The lack of a biomimetic tracheal substitute featured with cartilage ring/ vascularized connective tissue alternate structure (CVCAS) has significantly retarded a clinical breakthrough of tissue-engineered trachea in repairing extensive tracheal lesions. Herein, a novel modular strategy based on cartilage rings and biomaterial rings is used to generate a biomimetic trachea with CVCAS. Poly(sebacoyl diglyceride) and polycaprolactone (PCL) (PSeD/PCL) are blended to fabricate a porous scaffold with satisfactory mechanical properties, biodegradability, and biocompatibility. A cartilage ring is engineered in vitro using ring-shaped PSeD/PCL scaffold loaded with chondrocytes and cartilage tube is generated in vivo through the fusion of multiple modular cartilage rings. More importantly, biomimetic tracheas with CVCAS are successfully fabricated in vivo through alternately stacked cartilage rings and PSeD/PCL rings on a silicon tube. Notably, the engineered biomimetic trachea exhibits not only a bionic structure but also superior mechanical properties compared with the native rabbit trachea. Finally, segmental tracheal defects in rabbits are repaired by transplanting the biomimetic trachea with pedicled muscular flaps. The biomimetic trachea establishes stable blood supply and provided sufficient mechanical strength and biological function similar to those of native trachea. This work represents the first successful regeneration of biomimetic trachea with CVCAS and a promising approach for clinical application.

No abstract

No abstract

No abstract

Repairing cartilage defect is always an intractable problem in joint surgery field. Tissue engineering, in the industry, is universally considered as a decent solution for overcoming this challenge. Especially the three-dimensional (3D) scaffolds play a significant role in cartilage repair. Thereinto, the electrospinning has become a very attractive method for the preparation of scaffolds. In recent years. However, these scaffolds are limited in terms of their three-dimensional (3D) applications due to their two-dimensional (2D) structure and pore size which are smaller than a cartilage cellular diameter and thus limit the cellular migration in these structures. To address this issue, this study will present an promising post electrospinning approach that can transform two-dimensional scaffolds into three-dimensional scaffolds via the way of insitu gas foaming within the pores of the nanofiber membranes as the driving force. Our previous study reported that agelatin/polycaprolactone (GT:PCL) ratio of 7:3 might be suitable for the cartilage regeneration [Zheng R, et al The influence of Gelatin/PCL ratio and 3D construct shape of electrospun membranes on cartilage regeneration. Biomaterials 2014;35:152-164]. Therefore, in the present experiment, we chose the above ratio (GT:PCL = 7:3) to realize two types of scaffolds (2D and 3D scaffolds) transition via the gas-foaming technique and investigated whether the three-dimensional structure was more conducive to cartilage regeneration than 2D.The experiment results have revealed that 3D scaffolds can achieve a larger pore size, higher porosity and higher biocompatibility than 2D scaffolds. In addition, both scaffolds which were implanted with chondrocytes all had formed mature cartilage-like tissues after 8 weeks of culturing in rabbits, and the 3D scaffold formed a three-dimensional structure, whereas the 2D scaffold only formed a thin layer of cartilage. As the macroscopic and histological results showed after 12 weeks postoperation, in the 2D scaffold group, the defect was full of fibrillar connective tissue, and as shown by HE staining, obviously there is no staining with Saf-O/FG and toluidine blue on the surface of repaired site. On the contrary, in the 3D scaffold group, homogeneous and mature cartilaginous tissue were found in the defect area. The defect was filled with numerous new chondrocytes, and the histologicalstaining revealed a large amount of regenerated cartilage tissue which was perfectly integrated with normal cartilage tissue. The results distinctly indicated that the 3D scaffold led to better cartilage repair effects than the 2D scaffold. Generally speaking, the current study demonstrated that a gas-foaming three-dimensional electrospun nanofiber scaffold would be a potential platform for cartilage regeneration and might provide a potential treatment option for repairing articular cartilage defects.