1,154
Views
6
CrossRef citations to date
0
Altmetric
Research Article

CXCL1 microspheres: a novel tool to stimulate arteriogenesis

, , , , , , , , , , , , & show all
Pages 2919-2926 | Received 23 Sep 2015, Accepted 11 Nov 2015, Published online: 10 Dec 2015

Figures & data

Figure 1. PEA microspheres were prepared via an emulsification protocol. (A) Chemical structure of the poly(ester amide) (PEA) used as a building block for our PEA microspheres. (B) Schematic illustration of the formulation of PEA microspheres employing a water-in-oil-in-water (W1/O/W2) technique. (C) Optical and fluorescent microscopy images of PEA microspheres loaded with FITC-conjugated BSA (magnification 200×). A loading efficiency of > 85% was achieved.

Figure 1. PEA microspheres were prepared via an emulsification protocol. (A) Chemical structure of the poly(ester amide) (PEA) used as a building block for our PEA microspheres. (B) Schematic illustration of the formulation of PEA microspheres employing a water-in-oil-in-water (W1/O/W2) technique. (C) Optical and fluorescent microscopy images of PEA microspheres loaded with FITC-conjugated BSA (magnification 200×). A loading efficiency of > 85% was achieved.

Figure 2. Scanning electron microscopic visualization and size distribution of PEA microspheres. (A) A microsphere ensemble and (B) the surface of a single PEA microsphere, showing evident surface pores (magnification 570× and 2350×, respectively). (C) Size distribution histogram, displaying a normal distribution with a mean of 57.2 μm and a standard deviation of 17.7 μm. D'Agostino & Pearson omnibus normality test; p = ns.

Figure 2. Scanning electron microscopic visualization and size distribution of PEA microspheres. (A) A microsphere ensemble and (B) the surface of a single PEA microsphere, showing evident surface pores (magnification 570× and 2350×, respectively). (C) Size distribution histogram, displaying a normal distribution with a mean of 57.2 μm and a standard deviation of 17.7 μm. D'Agostino & Pearson omnibus normality test; p = ns.

Figure 3. Proliferation of HMVECs in the presence and absence of PEA microspheres. The microspheres do not exhibit cytotoxic effects. n = 4 per time point per condition; rANOVA; p = ns.

Figure 3. Proliferation of HMVECs in the presence and absence of PEA microspheres. The microspheres do not exhibit cytotoxic effects. n = 4 per time point per condition; rANOVA; p = ns.

Figure 4. Microsphere release versus endogenous production of CXCL1. (A) Cumulative CXCL1 release from PEA microspheres over the course of 28 d, showing a marked burst release of the incorporated chemokine followed by a period of sustained long-term protein dispensation. CXCL1 release from microspheres is a 100-fold higher than endogenous CXCL1 production in ligated hind limbs. n = 3. (B) Endogenous CXCL1 production in ligated and contralateral murine hind limbs, displaying increase of CXCL1 production in the ligated leg compared with the non-ligated leg. n = 2; ANOVA; *p < 0.05 compared with thigh musculature of the ligated leg.

Figure 4. Microsphere release versus endogenous production of CXCL1. (A) Cumulative CXCL1 release from PEA microspheres over the course of 28 d, showing a marked burst release of the incorporated chemokine followed by a period of sustained long-term protein dispensation. CXCL1 release from microspheres is a 100-fold higher than endogenous CXCL1 production in ligated hind limbs. n = 3. (B) Endogenous CXCL1 production in ligated and contralateral murine hind limbs, displaying increase of CXCL1 production in the ligated leg compared with the non-ligated leg. n = 2; ANOVA; *p < 0.05 compared with thigh musculature of the ligated leg.

Figure 5. Perfusion recovery after femoral artery ligation in mice treated with either saline, continuous CXCL1 infusion, non-loaded microspheres, or CXCL1-loaded microspheres. Continuous CXCL1 infusion and CXCL1-loaded microsphere injection enhance perfusion recovery at day 7 compared with both saline and empty microsphere conditions. CXCL1-loaded microspheres show enhanced perfusion recovery compared with all other groups at day 21 after ligation. n = 8–9; rANOVA; *p < 0.05.

Figure 5. Perfusion recovery after femoral artery ligation in mice treated with either saline, continuous CXCL1 infusion, non-loaded microspheres, or CXCL1-loaded microspheres. Continuous CXCL1 infusion and CXCL1-loaded microsphere injection enhance perfusion recovery at day 7 compared with both saline and empty microsphere conditions. CXCL1-loaded microspheres show enhanced perfusion recovery compared with all other groups at day 21 after ligation. n = 8–9; rANOVA; *p < 0.05.
Supplemental material

Supplemental_figure.tif

Download TIFF Image (2.8 MB)

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.