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.

Anatomy School of Medicine College of Medicine Nursing and Health Sciences National University of Ireland Galway Galway H91 TK33 Ireland

Department of Chemistry Royal College of Surgeons in Ireland Dublin 2 Ireland

Drug Delivery and Advanced Materials Team School of Pharmacy and Biomolecular Sciences Royal College of Surgeons in Ireland Dublin 2 Ireland

Faculty of Chemistry Institute of Physical Chemistry Brno University of Technology Purkynova 464 118 612 00 Brno Czech Republic

R and D Department Contipro Dolni Dobrouc 401 561 02 Dolni Dobrouc Czech Republic

SFI Research Centre for Medical Devices Galway and Dublin Ireland

The SFI Centre for Advanced Materials and Bioengineering Research ; Dublin 2 Ireland

Tissue Engineering Research Group Department of Anatomy and Regenerative Medicine Royal College of Surgeons in Ireland Dublin 2 Ireland

Trinity Centre for Biomedical Engineering Trinity College Dublin Dublin 2 Ireland

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Translational Studies on the Potential of a VEGF Nanoparticle-Loaded Hyaluronic Acid Hydrogel