Development of nano- and microscale chondroitin sulfate particles for controlled growth factor delivery

Abstract

Size scale plays an important role in the release properties and cellular presentation of drug delivery vehicles. Because negatively charged chondroitin sulfate (CS) is capable of electrostatically sequestering positively charged growth factors, CS-derived nanoscale micelles and microscale spheroids were synthesized as potential growth factor carriers to enhance differentiation of stem cells. Particles were characterized for morphology, size distribution, surface charge, cytocompatibility, as well as release of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). CS micelles were spherical and negatively charged with a bimodal distribution of 324.1 ± 8.5 nm and 73.2 ± 4.4 nm diameters, and CS microspheres possessed a rounded morphology and a diameter of 4.3 ± 0.93 μm. Positively charged TGF-β demonstrated minimal release after loading in CS microspheres, while negatively charged TNF-α exhibited substantial release over the first 15 hours, suggesting TGF-β1 electrostatically complexed with CS. The micelles and microparticles were found to be cytocompatible at moderate concentrations with marrow stromal cell (MSC) monolayers and within embryonic stem cell (ESC) embryoid bodies. These synthesis techniques, which allow the formation of CS-based carriers over a variety of nano-and microscale sizes, offer versatility for tailored release of positively charged growth factors and controlled CS presentation for a variety of stem cell-based applications in tissue engineering and regenerative medicine.

Platelet lysate and chondroitin sulfate loaded contact lenses to heal corneal lesions

“…Chondroitin sulfate solution was characterized by higher proliferation properties than platelet lysate while the platelet lysate and chondroitin sulfate mixture presented the highest proliferation properties indicating a synergic effect between biopolymer and hemoderivative, as observed in the experimental set up with 96 well plate. As previously reported, chondroitin sulfate was able to prolong the biological activity of growth factors by means of electrostatic interactions resulting in stabilization and reduced degradation of growth factors in solutions (Lim et al, 2011;Sandri et al, 2012).…”

Strategies for controlled delivery of biologics for cartilage repair

“…Many natural polymers, notably gelatin [107, 127–136], alginate [137], HA [137–140], chondroitin sulfate [109], and silk [126], have been used to create growth factor delivering MPs. Gelatin is a natural polymer derived from collagen, and by subjecting collagen precursors to either alkaline or acidic processing during the production of gelatin, basic or acidic gelatin with different isoelectric points can be obtained [127, 134].…”

Human Embryonic Stem Cell-Derived Cardiomyocytes Migrate in Response to Gradients of Fibronectin and Wnt5a

“…Support for this possibility comes from our experiments in the gap-closure assay, in which Wnt5a-stimulated hESC-CMs covered an *250-mm distance within a 24-h period. It might also be possible to harness the chemoattractant properties of Wnt5a by injecting Wnt5a-eluting controlled release microspheres [50,51] into the infarct border zone (perhaps with guidance by electroanatomic mapping). If this intervention resulted in an appropriately inductive Wnt5a gradient, hESC-CM grafts isolated in scar tissue might be drawn toward viable host muscle and/or better-coupled graft implants in the border zone.…”