Regulation of foreign body reaction using nanofibers and microRNAs
-
1
Nanyang Technological University, School of Chemical and Biomedical Engineering, Singapore
-
2
Nanyang Technological University, Lee Kong Chian School of Medicine, Singapore
Foreign body reaction is the host response towards surgically implanted biomaterials, which eventually leads to undesirable, excessive collagen deposition. Macrophages are known to mediate this process due to their ability to interact with fibroblasts in a reciprocal fashion. Combining the knowledge from recent studies regarding the role of microRNAs in macrophage polarization, we hypothesize that scaffold-mediated delivery of macrophage-polarizing microRNAs can modulate the extent of implant fibrosis. Poly(caprolactone-co-ethyl ethylene phosphate) (PCLEEP) nanofibers (387 ± 57 nm) loaded with microRNAs were electrospun for implantation into Sprague-Dawley rats subcutaneously. Implanted scaffolds, capable of sustained microRNA release for at least 88 days, were retrieved at Week 2 and evaluated using histological (Masson’s Trichrome) and immunohistochemical stainings. At 2 weeks post implantation, M2-inducing microRNAs resulted in the thinnest fibrous capsule formation (182.53 ± 22.75 μm and 206.64 ± 21.91 μm) as compared to plain fibers (324.2 ± 43.12 μm) or fibers that encapsulated scrambled microRNA (403.24 ± 48.81 μm, p < 0.01) or M1-inducing antagomiR (299.81 ± 32.76 μm). Besides that, treatment with M1-inducing antagomiR led to the most extensive cell infiltration (40.58 ± 0.86%) and largest distance infiltrated (589.2 ± 28.26 μm, p < 0.01). To test for species dependence, we implanted the relevant scaffolds into mice for 4 weeks and evaluated the fibrous capsule thickness. M2-inducing microRNA treatment resulted in significantly reduced fibrous thickness (106.27 ± 16.86 μm) as compared to scrambled microRNA treatment (299.51 ± 46.43 μm, p < 0.05). The similar experimental trends observed in the rat and murine models suggested that the effects of the microRNAs were species independent. In conclusion, we showed that scaffold-mediated delivery of M2-inducing microRNAs can reduce fibrosis. Ongoing studies include the improvement of microRNA delivery as well as quantifying different macrophage population to understand the observed phenomena.
References:
[1] The topographical effect of electrospun nanofibrous scaffolds on the in vivo and in vitro foreign body reaction
[2] Controlling fibrous capsule formation through long-term down-regulation of collagen type 1 (COL1A1) expression by nanofiber-mediated siRNA gene silencing
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
General Session Oral
Topic:
Fibrosis and biomaterials
Citation:
Lin
J,
Diao
H,
Milbreta
U,
Long
H and
Chew
S
(2016). Regulation of foreign body reaction using nanofibers and microRNAs.
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.00799
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
27 Mar 2016;
Published Online:
30 Mar 2016.