Chemotactic Activity of Site-Specific Multivalent Conjugates of Stromal Cell-Derived Factor 1<i>α</i> on Branched Nanoparticles

Abstract

Stromal cell-derived factor 1α (SDF1α) is a potent chemokine for the recruitment of stem cells. A challenge is to maintain its activity and control its release. In this study, we engineered a recombinant cysteine-SDF1α (cysSDF1α) protein, and performed multivalent conjugation of cysSDF1 through the maleimide functional group to two forms of branched nanoparticles: multi-arm poly (ethylene glycol) (MA-PEG) and hyaluronic acid (HA). We characterized the chemotactic activity of the conjugates, and determined how the molecular weight (MW) of MA-PEG and HA affected the chemotactic activity. CysSDF1α had similar efficiency to wild-type SDF1α in cell recruitment. Multivalent conjugation of cysSDF1α to low MW MA-PEG (~18 nm) did not significantly affect the chemotactic activity, while the conjugation of cysSDF1α to high MW MA-PEG (~72 nm) lowered the efficiency, possibly due to the larger spacing between conjugated SDF1α molecules. HA has a linear backbone and a high density of multivalent binding sites; however, the chemotactic activity of HA-linked cys-SDF1α was much lower, which further decreased with the increase of HA MW from 200 kDa (~0.78 µm) to 700 kDa (~2.7 µm). Digestion of HA into smaller fragments using hyaluronidase partially recovered the chemotactic activity of cysSDF1α, suggesting that high MW HA might exert steric hindrance for SDF1α binding to its receptors on cell surface and that HA could be used as a depot for SDF1α storage and release. These results demonstrate that multivalent conjugates of SDF1α to nanoparticles may be used to engineer SDF1α delivery for cell recruitment and tissue regeneration.

Rapid-Test Kit Creation of Cardiac Troponin I, A Reliable Biosensor for Naked-Eye Detection Method in Daily Usage and Pharmacokinetic Studies for myocardial Infarction, Systemic Amyloidosis, and Cardiovascular Disease

“…CVD causes a lack of oxygen or nutrition in the heart and can lead to death. Annually, the American Heart Association releases statistical reports on heart disease, stroke, and cardio-vascular risk factors, and considerable research efforts are devoted to CVD [3], including artificial polymer bypass graft transplants [4,5], stent material innovations, anti-thrombosis medicine studies [6,7], tissue engineering for artificial vascular grafts [5], tissue-repair medicine for ischemia [8], and the creation of biomarkers for detection [1,[9][10][11].…”

Rapid-Test Kit for Cardiac Troponin I: A Reliable Enzyme-Linked-Immuno-Substrate-Assay-Based Biosensor for Daily-Use Naked-Eye Detection and Pharmacokinetic Studies for Myocardial Infarction in Cardiovascular Disease

“…In cardiovascular diseases (CVDs), plaque accumulates in the coronary artery and affects blood flow, − resulting in a lack of oxygen or nutrition in the heart that can lead to death. The American Heart Association annually releases statistical reports on heart disease, stroke, and cardiovascular risk factors, and considerable research efforts are devoted to CVD. , This focus includes artificial polymer bypass graft transplants, ,− stent material innovations, antithrombosis medicine studies, ,− tissue engineering for artificial vascular grafts, ,, tissue repair medicine for ischemia, ,− and creating biomarkers for detection. ,,, …”

“…The American Heart Association annually releases statistical reports on heart disease, stroke, and cardiovascular risk factors, and considerable research efforts are devoted to CVD. 10,11 This focus includes artificial polymer bypass graft transplants, 7,12−21 stent material innovations, antithrombosis medicine studies, 12,22−33 tissue engineering for artificial vascular grafts, 13,19,60 tissue repair medicine for ischemia, 8,34−39 and creating biomarkers for detection. 8,33,36,40 Myocardial infarction (MI) refers to myocardial cell death due to ischemia or the unbalanced supply within coronary arteries.…”