Citation: Pouroutzidou, G.K.; Papadopoulou, L.; Lazaridou, M.; Tsachouridis, K.; Papoulia, C.; Patsiaoura, D.; Tsamesidis, I.; Chrissafis, K.; Vourlias, G.; Paraskevopoulos, K.M.; et al. Composite PLGA–Nanobioceramic Coating on Moxifloxacin-Loaded Akermanite 3D Porous Scaffolds for Bone Tissue Regeneration. Pharmaceutics 2023, 15, 819. https://doi.org/10.3390/ pharmaceutics15030819 Academic Editors: Bogdan Stefan Vasile and Ionela Andreea Neacsu Received: 27 January 2023 Revised: 18 February 2023 Accepted: 27 February 2023 Published: 2 March 2023 Copyright: © 2023 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/). pharmaceutics Article Composite PLGA–Nanobioceramic Coating on Moxifloxacin-Loaded Akermanite 3D Porous Scaffolds for Bone Tissue Regeneration Georgia K. Pouroutzidou 1,2, * , Lambrini Papadopoulou 3 , Maria Lazaridou 4 , Konstantinos Tsachouridis 5 , Chrysanthi Papoulia 1 , Dimitra Patsiaoura 1 , Ioannis Tsamesidis 2 , Konstantinos Chrissafis 1 , George Vourlias 1 , Konstantinos M. Paraskevopoulos 1 , Antonios D. Anastasiou 5 , Dimitrios N. Bikiaris 4 and Eleana Kontonasaki 2, * 1 Advanced Materials and Devices Laboratory, Faculty of Sciences, School of Physics, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece 2 Department of Prosthodontics, Faculty of Health Sciences, School of Dentistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece 3 School of Geology, Faculty of Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece 4 Faculty of Sciences, School of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece 5 Department of Chemical Engineering and Analytical Science, University of Manchester, Manchester M1 3AL, UK * Correspondence: gpourout@physics.auth.gr (G.K.P.); kont@dent.auth.gr (E.K.) Abstract: Silica-based ceramics doped with calcium and magnesium have been proposed as suit- able materials for scaffold fabrication. Akermanite (Ca 2 MgSi 2 O 7 ) has attracted interest for bone regeneration due to its controllable biodegradation rate, improved mechanical properties, and high apatite-forming ability. Despite the profound advantages, ceramic scaffolds provide weak fracture resistance. The use of synthetic biopolymers such as poly(lactic-co-glycolic acid) (PLGA) as coating materials improves the mechanical performance of ceramic scaffolds and tailors their degradation rate. Moxifloxacin (MOX) is an antibiotic with antimicrobial activity against numerous aerobic and anaerobic bacteria. In this study, silica-based nanoparticles (NPs) enriched with calcium and magnesium, as well as copper and strontium ions that induce angiogenesis and osteogene- sis, respectively, were incorporated into the PLGA coating. The aim was to produce composite akermanite/PLGA/NPs/MOX-loaded scaffolds through the foam replica technique combined with the sol–gel method to improve the overall effectiveness towards bone regeneration. The structural and physicochemical characterizations were evaluated. Their mechanical properties, apatite forming ability, degradation, pharmacokinetics, and hemocompatibility were also investigated. The addi- tion of NPs improved the compressive strength, hemocompatibility, and in vitro degradation of the composite scaffolds, resulting in them keeping a 3D porous structure and a more prolonged release profile of MOX that makes them promising for bone regeneration applications. Keywords: 3D porous scaffolds; foam replica technique; akermanite scaffolds; nanofillers; moxifloxacin- loaded scaffolds 1. Introduction Bone tissue engineering combines the principles and methods of engineering and life sciences in order to develop biological substitutes that will restore, preserve, and improve hard tissue function. This can be accomplished by integrating 3D porous scaffolds made of suitable biomaterials, cells, and biological compounds, including growth factors and active ingredients [1]. In order to reproduce the complex morphology of osteal tissue, osteoinductive materials that can integrate with the biological environment and promote bone regeneration are used in the fabrication of composite biodegradable and bioactive 3D porous scaffolds. The disadvantages of autologous grafts, as well as the prolonged Pharmaceutics 2023, 15, 819. https://doi.org/10.3390/pharmaceutics15030819 https://www.mdpi.com/journal/pharmaceutics