Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb
Summary: The induction of limb repair in adult vertebrates is a pressing, unsolved problem. Here, we characterize the effects of an integrated device that delivers drugs to severed hindlimbs of adult Xenopus laevis, which normally regenerate cartilaginous spikes after amputation. A wearable bioreact...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718315730 |
| _version_ | 1818309058724102144 |
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| author | Celia Herrera-Rincon Annie S. Golding Kristine M. Moran Christina Harrison Christopher J. Martyniuk Justin A. Guay Julia Zaltsman Hayley Carabello David L. Kaplan Michael Levin |
| author_facet | Celia Herrera-Rincon Annie S. Golding Kristine M. Moran Christina Harrison Christopher J. Martyniuk Justin A. Guay Julia Zaltsman Hayley Carabello David L. Kaplan Michael Levin |
| author_sort | Celia Herrera-Rincon |
| collection | DOAJ |
| description | Summary: The induction of limb repair in adult vertebrates is a pressing, unsolved problem. Here, we characterize the effects of an integrated device that delivers drugs to severed hindlimbs of adult Xenopus laevis, which normally regenerate cartilaginous spikes after amputation. A wearable bioreactor containing a silk protein-based hydrogel that delivered progesterone to the wound site immediately after hindlimb amputation for only 24 hr induced the regeneration of paddle-like structures in adult frogs. Molecular markers, morphometric analysis, X-ray imaging, immunofluorescence, and behavioral assays were used to characterize the differences between the paddle-like structures of successful regenerates and hypomorphic spikes that grew in untreated animals. Our experiments establish a model for testing therapeutic cocktails in vertebrate hindlimb regeneration, identify pro-regenerative activities of progesterone-containing bioreactors, and provide proof of principle of brief use of integrated device-based delivery of small-molecule drugs as a viable strategy to induce and maintain a long-term regenerative response. : The complexity of vertebrate limbs drives the search for regenerative treatments that trigger endogenous processes of repair. Herrera-Rincon et al. show that a wearable bioreactor containing progesterone, applied for only 24 hr, induces months of regenerative growth and patterning of amputated hindlimbs in the frog Xenopus laevis. Keywords: silk, hydrogel device, spike, frog, bioelectricity, regeneration, Xenopus, limb, bioreactor |
| first_indexed | 2024-12-13T07:24:08Z |
| format | Article |
| id | doaj.art-e70c2a2bcca24c8ab6bfa9fc5dc91f86 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T07:24:08Z |
| publishDate | 2018-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-e70c2a2bcca24c8ab6bfa9fc5dc91f862022-12-21T23:55:21ZengElsevierCell Reports2211-12472018-11-0125615931609.e7Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus HindlimbCelia Herrera-Rincon0Annie S. Golding1Kristine M. Moran2Christina Harrison3Christopher J. Martyniuk4Justin A. Guay5Julia Zaltsman6Hayley Carabello7David L. Kaplan8Michael Levin9Biology Department and Allen Discovery Center, Tufts University, Medford, MA, USADepartment of Chemical and Biological Engineering, Tufts University, Medford, MA, USABiology Department and Allen Discovery Center, Tufts University, Medford, MA, USABiology Department and Allen Discovery Center, Tufts University, Medford, MA, USACenter for Environmental and Human Toxicology and Department of Physiological Sciences, University of Florida, Gainesville, FL, USABiology Department and Allen Discovery Center, Tufts University, Medford, MA, USABiology Department and Allen Discovery Center, Tufts University, Medford, MA, USABiology Department and Allen Discovery Center, Tufts University, Medford, MA, USADepartment of Biomedical Engineering, Tufts University, Medford, MA, USABiology Department and Allen Discovery Center, Tufts University, Medford, MA, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Corresponding authorSummary: The induction of limb repair in adult vertebrates is a pressing, unsolved problem. Here, we characterize the effects of an integrated device that delivers drugs to severed hindlimbs of adult Xenopus laevis, which normally regenerate cartilaginous spikes after amputation. A wearable bioreactor containing a silk protein-based hydrogel that delivered progesterone to the wound site immediately after hindlimb amputation for only 24 hr induced the regeneration of paddle-like structures in adult frogs. Molecular markers, morphometric analysis, X-ray imaging, immunofluorescence, and behavioral assays were used to characterize the differences between the paddle-like structures of successful regenerates and hypomorphic spikes that grew in untreated animals. Our experiments establish a model for testing therapeutic cocktails in vertebrate hindlimb regeneration, identify pro-regenerative activities of progesterone-containing bioreactors, and provide proof of principle of brief use of integrated device-based delivery of small-molecule drugs as a viable strategy to induce and maintain a long-term regenerative response. : The complexity of vertebrate limbs drives the search for regenerative treatments that trigger endogenous processes of repair. Herrera-Rincon et al. show that a wearable bioreactor containing progesterone, applied for only 24 hr, induces months of regenerative growth and patterning of amputated hindlimbs in the frog Xenopus laevis. Keywords: silk, hydrogel device, spike, frog, bioelectricity, regeneration, Xenopus, limb, bioreactorhttp://www.sciencedirect.com/science/article/pii/S2211124718315730 |
| spellingShingle | Celia Herrera-Rincon Annie S. Golding Kristine M. Moran Christina Harrison Christopher J. Martyniuk Justin A. Guay Julia Zaltsman Hayley Carabello David L. Kaplan Michael Levin Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb Cell Reports |
| title | Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb |
| title_full | Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb |
| title_fullStr | Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb |
| title_full_unstemmed | Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb |
| title_short | Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb |
| title_sort | brief local application of progesterone via a wearable bioreactor induces long term regenerative response in adult xenopus hindlimb |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718315730 |
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