dc.contributor.author | Dolan, Eimear B. | |
dc.contributor.author | Varela, C. E. | |
dc.contributor.author | Mendez, K. | |
dc.contributor.author | Whyte, W. | |
dc.contributor.author | Levey, R. E. | |
dc.contributor.author | Robinson, S. T. | |
dc.contributor.author | Maye, E. | |
dc.contributor.author | O’Dwyer, J. | |
dc.contributor.author | Beatty, R. | |
dc.contributor.author | Rothman, A. | |
dc.contributor.author | Fan, Y. | |
dc.contributor.author | Hochstein, J. | |
dc.contributor.author | Rothenbucher, S. E. | |
dc.contributor.author | Wylie, R. | |
dc.contributor.author | Starr, J. R. | |
dc.contributor.author | Monaghan, M. | |
dc.contributor.author | Dockery, P. | |
dc.contributor.author | Duffy, G. P. | |
dc.contributor.author | Roche, E. T. | |
dc.date.accessioned | 2020-03-12T15:05:34Z | |
dc.date.available | 2020-03-12T15:05:34Z | |
dc.date.issued | 2019-08-28 | |
dc.identifier.citation | Dolan, E. B., Varela, C. E., Mendez, K., Whyte, W., Levey, R. E., Robinson, S. T., Maye, E., O’Dwyer, J., Beatty, R., Rothman, A., Fan, Y., Hochstein, J., Rothenbucher, S. E., Wylie, R., Starr, J. R., Monaghan, M., Dockery, P., Duffy, G. P., Roche, E. T. (2019). An actuatable soft reservoir modulates host foreign body response. Science Robotics, 4(33), eaax7043. doi: 10.1126/scirobotics.aax7043 | en_IE |
dc.identifier.issn | 2470-9476 | |
dc.identifier.uri | http://hdl.handle.net/10379/15845 | |
dc.description.abstract | The performance of indwelling medical devices that depend on an interface with soft tissue is plagued by complex, unpredictable foreign body responses. Such devices—including breast implants, biosensors, and drug delivery devices—are often subject to a collection of biological host responses, including fibrosis, which can impair device functionality. This work describes a milliscale dynamic soft reservoir (DSR) that actively modulates the biomechanics of the biotic-abiotic interface by altering strain, fluid flow, and cellular activity in the peri-implant tissue. We performed cyclical actuation of the DSR in a preclinical rodent model. Evaluation of the resulting host response showed a significant reduction in fibrous capsule thickness (P = 0.0005) in the actuated DSR compared with non-actuated controls, whereas the collagen density and orientation were not changed. We also show a significant reduction in myofibroblasts (P = 0.0036) in the actuated group and propose that actuation-mediated strain reduces differentiation and proliferation of myofibroblasts and therefore extracellular matrix production. Computational models quantified the effect of actuation on the reservoir and surrounding fluid. By adding a porous membrane and a therapy reservoir to the DSR, we demonstrate that, with actuation, we could (i) increase transport of a therapy analog and (ii) enhance pharmacokinetics and time to functional effect of an inotropic agent. The dynamic reservoirs presented here may act as a versatile tool to further understand, and ultimately to ameliorate, the host response to implantable biomaterials. | en_IE |
dc.description.sponsorship | The authors would like to acknowledge the support of the Centre of
Microscopy and Imaging (NUI Galway) and the Koch Imaging Core (MIT) for imaging expertise.
The authors would also like to thank Mark Canney. Kerry Thompson and David Connolly for
imaging technical support and Thibault Fresneau, Markus Horvath, Raymond O’Connor, Jack
Murphy, Jackson Hardin and James Prendergast for research assistance. Funding: ETR
acknowledges funding from the Mechanical Engineering Department and the Institute for Medical
Engineering and Science at the Massachusetts Institute of Technology. WW, STR and GPD
Science Robotics Manuscript Template Page 17 of 37
acknowledge funding from Science Foundation Ireland under grant SFI/12/RC/2278, Advanced
Materials and Bioengineering Research (AMBER) Centre, National University of Ireland and
Trinity College Dublin, Ireland. GPD, RL and EM acknowledge financial support from the National
University of Ireland Galway. EBD and GPD acknowledge The DRIVE project which has received
funding from the European Union's Horizon 2020 research and innovation program under grant
agreement number 645991. EBD and GPD acknowledges funding from European Molecular
Biology Organization Short Term Fellowship. STR has received funding from the European
Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant
agreement No. 713567. CEV acknowledges the financial support from the National Science
Foundation Graduate Research Fellowship Program. Any opinions, findings, and conclusions or
recommendations expressed in this material are those of the author(s) and do not necessarily reflect
the views of the National Science Foundation. This work was conducted with support from Harvard
Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing
Translational Sciences, National Institutes of Health Award UL 1TR002541) and financial
contributions from Harvard University and its affiliated academic healthcare centers. The content
is solely the responsibility of the authors and does not necessarily represent the official views of
Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National
Institutes of Health. Author contributions: EBD, CEV, KM, WW, STR, PD, GPD and ETR
designed the study. EBD, CEV, KM, WW, REL, JO’D, RB, AR, JH, STR, SER, EM, YF, RW,
MM performed the experiments. EBD, CV, KM, WW, STR, REL, EM, JRS, YF, MM, GPD and
ETR analyzed and reviewed the data. EBD, CEV, KM, STR, GPD and ETR wrote the manuscript.
All authors reviewed and edited the manuscript. Competing interests: There is a patent pending
on this work. Data and materials availability: All (other) data needed to evaluate the conclusions
in the paper are present in the paper or the Supplementary Materials. Devices can be obtained
through a material transfer agreement. | en_IE |
dc.format | application/pdf | en_IE |
dc.language.iso | en | en_IE |
dc.publisher | American Association for the Advancement of Science | en_IE |
dc.relation.ispartof | Science Robotics | en |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.title | An actuatable soft reservoir modulates host foreign body response | en_IE |
dc.type | Article | en_IE |
dc.date.updated | 2020-03-12T10:03:16Z | |
dc.identifier.doi | 10.1126/scirobotics.aax7043 | |
dc.local.publishedsource | https://dx.doi.org/10.1126/scirobotics.aax7043 | en_IE |
dc.description.peer-reviewed | peer-reviewed | |
dc.contributor.funder | Science Foundation Ireland | |
dc.contributor.funder | Horizon 2020 | |
dc.internal.rssid | 19876237 | |
dc.local.contact | Eimear Dolan, Biomedical Engineering 3031, College Of Engineering & Informa, Nui Galway. Email: eimear.dolan@nuigalway.ie | |
dc.local.copyrightchecked | Yes | |
dc.local.version | ACCEPTED | |
dcterms.project | SFI/12/RC/2278 | |
dcterms.project | info:eu-repo/grantAgreement/EC/H2020::RIA/645991/EU/Diabetes Reversing Implants with enhanced Viability and long-term Efficacy/DRIVE | |
dcterms.project | info:eu-repo/grantAgreement/EC/H2020::MSCA-COFUND-FP/713567/EU/Cutting Edge Training - Cutting Edge Technology/EDGE | |
nui.item.downloads | 864 | |