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Injectable nanoclay gels for angiogenesis
- Source :
- Acta biomaterialia. 100
- Publication Year :
- 2019
-
Abstract
- The retention and sustained activity of therapeutic proteins at delivery sites are goals of regenerative medicine. Vascular endothelial growth factor (VEGF) has significant potential in promoting the growth and regeneration of blood vessels but is intrinsically labile. This is exacerbated by the inflammatory microenvironments at sites requiring regeneration. For VEGF to be efficacious, it may require a carrier that stabilises it, protects it from degradation and retains it at the site of interest. In this study, we tested the hypothesis that injectable nanoclay gels comprising Laponiteā¢ XLG (a synthetic hectorite clay) can stabilise VEGF and retain it in the active form for therapeutic delivery. To achieve this, VEGF was incorporated in Laponite gels and its activity tested at a range of concentrations using in vitro cell culture tubulogenesis assays and in vivo angiogenesis assays. We found that VEGF-Laponite gels enhanced tubulogenesis in a dose-dependent manner in vitro. When administered subcutaneously in vivo, Laponite was retained at the injection site for up to a period of three weeks and promoted a 4-fold increase in blood vessel formation compared with that of alginate or vehicle controls as confirmed by CD31 staining. Notably, as compared to alginate, Laponite gels did not release VEGF, indicating a strong interaction between the growth factor and the nanoclay and suggesting that Laponite enhancement of VEGF efficacy is due to its retention at the implantation site for a prolonged period. Our approach provides a robust method for the delivery of bioactive recombinant VEGF without the necessity for complex hydrogel or protein engineering. STATEMENT OF SIGNIFICANCE: In medicine, it is important to deliver drugs to a particular location in the body. Often, however, the drugs are quickly broken down and carried away in the blood before they can exert their effect. In this study, we used a type of synthetic clay, called Laponiteā¢, to preserve a molecule, named VEGF, that stimulates the growth of blood vessels. Previously, we have been able to bind VEGF to the surface of clays, but the clay is not effective when injected or applied as a gel. Herein, we show that we can mix VEGF with the clay and that it strongly stimulates blood vessel growth. We speculate that this would be a useful material for skin wound healing.
- Subjects :
- CD31
Male
Vascular Endothelial Growth Factor A
Angiogenesis
medicine.medical_treatment
0206 medical engineering
Biomedical Engineering
Neovascularization, Physiologic
02 engineering and technology
Biochemistry
Injections
Biomaterials
chemistry.chemical_compound
Mice
In vivo
medicine
Human Umbilical Vein Endothelial Cells
Animals
Humans
Molecular Biology
Chemistry
Regeneration (biology)
Growth factor
Silicates
General Medicine
021001 nanoscience & nanotechnology
020601 biomedical engineering
In vitro
Cell biology
Vascular endothelial growth factor
medicine.anatomical_structure
Cell culture
Blood Vessels
Nanoparticles
0210 nano-technology
Gels
Biotechnology
Blood vessel
Subjects
Details
- ISSN :
- 18787568
- Volume :
- 100
- Database :
- OpenAIRE
- Journal :
- Acta biomaterialia
- Accession number :
- edsair.doi.dedup.....2d6fbe604d0fdfcd52f6f40d1fed2483