Details
| Original language | English |
|---|---|
| Pages (from-to) | 51-61 |
| Number of pages | 11 |
| Journal | BIOMATERIALS |
| Volume | 47 |
| Early online date | 4 Feb 2015 |
| Publication status | Published - Apr 2015 |
| Externally published | Yes |
Abstract
Implantation of a medical implant within the body inevitably triggers a host inflammatory response that negatively impacts its function and longevity. Nevertheless, the degree and severity of this response may be reduced by selecting appropriate materials, implant geometry, surface topography and surface treatment. Here we demonstrate a strategy to improve the biocompatibility of a chemically-driven closed-loop insulin delivery implant. A microfabricated microporous, poly(ethylene glycol)-grafted polydimethylsiloxane membrane was placed on top of the glucose-responsive insulin release plug of the implant. Implant biocompatibility was assessed in healthy rats while implant function was evaluated in a type 1 diabetic rat model. The microporous membrane with a small distance to the plug provided a geometric barrier to inflammatory cell migration and prevented leukocyte-mediated degradation of the plug for at least 30 days. Membrane-protected devices elicited a significantly milder inflammatory response and formation of a well-defined fibrous capsule at the device opening compared to unprotected devices. The device's glucose-responsiveness was nearly unchanged, although the insulin release rate decreased with decreasing pore size. The microporous membrane improved biocompatibility and prolonged invivo efficacy of the implant by ~3-fold. This work suggests the importance of implant design in modulating inflammatory response and thereby extending the functional duration of the implant.
Keywords
- Biocompatibility, Closed-loop insulin delivery implant, Diabetes, Drug delivery implant, Microfabrication, Microporous membrane
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biophysics
- Chemical Engineering(all)
- Bioengineering
- Materials Science(all)
- Ceramics and Composites
- Materials Science(all)
- Biomaterials
- Engineering(all)
- Mechanics of Materials
Sustainable Development Goals
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In: BIOMATERIALS, Vol. 47, 04.2015, p. 51-61.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Microfabricated microporous membranes reduce the host immune response and prolong the functional lifetime of a closed-loop insulin delivery implant in a type 1 diabetic rat model
AU - Li, Jason
AU - Chu, Michael K.L.
AU - Gordijo, Claudia R.
AU - Abbasi, Azhar Z.
AU - Chen, Kuan
AU - Adissu, Hibret A.
AU - Löhn, Matthias
AU - Giacca, Adria
AU - Plettenburg, Oliver
AU - Wu, Xiao Yu
N1 - Funding Information: This work was supported financially by the MaRS Innovation POP grant (No. 308147 ), the Ontario Research Fund: Research Excellence (ORF-RE) Nanomaterials grant (No. RE03-058 ) in collaboration with Sanofi Aventis; and the CIHR Equipment Grant. The NSERC CGS scholarship to J. Li, and the OGS scholarship and Ben Cohen top-up award to both J. Li and M. Chu are also acknowledged. The authors also acknowledge Dr. Barry Elkind at the MaRS Innovation for his stimulating discussion and Lily Morikawa for her excellent histology analysis at the Pathology Core of the Centre for Modeling Human Disease, at The Lunenfeld-Tanenbaum Research Institute ( www.cmhd.ca ).
PY - 2015/4
Y1 - 2015/4
N2 - Implantation of a medical implant within the body inevitably triggers a host inflammatory response that negatively impacts its function and longevity. Nevertheless, the degree and severity of this response may be reduced by selecting appropriate materials, implant geometry, surface topography and surface treatment. Here we demonstrate a strategy to improve the biocompatibility of a chemically-driven closed-loop insulin delivery implant. A microfabricated microporous, poly(ethylene glycol)-grafted polydimethylsiloxane membrane was placed on top of the glucose-responsive insulin release plug of the implant. Implant biocompatibility was assessed in healthy rats while implant function was evaluated in a type 1 diabetic rat model. The microporous membrane with a small distance to the plug provided a geometric barrier to inflammatory cell migration and prevented leukocyte-mediated degradation of the plug for at least 30 days. Membrane-protected devices elicited a significantly milder inflammatory response and formation of a well-defined fibrous capsule at the device opening compared to unprotected devices. The device's glucose-responsiveness was nearly unchanged, although the insulin release rate decreased with decreasing pore size. The microporous membrane improved biocompatibility and prolonged invivo efficacy of the implant by ~3-fold. This work suggests the importance of implant design in modulating inflammatory response and thereby extending the functional duration of the implant.
AB - Implantation of a medical implant within the body inevitably triggers a host inflammatory response that negatively impacts its function and longevity. Nevertheless, the degree and severity of this response may be reduced by selecting appropriate materials, implant geometry, surface topography and surface treatment. Here we demonstrate a strategy to improve the biocompatibility of a chemically-driven closed-loop insulin delivery implant. A microfabricated microporous, poly(ethylene glycol)-grafted polydimethylsiloxane membrane was placed on top of the glucose-responsive insulin release plug of the implant. Implant biocompatibility was assessed in healthy rats while implant function was evaluated in a type 1 diabetic rat model. The microporous membrane with a small distance to the plug provided a geometric barrier to inflammatory cell migration and prevented leukocyte-mediated degradation of the plug for at least 30 days. Membrane-protected devices elicited a significantly milder inflammatory response and formation of a well-defined fibrous capsule at the device opening compared to unprotected devices. The device's glucose-responsiveness was nearly unchanged, although the insulin release rate decreased with decreasing pore size. The microporous membrane improved biocompatibility and prolonged invivo efficacy of the implant by ~3-fold. This work suggests the importance of implant design in modulating inflammatory response and thereby extending the functional duration of the implant.
KW - Biocompatibility
KW - Closed-loop insulin delivery implant
KW - Diabetes
KW - Drug delivery implant
KW - Microfabrication
KW - Microporous membrane
UR - http://www.scopus.com/inward/record.url?scp=84922784007&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2015.01.005
DO - 10.1016/j.biomaterials.2015.01.005
M3 - Article
C2 - 25682160
AN - SCOPUS:84922784007
VL - 47
SP - 51
EP - 61
JO - BIOMATERIALS
JF - BIOMATERIALS
SN - 0142-9612
ER -