Pyridylamino‐β‐cyclodextrin as a Molecular Chaperone for Lipopolysaccharide Embedded in a Multilayered Polyelectrolyte Architecture

Jessel, Nadia; Schwinté, Pascale; Donohue, Ruth; Lavalle, Philippe; Boulmedais, Fouzia; Darcy, Raphael; Szalontai, Balázs; Voegel, J.‐C.; Ogier, Joëlle

doi:10.1002/adfm.200305089

Cited by 50 publications

(40 citation statements)

References 36 publications

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“…13,15,16,19,21,[35][36][37][38][39][40][41][42] Polymer processing technologies such as electrospinning 43 allow nanofiber formation down to the 10 nm scale. Recently, we reported that it is possible to incorporate active growth factors (BMP-2, TGF-β1) as nanoreservoirs to induce bone formation.…”

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confidence: 99%

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

Eap¹,

Keller²,

Schiavi³

et al. 2015

IJN

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New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 μm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days’ implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days’ implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration.

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confidence: 99%

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

Eap¹,

Keller²,

Schiavi³

et al. 2015

IJN

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“…Cyclodextrins (CDs) constitute a group of cyclic oligosaccharides that have been shown to improve the bioavailability of many drugs by forming inclusion complexes with them (17). CDs and certain derivatives also play an important role in drug formulation due to their effect on solubility, dissolution rate, chemical stability, absorption of drugs, and conformational stabilization of proteins and lipids through encapsulation of their hydrophobic moieties (13,14). This so-called ''molecular chaperone'' effect of CDs has been used to stabilize the conformation of lipid A adsorbed on LBL films (13).…”

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Multiple and time-scheduled in situ DNA delivery mediated by β-cyclodextrin embedded in a polyelectrolyte multilayer

Jessel

Oulad‐Abdelghani

Meyer

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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222

227

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The basic premise of gene therapy is that genes can be used to produce in situ therapeutic proteins. The controlled delivery of DNA complexes from biomaterials offers the potential to enhance gene transfer by maintaining an elevated concentration of DNA within the cellular microenvironment. Immobilization of the DNA to the substrate to which cells adhere maintains the DNA in the cell microenvironment for subsequent cellular internalization. Here, layer-by-layer (LBL) films made from poly(L-glutamic acid) (PLGA) and poly(L-lysine) (PLL) containing DNA were built in the presence of charged cyclodextrins. The biological activities of these polyelectrolyte films were tested by means of induced production of a specific protein in the nucleus or in the cytoplasm by cells in contact with the films. This type of coating offers the possibility for either simultaneous or sequential interfacial delivery of different DNA molecules aimed at cell transfection. These results open the route to numerous potential applications in patch vaccination, for example.gene delivery ͉ layer-by-layer films ͉ transfection T he basic premise of somatic gene therapy is that genes can be used to cause in vivo production of therapeutic proteins. Controlled and efficient gene delivery has implications in many fields ranging from basic science to clinical medicine. Current strategies to enhance gene delivery involve the complexation of DNA with cationic polymers or lipids delivery. Cationic polymers or lipids can self-assemble with DNA to form particles that are capable of being endocytosed by cells (1). These complexes reduce effective size and cellular degradation of DNA (2) and are often delivered as a bolus, added to culture wells in vitro. Bolus delivery of these complexes can be hindered by mass transport limitations or deactivation processes, such as degradation or aggregation. For example, in vitro studies have estimated that bolus addition of complexes to the culture media results in internalization of only 20% of the DNA added (3). These limitations motivated the development of alternative delivery strategies.The controlled delivery of DNA complexes from biomaterials offers the potential to enhance gene transfer by maintaining an elevated concentration of DNA within the cellular microenvironment (4). DNA delivery systems from biomaterials are designed to maintain elevated concentrations locally by supplying DNA to balance the loss by degradation. The continued presence of the DNA during cell division seems to facilitate entry into the nucleus (5). In recent years, considerable effort has been devoted to the design and the controlled fabrication of structured materials with functional properties (6). The layer-by-layer (LBL) buildup of polyelectrolyte films from oppositely charged polyelectrolytes (7) offers opportunities for the preparation of functionalized biomaterial coatings. This technique allows the preparation of supramolecular nano-architectures (8-13) exhibiting specific properties in terms of control of cell activation (8-11) ...

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“…Direct absorption of molecules and use of carriers such as dendrimers, micelles, nanoparticles, monomeric cyclodextrins, and prodrugs have been unable to overcome these barriers. [2][3][4] Diffusion kinetics prevent facile advanced engineering of release dynamics, and release is often modulated by increasing system complexity. For many drugs, burst release carries an increased risk of toxicity and short timescales limit general applicability.…”

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Layer‐by‐Layer Platform Technology for Small‐Molecule Delivery

et al. 2009

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Pyridylamino‐β‐cyclodextrin as a Molecular Chaperone for Lipopolysaccharide Embedded in a Multilayered Polyelectrolyte Architecture

Cited by 50 publications

References 36 publications

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

Multiple and time-scheduled in situ DNA delivery mediated by β-cyclodextrin embedded in a polyelectrolyte multilayer

Layer‐by‐Layer Platform Technology for Small‐Molecule Delivery

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