Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides
Abstract Background Delayed reconstruction of transection or laceration injuries of peripheral nerves is inflicted by a reduced regeneration capacity. Diabetic conditions, more frequently encountered in clinical practice, are known to further impair regeneration in peripheral nerves. Chitosan nerve...
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BMC
2017-07-01
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| Series: | BMC Neuroscience |
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| Online Access: | http://link.springer.com/article/10.1186/s12868-017-0374-z |
| _version_ | 1818614661677842432 |
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| author | Lena Stenberg Maria Stößel Giulia Ronchi Stefano Geuna Yaobin Yin Susanne Mommert Lisa Mårtensson Jennifer Metzen Claudia Grothe Lars B. Dahlin Kirsten Haastert-Talini |
| author_facet | Lena Stenberg Maria Stößel Giulia Ronchi Stefano Geuna Yaobin Yin Susanne Mommert Lisa Mårtensson Jennifer Metzen Claudia Grothe Lars B. Dahlin Kirsten Haastert-Talini |
| author_sort | Lena Stenberg |
| collection | DOAJ |
| description | Abstract Background Delayed reconstruction of transection or laceration injuries of peripheral nerves is inflicted by a reduced regeneration capacity. Diabetic conditions, more frequently encountered in clinical practice, are known to further impair regeneration in peripheral nerves. Chitosan nerve guides (CNGs) have recently been introduced as a new generation of medical devices for immediate peripheral nerve reconstruction. Here, CNGs were used for 45 days delayed reconstruction of critical length 15 mm rat sciatic nerve defects in either healthy Wistar rats or diabetic Goto-Kakizaki rats; the latter resembling type 2 diabetes. In short and long-term investigations, we comprehensively analyzed the performance of one-chambered hollow CNGs (hCNGs) and two-chambered CNGs (CFeCNGs) in which a chitosan film has been longitudinally introduced. Additionally, we investigated in vitro the immunomodulatory effect provided by the chitosan film. Results Both types of nerve guides, i.e. hCNGs and CFeCNGs, enabled moderate morphological and functional nerve regeneration after reconstruction that was delayed for 45 days. These positive findings were detectable in generally healthy as well as in diabetic Goto-Kakizaki rats (for the latter only in short-term studies). The regenerative outcome did not reach the degree as recently demonstrated after immediate reconstruction using hCNGs and CFeCNGs. CFeCNG-treatment, however, enabled tissue regrowth in all animals (hCNGs: only in 80% of animals). CFeCNGs did further support with an increased vascularization of the regenerated tissue and an enhanced regrowth of motor axons. One mechanism by which the CFeCNGs potentially support successful regeneration is an immunomodulatory effect induced by the chitosan film itself. Our in vitro results suggest that the pro-regenerative effect of chitosan is related to the differentiation of chitosan-adherent monocytes into pro-healing M2 macrophages. Conclusions No considerable differences appear for the delayed nerve regeneration process related to healthy and diabetic conditions. Currently available chitosan nerve grafts do not support delayed nerve regeneration to the same extent as they do after immediate nerve reconstruction. The immunomodulatory characteristics of the biomaterial may, however, be crucial for their regeneration supportive effects. |
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| format | Article |
| id | doaj.art-9dddaf9e7a5040f987883649b7eb0a0c |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-16T16:21:34Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
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| series | BMC Neuroscience |
