Development of a sustained release nano-in-gel delivery system for the chemotactic and angiogenic growth factor stromal-derived factor 1α

Stromal-Derived Factor 1α (SDF) is an angiogenic, chemotactic protein with significant potential for applications in a range of clinical areas, including wound healing, myocardial infarction and orthopaedic regenerative approaches. The 26-min in vivo half-life of SDF, however, has limited its clinical translation to date. In this study, we investigate the use of star-shaped or linear poly(glutamic acid) (PGA) polypeptides to produce PGA–SDF nanoparticles, which can be incorporated into a tyramine-modified hyaluronic acid hydrogel (HA–TA) to facilitate sustained localised delivery of SDF. The physicochemical properties and biocompatibility of the PGA–SDF nanoparticle formulations were extensively characterised prior to incorporation into a HA–TA hydrogel. The biological activity of the SDF released from the nano-in-gel system was determined on Matrigel^®, scratch and Transwell^® migration assays. Both star-shaped and linear PGA facilitated SDF nanoparticle formation with particle sizes from 255–305 nm and almost complete SDF complexation. Star-PGA–SDF demonstrated superior biocompatibility and was incorporated into a HA–TA gel, which facilitated sustained SDF release for up to 35 days in vitro. Released SDF significantly improved gap closure on a scratch assay, produced a 2.8-fold increase in HUVEC Transwell^® migration and a 1.5-fold increase in total tubule length on a Matrigel^® assay at 12 h compared to untreated cells. Overall, we present a novel platform system for the sustained delivery of bioactive SDF from a nano-in-gel system which could be adapted for a range of biomedical applications.