Triple-layered polyurethane prosthesis with wrinkles for repairing partial tracheal defects

Lee, Ja H.; Park, Hae S.; Oh, Se Heang; Lee, Jin H.; Kim, Jin R.; Kim, Hee Jin; Jung, Soo Yeon; Chung, Sung Min; Choi, Hong Shik; Kim, Han Soo

doi:10.1002/lary.24809

Cited by 13 publications

(13 citation statements)

References 16 publications

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“…Polyethylene terephthalate (PET) and polyurethane (PU) are FDA-approved polymers that have been used in humans for tracheal tissue engineering. [4][5][6]13 Using a lamb model, we demonstrated that seeding a PET + PU scaffold with autologous bone marrow-derived mononuclear cells (BM-MNC) attenuates stenosis and accelerates epithelialization. 8 However, graft stenosis resulting in airway obstruction is seen in all cases and must be managed with endoscopic interventions.…”

Section: Discussionmentioning

confidence: 99%

Mouse Model of Tracheal Replacement With Electrospun Nanofiber Scaffolds

Dharmadhikari

Best

King

et al. 2019

Ann Otol Rhinol Laryngol

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Objectives: The clinical experience with tissue-engineered tracheal grafts (TETGs) has been fraught with graft stenosis and delayed epithelialization. A mouse model of orthotopic replacement that recapitulates the clinical findings would facilitate the study of the cellular and molecular mechanisms underlying graft stenosis. Methods: Electrospun nanofiber tracheal scaffolds were created using nonresorbable (polyethylene terephthalate + polyurethane) and co-electrospun resorbable (polylactide-co-caprolactone/polyglycolic acid) polymers (n = 10/group). Biomechanical testing was performed to compare load displacement of nanofiber scaffolds to native mouse tracheas. Mice underwent orthotopic tracheal replacement with syngeneic grafts (n = 5) and nonresorbable (n = 10) and resorbable (n = 10) scaffolds. Tissue at the anastomosis was evaluated using hematoxylin and eosin (H&E), K5+ basal cells were evaluated with the help of immunofluorescence testing, and cellular infiltration of the scaffold was quantified. Micro computed tomography was performed to assess graft patency and correlate radiographic and histologic findings with respiratory symptoms. Results: Synthetic scaffolds were supraphysiologic in compression tests compared to native mouse trachea (P < .0001). Nonresorbable scaffolds were stiffer than resorbable scaffolds (P = .0004). Eighty percent of syngeneic recipients survived to the study endpoint of 60 days postoperatively. Mean survival with nonresorbable scaffolds was 11.40 ± 7.31 days and 6.70 ± 3.95 days with resorbable scaffolds (P = .095). Stenosis manifested with tissue overgrowth in nonresorbable scaffolds and malacia in resorbable scaffolds. Quantification of scaffold cellular infiltration correlated with length of survival in resorbable scaffolds (R2 = 0.95, P = .0051). Micro computed tomography demonstrated the development of graft stenosis at the distal anastomosis on day 5 and progressed until euthanasia was performed on day 11. Conclusion: Graft stenosis seen in orthotopic tracheal replacement with synthetic tracheal scaffolds can be modeled in mice. The wide array of lineage tracing and transgenic mouse models available will permit future investigation of the cellular and molecular mechanisms underlying TETG stenosis.

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Section: Discussionmentioning

confidence: 99%

Mouse Model of Tracheal Replacement With Electrospun Nanofiber Scaffolds

Dharmadhikari

Best

King

et al. 2019

Ann Otol Rhinol Laryngol

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“…Bronchoscopy using a rigid 4-mm 0 endoscope (Karl Storz, Tuttlingen, Germany) was performed at 2, 4, 6 and 8 weeks postoperatively (post implantation). The inner surface of the scaffold-grafted areas was examined, and we determined the following [4,7]: (1) narrowing of the lumen, (2) re-epithelization, (3) formation of granulation tissue around the scaffoldgrafted area and (4) integration of the implanted scaffolds. Degree of stenosis was classified on a four-point scale: 0-10%, no narrowing noted; 11-50%, mild narrowing; 51-70%, moderate narrowing; and >71%, severe narrowing.…”

