Long-term functional reconstruction of segmental tracheal defect by pedicled tissue-engineered trachea in rabbits
ABSTRACT Due to lack of satisfactory tracheal substitutes, reconstruction of long segmental tracheal defects (>6 cm) is always a major challenge in trachea surgery. Tissue-engineered trachea (TET) provides a promising approach to address this challenge, but no breakthrough has been achieved yet in repairing segmental tracheal defect. The longest survival time only reached 60 days. The leading reasons for the failure of segmental tracheal defect reconstruction were mainly related to airway stenosis (caused by the overgrowth of granulation tissue), airway collapse (caused by cartilage softening) and mucous impaction (mainly caused by lack of epithelium). To address these problems, the current study proposed an improved strategy, which involved in vitro pre-culture, in vivo maturation, and pre-vascularization of TET grafts as well as the use of silicone stent. The results demonstrated that the two-step strategy of in vitro pre-culture plus in vivo implantation could successfully regenerate tubular cartilage with a mechanical strength similar to native trachea in immunocompetent animals. The use of silicone stents effectively depressed granulation overgrowth, prevented airway stenosis, and thus dramatically enhanced the survival rate at the early stage post-operation. Most importantly, through intramuscular implantation and transplantation with pedicled muscular flap, the TET grafts established stable blood supply, which guaranteed maintenance of tubular cartilage structure and function, accelerated epithelialization of TET grafts, and thus realized long-term functional reconstruction of segmental tracheal defects. The integration of all these improved strategies finally realized long-term survival of animals: 60% of rabbits survived over 6 months. The current improved strategy provided a promising approach for long-term functional reconstruction of long segmental tracheal defect.
SourceAvailable from: Fergal J. O’Brien[Show abstract] [Hide abstract]
ABSTRACT: Currently, lung disease and major airway trauma constitute a major global healthcare burden with limited treatment options. Airway diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) have been identified as the fifth highest cause of mortality worldwide and are estimated to rise to fourth place by 2030. Alternate approaches and therapeutic modalities are urgently needed to improve clinical outcomes for chronic lung disease. This can be achieved through tissue engineering of the respiratory tract. Interest is growing in the use of airway tissue engineered constructs as both a research tool to further our understanding of airway pathology, validate new drugs and pave the way for novel drug therapies, and also as regenerative medical devices or as an alternative to transplant tissue. This review provides a concise summary of the field of respiratory tissue engineering to date. An initial overview of airway anatomy and physiology is given, followed by a description of the stem cell populations and signalling processes involved in parenchymal healing and tissue repair. We then focus on the different biomaterials and tissue engineered systems employed in upper and lower respiratory tract engineering, and give a final perspective of the opportunities and challenges facing the field of respiratory tissue engineering.Tissue Engineering Part B Reviews 01/2015; DOI:10.1089/ten.TEB.2014.0525 · 4.64 Impact Factor
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ABSTRACT: Organization of airway epithelium determines ciliary beat direction and coordination for proper mucociliary clearance. Fluidic shear stresses have the potential to influence ciliary organization. Here, an in vitro fluidic flow system was developed for inducing long-term airflow shear stresses on airway epithelium with a view to influencing epithelial organization. Our system consists of a fluidic device for cell culture, integrated into a humidified airflow circuit. The fluidic device has a modular design and is made from a combination of polystyrene and adhesive components incorporated into a 6-well filter membrane insert. We demonstrate the system operates within physiologically relevant shear and pressure ranges and estimate the shear stress exerted on the epithelial cell layer as a result of air flow using a computational model. For both the bronchial epithelial cell line BEAS2B and primary human tracheal airway epithelial cells, we demonstrate that cells remain viable within the device when exposed to airflow for 24 h and that normal differentiation and cilia formation occurs. Furthermore, we demonstrate the utility of our device for exploring the impact of exposing cells to airflow: our tool enables quantification of cytoskeletal organization, and is compatible with in situ bead assays to assess the orientation of cilia beating.Biomicrofluidics 11/2014; 8(6):064104. DOI:10.1063/1.4901930 · 3.77 Impact Factor
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ABSTRACT: It is commonly stated that tissue engineering is the most promising approach to treat or replace failing tissues/organs. For this aim, a specific strategy should be planned including proper selection of biomaterials, fabrication techniques, cell lines, and signaling cues. A great effort has been pursued to develop suitable scaffolds for the restoration of a variety of tissues and a huge number of protocols ranging from in vitro to in vivo studies, the latter further differentiating into several procedures depending on the type of implantation (i.e., subcutaneous or orthotopic) and the model adopted (i.e., animal or human), have been developed. All together, the published reports demonstrate that the proposed tissue engineering approaches spread toward multiple directions. The critical review of this scenario might suggest, at the same time, that a limited number of studies gave a real improvement to the field, especially referring to in vivo investigations. In this regard, the present paper aims to review the results of in vivo tissue engineering experimentations, focusing on the role of the scaffold and its specificity with respect to the tissue to be regenerated, in order to verify whether an extracellular matrix-like device, as usually stated, could promote an expected positive outcome.BioMed Research International 01/2014; 2014:398069. DOI:10.1155/2014/398069 · 2.71 Impact Factor