Engineered Tissue–Stent Biocomposites as Tracheal Replacements

Zhao, Liping; Sundaram, Sumati; Le, Andrew; Huang, Angela; Zhang, Jiasheng; Hatachi, Go; Beloiartsev, Arkadi; Caty, Michael G.; Yi, Tai; Leiby, Katherine L.; Gard, Ashley L.; Kural, Mehmet H.; Gui, Liqiong; Rocco, Kevin A.; Sivarapatna, Amogh; Calle, Elizabeth A.; Greaney, Allison M.; Urbani, Luca; Maghsoudlou, Panagiotis; Burns, Alan J.; Coppi, Paolo De; Niklason, Laura E.

doi:10.1089/ten.tea.2016.0132

Cited by 33 publications

(33 citation statements)

References 46 publications

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“…Other studies investigated the mechanics of the lung as an entire functioning organ, and only a few explicitly considered the airways beyond the trachea, which support pulmonary function and are the sites of obstruction upon collapse due to remodeling and disease (25,51,59). Although research regarding tracheomalacia and tracheal stent replacements benefit from these explorations, the vast majority of lung diseases are intraparenchymal, impacting the smaller bronchioles observed to occlude during expiation, for which no mechanical property data are currently available (32,36,69). Furthermore, the time-dependent mechanical responses of the airways have been minimally investigated, whereas they have been thoroughly documented and shown to be physiologically relevant in other organs (18,56).…”

Section: Motivationmentioning

confidence: 99%

Mechanical properties of the airway tree: heterogeneous and anisotropic pseudoelastic and viscoelastic tissue responses

Eskandari

Arvayo

Levenston

2018

Journal of Applied Physiology

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Airway obstruction and pulmonary mechanics remain understudied despite lung disease being the third cause of death in the United States. Lack of relevant data has led computational pulmonary models to infer mechanical properties from available material data for the trachea. Additionally, the time-dependent, viscoelastic behaviors of airways have been largely overlooked, despite their potential physiological relevance and utility as metrics of tissue remodeling and disease progression. Here, we address the clear need for airway-specific material characterization to inform biophysical studies of the bronchial tree. Specimens from three airway levels (trachea, large bronchi, and small bronchi) and two orientations (axial and circumferential) were prepared from five fresh pig lungs. Uniaxial tensile tests revealed substantial heterogeneity and anisotropy. Overall, the linear pseudoelastic modulus was significantly higher axially than circumferentially (30.5 ± 3.1 vs. 8.4 ± 1.1 kPa) and significantly higher among circumferential samples for small bronchi than for the trachea and large bronchi (12.5 ± 1.9 vs. 6.0 ± 0.6 and 6.6 ± 0.9 kPa). Circumferential samples exhibited greater percent stress relaxation over 300 s than their axial counterparts (38.0 ± 1.4 vs. 23.1 ± 1.5%). Axial and circumferential trachea samples displayed greater percent stress relaxation (26.4 ± 1.6 and 42.5 ± 1.7%) than corresponding large and small bronchi. This ex vivo pseudoelastic and viscoelastic characterization reveals novel anisotropic and heterogeneous behaviors and equips us to construct airway-specific constitutive relations. Our results establish necessary fundamentals for airway mechanics, laying the groundwork for future studies to extend to clinical questions surrounding lung injury, and further directly enables computational tools for lung disease obstruction predictions. NEW & NOTEWORTHY Understanding the mechanics of the lung is necessary for investigating disease progression. Trachea mechanics comprises the vast majority of ex vivo airway tissue characterization despite distal airways being the site of disease manifestation and occlusion. Furthermore, viscoelastic studies are scarce, whereas time-dependent behaviors could be potential physiological metrics of tissue remodeling. In this study, the critical need for airway-specific material properties is addressed, reporting bronchial tree anisotropic and heterogeneous material properties.