| spelling | doaj.art-9dddaf9e7a5040f987883649b7eb0a0c2022-12-21T22:24:53ZengBMCBMC Neuroscience1471-22022017-07-0118112710.1186/s12868-017-0374-zRegeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guidesLena Stenberg0Maria Stößel1Giulia Ronchi2Stefano Geuna3Yaobin Yin4Susanne Mommert5Lisa Mårtensson6Jennifer Metzen7Claudia Grothe8Lars B. Dahlin9Kirsten Haastert-Talini10Department of Translational Medicine – Hand Surgery, Lund UniversityInstitute of Neuroanatomy and Cell Biology, Hannover Medical SchoolDepartment of Clinical and Biological Sciences, and Cavalieri Ottolenghi Neuroscience Institute, University of TurinDepartment of Clinical and Biological Sciences, and Cavalieri Ottolenghi Neuroscience Institute, University of TurinDepartment of Translational Medicine – Hand Surgery, Lund UniversityDivision of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical SchoolDepartment of Translational Medicine – Hand Surgery, Lund UniversityInstitute of Neuroanatomy and Cell Biology, Hannover Medical SchoolInstitute of Neuroanatomy and Cell Biology, Hannover Medical SchoolDepartment of Translational Medicine – Hand Surgery, Lund UniversityInstitute of Neuroanatomy and Cell Biology, Hannover Medical SchoolAbstract Background Delayed reconstruction of transection or laceration injuries of peripheral nerves is inflicted by a reduced regeneration capacity. Diabetic conditions, more frequently encountered in clinical practice, are known to further impair regeneration in peripheral nerves. Chitosan nerve guides (CNGs) have recently been introduced as a new generation of medical devices for immediate peripheral nerve reconstruction. Here, CNGs were used for 45 days delayed reconstruction of critical length 15 mm rat sciatic nerve defects in either healthy Wistar rats or diabetic Goto-Kakizaki rats; the latter resembling type 2 diabetes. In short and long-term investigations, we comprehensively analyzed the performance of one-chambered hollow CNGs (hCNGs) and two-chambered CNGs (CFeCNGs) in which a chitosan film has been longitudinally introduced. Additionally, we investigated in vitro the immunomodulatory effect provided by the chitosan film. Results Both types of nerve guides, i.e. hCNGs and CFeCNGs, enabled moderate morphological and functional nerve regeneration after reconstruction that was delayed for 45 days. These positive findings were detectable in generally healthy as well as in diabetic Goto-Kakizaki rats (for the latter only in short-term studies). The regenerative outcome did not reach the degree as recently demonstrated after immediate reconstruction using hCNGs and CFeCNGs. CFeCNG-treatment, however, enabled tissue regrowth in all animals (hCNGs: only in 80% of animals). CFeCNGs did further support with an increased vascularization of the regenerated tissue and an enhanced regrowth of motor axons. One mechanism by which the CFeCNGs potentially support successful regeneration is an immunomodulatory effect induced by the chitosan film itself. Our in vitro results suggest that the pro-regenerative effect of chitosan is related to the differentiation of chitosan-adherent monocytes into pro-healing M2 macrophages. Conclusions No considerable differences appear for the delayed nerve regeneration process related to healthy and diabetic conditions. Currently available chitosan nerve grafts do not support delayed nerve regeneration to the same extent as they do after immediate nerve reconstruction. The immunomodulatory characteristics of the biomaterial may, however, be crucial for their regeneration supportive effects.http://link.springer.com/article/10.1186/s12868-017-0374-zChitosan nerve guideDelayed nerve reconstructionDiabetesRegenerative matrixImmunomodulation |
| spellingShingle | Lena Stenberg Maria Stößel Giulia Ronchi Stefano Geuna Yaobin Yin Susanne Mommert Lisa Mårtensson Jennifer Metzen Claudia Grothe Lars B. Dahlin Kirsten Haastert-Talini Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides BMC Neuroscience Chitosan nerve guide Delayed nerve reconstruction Diabetes Regenerative matrix Immunomodulation |
| title | Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides |
| title_full | Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides |
| title_fullStr | Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides |
| title_full_unstemmed | Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides |
| title_short | Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides |
| title_sort | regeneration of long distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides |
| topic | Chitosan nerve guide Delayed nerve reconstruction Diabetes Regenerative matrix Immunomodulation |
| url | http://link.springer.com/article/10.1186/s12868-017-0374-z |
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