Evaluation of Bilayer Silk Fibroin Grafts for Tubular Esophagoplasty in a Porcine Defect Model

Gündoğdu, Gökhan; Morhardt, Duncan R.; Cristofaro, Vivian; Algarrahi, Khalid; Yang, Xuehui; Costa, Kyle; Alegria, Cinthia Galvez; Sullivan, Maryrose P.; Mauney, Joshua R.

doi:10.1089/ten.tea.2020.0061

Cited by 9 publications

(6 citation statements)

References 39 publications

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“…Indeed, BLSF grafts were capable of promoting multi-layered, urothelial formation in neotissues with prominent UP3A and pan-CK protein expression. This pattern of constructive remodeling is similar to our previous observations using BLSF scaffolds for bladder and esophageal tissue repair (Affas et al, 2019;Gundogdu et al, 2021).…”

Section: Discussionsupporting

confidence: 90%

“…However, histological and IHC evaluations confirmed that central neotissue areas supported by BLSF grafts were immature at sacrifice relative to peripheral neotissues and NSC suggesting longer periods of stenting may be necessary for complete regeneration and stricture prevention. Indeed, the duration of stent deployment has been shown to play a major role in determining the risk of stricture occurrence in reconstructed visceral hollow organs (Takimoto et al, 1994;Gundogdu et al, 2021). In addition, the in vivo degradation profile of BLSF matrices was also found to be insufficient for maintaining upper urinary tract function following stent removal.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Bi-Layer Silk Fibroin Grafts for Tubular Ureteroplasty in a Porcine Defect Model

Gündoğdu

Okhunov

Cristofaro

et al. 2021

Front. Bioeng. Biotechnol.

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Ureteral reconstruction with autologous tissue grafts is often limited by tissue availability and donor site morbidity. This study investigates the performance of acellular, bi-layer silk fibroin (BLSF) scaffolds in a porcine model of ureteroplasty. Tubular ureteroplasty with BLSF grafts in combination with transient stenting for 8 weeks was performed in adult female, Yucatan, mini-swine (N = 5). Animals were maintained for 12 weeks post-op with imaging of neoconduits using ultrasonography and retrograde ureteropyelography carried out at 2 and 4 weeks intervals. End-point analyses of ureteral neotissues and unoperated controls included histological, immunohistochemical (IHC), histomorphometric evaluations as well as ex vivo functional assessments of contraction/relaxation. All animals survived until scheduled euthanasia and displayed mild hydronephrosis (Grades 1-2) in reconstructed collecting systems during the 8 weeks stenting period with one animal presenting with a persistent subcutaneous fistula at 2 weeks post-op. By 12 weeks of scaffold implantation, unstented neoconduits led to severe hydronephrosis (Grade 4) and stricture formation in the interior of graft sites in 80% of swine. Bulk scaffold extrusion into the distal ureter was also apparent in 60% of swine contributing to ureteral obstruction. However, histological and IHC analyses revealed the formation of innervated, vascularized neotissues with a-smooth muscle actin+ and SM22α+ smooth muscle bundles as well as uroplakin 3A+ and pan-cytokeratin + urothelium. Ex vivo contractility and relaxation responses of neotissues were similar to unoperated control segments. BLSF biomaterials represent emerging platforms for tubular ureteroplasty, however further optimization is needed to improve in vivo degradation kinetics and mitigate stricture formation.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Evaluation of Bi-Layer Silk Fibroin Grafts for Tubular Ureteroplasty in a Porcine Defect Model

Gündoğdu

Okhunov

Cristofaro

et al. 2021

Front. Bioeng. Biotechnol.

