Bionic tracheal tissue regeneration using a ring-shaped scaffold comprised of decellularized cartilaginous matrix and silk fibroin

Abstract

Reconstruction of full-circumferential segmental tracheal defect remains an international dilemma and the key challenge is the lack of a bionic tracheal substitute, with a specific configuration of cartilaginous rings interspersed with vascularized fibrous tissue (CRVFT). We previously demonstrated the formation of a bionic tracheal substitute with CRVFT in-vivo. However, it is still desirable to develop a scaffold with proper mechanical strength and chondroinductive activity to promote in-vivo cartilage formation, which could circumvent the painstaking procedure of in-vitro cultivation. Herein, we prepared a ring-shaped porous silk fibroin (SF)-reinforced decellularized cartilaginous matrix (DCM) (DCM/SF) scaffold, which displayed suitable pore size (206.7 ± 12.5 μm) and porosity (92.7 ± 2.5%) and was biocompatible for cell colonization. The addition of SF considerable enhanced anti-contraction capacity and Young's modulus, while diminishing water absorption and degradation rate of the DCM/SF scaffold. Further, the DCM/SF scaffold obviously promoted chondrogenesis of the embedded bone marrow stem cells (BMSCs), compared to DCM or SF scaffold alone. In addition, a cartilaginous ring was formed using the DCM/SF scaffold, which was repopulated with BMSCs after subcutaneous implantation in nude mouse. Moreover, a bionic tracheal tissue with remarkable CRVFT was achieved via the interrupted stacking of BMSC-DCM/SF constructs on a stent, before subcutaneous implantation into a rabbit for 4 weeks. The bionic trachea was fully revascularized and displayed comparable biochemical compositions and mechanical strength resembling to those of normal trachea. This study introduces a reliable new approach for bionic tracheal tissue regeneration and significantly advances the ongoing repair of segmental tracheal defect.