Peripheral nerve regeneration using a bioresorbable silk fibroin-based artificial nerve conduit fabricated via a novel freeze–thaw process

Abstract While silk fibroin (SF) obtained from silkworm cocoons is expected to become a next-generation natural polymer, a fabrication method for SF-based artificial nerve conduits (SFCs) has not yet been established. Here, we report a bioresorbable SFC, fabricated using a novel freeze–thaw process,...

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Main Authors: Tomoki Matsuo, Hiroo Kimura, Takayuki Nishijima, Yasuhiro Kiyota, Taku Suzuki, Narihito Nagoshi, Shinsuke Shibata, Tomoko Shindo, Nobuko Moritoki, Makoto Sasaki, Sarara Noguchi, Yasushi Tamada, Masaya Nakamura, Takuji Iwamoto
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-88221-y
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author Tomoki Matsuo
Hiroo Kimura
Takayuki Nishijima
Yasuhiro Kiyota
Taku Suzuki
Narihito Nagoshi
Shinsuke Shibata
Tomoko Shindo
Nobuko Moritoki
Makoto Sasaki
Sarara Noguchi
Yasushi Tamada
Masaya Nakamura
Takuji Iwamoto
author_facet Tomoki Matsuo
Hiroo Kimura
Takayuki Nishijima
Yasuhiro Kiyota
Taku Suzuki
Narihito Nagoshi
Shinsuke Shibata
Tomoko Shindo
Nobuko Moritoki
Makoto Sasaki
Sarara Noguchi
Yasushi Tamada
Masaya Nakamura
Takuji Iwamoto
author_sort Tomoki Matsuo
collection DOAJ
description Abstract While silk fibroin (SF) obtained from silkworm cocoons is expected to become a next-generation natural polymer, a fabrication method for SF-based artificial nerve conduits (SFCs) has not yet been established. Here, we report a bioresorbable SFC, fabricated using a novel freeze–thaw process, which ensures biosafety by avoiding any harmful chemical additives. The SFC demonstrated favorable biocompatibility (high hydrophilicity and porosity with a water content of > 90%), structural stability (stiffness, toughness, and elasticity), and biodegradability, making it an ideal candidate for nerve regeneration. We evaluated the nerve-regenerative effects of the SFC in a rat sciatic-nerve-defect model, including its motor and sensory function recovery as well as histological regeneration. We found that SFC transplantation significantly promoted functional recovery and nerve regeneration compared to silicone tubes and was almost equally effective as autologous nerve transplantation. Histological analyses indicated that vascularization and M2 macrophage recruitment were pronounced inside the SFC. These results suggest that the unique properties of the SFC further enhanced the peripheral nerve regeneration mechanism. As no SFC has been applied in clinical practice, the SFC reported herein may be a promising candidate for repairing extensive peripheral nerve defects.
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spelling doaj-art-1935e6a803144f62b19412153547dc322025-02-02T12:24:42ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-88221-yPeripheral nerve regeneration using a bioresorbable silk fibroin-based artificial nerve conduit fabricated via a novel freeze–thaw processTomoki Matsuo0Hiroo Kimura1Takayuki Nishijima2Yasuhiro Kiyota3Taku Suzuki4Narihito Nagoshi5Shinsuke Shibata6Tomoko Shindo7Nobuko Moritoki8Makoto Sasaki9Sarara Noguchi10Yasushi Tamada11Masaya Nakamura12Takuji Iwamoto13Department of Orthopaedic Surgery, Keio University School of MedicineDepartment of Orthopaedic Surgery, Keio University School of MedicineDepartment of Orthopaedic Surgery, Keio University School of MedicineDepartment of Orthopaedic Surgery, Keio University School of MedicineDepartment of Orthopaedic Surgery, Keio University School of MedicineDepartment of Orthopaedic Surgery, Keio University School of MedicineDivision of Microscopic Anatomy, Graduate School of Medical and Dental Sciences, Niigata UniversityElectron Microscope Laboratory, Keio University School of MedicineElectron Microscope Laboratory, Keio University School of MedicineFaculty of Advanced Science and Technology, Kumamoto UniversityMaterials Development Department, Kumamoto Industrial Research InstituteFaculty of Textile Science and Technology, Shinshu UniversityDepartment of Orthopaedic Surgery, Keio University School of MedicineDepartment of Orthopaedic Surgery, Keio University School of MedicineAbstract While silk fibroin (SF) obtained from silkworm cocoons is expected to become a next-generation natural polymer, a fabrication method for SF-based artificial nerve conduits (SFCs) has not yet been established. Here, we report a bioresorbable SFC, fabricated using a novel freeze–thaw process, which ensures biosafety by avoiding any harmful chemical additives. The SFC demonstrated favorable biocompatibility (high hydrophilicity and porosity with a water content of > 90%), structural stability (stiffness, toughness, and elasticity), and biodegradability, making it an ideal candidate for nerve regeneration. We evaluated the nerve-regenerative effects of the SFC in a rat sciatic-nerve-defect model, including its motor and sensory function recovery as well as histological regeneration. We found that SFC transplantation significantly promoted functional recovery and nerve regeneration compared to silicone tubes and was almost equally effective as autologous nerve transplantation. Histological analyses indicated that vascularization and M2 macrophage recruitment were pronounced inside the SFC. These results suggest that the unique properties of the SFC further enhanced the peripheral nerve regeneration mechanism. As no SFC has been applied in clinical practice, the SFC reported herein may be a promising candidate for repairing extensive peripheral nerve defects.https://doi.org/10.1038/s41598-025-88221-ySilk fibroinNerve conduitArtificial nerveScaffoldPeripheral nerve injuryNerve regeneration
spellingShingle Tomoki Matsuo
Hiroo Kimura
Takayuki Nishijima
Yasuhiro Kiyota
Taku Suzuki
Narihito Nagoshi
Shinsuke Shibata
Tomoko Shindo
Nobuko Moritoki
Makoto Sasaki
Sarara Noguchi
Yasushi Tamada
Masaya Nakamura
Takuji Iwamoto
Peripheral nerve regeneration using a bioresorbable silk fibroin-based artificial nerve conduit fabricated via a novel freeze–thaw process
Scientific Reports
Silk fibroin
Nerve conduit
Artificial nerve
Scaffold
Peripheral nerve injury
Nerve regeneration
title Peripheral nerve regeneration using a bioresorbable silk fibroin-based artificial nerve conduit fabricated via a novel freeze–thaw process
title_full Peripheral nerve regeneration using a bioresorbable silk fibroin-based artificial nerve conduit fabricated via a novel freeze–thaw process
title_fullStr Peripheral nerve regeneration using a bioresorbable silk fibroin-based artificial nerve conduit fabricated via a novel freeze–thaw process
title_full_unstemmed Peripheral nerve regeneration using a bioresorbable silk fibroin-based artificial nerve conduit fabricated via a novel freeze–thaw process
title_short Peripheral nerve regeneration using a bioresorbable silk fibroin-based artificial nerve conduit fabricated via a novel freeze–thaw process
title_sort peripheral nerve regeneration using a bioresorbable silk fibroin based artificial nerve conduit fabricated via a novel freeze thaw process
topic Silk fibroin
Nerve conduit
Artificial nerve
Scaffold
Peripheral nerve injury
Nerve regeneration
url https://doi.org/10.1038/s41598-025-88221-y
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