A two-stage in vivo approach for implanting a 3D printed tissue-engineered tracheal replacement graft: A proof of concept

Frejo, Lidia; Goldstein, Todd; Swami, Pooja; Patel, Neha A.; Grande, Daniel; Zeltsman, David; Smith, Lee P.

doi:10.1016/j.ijporl.2022.111066

Cited by 10 publications

(8 citation statements)

References 51 publications

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“…Typically, tissues matrix distinguishes fibrous elements (e.g., collagen and elastic fibers) and macromolecules (e.g., proteoglycans) organized in a network [ 141 ]. As regards the trachea, its viscoelastic properties convey from its ECM composition of glycosaminoglycans (15–30%), collagen (50–75%), and water (70–80%) [ 142 , 143 ]. Although ionic detergents in tracheal decellularization are very successful, they may affect the natural tissue structure disrupting ECM structure, eliminating growth factors and/or denaturing essential proteins [ 124 , 144 ]; thus, the non-ionic detergent Tergitol TM was preferred.…”

Section: Discussionmentioning

confidence: 99%

“…Masson’s Trichrome staining confirmed collagen maintenance in DecellT and CryoT at the cartilagineous compartment, with a histological appearance resembling that of NativeT. This is essential to assure cartilage integrity [ 143 ]. This evidence was also supported by quantification analysis, showing no differences among groups at this level.…”

Section: Discussionmentioning

confidence: 99%

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Development and In Vitro/In Vivo Comparative Characterization of Cryopreserved and Decellularized Tracheal Grafts

Stocco

Barbon

Mammana

et al. 2023

Cells

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Tracheal reconstruction represents a challenge when primary anastomosis is not feasible. Within this scenario, the study aim was to develop a new pig-derived decellularized trachea (DecellT) to be compared with the cryopreserved counterpart (CryoT) for a close predictive analysis. Tracheal segments underwent decellularization by a physical + enzymatic + chemical method (12 cycles); in parallel, cryopreserved samples were also prepared. Once decellularized (histology/DNA quantification), the two groups were characterized for Alpha-Gal epitopes/structural proteins (immunohistochemistry/histology/biochemical assays/second harmonic generation microscopy)/ultrastructure (Scanning Electron Microscopy (SEM))/mechanical behaviour. Cytotoxicity absence was assessed in vitro (extract-test assay/direct seeding, HM1SV40 cell line) while biocompatibility was verified in BALB/c mice, followed by histological/immunohistochemical analyses and SEM (14 days). Decellularization effectively removed Alpha-Gal epitopes; cartilage histoarchitecture was retained in both groups, showing chondrocytes only in the CryoT. Cryopreservation maintained few respiratory epithelium sparse cilia, not detectable in DecellT. Focusing on ECM, preserved structural/ultrastructural organization and collagen content were observed in the cartilage of both; conversely, the GAGs were significantly reduced in DecellT, as confirmed by mechanical study results. No cytotoxicity was highlighted by CryoT/DecellT in vitro, as they were also corroborated by a biocompatibility assay. Despite some limitations (cells presence/GAGs reduction), CryoT/DecellT are both appealing options, which warrant further investigation in comparative in vivo studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Development and In Vitro/In Vivo Comparative Characterization of Cryopreserved and Decellularized Tracheal Grafts

Stocco

Barbon

Mammana

et al. 2023

Cells

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“…For examples, 3D bioprinting has gained a significant amount of attention as it enables the fabrication of tissue‐engineered constructs with complex structures. As such, 3D bioprinting techniques have been utilized to generate scaffolds for diverse tissues, including skin, 57 cartilage, 58 bone, 59 and trachea 60 . Notably, regardless of types of cells, pH of collagen‐based bioinks were adjusted mostly to be neutralized.…”

