  Citation: Tryba, A.M.; Krok-Borkowicz, M.; Kula, M.; Piergies, N.; Marzec, M.; Wegener, E.; Fr ˛ aczyk, J.; Jordan, R.; Kolesi ´ nska, B.; Scharnweber, D.; et al. Surface Functionalization of Poly(L-lactide- co-glycolide) Membranes with RGD-Grafted Poly(2-oxazoline) for Periodontal Tissue Engineering. J. Funct. Biomater. 2022, 13, 4. https:// doi.org/10.3390/jfb13010004 Academic Editor: Florin Miculescu Received: 15 December 2021 Accepted: 4 January 2022 Published: 7 January 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/). Journal of Functional Biomaterials Article Surface Functionalization of Poly( L-lactide-co-glycolide) Membranes with RGD-Grafted Poly(2-oxazoline) for Periodontal Tissue Engineering Anna M. Tryba 1 , Malgorzata Krok-Borkowicz 1 , Michal Kula 1 , Natalia Piergies 2 , Mateusz Marzec 3 , Erik Wegener 4 , Justyna Fr ˛ aczyk 5 , Rainer Jordan 4 , Beata Kolesi ´ nska 5 , Dieter Scharnweber 6 , Czeslawa Paluszkiewicz 2 and El ˙ zbieta Pamula 1, * 1 Department of Biomaterials and Composites, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, Al. Mickiewicza 30, 30-059 Kraków, Poland; amtryba@agh.edu.pl (A.M.T.); krok@agh.edu.pl (M.K.-B.); kula.michal96@gmail.com (M.K.) 2 Institute of Nuclear Physics, Polish Academy of Sciences, ul. Radzikowskiego 152, 31-342 Kraków, Poland; natalia.piergies@ifj.edu.pl(N.P.); Czeslawa.Paluszkiewicz@ifj.edu.pl (C.P.) 3 Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, Al. Mickiewicza 30, 30-059 Kraków, Poland; marzecm@agh.edu.pl 4 Faculty of Chemistry and Food Chemistry, Technische Universität Dresden, Mommsenstr, 401069 Dresden, Germany; erik.wegener@mailbox.tu-dresden.de (E.W.); Rainer.Jordan@tu-dresden.de (R.J.) 5 Faculty of Chemistry, Institute of Organic Chemistry, Lód´ z University of Technology, ul. ˙ Zeromskiego 116, 90-924 Lód´ z, Poland; justyna.fraczyk@p.lodz.pl (J.F.); kolesins@p.lodz.pl (B.K.) 6 Max Bergmann Center of Biomaterials, Technische Universität Dresden, Budapester Str. 27, 01069 Dresden, Germany; Dieter.Scharnweber@tu-dresden.de * Correspondence: epamula@agh.edu.pl Abstract: Bone tissue defects resulting from periodontal disease are often treated using guided tissue regeneration (GTR). The barrier membranes utilized here should prevent soft tissue infiltration into the bony defect and simultaneously support bone regeneration. In this study, we designed a degradable poly(L-lactide-co-glycolide) (PLGA) membrane that was surface-modified with cell adhesive arginine-glycine-aspartic acid (RGD) motifs. For a novel method of membrane manufacture, the RGD motifs were coupled with the non-ionic amphiphilic polymer poly(2-oxazoline) (POx). The RGD-containing membranes were then prepared by solvent casting of PLGA, POx coupled with RGD (POx_RGD), and poly(ethylene glycol) (PEG) solution in methylene chloride (DCM), followed by DCM evaporation and PEG leaching. Successful coupling of RGD to POx was confirmed spec- troscopically by Raman, Fourier transform infrared in attenuated reflection mode (FTIR-ATR), and X-ray photoelectron (XPS) spectroscopy, while successful immobilization of POx_RGD on the mem- brane surface was confirmed by XPS and FTIR-ATR. The resulting membranes had an asymmetric microstructure, as shown by scanning electron microscopy (SEM), where the glass-cured surface was more porous and had a higher surface area then the air-cured surface. The higher porosity should support bone tissue regeneration, while the air-cured side is more suited to preventing soft tissue infiltration. The behavior of osteoblast-like cells on PLGA membranes modified with POx_RGD was compared to cell behavior on PLGA foil, non-modified PLGA membranes, or PLGA membranes modified only with POx. For this, MG-63 cells were cultured for 4, 24, and 96 h on the membranes and analyzed by metabolic activity tests, live/dead staining, and fluorescent staining of actin fibers. The results showed bone cell adhesion, proliferation, and viability to be the highest on membranes modified with POx_RGD, making them possible candidates for GTR applications in periodontology and in bone tissue engineering. Keywords: poly(L-lactide-co-glycolide); poly(ethylene glycol); poly(2-oxazoline); RGD sequences; phase separation; periodontology; osteoblast-like cells; guided tissue regeneration (GTR); bone tissue engineering J. Funct. Biomater. 2022, 13, 4. https://doi.org/10.3390/jfb13010004 https://www.mdpi.com/journal/jfb