Section: Bronchoscopymentioning

confidence: 99%

“…Partial reconstruction of a human airway with a tissue-engineered prosthesis was successfully performed by Omori et al [6] in 2002. In addition, many types of artificial tracheal patches for partial reconstruction have shown satisfactory experimental results [4,7,8]. In contrast, a circumferential or total reconstruction of trachea is more challenging.…”

Section: Introductionmentioning

confidence: 99%

An omentum-cultured 3D-printed artificial trachea: in vivo bioreactor

Park

Lee

Jung

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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The purpose of this study was to evaluate whether the prior implantation of a 3D-printed polycaprolactone (PCL) artificial trachea in the omentum is beneficial for revascularization of the scaffold and reduces associated complications in the reconstruction of a circumferential tracheal defect. Ten New Zealand rabbits were divided into 2 groups: (1) PCL-OC group (PCL scaffold cultured in omentum for 2 weeks before transplantation) and (2) PCL group. In the PCL-OC group, newly formed connective tissue completely covered the luminal surface of the scaffold with mild inflammation at 2 weeks postoperatively; a minor degree of stenosis was noted at 8 weeks postoperatively. The PCL group showed scaffold exposure without any tissue regeneration at 2 weeks postoperatively, and a moderate degree of luminal stenosis 6 weeks after implantation. Histology revealed highly organized regenerated tissue composed of ciliated respiratory epithelium, and submucosal layer in the PCL-OC group. Neo-cartilage regeneration was noted in part of the regenerated tissue. The PCL group demonstrated severe inflammation and an unorganized structure compared to that of the PCL-OC group. In vivo omentum culture of the tracheal scaffold before transplantation is beneficial for rapid re-epithelialization and revascularization of the scaffold. It also prevents postoperative luminal stenosis.

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“…Polyethylene terephthalate (PET) and polyurethane (PU), which are both FDA-approved polymers, have both been explored in combination and in isolation. [31][32][33] Modification of the PET/PU ratios can result in biomechanical characteristics similar to native trachea. The PET-only grafts demonstrated greater seeded cell retention, but both constructs demonstrated viability in vivo.…”

Section: Scaffoldsmentioning

confidence: 99%

Clinical Translation of Tissue Engineered Trachea Grafts

Chiang

Pepper

Best

et al. 2016

Ann Otol Rhinol Laryngol

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Objective To provide a state-of-the-art review discussing recent achievements in tissue engineered tracheal reconstruction. Data Sources and Review Methods A structured PubMed search of the current literature up to and including October 2015. Representative articles that discuss the translation of tissue engineered tracheal grafts (TETG) were reviewed. Conclusions The integration of a biologically compatible support with autologous cells has resulted in successful regeneration of respiratory epithelium, cartilage, and vascularization with graft patency, although the optimal construct composition has yet to be defined. Segmental TETG constructs are more commonly complicated by stenosis and delayed epithelialization when compared to patch tracheoplasty. Implications for Practice The recent history of human TETG recipients represents revolutionary proof of principle studies in regenerative medicine. Application of TETG remains limited to a compassionate use basis; however, defining the mechanisms of cartilage formation, epithelialization, and refinement of in vivo regeneration will advance the translation of TETG from the bench to the bedside.

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Triple-layered polyurethane prosthesis with wrinkles for repairing partial tracheal defects

Abstract: NA.

Cited by 13 publications

References 16 publications

Mouse Model of Tracheal Replacement With Electrospun Nanofiber Scaffolds

Mouse Model of Tracheal Replacement With Electrospun Nanofiber Scaffolds

An omentum-cultured 3D-printed artificial trachea: in vivo bioreactor

Clinical Translation of Tissue Engineered Trachea Grafts

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