmHg to 110mmHg. Meanwhile, the data of bent are gained and the curve of stress-straining is depicted. Rresidual stress exists in porcine trachea, and trachea membrane disrupts with the increasing of endotracheal pressure; meanwhile, the porcine trachea possesses fine properties such as radial pedestal, bending and elongation.

Over the past 10 years, much progress in the development of tracheal substitute by using tissue engineering techniques has been made. Nevertheless, some issues such as optimal extracellular matrix, cell culturing and seeding, epithelial regeneration, and revascularization remain the most stimulating challenges in tissue engineering science. It is stated that new study strategies and approaches should be explored to tackle these key problems in the near future. Here we present a review in the attempts to summarize the current advances in tissue-engineered trachea, and to look forward the prospects.

Vitrification is a promising alternative to tissue preservation, which will greatly avoid the ice-crystal formation and circumvent the hazardous effects associated with ice formation during the entire procedures. In this study, we evaluate the effect of vitreous cryopreservation of rabbit trachea by comparing the vitrification procedure with the conventional computer-programmed slow freezing approaches. Harvested tracheae were tailored and divided into groups and cryopreserved by vitrification and programmed freezing, respectively. The morphology and ultrastructure of the thawed tracheal fragments were examined by using HE staining, TUNEL test, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to assess the integrity of the tracheal fragments. The morphological studies demonstrated both cryopreservation procedure retain the interity of trachea, and that epithelium mucosae, cilia and cartilage cells were in good shape. Compared with slow freezing methods, vitrification was less detrimental to cartilage cells and had a higher survival rate of chondrocytes and coverage of epithelium and cilia. Therefore, vitrification method is a more satisfactory method to preserve trachea, the survival of chondrocytes in situ in cartilage tissue is adequate, and respiratory epithelium is soundly preserved.

Objective: To review the recent research progress of base and clinical application of tracheal replacement., Methods: Literature concerning tracheal prosthesis and the current achievements were extensively and comprehensively reviewed., Results: Most tracheal lesions can be resected and achieve primary reconstruction, but the resectable length was limited. Tracheal replacement was an efficient and feasible way to substitute the defects resulting from extended resection., Conclusion: New techniques such as tissue engineering, tracheal transplantation, new tracheal prosthesis of biomaterials break fresh ground for the more rapid development of tracheal surgery.

Objective: To review the research advances of the tracheal prosthesis., Methods: The articles concerned in recent years were extensively reviewed., Results: There were still many arguments about the use of tracheal substitutes. A variety of artificial trachea had been designed and assessed, but so far none of them had been satisfactory for clinical use. The failures were mainly due to their high mortality and incidence of complication such as prosthesis defluvium, granuloma formation, local infection, air leakage, anastomotic stenosis or obstruction., Conclusion: The major causes of the poor effectiveness by the use of tracheal prosthesis are closely related to its biological compatibilities. The selected biomaterials and the design of prosthesis hold the key to a breakthrough in research and clinical use of tracheal prosthesis.

Purpose: To investigate the feasibility of using a new tracheal prosthesis made of biomaterials to replace extensive circumferential tracheal defects., Description: Three types of tracheal prostheses were developed and studied. Type I prosthesis was used in 8 mongrel dogs (group A), type II in 4 dogs (group B), and type III in 4 dogs (group C)., Evaluation: In group A, one died from prosthetic dehiscence, another from anastomotic leakage, and the others had uneventful postoperative courses. The implanted prosthesis was completely incorporated with the recipient trachea, where different lengths of reepithelialization occurred on the luminal surface of the reconstructed trachea. Macroscopic examination showed scattered and different sizes of neo-ossification surrounding the implanted prosthesis. The prosthesis was radioopaque when exposed to routine x rays. In contrast, a relatively high number of complications occurred postoperatively in groups B and C., Conclusions: Type I tracheal prosthesis, with further improvements, may be the optimal tracheal graft to replace circumferential tracheal defects, and appears very promising for clinical application.

Cytotoxicity and cytocompatibility remains the principal theme for biomaterials application in medicine. The purpose of this study was to investigate the cytotoxicity and cytocompatibility of collagen/hydroxyapatite(CHA) composite material in vitro in order to provide useful scientific basis for clinical use. Cellular cultivation in vitro and MTT assay were conducted for evaluating the composite material's influence on the morphology, growth and proliferation of cultured cell(L-929 cell). The hemolysis test was also performed for evaluating the impact on the function and metabolism of erythrocyte. These results demonstrated that the CHA composite material had no cytotoxicity and no hemolytic effect, and it might not be harmful to the morphology of the L-929 cell. The growth and proliferation of the L-929 cell could not be inhibited significantly. The cytotoxicity score of the composite material was grade 0. The hemolysis rate was 1.85%. In conclusion, collagen/hydroxyapatite (CHA) composite material might have good cytocompatibility and be safe for clinical use.

Formation of functional and perfusable vascular network is critical to ensure the long‐term survival and functionality of the engineered tissue tracheae after transplantation. However, the greatest challenge in tracheal‐replacement therapy is the promotion of tissue regeneration by rapid graft vascularization. Traditional prevascularization methods for tracheal grafts typically utilize omentum or muscle flap wrapping, which requires a second operation; vascularized segment tracheal orthotopic transplantation in one step remains difficult. This study proposes a method to construct a tissue‐engineered tracheal graft, which directly forms the microvascular network after orthotopic transplantation in vivo. The focus of this study was the preparation of a hybrid tracheal graft that is non‐immunogenic, has good biomechanical properties, supports cell proliferation, and quickly vascularizes. The results showed that vacuum‐assisted decellularized trachea‐polycaprolactone hybrid scaffold could match most of the above requirements as closely as possible. Furthermore, endothelial progenitor cells (EPCs) were extracted and used as vascularized seed cells and seeded on the surfaces of hybrid grafts before and during the tracheal orthotopic transplantation. The results showed that the microvascularized tracheal grafts formed maintained the survival of the recipient, showing a satisfactory therapeutic outcome. This is the first study to utilize EPCs for microvascular construction of long‐segment trachea in one‐step; the approach represents a promising method for microvascular tracheal reconstruction. [ABSTRACT FROM AUTHOR]

Tissue engineering technology provides effective alternative treatments for tracheal reconstruction. The formation of a functional microvascular network is essential to support cell metabolism and ensure the long-term survival of grafts. Although several tracheal replacement therapy strategies have been developed in the past, the critical significance of the formation of microvascular networks in 3D scaffolds has not attracted sufficient attention. Here, we review key technologies and related factors of microvascular network construction in tissue-engineered trachea and explore optimized preparation processes of vascularized functional tissues for clinical applications. [ABSTRACT FROM AUTHOR]