This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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 a site of interest. In this study we tested the hypothesis that injectable nanoclay gels composed of Laponite XLG can stabilise VEGF and retain it in 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 vivo cell culture tubulogenesis assays and in vivo angiogenesis assays. We found that VEGF-Laponite gels enhanced tubulogenesis in a dose-dependent manner in vivo. When administered subcutaneously in vivo Laponite was retained at an injection site for up to a period of three weeks and promoted a 4-fold increase in blood vessel formation compared with alginate or vehicle controls as confirmed by CD31 staining. Notably, in contrast 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 an implantation site over a prolonged period. Our approach provides a robust method for delivery of bioactive recombinant VEGF without the necessity for complex hydrogel or protein engineering.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.