Functional Trachea Reconstruction Using 3D‐Bioprinted Native‐Like Tissue Architecture Based on Designable Tissue‐Specific Bioinks

Abstract

Functional segmental trachea reconstruction remains a remarkable challenge in the clinic. To date, functional trachea regeneration with alternant cartilage‐fibrous tissue‐mimetic structure similar to that of the native trachea relying on the three‐dimensional (3D) bioprinting technology has seen very limited breakthrough. This fact is mostly due to the lack of tissue‐specific bioinks suitable for both cartilage and vascularized fibrous tissue regeneration, as well as the need for firm interfacial integration between stiff and soft tissues. Here, a novel strategy is developed for 3D bioprinting of cartilage‐vascularized fibrous tissue‐integrated trachea (CVFIT), utilizing photocrosslinkable tissue‐specific bioinks. Both cartilage‐ and fibrous tissue‐specific bioinks created by this study provide suitable printability, favorable biocompatibility, and biomimetic microenvironments for chondrogenesis and vascularized fibrogenesis based on the multicomponent synergistic effect through the hybrid photoinitiated polymerization reaction. As such, the tubular analogs are successfully bioprinted and the ring‐to‐ring alternant structure is tightly integrated by the enhancement of interfacial bonding through the amidation reaction. The results from both the trachea regeneration and the in situ trachea reconstruction demonstrate the satisfactory tissue‐specific regeneration along with realization of mechanical and physiological functions. This study thus illustrates the 3D‐bioprinted native tissue‐like trachea as a promising alternative for clinical trachea reconstruction.

Fabrication of biphasic cartilage-bone integrated scaffolds based on tissue-specific photo-crosslinkable acellular matrix hydrogels

“…Currently, photo-crosslinkable hydrogels based on tissue-specific decellularized extracellular matrix (dECM) have been considered one of the most suitable choices to fabricate biomimetic scaffolds, because of the spatiotemporal controllability of the photo-crosslinking method [ [21] , [22] , [23] , [24] , [25] , [26] ] and the accurate microenvironment biomimic of tissue-specific dECM with respect to intricate composition, architecture, and topological structure [ [27] , [28] , [29] , [30] , [31] ]. To date, photo-crosslinkable dECM-derived scaffolds have mainly focused on soft tissue and organs, such as kidney or muscle [ 30 , 31 ], and few studies have reported constructing dECM-derived photo-crosslinkable hydrogels based on hard tissue, such as cartilage or bone [ [32] , [33] , [34] , [35] ]. Due to the compact structure of cartilage and highly mineralized components of bone [ [36] , [37] , [38] ], they are both quite difficult to prepare as soluble photo-crosslinkable dECM hydrogel.…”

Reconstruction of tracheal window-shape defect by 3D printed polycaprolatone scaffold coated with Silk Fibroin Methacryloyl

“…The maintenance of longitudinal tension and radial compression mechanical properties is an important factor to prevent airway collapse. [38] The stretched and compression test results of this study showed that the longitudinal and radial mechanical properties of 3D printed PCL scaffold and the hybrid scaffold were significantly better than native trachea. However, in the stretched process, the longitudinal ductility of native trachea was better than PCL and the hybrid scaffold, which may be related to the own physical properties of the material.…”

Preclinical and clinical orthotopic transplantation of decellularized/engineered tracheal scaffolds: A systematic literature review

“…Homogeneous cartilage regeneration was observed in presence of the higher matrix content and derived 3D, tubular, trachea-shaped devices also revealed efficient in circumferential tracheal lesion repair in rabbit. Additionally, Huo et al, 120 reported the efficient fabrication of a “cartilage-vascularized fibrous tissue-integrated trachea,” recurring to 3D-bioprinting and new photocrosslinkable tissue-specific bioinks loaded with chondrocytes/fibroblasts. The inks were made of [methacryloyl-modified gelatin, chondroitin sulfate, and cartilage acellular matrix] (the first) and [methacrylate-modified hyaluronic acid, 8-arm-polyethylene glycol-succinic acid ester and methacryloyl-modified derm acellular matrix] (the second).…”