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“…Our results suggest that the deployment of caspase inhibitors to encourage www.nature.com/scientificreports/ esophageal tissue regeneration may be a promising therapeutic approach in cases wherein epithelial formation is impeded following surgical reconstruction. Preclinical investigations of acellular biomaterials for reconstruction of long-gap, tubular esophageal defects often show deficiencies in the ability of tissue engineered grafts to support skeletal muscle formation as well as de novo vascularization and innervation of neotissues 44,45 . A better understanding of signal transduction pathways which govern myogenesis, neurogenesis, and vascularization during healing of patch defects as described in the current study may inform the development of instructive biomaterial designs which can improve tubular neotissue maturation via controlled release of selective pathway agonists.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts

Gündoğdu

Tosun

Morhardt

et al. 2021

Sci Rep

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Constructive remodeling of focal esophageal defects with biodegradable acellular grafts relies on the ability of host progenitor cell populations to repopulate implant regions and facilitate growth of de novo functional tissue. Intrinsic molecular mechanisms governing esophageal repair processes following biomaterial-based, surgical reconstruction is largely unknown. In the present study, we utilized mass spectrometry-based quantitative proteomics and in silico pathway evaluations to identify signaling cascades which were significantly activated during neoepithelial formation in a Sprague Dawley rat model of onlay esophagoplasty with acellular silk fibroin scaffolds. Pharmacologic inhibitor and rescue experiments revealed that epithelialization of neotissues is significantly dependent in part on pro-survival stimuli capable of suppressing caspase activity in epithelial progenitors via activation of hepatocyte growth factor receptor (c-MET), tropomyosin receptor kinase A (TrkA), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) signaling mechanisms. These data highlight the molecular machinery involved in esophageal epithelial regeneration following surgical repair with acellular implants.

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“…The multi-step method is based on the perspective of esophageal structure bionics, combining different layers of scaffold materials through a certain link method. Joshua et al prepared the silk fibroin double-layer scaffold by solution pouring ( Gundogdu et al, 2021 ). Rossella et al used electrospinning and temperature-induced sedimentation to construct two double-layer scaffolds ( Pisani et al, 2020 ).…”

Section: Multi-layer Esophageal Scaffoldsmentioning

confidence: 99%

“…If the adhesion between scaffolds is poor, the multi-layer scaffolds will fall off or shift, which will seriously affect the repair effect of the esophagus. The connection modes between the layers of multi-layer scaffolds include the solution casting method ( Gundogdu et al, 2021 ), temperature-induced precipitation method ( Dorati et al, 2017 ), solvent volatilization method of electrospinning ( Chung et al, 2015 ), and glue bonding ( Deng et al, 2019 ). The first three methods are not universally applicable because solutions or solvents may dissolve the active components such as protein, growth factor in the scaffold, and too high or low temperature is not conducive to the introduction of proteins and cells into the scaffold.…”

Section: Problems and Challengesmentioning

confidence: 99%

Development and Prospect of Esophageal Tissue Engineering

Fang

et al. 2022

Front. Bioeng. Biotechnol.

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Currently, patients with esophageal cancer, especially advanced patients, usually use autologous tissue for esophageal alternative therapy. However, an alternative therapy is often accompanied by serious complications such as ischemia and leakage, which seriously affect the prognosis of patients. Tissue engineering has been widely studied as one of the ideal methods for the treatment of esophageal cancer. In view of the complex multi-layer structure of the natural esophagus, how to use the tissue engineering method to design the scaffold with structure and function matching with the natural tissue is the principle that the tissue engineering method must follow. This article will analyze and summarize the construction methods, with or without cells, and repair effects of single-layer scaffold and multi-layer scaffold. Especially in the repair of full-thickness and circumferential esophageal defects, the flexible design method and the binding force between the layers of the scaffold are very important. In short, esophageal tissue engineering technology has broad prospects and plays a more and more important role in the treatment of esophageal diseases.

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Evaluation of Bilayer Silk Fibroin Grafts for Tubular Esophagoplasty in a Porcine Defect Model

Cited by 9 publications

References 39 publications

Evaluation of Bi-Layer Silk Fibroin Grafts for Tubular Ureteroplasty in a Porcine Defect Model

Evaluation of Bi-Layer Silk Fibroin Grafts for Tubular Ureteroplasty in a Porcine Defect Model

Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts

Development and Prospect of Esophageal Tissue Engineering

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