Coline Pinese

Pharmaceutics 2022, 14, 1854

Eloise Kerignard, Audrey Bethry, Chloé Falcoz, Benjamin Nottelet and Coline Pinese

ABSTRACT

Cardiovascular diseases are the leading cause of death globally. Myocardial infarction in particular leads to a high rate of mortality, and in the case of survival, to a loss of myocardial functionality due to post-infarction necrosis. This functionality can be restored by cell therapy or biomaterial implantation, and the need for a rapid regeneration has led to the development of bioactive patches, in particular through the incorporation of growth factors (GF). In this work, we designed hybrid patches composed of polymer nanofibers loaded with HGF and IGF and associated with a collagen membrane. Among the different copolymers studied, the polymers and their porogens PLA-Pluronic-PLA + PEG and PCL + Pluronic were selected to encapsulate HGF and IGF. While 89 and 92% of IGF were released in 2 days, HGF was released up to 58% and 50% in 35 days from PLA-Pluronic-PLA + PEG and PCL + Pluronic nanofibers, respectively. We also compared two ways of association for the loaded nanofibers and the collagen membrane, namely a direct deposition of the nanofibers on a moisturized collagen membrane (wet association), or entrapment between collagen layers (sandwich association). The interfacial cohesion and the degradation properties of the patches were evaluated. We also show that the sandwich association decreases the burst release of HGF while increasing the release efficiency. Finally, we show that the patches are cytocompatible and that the presence of collagen and IGF promotes the proliferation of C2C12 myoblast cells for 11 days. Taken together, these results show that these hybrid patches are of interest for cardiac muscle regeneration.

Molecules 2022, 27(13), 4154

Karima Belabbes, Coline Pinese *, Christopher Yusef Leon-Valdivieso, Audrey Bethry, Xavier Garric

ABSTRACT

PLA nanofibers are of great interest in tissue engineering due to their biocompatibility and morphology; moreover, their physical properties can be tailored for long-lasting applications. One of the common and efficient methods to improve polymer properties and slow down their degradation is sol-gel covalent crosslinking. However, this method usually results in the formation of gels or films, which undervalues the advantages of nanofibers. Here, we describe a dual process sol-gel/electrospinning to improve the mechanical properties and stabilize the degradation of PLA scaffolds. For this purpose, we synthesized star-shaped PLAs and functionalized them with triethoxysilylpropyl groups (StarPLA-PTES) to covalently react during nanofibers formation. To achieve this, we evaluated the use of (1) a polymer diluent and (2) different molecular weights of StarPLA on electrospinnability, StarPLA-PTES condensation time and crosslinking efficiency. Our results show that the diluent allowed the fiber formation and reduced the condensation time, while the addition of low-molecular-weight StarPLA-PTES improved the crosslinking degree, resulting in stable matrices even after 6 months of degradation. Additionally, these materials showed biocompatibility and allowed the proliferation of fibroblasts. Overall, these results open the door to the fabrication of scaffolds with enhanced stability and prospective long-term applications

Materials Science and Engineering: C Volume 129, October 2021, 112339

Louis Gangolphe, Christopher Y.Leon Valdivieso, Benjamin Nottelet, Stéphane Déjean, Audrey Bethry, Coline Pinese, Frédéric Bossard and Xavier Garric

Electrospun scaffolds combine suitable structural characteristics that make them strong candidates for their use in tissue engineering. These features can be tailored to optimize other physiologically relevant attributes (e.g. mechanical anisotropy and cellular affinity) while ensuring adequate degradation rates of the biomaterial. Here, we present the fabrication of microstructured scaffolds by using a combination of micropatterned electrospinning collectors (honeycomb- or square-patterned) and poly(lactic acid) (PLA)-based copolymers (linear or star-shaped). The resulting materials showed appropriate macropore size and fiber alignment that were key parameters to enhance their anisotropic properties in protraction. Moreover, their elastic modulus, which was initially similar to that of soft tissues, gradually changed in hydrolytic conditions, matching the degradation profile in a 2- to 3-month period. Finally, honeycomb-structured scaffolds exhibited enhanced cellular proliferation compared to standard electrospun mats, while cell colonization was shown to be guided by the macropore contour. Taking together, these results provide new insight into the rational design of microstructured materials that can mimic the progressive evolution of properties in soft tissue regeneration

Eur. Pol. J. 139, 109990 (2020)

L.V. Arsenie, C. Pinese, A. Bethry, L. Valot, P. Verdie, B. Nottelet, G. Subra, V. Darcos, X. Garric

ABSTRACT

Abstract Poly(lactide) (PLA) is a widely used biomaterial in many biomedical applications. However, it is inert and therefore lacks bioactivity, which is a major drawback in addressing tissue regeneration issues. This work aims to develop new implantable biomaterials composed of PLAs functionalized with bioactive peptides. For that purpose, we set up an original synthesis based on star-PLA bearing triethoxysilyl propyl groups (PLA-PTES) and bifunctional silylated peptides that react together via sol-gel process to create a bioactive network. We demonstrate that the molecular weight of the PLA and the quantity of peptide have a large influence on the crosslinking efficiency, the mechanical properties and the biodegradability of the resulting materials. The presence of peptide increases the crosslinking efficiency of the networks resulting in more rigid networks with stable mechanical properties up to 8 weeks. At last, the potential of this new type of hybrid biomaterials for soft tissue engineering was demonstrated through cells adhesion assays that showed a significant enhancement of fibroblasts adhesion

Star-poly(lactide)-peptide hybrid networks as bioactive materials