Long-term functional reconstruction of segmental tracheal defect by pedicled tissue-engineered trachea in rabbits

Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai Stem Cell Institute, Shanghai, PR China
Biomaterials (Impact Factor: 8.56). 02/2013; 34(13). DOI: 10.1016/j.biomaterials.2013.01.060
Source: PubMed


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.

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    ABSTRACT: To address the increasing need for improved tissue substitutes, tissue engineering seeks to create synthetic, three-dimensional scaffolds made from polymeric materials, incorporating cells and growth factors to induce new tissue formation. Materials science, in conjunction with biotechnology, can satisfy these needs by developing artificial, synthetic substitutes and organ implants. Here, scaffold ability to promote cell growth and differentiation is a key point and, in this framework, orthogonal chemistry has led the field of biomaterial science into a new area of selective, versatile and biocompatible nature. In particular, the possibility to modify and functionalize scaffolds with compounds that are able to improve mechanical properties or cell viability and improve their differentiation in a tailorable manner opens new opportunities for researchers. In this review, we seek to emphasize the recent endeavors of exploiting this versatile chemistry toward the development of new cell culture scaffolds.
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    ABSTRACT: Tissue engineering can provide alternatives to current methods for tracheal reconstruction. Here we describe an approach for ectopic engineering of vascularized trachea based on the implantation of co-cultured scaffolds surrounded by a muscle flap. Poly(L-lactic-co-glycolic acid) (PLGA) or poly(ε-caprolactone) (PCL) scaffolds were seeded with chondrocytes, bone marrow stem cells and co-cultured both cells respectively (8 groups), wrapped in a pedicled muscle flap, placed as an ectopic culture on the abdominal wall of rabbits (n = 24), and harvested after two and four weeks. Analysis of the biochemical and mechanical properties demonstrated that the PCL scaffold with co-culture cells seeding displayed the optimal chondrogenesis with adequate rigidity to maintain the cylindrical shape and luminal patency. Histological analysis confirmed that cartilage formed in the co-culture groups contained a more homogeneous and higher extracellular matrix content. The luminal surfaces appeared to support adequate epithelialization due to the formation of vascularized capsular tissue. A prefabricated neo-trachea was transferred to the defect as a tracheal replacement and yielded satisfactory results. These encouraging results indicate that our co-culture approach may enable the development of a clinically applicable neo-trachea.
    No preview · Article · Nov 2013 · Biomaterials
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    ABSTRACT: This review summarizes efforts to generate an autologous tissue-engineered trachea (TET) using various biomaterial or cell sources to make tracheal cartilage to form the structural components of a functional tracheal replacement. Biomechanical assessments of the TET showed that the cartilage stiffness was excellent in the nude models; however, the sheep autologous TET did not provide sufficient support and collapsed easily. As a result, tissue engineering technology is still far from allowing the functional recovery of patients who suffer from severe tracheal disease. On the other hand, there are several clinical reports seeding cells to decellularized tissue using tissue engineering techniques. However, the working mechanisms of the tissue-engineered trachea remain unclear. Nevertheless, we believe that the field of tissue engineering has great potential for surmounting these obstacles and allowing us to generate functional tracheal replacements in the near future. Anat Rec, 2013. © 2013 Wiley Periodicals, Inc.
    Preview · Article · Jan 2014 · The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology
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