Migration of marrow stromal cells in response to sustained release of stromal-derived factor-1α from poly(lactide ethylene oxide fumarate) hydrogels


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Abstract

Stromal derived factor-1α (SDF-1α) 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-1α from degradable poly(lactide ethylene oxide fumarate) (PLEOF) hydrogels and to determine the effect of sustained release of SDF-1α 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-1α loaded PLEOF hydrogels. The hydrogels were characterized with respect to sol fraction, water uptake, degradation, SDF-1α 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-1α 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-1α 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-1α in the proliferative phase of healing for recruitment of progenitor cells in tissue engineering applications.

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