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Section: Motivationmentioning

confidence: 99%

Mechanical properties of the airway tree: heterogeneous and anisotropic pseudoelastic and viscoelastic tissue responses

Eskandari

Arvayo

Levenston

2018

Journal of Applied Physiology

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“…Techniques to improve the quality of cells for transplantation, either through adult stem cell isolation and expansion [11] or induced pluripotent stem (iPS) cell technology [12] , [13] , [14] , [15] , [16] , are being investigated but the scaffolds onto which cells are seeded also need to be refined. There is currently little consensus on the optimal scaffold for tracheal bioengineering purposes with decellularized [6] , [8] , synthetic [17] and hybrid stent-based [18] scaffolds at various stages of development.…”

Section: Introductionmentioning

confidence: 99%

Vacuum-assisted decellularization: an accelerated protocol to generate tissue-engineered human tracheal scaffolds

et al. 2017

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Patients with large tracheal lesions unsuitable for conventional endoscopic or open operations may require a tracheal replacement but there is no present consensus of how this may be achieved. Tissue engineering using decellularized or synthetic tracheal scaffolds offers a new avenue for airway reconstruction. Decellularized human donor tracheal scaffolds have been applied in compassionate-use clinical cases but naturally derived extracellular matrix (ECM) scaffolds demand lengthy preparation times. Here, we compare a clinically applied detergent-enzymatic method (DEM) with an accelerated vacuum-assisted decellularization (VAD) protocol. We examined the histological appearance, DNA content and extracellular matrix composition of human donor tracheae decellularized using these techniques. Further, we performed scanning electron microscopy (SEM) and biomechanical testing to analyze decellularization performance. To assess the biocompatibility of scaffolds generated using VAD, we seeded scaffolds with primary human airway epithelial cells in vitro and performed in vivo chick chorioallantoic membrane (CAM) and subcutaneous implantation assays. Both DEM and VAD protocols produced well-decellularized tracheal scaffolds with no adverse mechanical effects and scaffolds retained the capacity for in vitro and in vivo cellular integration. We conclude that the substantial reduction in time required to produce scaffolds using VAD compared to DEM (approximately 9 days vs. 3–8 weeks) does not compromise the quality of human tracheal scaffold generated. These findings might inform clinical decellularization techniques as VAD offers accelerated scaffold production and reduces the associated costs.

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“…Recent advancements in tracheal grafts are broadly focused on preventing adverse host response, [73][74][75] capturing complex native mechanical behavior, [76][77][78][79][80][81] and improving functional integration upon implantation. 76,[82][83][84][85] The Cho group of South Korea has developed a polymeric tracheal replacement graft designed with a ''bellows'' configuration, comprising polycaprolactone, to attempt to capture native-like structure and mechanical behavior. 77 The host response to the bellows-type implant was not significantly more inflammatory than a syngeneic allograft.…”

Section: Preclinical Promisementioning

confidence: 99%

The History of Engineered Tracheal Replacements: Interpreting the Past and Guiding the Future

Greaney

Niklason

2021

Tissue Engineering Part B: Reviews

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The development of a tracheal graft to replace long-segment defects has thwarted clinicians and engineers alike for over 100 years. To better understand the challenges facing this field today, we have consolidated all published reports of engineered tracheal grafts used to repair long-segment circumferential defects in humans, from the first in 1898 to the most recent in 2018, totaling 290 clinical cases. Distinct trends emerge in the types of grafts used over time, including repair using autologous fascia, rigid tubes of various inert materials, and pretreated cadaveric allografts. Our analysis of maximum clinical follow-up, as a proxy for graft performance, revealed that the Leuven protocol has a significantly longer clinical follow-up time than all other methods of airway reconstruction. This method involves transplanting a cadaveric tracheal allograft that is first prevascularized heterotopically in the recipient. We further quantified graft-related causes of mortality, revealing failure modes that have been resolved, and those that remain a hurdle, such as graft mechanics. Finally, we briefly summarize recent preclinical work in tracheal graft development. In conclusion, we synthesized top clinical care priorities and design criteria to inform and inspire collaboration between engineers and clinicians toward the development of a functional tracheal replacement graft.

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Engineered Tissue–Stent Biocomposites as Tracheal Replacements

Cited by 33 publications

References 46 publications

Mechanical properties of the airway tree: heterogeneous and anisotropic pseudoelastic and viscoelastic tissue responses

Mechanical properties of the airway tree: heterogeneous and anisotropic pseudoelastic and viscoelastic tissue responses

Vacuum-assisted decellularization: an accelerated protocol to generate tissue-engineered human tracheal scaffolds

The History of Engineered Tracheal Replacements: Interpreting the Past and Guiding the Future

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