TY - JOUR
T1 - Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon
AU - Shi, Guidong
AU - Koichi, Nakagawa
AU - Wan, Rou
AU - Wang, Yicun
AU - Reisdorf, Ramona
AU - Wilson, Abigayle
AU - Huang, Tony C.T.
AU - Amadio, Peter C.
AU - Meves, Alexander
AU - Zhao, Chunfeng
AU - Moran, Steven L.
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2024/3
Y1 - 2024/3
N2 - 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.
AB - 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.
KW - Adhesion
KW - Flexor tendon repair
KW - Gelatin
KW - Pentamidine
KW - Turkey model
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U2 - 10.1016/j.jot.2023.10.007
DO - 10.1016/j.jot.2023.10.007
M3 - Article
AN - SCOPUS:85187674141
SN - 2214-031X
VL - 45
SP - 75
EP - 87
JO - Journal of Orthopaedic Translation
JF - Journal of Orthopaedic Translation
ER -