Biomimetic Trachea Engineering via a Modular Ring Strategy Based on Bone‐Marrow Stem Cells and Atelocollagen for Use in Extensive Tracheal Reconstruction

Abstract

The fabrication of biomimetic tracheas with a architecture of cartilaginous rings alternately interspersed between vascularized fibrous tissue (CRVFT) has the potential to perfectly recapitulate the normal tracheal structure and function. Herein, the development of a customized chondroitin‐sulfate‐incorporating type‐II atelocollagen (COL II/CS) scaffold with excellent chondrogenic capacity and a type‐I atelocollagen (COL I) scaffold to facilitate the formation of vascularized fibrous tissue is described. An efficient modular ring strategy is then adopted to develop a CRVFT‐based biomimetic trachea. The in vitro engineering of cartilaginous rings is achieved via the recellularization of ring‐shaped COL II/CS scaffolds using bone marrow stem cells as a mimetic for native cartilaginous ring tissue. A CRVFT‐based trachea with biomimetic mechanical properties, composed of bionic biochemical components, is additionally successfully generated in vivo via the alternating stacking of cartilaginous rings and ring‐shaped COL I scaffolds on a silicone pipe. The resultant biomimetic trachea with pedicled muscular flaps is used for extensive tracheal reconstruction and exhibits satisfactory therapeutic outcomes with structural and functional properties similar to those of native trachea. This is the first study to utilize stem cells for long‐segmental tracheal cartilaginous regeneration and this represents a promising method for extensive tracheal reconstruction.

Acellular cartilage matrix biomimetic scaffold with immediate enrichment of autologous bone marrow mononuclear cells to repair articular cartilage defects

“…Among them, bone marrow-derived mesenchymal stem cells are one of the most recognized sources of mesenchymal stem cells with multiple applications and long-term proliferation properties. However, autologous bone marrow stromal cells need additional isolation and culture processes [ 39 , 40 ], which cannot achieve immediate repair of cartilage defects such as acute trauma. In this research, the aspirated bone marrow was processed by density gradient centrifugation to obtain MNCs [ 41 , 42 ], a heterogeneous cell population that can be directly enriched into scaffolds for in vivo experiments.…”

Bevacizumab‐Laden Nanofibers Simulating an Antiangiogenic Niche to Improve the Submuscular Stability of Stem Cell Engineered Cartilage

“…After 5 days, the medium was changed to remove all non‐adherent cells following previously reported protocols. [ 48 ] BMSCs at P2 were harvested for use.…”

Enhancing Stem Cell-Based Therapeutic Potential by Combining Various Bioengineering Technologies

“… Dikina et al (2015) developed high-cell density, scaffold-free BM-MSC-derived cartilaginous rings and tubes, in which TGF β1-delivering gelatin microspheres were incorporated to enhance the chondrogenic differentiation efficiency of MSCs. Xu et al (2021) developed chondroitin-sulfate-incorporated type-II atelocollagen (COL II/CS) biomimetic tracheas with significant chondrogenic potential using BM-MSCs to facilitate the formation of vascularized fibrous tissues and subsequently mimic the tracheal structure and function. The biomimetic tracheas exhibited successful tracheal reconstruction and showed satisfactory therapeutic outcomes in vivo ( Xu et al, 2021 ).…”

“… Xu et al (2021) developed chondroitin-sulfate-incorporated type-II atelocollagen (COL II/CS) biomimetic tracheas with significant chondrogenic potential using BM-MSCs to facilitate the formation of vascularized fibrous tissues and subsequently mimic the tracheal structure and function. The biomimetic tracheas exhibited successful tracheal reconstruction and showed satisfactory therapeutic outcomes in vivo ( Xu et al, 2021 ).…”