Section: Discussionmentioning

confidence: 99%

“…As such, 3D bioprinting techniques have been utilized to generate scaffolds for diverse tissues, including skin, 57 cartilage, 58 bone, 59 and trachea. 60 Notably, regardless of types of cells, pH of collagen-based bioinks were adjusted mostly to be neutralized. Therefore, considering the biological and structural effects of gelation pH on cells and collagen gel, the cell-specific validation of gelation pH is likely to enhance advantages of 3D printing technique.…”

Section: Discussionmentioning

confidence: 99%

Controlling collagen gelation pH to enhance biochemical, structural, and biomechanical properties of tissue‐engineered menisci

Kim

Bonassar

2022

J Biomedical Materials Res

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Collagen‐based hydrogels have been widely used in biomedical applications due to their biocompatibility. Enhancing mechanical properties of collagen gels remains challenging while maintaining biocompatibility. Here, we demonstrate that gelation pH has profound effects on cellular activity, collagen fibril structure, and mechanical properties of the fibrochondrocyte‐seeded collagen gels in both short‐ and long‐terms. Acidic and basic gelation pH, below pH 7.0 and above 8.5, resulted in dramatic cell death. Gelation pH ranging from 7.0 to 8.5 showed a relatively high cell viability. Furthermore, physiologic gelation (pH 7.5) showed the greatest collagen deposition while glycosaminoglycan deposition appeared independent of gelation pH. Scanning electron microscopy showed that neutral and physiologic gelation pH, 7.0 and 7.5, exhibited well‐aligned collagen fibril structure on day 0 and enhanced collagen fibril structure with laterally joined fibrils on day 30. However, basic pH, 8.0 and 8.5, displayed a densely packed collagen fibril structure on day 0, which was also persistent on day 30. Initial equilibrium modulus increased with increasing gelation pH. Notably, after 30 days of culture, gelation pH of 7.5 and 8.0 showed the highest equilibrium modulus, reaching 150 –160 kPa. While controlling gelation pH is simply achieved compared with other strategies to improve mechanical properties, its influences on biochemical and biomechanical properties of the collagen gel are long‐lasting. As such, gelation pH is a useful means to modulate both biochemical and biomechanical properties of the collagen‐based hydrogels and can be utilized for diverse types of tissue engineering due to its simple application.

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“…To successfully develop an ideal and functional tracheal graft, native trachea characteristics, from anatomy to biomechanics, must be considered and matched. 26 The trachea is a vascularized hollow tubular structure, laterally rigid (to prevent collapse) and longitudinally flexible (to follow head/neck movements). 27 It starts at C6 level, following the laryngeal cricoid cartilage, up to the carina, at T4; hence it can be divided in two segments: cervical (C6-C7) and thoracic (T1-T4).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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Severe tracheal injuries that cannot be managed by mobilization and end-to-end anastomosis represent an unmet clinical need and an urgent challenge to face in surgical practice; within this scenario, decellularized scaffolds (eventually bioengineered) are currently a tempting option among tissue engineered substitutes. The success of a decellularized trachea is expression of a balanced approach in cells removal while preserving the extracellular matrix (ECM) architecture/mechanical properties. Revising the literature, many Authors report about different methods for acellular tracheal ECMs development; however, only few of them verified the devices effectiveness by an orthotopic implant in animal models of disease. To support translational medicine in this field, here we provide a systematic review on studies recurring to decellularized/bioengineered tracheas implantation. After describing the specific methodological aspects, orthotopic implant results are verified. Furtherly, the only three clinical cases of compassionate use of tissue engineered tracheas are reported with a focus on outcomes.

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A two-stage in vivo approach for implanting a 3D printed tissue-engineered tracheal replacement graft: A proof of concept

Cited by 10 publications

References 51 publications

Development and In Vitro/In Vivo Comparative Characterization of Cryopreserved and Decellularized Tracheal Grafts

Development and In Vitro/In Vivo Comparative Characterization of Cryopreserved and Decellularized Tracheal Grafts

Controlling collagen gelation pH to enhance biochemical, structural, and biomechanical properties of tissue‐engineered menisci

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

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