title: Tunable Controlled Release of Bioactive SDF-1α via Protein Specific Interactions within Fibrin/Nanoparticle Composites.
abstract: The chemokine, stromal cell-derived factor 1α (SDF-1α), is a key regulator of the endogenous neural progenitor/stem cell-mediated regenerative response after neural injury. Increased and sustained bioavailability of SDF-1α in the peri-injury region is hypothesized to modulate this endogenous repair response. Here, we describe poly(lactic-co-glycolic) acid (PLGA) nanoparticles capable of releasing bioactive SDF-1α in a sustained manner over 60days after a burst of 23%. Moreover, we report a biphasic cellular response to SDF-1α concentrations thus the large initial burst release in an in vivo setting may result in supratherapeutic concentrations of SDF-1α. Specific protein-protein interactions between SDF-1α and fibrin (as well as its monomer, fibrinogen) were exploited to control the magnitude of the burst release. Nanoparticles embedded in fibrin significantly reduced the amount of SDF-1α released after 72 hrs as a function of fibrin density. Therefore, the nanoparticle/fibrin composites represented a means to independently tune the magnitude of the burst phase release from the nanoparticles while perserving a bioactive depot of SDF-1α for release over 60days.
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
authors.forename: D
authors.initials: D
authors.lastname: Dutta
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
authors.forename: C
authors.initials: C
authors.lastname: Fauer
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Mulleneux
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Stabenfeldt