Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis
Alexey Fayzullin,
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,
Anatoly Shekhter
Affiliations
Alexey Fayzullin
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
Semyon Churbanov
Department of Advanced Biomaterials, Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
Natalia Ignatieva
Chemistry Department, Lomonosov Moscow State University, Leninskiye Gory 1-3, 119991 Moscow, Russia
Olga Zakharkina
Institute of Photon Technologies, Federal Scientific Research Centre “Crystallography and Photonics” of Russian Academy of Sciences, 2 Pionerskaya st., Troitsk, 142190 Moscow, Russia
Mark Tokarev
Sklifosovsky Institute for Clinical Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
Daniil Mudryak
Sklifosovsky Institute for Clinical Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
Yana Khristidis
World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
Maxim Balyasin
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
Alexandr Kurkov
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
Elena N. Golubeva
Chemistry Department, Lomonosov Moscow State University, Leninskiye Gory 1-3, 119991 Moscow, Russia
Nadejda A. Aksenova
Department of Advanced Biomaterials, Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
Tatyana Dyuzheva
Sklifosovsky Institute for Clinical Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
Peter Timashev
Department of Advanced Biomaterials, Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., 119991 Moscow, Russia
Anna Guller
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
Anatoly Shekhter
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
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 (0) 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.