In Vitro Study of Degradation Behavior, Cytotoxicity, and Cell Adhesion of the Atactic Polylactic Acid for Biomedical Pu

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ORIGINAL PAPER

In Vitro Study of Degradation Behavior, Cytotoxicity, and Cell Adhesion of the Atactic Polylactic Acid for Biomedical Purposes Alexander G. Morozov1   · Danila A. Razborov1 · Tatevik A. Egiazaryan1 · Maxim A. Baten’kin1 · Diana Ya. Aleynik2 · Marfa N. Egorikhina2 · Yulia P. Rubtsova2 · Irina N. Charikova2 · Sergei A. Chesnokov1 · Igor L. Fedushkin1

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract An atactic poly-d,l-lactide (PLA) is obtained via ring-opening polymerization (ROP) of lactide stereoisomers mixture catalyzed by the magnesium and calcium acenaphthylenebisamido complexes. The polymer is characterized by gel-permeation chromatography, NMR spectroscopy, and mass spectrometry. The hydrolytic degradation behavior, cytotoxicity, and cell adhesion of the resulting PLA are evaluated. The polymer degrades in phosphate-buffered saline, releasing water-soluble low molecular products that significantly influence dermal fibroblast growth. Polymer demonstrates no cytotoxicity that, along with cell adhesion and their high proliferative activity toward the PLA obtained, proves its biocompatibility. Keywords  Lactide · Ring-opening polymerization · Alkali-earth metal complexes · Polylactic acid · Hydrolytic degradation · Cytotoxicity · Cell adhesion · Biocompatibility

Introduction Ring-opening polymerization (ROP) of lactides and lactones catalyzed by metal complexes is one of the most effective methods for highly-controlled producing biocompatible polyesters [1]. Due to their structural properties, hydrolytic instability, and non-toxicity, these polymers are applied in medicine as bioresorbable implants, suture material, and systems Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1092​4-020-01803​-x) contains supplementary material, which is available to authorized users.

for targeted drug delivery [2, 3]. Polylactide (PLA), which is obtained by the ROP of cyclic diesters of lactic acid, namely lactides, can be produced from renewable natural raw materials [4]. In 2017 we reported [5] on approach for the synthesis of lactides from lactic acid and its esters in the presence of inorganic lanthanide compounds. It should be noted that rare-earths demonstrate from low to moderate toxicity depending on the nature of metals, coordination environment, solubility, dose, and time exposure [6, 7]. Concurrently, several lanthanide-based compounds produce health benefits revealing anticancer properties [8–10], anti-inflammatory activity

* Alexander G. Morozov [email protected]

Irina N. Charikova [email protected]

Danila A. Razborov [email protected]

Sergei A. Chesnokov [email protected]

Tatevik A. Egiazaryan tatka‑[email protected]

Igor L. Fedushkin [email protected]

Maxim A. Baten’kin [email protected]

1



G. A. Razuvaev Institute of Organometallic Chemistry of Russian Academy of Sciences, Nizhny Novgorod, Russia 603950

2



Privolzhsky Research Medical University of the Ministry of Health Care of the Russian Fed