Sustained delivery of SDF-1α from heparin-based hydrogels to attract circulating pro-angiogenic cells

Prokoph, Silvana; Chavakis, Emmanouil; Levental, Kandice R.; Zieris, Andrea; Freudenberg, Uwe; Dimmeler, Stefanie; Werner, Carsten

doi:10.1016/j.biomaterials.2012.03.039

Cited by 149 publications

(123 citation statements)

References 48 publications

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“…Indeed, the use of different bioactive peptides as substitutes for cell therapy has been successfully tested in cardiac regeneration and other specialties. 17,[39][40][41][42] In the present study, we selected RGD, a tripeptide composed of arginine-glycine-aspartate that mimics the integrin-binding site of cells and the extracellular matrix 43 and has already been successfully tested as a biofunctionalization motif. 44 Grafting of RGD on a polymer was compared, again in a head-to-head fashion, with ADSC selected because of their ease of procurement, richness of their secretome, and potential for human applications.…”

Section: Figmentioning

confidence: 99%

Polymer-Based Reconstruction of the Inferior Vena Cava in Rat: Stem Cells or RGD Peptide?

Pontailler

Illangakoon

Williams

et al. 2015

Tissue Engineering Part A

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As part of a program targeted at developing a resorbable valved tube for replacement of the right ventricular outflow tract, we compared three biopolymers (polyurethane [PU], polyhydroxyalkanoate (the poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxyvalerate) [PHBVV]), and polydioxanone [PDO]) and two biofunctionalization techniques (using adipose-derived stem cells [ADSCs] or the arginine-glycine-aspartate [RGD] peptide) in a rat model of partial inferior vena cava (IVC) replacement. Fifty-three Wistar rats first underwent partial replacement of the IVC with an acellular electrospun PDO, PU, or PHBVV patch, and 31 nude rats subsequently underwent the same procedure using a PDO patch biofunctionalized either by ADSC or RGD. Results were assessed both in vitro (proliferation and survival of ADSC seeded onto the different materials) and in vivo by magnetic resonance imaging ( MRI), histology, immunohistochemistry [against markers of vascular cells (von Willebrand factor [vWF], smooth muscle actin [SMA]), and macrophages ([ED1 and ED2] immunostaining)], and enzyme-linked immunosorbent assay (ELISA; for the expression of various cytokines and inducible NO synthase). PDO showed the best in vitro properties. Six weeks after implantation, MRI did not detect significant luminal changes in any group. All biopolymers were evenly lined by vWF-positive cells, but only PDO and PHBVV showed a continuous layer of SMA-positive cells at 3 months. PU patches resulted in a marked granulomatous inflammatory reaction. The ADSC and RGD biofunctionalization yielded similar outcomes. These data confirm the good biocompatibility of PDO and support the concept that appropriately peptide-functionalized polymers may be successfully substituted for cell-loaded materials.

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Section: Figmentioning

confidence: 99%

Polymer-Based Reconstruction of the Inferior Vena Cava in Rat: Stem Cells or RGD Peptide?

Pontailler

Illangakoon

Williams

et al. 2015

Tissue Engineering Part A

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“…69 Binding to sulfated glycosaminoglycans (GAGs) in the ECM, such as heparin, is pivotal to locally accumulating and protecting such proteins against degradation. 58 While alginate is known to also have an affinity for heparinbinding proteins, other biomaterials are modified by incorporating heparin to tune protein binding and control release. 19,32 Herein, chemokine gradients were sustainably generated by incorporating SDF-1 within StarPEG-heparin hydrogels.…”

Section: Delivery Of Soluble Factors For Enhanced Recruitmentmentioning

confidence: 99%

“…19,32 Herein, chemokine gradients were sustainably generated by incorporating SDF-1 within StarPEG-heparin hydrogels. 58 Here, the release profile of SDF-1 may be altered by precisely varying the loading concentration and by matrix metalloprotease (MMP)-mediated hydrogel cleavage. Implantation of these biofunctionalized hydrogels led to increased homing of systemically administered CellTracker CM-DIL-labaled human EPCs along the established gradient of SDF-1.…”

Section: Delivery Of Soluble Factors For Enhanced Recruitmentmentioning

confidence: 99%

“…Implantation of these biofunctionalized hydrogels led to increased homing of systemically administered CellTracker CM-DIL-labaled human EPCs along the established gradient of SDF-1. 58 However, SDF-1 is also cleaved by exopeptidases and MMP-2, local proteases that are activated in the inflammatory environment of injured tissue. 69 Therefore, other strategies have employed delivery of a protease-resistant SDF-1 designed to retain in vivo bioactivity upon controlled nanofiber-mediated delivery within infarcted myocardium in rats.…”

