Citation: Proshin, P.I.; Abdurashitov, A.S.; Sindeeva, O.A.; Ivanova, A.A.; Sukhorukov, G.B. Additive Manufacturing of Drug-Eluting Multilayer Biodegradable Films. Polymers 2022, 14, 4318. https:// doi.org/10.3390/polym14204318 Academic Editor: Evgenia Korzhikova-Vlakh Received: 29 September 2022 Accepted: 12 October 2022 Published: 14 October 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). polymers Article Additive Manufacturing of Drug-Eluting Multilayer Biodegradable Films Pavel I. Proshin 1, * ,† , Arkady S. Abdurashitov 1,† , Olga A. Sindeeva 1 , Anastasia A. Ivanova 2 and Gleb B. Sukhorukov 1,3,4, * ,† 1 A.V. Zelmann Center for Neurobiology and Brain Rehabilitation, Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, 121205 Moscow, Russia 2 Skoltech Center for Petroleum Science and Engineering, Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, 121205 Moscow, Russia 3 School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK 4 Siberian State Medical University, Moskovskiy Trakt, 2, 634050 Tomsk, Russia * Correspondence: pavel.proshin@skoltech.ru (P.I.P.); g.sukhorukov@qmul.ac.uk (G.B.S.) † These authors contributed equally to this work. Abstract: Drug-eluting films made of bioresorbable polymers are a widely used tool of modern personalized medicine. However, most currently existing methods of producing coatings do not go beyond the laboratory, as they have low encapsulation efficiency and/or difficulties in scaling up. The PLACE (Printed Layered Adjustable Cargo Encapsulation) technology proposed in this article uses an additive approach for film manufacturing. PLACE technology is accessible, scalable, and reproducible in any laboratory. As a demonstration of the technology capabilities, we fabri- cated layered drug-eluting polyglycolic acid films containing different concentrations of Cefazolin antibiotic. The influence of the amount of loaded drug component on the film production process and the release kinetics was studied. The specific loading of drugs was significantly increased to 200–400 μg/cm 2 while maintaining the uniform release of Cefazolin antibiotic in a dosage sufficient for local antimicrobial therapy for 14 days. The fact that the further increase in the drug amount results in the crystallization of a substance, which can lead to specific defects in the cover film for- mation and accelerated one-week cargo release, was also shown, and options for further technology development were proposed. Keywords: biopolymers; drug-eluting coatings; zero-order release; 3D printing; polymer films; additive manufacturing 1. Introduction Site-specific drug delivery by using bioresorbable polymer drug-eluting films (DEFs) has been used already over two decades and has become widespread in applications of various medical devices [1,2]. The drug coating made of various biocompatible polymers, presumably polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA) and their copolymers, maintains a drug concentration at the application site that is similar or even superior to that of systemic therapy, while using a much lower total dose [3]. Reducing systemic toxicity is consistent with the principles of personalized medicine, as it increases the variability in the choice of drugs for patients with intolerance to high systemic drug concentrations and the effectiveness of treatment. Because of that, the use of antibiotic- releasing antimicrobial films significantly reduces the risks of bacterial contamination of dental devices and orthopedic implants [4–6], and the use of a combination of a drug and a coronary stent in the form of a drug-eluting stent has established itself as the most popular treatment option for restoring blood flow in occluded vessels [7]. Polymers 2022, 14, 4318. https://doi.org/10.3390/polym14204318 https://www.mdpi.com/journal/polymers