Brain decellularized extracellular matrix (ECM) can be an attractive scaffold capable of mimicking the native ecosystem of the central nervous system tissue. We studied the in vitro response of neural cultures exposed to region-specific brain decellularized ECM scaffolds from three distinct neuroanatomical sections: cortex, cerebellum and remaining areas. First, each brain region was evaluated with the isotropic fractionator method to understand the cellular composition of the different cerebral areas. Second, the cerebral regions were subjected to the decellularization process and their respective characterization using molecular, histological, and ultrastructural techniques. Third, the levels of neurotrophic factors in the decellularized brain scaffold were analyzed. Fourth, we studied the region-specific brain decellularized ECM as a mimetic platform for the maturation of PC12 cells, as a unidirectional model of differentiation. Finally, in vitro studies were carried out to evaluate the cell recovery capacity of brain decellularized ECM under stroke-mimetic conditions. Our results show that region-specific brain decellularized ECM can serve as a biomimetic scaffold capable of promoting the growth of neural lineage cells and, in addition, it possesses a combination of structural and biochemical signals (e.g., neurotrophic factors) that are capable of inducing cell phenotypic changes and promote viability and cell recovery in a stroke/ischemia model in vitro.

The regeneration and functional recovery of tracheal tissue are of paramount importance in the research of tissue-engineered trachea. Current constructs still face some limitations in simulating the complex natural microenvironment and achieving better regenerative capacity and functional recovery. To address these challenges, the application of hydrogels with three-dimensional (3D) network structure and extracellular matrix derived from decellularized tissues and cells has become a more promising strategy. This study aims to introduce a novel bilayer multifunctional tissue-engineered tracheal substitute. Firstly, the mesh polycaprolactone (PCL) scaffold was printed by 3D printing technology, and the concentration of Silk Fibroin Methacryloyl (SilMA) hydrogel suitable for cell adhesion and proliferation and the concentration of Hyaluronic Acid Methacryloyl (HAMA) hydrogel suitable for 3D culture of chondrocytes were selected. Subsequently, the decellularized cartilaginous matrix (DCM) solution was obtained and the concentration that promotes chondrocyte proliferation and migration was screened. Finally, the multifunctional tracheal substitute, which features a HAMA-DCM composite hydrogel loaded with autologous chondrocytes as the basic framework to simulate the outer cartilaginous layer, and a 3D-printed PCL mesh scaffold coated with SilMA hydrogel loaded with autologous epithelial cells serves as internal support to simulate the inner airway epithelial layer, was prepared. Whether it was for repairing window-shape defect for 8 w or conducting long-segment in situ transplantation for 12 w, it achieved satisfactory surgical outcomes, including epithelial crawling, cartilage regeneration, and vascular remodeling.

Tracheal replacement is a promising approach for treating tracheal defects that are caused by conditions such as stenosis, trauma, or tumors. However, slow postoperative epithelial regeneration often leads to complications, such as infection and granulation tissue formation. Ferroptosis, which is an iron-dependent form of regulated cell death, limits the proliferation of tracheal basal cells (TBCs), which are essential for the epithelialization of tissue-engineered tracheas (TETs). This study explored the potential of ferrostatin-1 (FER-1), which is a ferroptosis inhibitor, to increase TBC proliferation and accelerate the epithelialization of 3D-printed TETs.

TBCs were isolated from rabbit bronchial mucosal tissues and cultured in vitro. Ferroptosis was induced in TBCs at passage 2, as shown by increased reactive oxygen species (ROS) levels, Fe2⁺ accumulation, decreased ATP contents, and mitochondrial damage. TBCs were treated with FER-1 (1 μM) for 48 h to inhibit ferroptosis. The effects on ROS levels, Fe2⁺ levels, ATP contents, and mitochondrial morphology were measured. For in vivo experiments, FER-1-treated TBCs were seeded onto 3D-printed polycaprolactone (PCL) scaffolds, which were implanted into rabbits with tracheal injury. Epithelial regeneration and granulation tissue formation were evaluated 6 months after surgery.