Section: Delivery Of Soluble Factors For Enhanced Recruitmentmentioning

confidence: 99%

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The Role of Synthetic Extracellular Matrices in Endothelial Progenitor Cell Homing for Treatment of Vascular Disease

Williams

Silva

2015

Ann Biomed Eng

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“…Therefore, drug delivery approaches have been developed to release SDF1α to promote tissue regeneration [12] following myocardial infarction [13] [14], muscle [15], liver [16], and neural regeneration [17]. Several methods have been developed to immobilize SDF1α onto delivery vehicles, mainly relying on heparin-mediated binding, in which the heparin covalently links to the vehicles via an NH 2 -PEG-NH 2 linker or hydrogel linker, and SDF1α is then immobilized to the conjugated heparin through its heparin-binding domain [18]- [24]. It has been shown that clustering of vascular endothelial growth factors [25], fibroblast growth factor-2 [26], or epidermal growth factors synergistically increases the activity by inducing receptor dimerization [27].…”

Section: Introductionmentioning

confidence: 99%

Chemotactic Activity of Site-Specific Multivalent Conjugates of Stromal Cell-Derived Factor 1<i>α</i> on Branched Nanoparticles

Hsieh¹,

Huang²,

Patel³

et al. 2018

JBNB

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Stromal cell-derived factor 1α (SDF1α) is a potent chemokine for the recruitment of stem cells. A challenge is to maintain its activity and control its release. In this study, we engineered a recombinant cysteine-SDF1α (cysSDF1α) protein, and performed multivalent conjugation of cysSDF1 through the maleimide functional group to two forms of branched nanoparticles: multi-arm poly (ethylene glycol) (MA-PEG) and hyaluronic acid (HA). We characterized the chemotactic activity of the conjugates, and determined how the molecular weight (MW) of MA-PEG and HA affected the chemotactic activity. CysSDF1α had similar efficiency to wild-type SDF1α in cell recruitment. Multivalent conjugation of cysSDF1α to low MW MA-PEG (~18 nm) did not significantly affect the chemotactic activity, while the conjugation of cysSDF1α to high MW MA-PEG (~72 nm) lowered the efficiency, possibly due to the larger spacing between conjugated SDF1α molecules. HA has a linear backbone and a high density of multivalent binding sites; however, the chemotactic activity of HA-linked cys-SDF1α was much lower, which further decreased with the increase of HA MW from 200 kDa (~0.78 µm) to 700 kDa (~2.7 µm). Digestion of HA into smaller fragments using hyaluronidase partially recovered the chemotactic activity of cysSDF1α, suggesting that high MW HA might exert steric hindrance for SDF1α binding to its receptors on cell surface and that HA could be used as a depot for SDF1α storage and release. These results demonstrate that multivalent conjugates of SDF1α to nanoparticles may be used to engineer SDF1α delivery for cell recruitment and tissue regeneration.

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Sustained delivery of SDF-1α from heparin-based hydrogels to attract circulating pro-angiogenic cells

Cited by 149 publications

References 48 publications

Polymer-Based Reconstruction of the Inferior Vena Cava in Rat: Stem Cells or RGD Peptide?

Polymer-Based Reconstruction of the Inferior Vena Cava in Rat: Stem Cells or RGD Peptide?

The Role of Synthetic Extracellular Matrices in Endothelial Progenitor Cell Homing for Treatment of Vascular Disease

Chemotactic Activity of Site-Specific Multivalent Conjugates of Stromal Cell-Derived Factor 1<i>α</i> on Branched Nanoparticles

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Sustained delivery of SDF-1α from heparin-based hydrogels to attract circulating pro-angiogenic cells

Cited by 149 publications

References 48 publications

Polymer-Based Reconstruction of the Inferior Vena Cava in Rat: Stem Cells or RGD Peptide?

Polymer-Based Reconstruction of the Inferior Vena Cava in Rat: Stem Cells or RGD Peptide?

The Role of Synthetic Extracellular Matrices in Endothelial Progenitor Cell Homing for Treatment of Vascular Disease

Chemotactic Activity of Site-Specific Multivalent Conjugates of Stromal Cell-Derived Factor 1&lt;i&gt;α&lt;/i&gt; on Branched Nanoparticles

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Product

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Chemotactic Activity of Site-Specific Multivalent Conjugates of Stromal Cell-Derived Factor 1<i>α</i> on Branched Nanoparticles