Heparinized chitosan/hydroxyapatite scaffolds stimulate angiogenesis

Abstract

Formation of blood vessels during bone regeneration represents a major challenge for tissue engineered constructs. Poor revascularization can lead to scaffold failure and consequently, leads to non-healing fracture. Heparin is known to bind with angiogenic growth factors influencing the process of new blood vessels formation. There are several problems associated with the use of growth factors in clinic such as low stability, controlled delivery to the site, and price. The aim of the present study was to explore the potential of heparin to produce pro-angiogenic bone regeneration materials. Chitosan/hydroxyapatite freeze-gelled scaffolds were prepared and loaded with heparin. Different concentrations of heparin were successfully loaded onto the scaffolds, its release from the scaffold was analysed by toluidine blue assay and their angiogenic effect was evaluated by chorioallantoic membrane (CAM) assay to determine the optimal concentration of heparin to induce a proangiogenic effect. It was noted that low heparin concentrations exhibited a positive effect, with approximately 28μg per scaffold indicating a significant increment in blood vessels. The synthesized materials showed no cytotoxic effects when evaluated by using U2OS cell line.

Influence of pH in the synthesis of calcium phosphate based nanostructures with enhanced bioactivity and pro‐angiogenic properties

“…Christopher et al demonstrate that Hypoxia is a significant trigger for vascular bed growth. When tissues develop beyond the limit of oxygen diffusion, hypoxia drives vessel growth via signaling through hypoxia‐inducible transcription factors for angiogenesis 42 . Pezzatini et al reported that HAp nanoparticles could enhance activation, endothelial nitric oxide synthase (eNOS), and fibroblast growth factor‐2 expression during angiogenesis 43 …”

“…When tissues develop beyond the limit of oxygen diffusion, hypoxia drives vessel growth via signaling through hypoxia-inducible transcription factors for angiogenesis. 42 Pezzatini et al reported that HAp nanoparticles could enhance activation, endothelial nitric oxide synthase (eNOS), and fibroblast growth factor-2 expression during angiogenesis. 43 The results from the CEA assay are validated by Wimasis Win-CAM software, which is employed to scrutinize the insights of newly sprouted blood vessels more specifically by categorizing the branching points, total segments, vessel network length, and vessel density shown in Figure 13A-D. From Figure 13A, the M-CP material has 26% and 27% higher branching points of new blood vessels compared with MH-CP and H-CP respectively.…”

Hydroxyapatite/hyperbranched polyitaconic acid/chitosan composite scaffold for bone tissue engineering

“…22 Therefore, CS/HAP composite scaffolds have been thoroughly studied in the field of bone tissue engineering applications. [22][23][24][25][26][27] Generally, because of biocompatibility and osteoconductivity, 28 hydroxyapatite, is the main component of natural bone which is originally composes of a complex nanocomposite material made up of both inorganic and organic components. [29][30][31] Nevertheless, the medical use of CS/HAP composite scaffold is restricted due to the poor rheological properties of the scaffold.…”