FER-1 treatment significantly reduced ferroptosis marker levels in vitro; that is, FER-1 treatment decreased ROS and Fe2⁺ accumulation, ameliorated mitochondrial structures, and increased ATP levels. TBC proliferation and viability were increased after ferroptosis inhibition. In vivo, the group that received 3D-printed scaffolds seeded with TBCs exhibited accelerated TET epithelialization and reduced granulation tissue formation compared with the control groups. These results suggest that inhibiting ferroptosis with FER-1 improves TBC function, leading to more efficient tracheal repair.

Ferrostatin-1 effectively inhibits ferroptosis in tracheal basal cells, promoting their viability and proliferation. This results in faster epithelialization of tissue-engineered tracheas, offering a promising strategy for improving tracheal reconstruction outcomes and reducing complications such as infection and granulation tissue formation. Future studies are needed to further investigate the molecular mechanisms underlying ferroptosis in TBCs and its potential clinical applications.

Partially decellularized tracheal grafts (PDTG) are potential candidates for tracheal replacement as they support neotissue formation without stenosis or rejection. However, the effects of partial decellularization (PD) on extracellular matrix (ECM) and chondrocytes are not currently understood, limiting PDTG translatability for clinical use. We aim to quantify the impact of PD on trachea using mouse and rabbit models.

An animal model.

Research Institute affiliated with a Tertiary Pediatric Hospital.

PDTG and syngeneic tracheal grafts (STG) were implanted orthotopically in mice for 1 month (N = 10/group). Grafts were analyzed with mechanical testing, chondrocyte viability, and protein integrity. We tested the scalability of PDTG at a pediatric scale using a rabbit model at 3- and 6-month timepoints (N = 3/timepoint). Histologic and radiographic analyses were performed to assess chondrocyte viability and neotissue formation. Rabbit PDTG and native chondrocytes were isolated and cultured assessing PD effect on proliferation.

PD of mouse trachea eliminated all epithelial cells, maintained chondrocyte viability, and did not reduce graft mechanical properties or ECM proteins. Overall, collagen and glycosaminoglycans had similar expression and integrity in PDTG and STG. PDTG retained graft patency and supported epithelialization and vascularization. Like mice, PD of rabbit trachea achieved these goals, but had increased radiodensity. Unlike mice, rabbit PDTG had greater chondrocyte and ECM loss in vivo. Unique to rabbits, PD reduced chondrocyte proliferation in vitro compared to native chondrocytes.

Despite similar pre-implantation metrics to the successful mouse model and support of neotissue formation, human-scale PDTG demonstrated greater chondrocyte and ECM loss.

Airway pathology is a complex and incompletely mastered field. Historically, its management was rudimentary, with tracheostomies performed in ancient Egypt, and progress remained stagnant for millennia. Significant advances began in the late 19th century, followed by notable surgical and anesthetic progress in the mid-20th century. The 1952 polio epidemic spurred further development, with tracheal resection and anastomosis as the first major milestone, later extending to the larynx and carina. All significant advances in airway surgery ended in the latter half of the 20th century, with minimal progress since. This article analyzes its atypical evolution of an initial step that awaited millennia for subsequent advances, only to halt again in recent times.

The field of three dimensional (3D) bioprinting has witnessed significant advancements, with bioinks playing a crucial role in enabling the fabrication of complex tissue constructs. This review explores the innovative bioinks that are currently shaping the future of 3D bioprinting, focusing on their composition, functionality, and potential for tissue engineering, drug delivery, and regenerative medicine. The development of bioinks, incorporating natural and synthetic materials, offers unprecedented opportunities for personalized medicine. However, the rapid technological progress raises regulatory challenges regarding safety, standardization, and long-term biocompatibility. This paper addresses these challenges, examining the current regulatory frameworks and the need for updated guidelines to ensure patient safety and product efficacy. By highlighting both the technological potential and regulatory hurdles, this review offers a comprehensive overview of the future landscape of bioinks in bioprinting, emphasizing the necessity for cross-disciplinary collaboration between scientists, clinicians, and regulatory bodies to achieve successful clinical applications.

