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Article

Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis

1
Department of Experimental Morphology and Biobanking, Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
2
World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
3
The Graduate School of Biomedical Engineering, University of New South Wales, Kensington, Sydney, NSW 2060, Australia
4
The Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, Sydney, NSW 2060, Australia
5
Department of Advanced Biomaterials, Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
6
Chemistry Department, Lomonosov Moscow State University, Leninskiye Gory 1-3, 119991 Moscow, Russia
7
Institute of Photon Technologies, Federal Scientific Research Centre “Crystallography and Photonics” of Russian Academy of Sciences, 2 Pionerskaya st., Troitsk, 142190 Moscow, Russia
8
Sklifosovsky Institute for Clinical Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
9
Department of Polymers and Composites, N.N. Semenov Federal Research Center for Chemical Physics, 4 Kosygin st., 119991 Moscow, Russia
10
Laboratory of Clinical Smart Nanotechnologies, Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
*
Author to whom correspondence should be addressed.
Equally contributed first co-authors.
Academic Editor: Stefania Raimondo
Biomedicines 2021, 9(8), 853; https://doi.org/10.3390/biomedicines9080853
Received: 18 June 2021 / Revised: 19 July 2021 / Accepted: 19 July 2021 / Published: 21 July 2021
(This article belongs to the Special Issue Feature Papers in "Biomedical Materials and Nanomedicine")
Peri-implant fibrosis (PIF) increases the postsurgical risks after implantation and limits the efficacy of the implantable drug delivery systems (IDDS). Pirfenidone (PF) is an oral anti-fibrotic drug with a short (<3 h) circulation half-life and strong adverse side effects. In the current study, disk-shaped IDDS prototype combining polylactic acid (PLA) and PF, [email protected], with prolonged (~3 days) PF release (in vitro) was prepared. The effects of the [email protected] implants on PIF were examined in the rabbit ear skin pocket model on postoperative days (POD) 30 and 60. Matching blank PLA implants (PLA0) and PLA0 with an equivalent single-dose PF injection performed on POD0 (PLA0+injPF) served as control. On POD30, the intergroup differences were observed in α-SMA, iNOS and arginase-1 expressions in [email protected] and PLA0+injPF groups vs. PLA0. On POD60, PIF was significantly reduced in [email protected] group. The peri-implant tissue thickness decreased (532 ± 98 μm vs. >1100 μm in control groups) approaching the intact derma thickness value (302 ± 15 μm). In [email protected] group, the implant biodegradation developed faster, while arginase-1 expression was suppressed in comparison with other groups. This study proves the feasibility of the local control of fibrotic response on implants via modulation of foreign body reaction with slowly biodegradable PF-loaded IDDS. View Full-Text
Keywords: implantable drug delivery systems; pirfenidone; polylactic acid; polymer implants; foreign body reaction; fibrosis; peri-implant fibrosis; anti-fibrotic therapy; quantitative histopathology; collagen implantable drug delivery systems; pirfenidone; polylactic acid; polymer implants; foreign body reaction; fibrosis; peri-implant fibrosis; anti-fibrotic therapy; quantitative histopathology; collagen
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MDPI and ACS Style

Fayzullin, A.; Churbanov, S.; Ignatieva, N.; Zakharkina, O.; Tokarev, M.; Mudryak, D.; Khristidis, Y.; Balyasin, M.; Kurkov, A.; Golubeva, E.N.; Aksenova, N.A.; Dyuzheva, T.; Timashev, P.; Guller, A.; Shekhter, A. Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis. Biomedicines 2021, 9, 853. https://doi.org/10.3390/biomedicines9080853

AMA Style

Fayzullin A, Churbanov S, Ignatieva N, Zakharkina O, Tokarev M, Mudryak D, Khristidis Y, Balyasin M, Kurkov A, Golubeva EN, Aksenova NA, Dyuzheva T, Timashev P, Guller A, Shekhter A. Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis. Biomedicines. 2021; 9(8):853. https://doi.org/10.3390/biomedicines9080853

Chicago/Turabian Style

Fayzullin, Alexey, Semyon Churbanov, Natalia Ignatieva, Olga Zakharkina, Mark Tokarev, Daniil Mudryak, Yana Khristidis, Maxim Balyasin, Alexandr Kurkov, Elena N. Golubeva, Nadejda A. Aksenova, Tatyana Dyuzheva, Peter Timashev, Anna Guller, and Anatoly Shekhter. 2021. "Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis" Biomedicines 9, no. 8: 853. https://doi.org/10.3390/biomedicines9080853

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