title: Migration of marrow stromal cells in response to sustained release of stromal-derived factor-1alpha from poly(lactide ethylene oxide fumarate) hydrogels.
abstract: Stromal derived factor-1alpha (SDF-1alpha) is an important chemokine in stem cell trafficking and plays a critical role in the homing of bone marrow stromal (BMS) cells. However, its use in tissue regeneration is limited by its relatively short half-life and the time-dependent nature of cell homing to the site of injury. The objective of this work was to investigate the release characteristics of SDF-1alpha from degradable poly(lactide ethylene oxide fumarate) (PLEOF) hydrogels and to determine the effect of sustained release of SDF-1alpha on migration of BMS cells. Three PLEOF hydrogels with poly(l-lactide) (PLA) fractions of 6%, 9%, and 24% by weight were synthesized. After the addition of chemokine, the polymerizing mixture was crosslinked to produce SDF-1alpha loaded PLEOF hydrogels. The hydrogels were characterized with respect to sol fraction, water uptake, degradation, SDF-1alpha loading efficiency and release kinetics, and migration rate of bone marrow stromal (BMS) cells. The more hydrophilic hydrogels with 6% and 9% PLA fraction had a pronounced burst release followed by a period of sustained release by diffusion for 21 days. The more hydrophobic hydrogel with 24% PLA fraction had a less pronounced burst release and displayed a slow but constant release by diffusion between days 1 and 9 followed by a fast release by diffusion-degradation from days 9 to 18. The fraction of active SDF-1alpha released from 6%, 9%, and 24% hydrogels after 21 days was 34.3%, 32.3%, and 35.8%, respectively. The migration of BMS cells in response to time-released SDF-1alpha closely followed the protein release kinetics from the hydrogels. The biodegradable PLEOF hydrogel may potentially be useful as a delivery matrix for sustained release of SDF-1alpha in the proliferative phase of healing for recruitment of progenitor cells in tissue engineering applications.
authors.affiliation: Biomimetic Materials and Tissue Engineering Laboratories, Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, United States.
authors.forename: Xuezhong
authors.initials: X
authors.lastname: He
authors.forename: Junyu
authors.initials: J
authors.lastname: Ma
authors.forename: Esmaiel
authors.initials: E
authors.lastname: Jabbari
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis; D020100:Hydrogels / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D011091:Polyesters / Q000008:administration & dosage* / Q000138:chemical synthesis; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000138:chemical synthesis; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000187:drug effects*
chemical_list: D054377:Chemokine CXCL12; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D011091:Polyesters; C512585:poly(L-lactide-co-ethylene oxide-co-fumarate); D011092:Polyethylene Glycols