Functional segmental trachea reconstruction is a critical concern in thoracic surgery, and tissue-engineered trachea (TET) holds promise as a potential solution. However, current TET falls short in fully restoring physiological function due to the lack of the intricate multi-tissue structure found in natural trachea. In this research, a multi-tissue integrated tissue-engineered trachea (MI-TET) is successfully developed by orderly assembling various cells (chondrocytes, fibroblasts and epithelial cells) on 3D-printed PGS bioelastomer scaffolds. The MI-TET closely resembles the complex structures of natural trachea and achieves the integrated regeneration of four essential tracheal components: C-shaped cartilage ring, O-shaped vascularized fiber ring, axial fiber bundle, and airway epithelium. Overall, the MI-TET demonstrates highly similar multi-tissue structures and physiological functions to natural trachea, showing promise for future clinical advancements in functional TETs.

In recent years, there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident cells. Biomaterials, in particular, have garnered significant interest for their potential to serve as natural scaffolds for cells. In this editorial, we provide commentary on the study by Wang et al, in a recently published issue of World J Stem Cells, which investigates the use of a decellularized xenogeneic extracellular matrix (ECM) derived from antler stem cells for repairing osteochondral defects in rat knee joints. Our focus lies specifically on the crucial role of biological scaffolds as a strategy for augmenting stem cell potential and regenerative capabilities, thanks to the establishment of a favorable microenvironment (niche). Stem cell differentiation heavily depends on exposure to intrinsic properties of the ECM, including its chemical and protein composition, as well as the mechanical forces it can generate. Collectively, these physicochemical cues contribute to a bio-instructive signaling environment that offers tissue-specific guidance for achieving effective repair and regeneration. The interest in mechanobiology, often conceptualized as a form of "structural memory", is steadily gaining more validation and momentum, especially in light of findings such as these.

Tissue engineering application in otology spans a distance from the pinna to auditory nerve covered with specialized tissues and functions such as sense of hearing and aesthetics. It holds the potential to address the barriers of lack of donor tissue, poor tissue match, and transplant rejection through provision of new and healthy tissues similar to the host and possesses the capacity to renew, to regenerate, and to repair in-vivo and was shown to be a bypasses for any need to immunosuppression. This review aims to investigate the application of tissue engineering in otology and to evaluate the achievements and challenges in external, middle and inner ear sections. Since gaining the recent knowledge and training on use of different scaffolds is essential for otology specialists and who look for the recovery of ear function and aesthetics of patients, it is shown in this review how utilizing tissue engineering and cell transplantation, regenerative medicine can provide advancements in hearing and ear aesthetics to fit different patients' needs.

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.

Patients affected by long-segment tracheal defects or stenoses represent an unsolved surgical issue, since they cannot be treated with the conventional surgery of tracheal resection and consequent anastomosis. Hence, different strategies for tracheal replacement have been proposed (synthetic materials, aortic allografts, transplantation, autologous tissue composites, and tissue engineering), each with advantages and drawbacks. Tracheal tissue engineering, on the other hand, aims at recreating a fully functional tracheal substitute, without the need for the patient to receive lifelong immunosuppression or endotracheal stents. Tissue engineering approaches involve the use of a scaffold, stem cells, and humoral signals. This paper reviews the main aspects of tracheal TE, starting from the choice of the scaffold to the type of stem cells that can be used to seed the scaffold, the methods for their culture and expansion, the issue of graft revascularization at the moment of in vivo implantation, and experimental models of tracheal research. Moreover, a critical insight on the state of the art of tracheal tissue engineering is also presented.

