Layer-by-Layer Incorporation of Growth Factors in Decellularized Aortic Heart Valve Leaflets

Cock, Liesbeth J. De; Koker, Stefaan De; Vos, Filip De; Vervaet, Chris; Remon, Jean‐Paul; Geest, Bruno G. De

doi:10.1021/bm9014649

Cited by 41 publications

(39 citation statements)

References 44 publications

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“…(1)], indicating that 50% of the peptide was released in the first 34 min. This release behavior is typical of protein that is allowed to diffuse freely once it is desorbed from a surface 15, 34. Release kinetics are mainly driven by the equilibrium partitioning between bound and free α‐MSH in solution.…”

Section: Resultsmentioning

confidence: 99%

“…This release behavior is typical of protein that is allowed to diffuse freely once it is desorbed from a surface. 15,34 Release kinetics are mainly driven by the equilibrium partitioning between bound and free a-MSH in solution. Weaker interactions between loosely bound a-MSH, as well as the high concentration gradient at the start of the release experiment may contribute to the observed burst release.…”

Section: Release Of A-msh From Plga Microspheresmentioning

confidence: 99%

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Coating and release of an anti‐inflammatory hormone from PLGA microspheres for tissue engineering

Palmer

Gras

et al. 2011

J Biomedical Materials Res

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Many biomaterials used in tissue engineering cause a foreign body response in vivo, which left untreated can severely reduce the effectiveness of tissue regeneration. In this study, an anti-inflammatory hormone α-melanocyte stimulating hormone (α-MSH) was physically adsorbed to the surface of biodegradable poly (lactic-co-glycolic) acid (PLGA) microspheres to reduce inflammatory responses to this material. The stability and adsorption isotherm of peptide binding were characterized. The peptide secondary structure was not perturbed by the adsorption and subsequent desorption process. The α-MSH payload was released over 72 h and reduced the expression of the inflammatory cytokine, Tumor necrosis factor-α (TNF-α) in lipopolysaccharide activated RAW 264.7 macrophage cells, indicating that the biological activity of α-MSH was preserved. α-MSH coated PLGA microspheres also appeared to reduce the influx of inflammatory cells in a subcutaneous implantation model in rats. This study demonstrates the potential of α-MSH coatings for anti-inflammatory delivery and this approach may be applied to other tissue engineering applications.

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Section: Resultsmentioning

confidence: 99%

Section: Release Of A-msh From Plga Microspheresmentioning

confidence: 99%

Coating and release of an anti‐inflammatory hormone from PLGA microspheres for tissue engineering

Palmer

Gras

et al. 2011

J Biomedical Materials Res

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“…The sustained and control-released growth factor from such modified PEMs may be an alternative strategy to improve in situ stem cell adhesion, differentiation and growth. It was recently reported that bFGF could be loaded via layer-by-layer electrostatic deposition [20]. In present study, we used VEGF instead of bFGF because of its specificity to EPC [21].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Heparin-VEGF Multilayer on the Biocompatibility of Decellularized Aortic Valve with Platelet and Endothelial Progenitor Cells

Wang

Zhou

et al. 2013

PLoS ONE

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The application of polyelectrolyte multilayer films is a new, versatile approach to surface modification of decellularized tissue, which has the potential to greatly enhance the functionality of engineered tissue constructs derived from decellularized organs. In the present study, we test the hypothesis that Heparin- vascular endothelial growth factor (VEGF) multilayer film can not only act as an antithrombotic coating reagent, but also induce proliferation of endothelial progenitor cells (EPCs) on the decellularized aortic heart valve. SEM demonstrated the adhesion and geometric deformation of platelets. The quantitative assay of platelet activation was determined by measuring the production of soluble P-selectin. Binding and subsequent release of heparin and VEGF from valve leaflets were assessed qualitatively by laser confocal scanning microscopy and quantitatively by ELISA methods. Human blood derived EPCs were cultured and the adhesion and growth of EPCs on the surface modified valvular scaffolds were assessed. The results showed that Heparin-VEGF multilayer film improved decellularized valve haemocompatibility with respect to a substantial reduction of platelet adhesion. Release of VEGF from the decellularized heart valve leaflets at physiological conditions was sustained over 5 days. In vitro biological tests demonstrated that EPCs achieved better adhesion, proliferation and migration on the coatings with Heparin-VEGF multilayer film. Combined, these results indicate that Heparin-VEGF multilayer film could be used to cover the decellularized porcine aortic valve to decrease platelet adhesion while exhibiting excellent EPCs biocompatibility.

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“…32,47,48 Therefore, the pore size in the porous PLGA microspheres here should easily accommodate the formation of the multilayer films on the internal pore walls without significant pore blockage, consistent with our observations. Even without the addition of multilayer films, the low level burst release of a-MSH observed here was a significant improvement over previous studies using non porous microspheres where 60-80% of the loaded peptides (including a-MSH) or proteins was released within 2 h. 10,29,49 This is attributed to the pores in our system, which provide a more tortuous path for the peptide, reducing its release rate relative to unhindered diffusion from a nonporous surface. The small mass of a-MSH released in the initial burst is expected to result from a-MSH bound loosely on the surface or close to the external surface where pore tortuosity had little effect on diffusion.…”

Section: Discussionmentioning

confidence: 54%

Porous PLGA microspheres tailored for dual delivery of biomolecules via layer‐by‐layer assembly

Palmer

Mitchell

et al. 2014

J Biomedical Materials Res

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Tissue engineering is a complex and dynamic process that requires varied biomolecular cues to promote optimal tissue growth. Consequently, the development of delivery systems capable of sequestering more than one biomolecule with controllable release profiles is a key step in the advancement of this field. This study develops multilayered polyelectrolyte films incorporating alpha-melanocyte stimulating hormone (α-MSH), an anti-inflammatory molecule, and basic fibroblast growth factor (bFGF). The layers were successfully formed on macroporous poly lactic-co-glycolic acid microspheres produced using a combined inkjet and thermally induced phase separation technique. Release profiles could be varied by altering layer properties including the number of layers and concentrations of layering molecules. α-MSH and bFGF were released in a sustained manner and the bioactivity of α-MSH was shown to be preserved using an activated macrophage cell assay in vitro. The system performance was also tested in vivo subcutaneously in rats. The multilayered microspheres reduced the inflammatory response induced by a carrageenan stimulus 6 weeks after implantation compared to the non-layered microspheres without the anti-inflammatory and growth factors, demonstrating the potential of such multilayered constructs for the controlled delivery of bioactive molecules.

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Layer-by-Layer Incorporation of Growth Factors in Decellularized Aortic Heart Valve Leaflets

Cited by 41 publications

References 44 publications

Coating and release of an anti‐inflammatory hormone from PLGA microspheres for tissue engineering

Coating and release of an anti‐inflammatory hormone from PLGA microspheres for tissue engineering

The Effect of Heparin-VEGF Multilayer on the Biocompatibility of Decellularized Aortic Valve with Platelet and Endothelial Progenitor Cells

Porous PLGA microspheres tailored for dual delivery of biomolecules via layer‐by‐layer assembly

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