Deconstructing tissue engineered trachea: Assessing the role of synthetic scaffolds, segmental replacement and cell seeding on graft performance

Dharmadhikari, Sayali; Liu, Lumei; Shontz, Kimberly M.; Wiet, Matthew; White, Alan; Goins, Andrew; Akula, Himani; Johnson, Jed; Reynolds, Susan D.; Breuer, Christopher K.; Chiang, Tendy

doi:10.1016/j.actbio.2019.11.008

Cited by 31 publications

(64 citation statements)

References 36 publications

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“…Segmental tracheal replacement was performed in C57BL/6 mice using STG ( N = 8) and DTS ( N = 12). 7 Briefly, upon anesthesia and sedation of an animal, a midline incision was made from the sternum to the hyoid bone in an aseptic fashion. The strap muscles were separated, and the trachea was dissected from the recurrent laryngeal nerves and esophagus.…”

Section: Methodsmentioning

confidence: 99%

“…Grafts were sectioned in both axial and longitudinal orientations for pre-implant characterization and in the longitudinal plane following explant to assess the host-graft interface. 7 Grafts ( N = 13) were randomly selected from three separate decellularization cohorts and stained with Masson’s Trichrome, Alcian Blue, and Hematoxylin and Eosin (H&E) (Sigma–Aldrich, St. Louis, MO, USA) to confirm reproducibility of the protocol. Longitudinal sections of explanted tracheal grafts underwent immunofluorescence with quantification of epithelial and endothelial cells.…”

Section: Methodsmentioning

confidence: 99%

“… 5 Allograft outcomes have been limited due to graft immunogenicity and synthetic tracheal scaffolds have exhibited poor epithelialization and neovascularization. 6 , 7 Initially, decellularization was geared toward removal of all native cellular material, thus limiting immunogenicity while preserving a natural scaffold composed of extracellular matrix (ECM). 8 , 9 Decellularized trachea have exhibited regeneration in pre-clinical models, however their clinical applications have remained limited.…”

Section: Introductionmentioning

confidence: 99%

“… 18 , 19 We have developed a mouse model of orthotopic tracheal replacement which permits the assessment of the tracheal replacements in vivo. 7 , 20 Using this model, we studied the impact of partial decellularization on graft matrisome composition, chondrocyte viability, micro-mechanical properties, and evaluated the regenerative capacity of partially decellularized tracheal scaffolds (DTS) in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Regeneration of partially decellularized tracheal scaffolds in a mouse model of orthotopic tracheal replacement

et al. 2021

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Decellularized tracheal scaffolds offer a potential solution for the repair of long-segment tracheal defects. However, complete decellularization of trachea is complicated by tracheal collapse. We created a partially decellularized tracheal scaffold (DTS) and characterized regeneration in a mouse model of tracheal transplantation. All cell populations except chondrocytes were eliminated from DTS. DTS maintained graft integrity as well as its predominant extracellular matrix (ECM) proteins. We then assessed the performance of DTS in vivo. Grafts formed a functional epithelium by study endpoint (28 days). While initial chondrocyte viability was low, this was found to improve in vivo. We then used atomic force microscopy to quantify micromechanical properties of DTS, demonstrating that orthotopic implantation and graft regeneration lead to the restoration of native tracheal rigidity. We conclude that DTS preserves the cartilage ECM, supports neo-epithelialization, endothelialization and chondrocyte viability, and can serve as a potential solution for long-segment tracheal defects.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Regeneration of partially decellularized tracheal scaffolds in a mouse model of orthotopic tracheal replacement

et al. 2021

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“…Recently, tissue engineering technologies based on combinations of autologous cells and biomaterials have been pursued to develop an ideal tracheal substitute ( Park et al, 2019 ; Dharmadhikari et al, 2020 ). However, the clinical performance of tissue-engineered tracheal substitutes has yet to meet its theoretical potential, which is mainly ascribed to their inadequate anatomy and function ( Mansfield et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

3D Printed Biomimetic PCL Scaffold as Framework Interspersed With Collagen for Long Segment Tracheal Replacement

She

Fan

Wang

et al. 2021

Front. Cell Dev. Biol.

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The rapid development of tissue engineering technology has provided new methods for tracheal replacement. However, none of the previously developed biomimetic tracheas exhibit both the anatomy (separated-ring structure) and mechanical behavior (radial rigidity and longitudinal flexibility) mimicking those of native trachea, which greatly restricts their clinical application. Herein, we proposed a biomimetic scaffold with a separated-ring structure: a polycaprolactone (PCL) scaffold with a ring-hollow alternating structure was three-dimensionally printed as a framework, and collagen sponge was embedded in the hollows amid the PCL rings by pouring followed by lyophilization. The biomimetic scaffold exhibited bionic radial rigidity based on compressive tests and longitudinal flexibility based on three-point bending tests. Furthermore, the biomimetic scaffold was recolonized by chondrocytes and developed tracheal cartilage in vitro. In vivo experiments showed substantial deposition of tracheal cartilage and formation of a biomimetic trachea mimicking the native trachea both structurally and mechanically. Finally, a long-segment tracheal replacement experiment in a rabbit model showed that the engineered biomimetic trachea elicited a satisfactory repair outcome. These results highlight the advantage of a biomimetic trachea with a separated-ring structure that mimics the native trachea both structurally and mechanically and demonstrates its promise in repairing long-segment tracheal defects.

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Utilization of an Acellular Cartilage Matrix‐Based Photocrosslinking Hydrogel for Tracheal Cartilage Regeneration and Circumferential Tracheal Repair

Sun

Yang

Wang

et al. 2022

Adv Funct Materials

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Acellular cartilage matrix (ACM)‐based hydrogels hold promise for use in the context of tracheal cartilage regeneration owing to the ease with which they can be molded into specific shapes and their intrinsic cartilage‐specific microenvironmental properties. In this report, an acrylic anhydride‐modified ACM (Ac‐matrix) hydrogel is fabricated for utilization in the context of tracheal cartilage regeneration and circumferential tracheal repair. Hydrogels are successfully prepared with a range of Ac‐matrix concentrations (4%, 6%, and 8%) and found that mechanical strength increases with rising Ac‐matrix concentrations whereas swelling and degradation ratio values decline. These Ac‐matrix hydrogels exhibit satisfactory cytocompatibility when loaded with chondrocytes. Chondrocyte‐loaded 6% hydrogels are able to support cartilage formation both in vitro and in vivo across a range of chondrocyte densities (5, 10, 20, and 40 million chondrocytes per mL), with increasing density being conducive to more homogenous cartilage formation. A homogeneously tubular tracheal cartilage construct is additionally generated and supports circumferential tracheal reconstruction in a rabbit tracheal lesion model system, with a biological structure and function consistent with those of the native trachea. These results suggest that this Ac‐matrix hydrogel platform is well‐suited to use in the context of tracheal cartilage regeneration, thus offering the potential to support circumferential tracheal reconstruction.

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Deconstructing tissue engineered trachea: Assessing the role of synthetic scaffolds, segmental replacement and cell seeding on graft performance

Cited by 31 publications

References 36 publications

Regeneration of partially decellularized tracheal scaffolds in a mouse model of orthotopic tracheal replacement

Regeneration of partially decellularized tracheal scaffolds in a mouse model of orthotopic tracheal replacement

3D Printed Biomimetic PCL Scaffold as Framework Interspersed With Collagen for Long Segment Tracheal Replacement

Utilization of an Acellular Cartilage Matrix‐Based Photocrosslinking Hydrogel for Tracheal Cartilage Regeneration and Circumferential Tracheal Repair

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