The repair and regeneration of tissues and organs using engineered biomaterials has attracted great interest in tissue engineering and regenerative medicine. Recent advances in organoids and engineered organs technologies have enabled scientists to generate 3D tissue that recapitulate the structural and functional characteristics of native organs, opening up new avenues in regenerative medicine. The matrix is one of the most important aspects for improving organoids and engineered organs construction. However, the clinical application of these techniques remained a big challenge because current commercial matrix does not represent the complexity of native microenvironment, thereby limiting the optimal regenerative capacity. Decellularized extracellular matrix (dECM) is expected to maintain key native matrix biomolecules and is believed to hold enormous potential for regenerative medicine applications. Thus, it is worth investigating whether the dECM can be used as matrix for improving organoid and engineered organs construction. In this review, the characteristics of dECM and its preparation method were summarized. In addition, the present review highlights the applications of dECM in the fabrication of organoids and engineered organs.

Patients with long-segment airway stenosis not amenable to conventional surgery may benefit from tracheal transplantation. However, this procedure has been only anecdotally reported, and its indications, techniques, and outcomes have not been extensively reviewed.

We conducted a systematic Literature search to identify all original articles reporting attempts at tracheal transplantation in humans.

Of 699 articles found by the initial search, 11 were included in the systematic review, describing 14 cases of tracheal transplantation. Patients underwent transplantation for benign stenosis in nine cases, and for malignancies in five cases. In 12 cases blood supply to the trachea was provided by wrapping the graft in a vascularized recipient's tissue, while in 2 cases the trachea was directly transplanted as a vascularized composite allograft. The transplantation procedure was aborted before orthotopic transplantation in two patients. Among the remaining 12 patients, there was 1 operative mortality, while 4 patients experienced complications. Immunosuppressants drugs were administered to the majority of patients postoperatively, and only one group of authors attempted their withdrawal, in five patients. At the end of follow-up, all 11 patients surviving the operation were alive, but 2 had a recurrent tracheal stenosis requiring an airway appliance for breathing.

Human tracheal transplantation is still at an embryonic phase. Studies available in the Literature report different surgical techniques, and information on long-term outcomes is still limited. Future research is needed in order to understand the clinical value of this procedure.

Tissue loss and end-stage organ failure are serious health problems across the world. Natural and synthetic polymer scaffold material based artificial organs play an important role in the field of tissue engineering and organ regeneration, but they are not from the body and may cause side effects such as rejection. In recent years, the biomimetic decellularized scaffold based materials have drawn great attention in the tissue engineering field for their good biocompatibility, easy modification, and excellent organism adaptability. Therefore, in this review, we comprehensively summarize the application of decellularized scaffolds in tissue engineering and biomedicine in recent years. The preparation methods, modification strategies, construction of artificial tissues, and application in biomedical applications are discussed. We hope that this review will provide a useful reference for research on decellularized scaffolds and promote their application tissue engineering.

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.

In recent years, three-dimensional (3D) bioprinting has been widely utilized as a novel manufacturing technique by more and more researchers to construct various tissue substitutes with complex architectures and geometries. Different biomaterials, including natural and synthetic materials, have been manufactured into bioinks for tissue regeneration using 3D bioprinting. Among the natural biomaterials derived from various natural tissues or organs, the decellularized extracellular matrix (dECM) has a complex internal structure and a variety of bioactive factors that provide mechanistic, biophysical, and biochemical signals for tissue regeneration and remodeling. In recent years, more and more researchers have been developing the dECM as a novel bioink for the construction of tissue substitutes. Compared with other bioinks, the various ECM components in dECM-based bioink can regulate cellular functions, modulate the tissue regeneration process, and adjust tissue remodeling. Therefore, we conducted this review to discuss the current status of and perspectives on dECM-based bioinks for bioprinting in tissue engineering. In addition, the various bioprinting techniques and decellularization methods were also discussed in this study.