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An actuatable soft reservoir modulates host foreign body response.

Authors :
Dolan EB
Varela CE
Mendez K
Whyte W
Levey RE
Robinson ST
Maye E
O'Dwyer J
Beatty R
Rothman A
Fan Y
Hochstein J
Rothenbucher SE
Wylie R
Starr JR
Monaghan M
Dockery P
Duffy GP
Roche ET
Source :
Science robotics [Sci Robot] 2019 Aug 28; Vol. 4 (33).
Publication Year :
2019

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.<br /> (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Details

Language :
English
ISSN :
2470-9476
Volume :
4
Issue :
33
Database :
MEDLINE
Journal :
Science robotics
Publication Type :
Academic Journal
Accession number :
33137787
Full Text :
https://doi.org/10.1126/scirobotics.aax7043