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. 2010 May 10;390(2):107-16.
doi: 10.1016/j.ijpharm.2009.12.063. Epub 2010 Feb 26.

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

Xuezhong He  1 , Junyu Ma, Esmaiel Jabbari
Affiliations

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

Xuezhong He et al. Int J Pharm. .

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.

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Figures

Figure 1
Figure 1
Schematic diagram to demonstrate the procedure for measuring the rate of migration of BMS cells in response to the released SDF-1α from the hydrogels using an 8-µm pore size Millipore MultiScreen-MIC 96-transwell plate.
Figure 2
Figure 2
Effect of PLA fraction on swelling ratio and sol fraction of PLEOF hydrogel. Error bars correspond to means ± SD (n=4).
Figure 3
Figure 3
Effect of PLA fraction on degradation kinetics of PLEOF hydrogel in serum free DMEM media at Hydrolytic at 37°C. Error bars correspond to means ± SD (n=4).
Figure 4
Figure 4
Effect of PLA fraction on SDF-1α loading efficiency in PLEOF hydrogel. Error bars correspond to means ± SD (n=4).
Figure 5
Figure 5
Effect of PLA fraction on release kinetics of SDF-1α from PLEOF hydrogels. Error bars correspond to means ± SD (n=4).
Figure 6
Figure 6
Effect of calcein AM labeling on viability and proliferation of BMS cells. Error bars correspond to means ± SD (n=4).
Figure 7
Figure 7
Effect of SDF-1α concentration on migration of BMS cells. Error bars correspond to means ± SD (n=4).
Figure 8
Figure 8
The extent of migration of BMS cells in response to the released SDF-1α from PLEOF hydrogels with different PLA to PEG ratios. Error bars correspond to means ± SD (n=4).
See this image and copyright information in PMC

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