Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon

Background: Prevention of adhesion formation following flexor tendon repair is essential for restoration of normal finger function. Although many medications have been studied in the experimental setting to prevent adhesions, clinical application is limited due to the complexity of application and d...

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Main Authors: Guidong Shi, Nakagawa Koichi, Rou Wan, Yicun Wang, Ramona Reisdorf, Abigayle Wilson, Tony C.T. Huang, Peter C. Amadio, Alexander Meves, Chunfeng Zhao, Steven L. Moran
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Journal of Orthopaedic Translation
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2214031X23000815
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author Guidong Shi
Nakagawa Koichi
Rou Wan
Yicun Wang
Ramona Reisdorf
Abigayle Wilson
Tony C.T. Huang
Peter C. Amadio
Alexander Meves
Chunfeng Zhao
Steven L. Moran
author_facet Guidong Shi
Nakagawa Koichi
Rou Wan
Yicun Wang
Ramona Reisdorf
Abigayle Wilson
Tony C.T. Huang
Peter C. Amadio
Alexander Meves
Chunfeng Zhao
Steven L. Moran
author_sort Guidong Shi
collection DOAJ
description Background: Prevention of adhesion formation following flexor tendon repair is essential for restoration of normal finger function. Although many medications have been studied in the experimental setting to prevent adhesions, clinical application is limited due to the complexity of application and delivery in clinical translation. Methods: In this study, optimal dosages of gelatin and pentamidine were validated by gelatin concentration test. Following cell viability, cell migration, live and dead cell, and cell adhesion assay of the Turkey tenocytes, a model of Turkey tendon repair was established to evaluate the effectiveness of the Pentamidine-Gelatin sheet. Results: Pentamidine carried with gelatin, a Food and drug administration (FDA) approved material for drug delivery, showed good dynamic release, biocompatibility, and degradation. The optimal dose of pentamidine (25ug) was determined in the in vivo study using tenocyte viability, migration, and cell adhesion assays. Further biochemical analyses demonstrated that this positive effect may be due to pentamidine downregulating the Wnt signaling pathway without affecting collagen expression. Conclusions: We tested a FDA-approved antibiotic, pentamidine, for reducing adhesion formation after flexor tendon repair in both in vitro and in vivo using a novel turkey animal model. Compared with the non-pentamidine treatment group, pentamidine treated turkeys had significantly reduced adhesions and improved digit function after six weeks of tendon healing. The translational potential of this article: This study for the first time showed that a common clinical drug, pentamidine, has a potential for clinical application to reduce tendon adhesions and improve tendon gliding function without interfering with tendon healing.
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spelling doaj.art-a233358cd01c4567869a118bea43c66f2024-04-18T04:20:25ZengElsevierJournal of Orthopaedic Translation2214-031X2024-03-01457587Pentamidine-loaded gelatin decreases adhesion formation of flexor tendonGuidong Shi0Nakagawa Koichi1Rou Wan2Yicun Wang3Ramona Reisdorf4Abigayle Wilson5Tony C.T. Huang6Peter C. Amadio7Alexander Meves8Chunfeng Zhao9Steven L. Moran10Department of Orthopaedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USADepartment of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USADepartment of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USADepartment of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USADepartment of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USADepartment of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USADivision of Plastic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USADepartment of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USADepartment of Dermatology, Mayo Clinic, Rochester, MN, USADepartment of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; Corresponding author. Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.Division of Plastic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA; Corresponding author. Division of Plastic Surgery, Mayo Clinic 200 First Street SW, Rochester, MN, 55905, USA.Background: Prevention of adhesion formation following flexor tendon repair is essential for restoration of normal finger function. Although many medications have been studied in the experimental setting to prevent adhesions, clinical application is limited due to the complexity of application and delivery in clinical translation. Methods: In this study, optimal dosages of gelatin and pentamidine were validated by gelatin concentration test. Following cell viability, cell migration, live and dead cell, and cell adhesion assay of the Turkey tenocytes, a model of Turkey tendon repair was established to evaluate the effectiveness of the Pentamidine-Gelatin sheet. Results: Pentamidine carried with gelatin, a Food and drug administration (FDA) approved material for drug delivery, showed good dynamic release, biocompatibility, and degradation. The optimal dose of pentamidine (25ug) was determined in the in vivo study using tenocyte viability, migration, and cell adhesion assays. Further biochemical analyses demonstrated that this positive effect may be due to pentamidine downregulating the Wnt signaling pathway without affecting collagen expression. Conclusions: We tested a FDA-approved antibiotic, pentamidine, for reducing adhesion formation after flexor tendon repair in both in vitro and in vivo using a novel turkey animal model. Compared with the non-pentamidine treatment group, pentamidine treated turkeys had significantly reduced adhesions and improved digit function after six weeks of tendon healing. The translational potential of this article: This study for the first time showed that a common clinical drug, pentamidine, has a potential for clinical application to reduce tendon adhesions and improve tendon gliding function without interfering with tendon healing.http://www.sciencedirect.com/science/article/pii/S2214031X23000815AdhesionFlexor tendon repairGelatinPentamidineTurkey model
spellingShingle Guidong Shi
Nakagawa Koichi
Rou Wan
Yicun Wang
Ramona Reisdorf
Abigayle Wilson
Tony C.T. Huang
Peter C. Amadio
Alexander Meves
Chunfeng Zhao
Steven L. Moran
Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon
Journal of Orthopaedic Translation
Adhesion
Flexor tendon repair
Gelatin
Pentamidine
Turkey model
title Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon
title_full Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon
title_fullStr Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon
title_full_unstemmed Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon
title_short Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon
title_sort pentamidine loaded gelatin decreases adhesion formation of flexor tendon
topic Adhesion
Flexor tendon repair
Gelatin
Pentamidine
Turkey model
url http://www.sciencedirect.com/science/article/pii/S2214031X23000815
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