Abstract :
[en] Porous polymer scaffolds are widely investigated as temporary implants in regenerative medicine to repair damaged tissues. While biocompatibility, degradability, mechanical properties comparable to the native tissues and controlled porosity are prerequisite for these scaffolds, their loading with pharmaceutical or biological active ingredients such as growth factors, in particular proteins, opens up new perspective for tissue engineering applications. This implies the development of scaffold loading strategies that minimize the risk of protein denaturation and allow to control their release profile. This work reports on a straightforward method for preparing bioactive dextran-based scaffolds from high internal phase emulsion (HIPE) templates containing poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) serving both as co-stabilizers for the emulsion and nanocarriers for drug or therapeutic protein models. Scaffold synthesis are achieved by photocuring of methacrylated dextran located in the external phase of a HIPE stabilized by the NPs in combination or not with a non-ionic surfactant. Fluorescent labelling of the NPs highlights their integration in the scaffold. The introduction of NPs, and even more so when combined with a surfactant, increases the stability and mechanical properties of the scaffolds. Cell viability tests demonstrate the non-toxic nature of these NPs-loaded scaffolds. The study of the release of a model protein from the scaffold, namely lysozyme, shows that its encapsulation in nanoparticles decreases the release rate and provides additional control over the release profile.
Funding text :
This work was funded by the Institut National de la Sante et de la Recherche Medicale (INSERM) the University of Nantes, and the University of Angers. M.D obtained a postdoctoral fellowship from " Région Pays de la Loire " through Bioactive Scaffolds from Pickering Emulsions for Enhanced Bone Osteogenesis "Speebo" project, part of the Bioregate program. A.D. is FNRS Senior Research Associate and thanks the F.R.S.-FNRS for financial support. The authors acknowledge the SC3M plateform from the Inserm/NU/ONIRIS UMR1229 RMeS Laboratory and SFR François Bonamy-UMS 016, as well as the GIGA Cell Imaging core facility. F.B. also thanks the French National Agency for Research (ANR) under the frame of EuroNanoMed III (project GLIOSILK) [ANR-19-ENM3-0003-01] (FB as a member of the funded team) and the "Comité Départemental de Maine-et-Loire de la Ligue contre le Cancer" under the frame of the FusTarG project (FB as a member of the funded team). The program VINCI 2020 - Université Franco Italienne (project number: C3-1419, "Novel nanotechnological approaches for glioblastoma targeting" attributed to FB) also supported this research through a PhD fellowship to AR. The authors are also grateful to Dr. Virginie Bertrand from ULiege for skillful assistance with cell culture tests, to Gregory Cartigny, Valerie Collard and Martine Dejeneffe from ULiege for their regular help with polymer synthesis, NMR and microscopy analyses.
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