2. Academic Validation
  3. Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis

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

  • Biomedicines. 2021 Jul 21;9(8):853. doi: 10.3390/biomedicines9080853.
Alexey Fayzullin 1 2 3 4,  Semyon Churbanov 5,  Natalia Ignatieva 6,  Olga Zakharkina 7,  Mark Tokarev 8,  Daniil Mudryak 8,  Yana Khristidis 2,  Maxim Balyasin 1,  Alexandr Kurkov 1,  Elena N Golubeva 6,  Nadejda A Aksenova 5 9,  Tatyana Dyuzheva 8,  Peter Timashev 5 6 7 9 10,  Anna Guller 1 2 3 4,  Anatoly Shekhter 1
Affiliations

Affiliations

  • 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.
PMID: 34440057 DOI: 10.3390/biomedicines9080853
Abstract

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, PLA@PF, with prolonged (~3 days) PF release (in vitro) was prepared. The effects of the PLA@PF 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 PLA@PF and PLA0+injPF groups vs. PLA0. On POD60, PIF was significantly reduced in PLA@PF 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 PLA@PF 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.

Keywords

anti-fibrotic therapy; collagen; fibrosis; foreign body reaction; implantable drug delivery systems; peri-implant fibrosis; pirfenidone; polylactic acid; polymer implants; quantitative histopathology.

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