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Cholic acid functionalized star poly(DL-lactide) was synthesized through the ring-opening polymerization of DL-lactide initiated by cholic acid. The properties and cell behaviour of the cholic acid functionalized star poly(DL-lactide) were investigated as compared with linear poly(DL-lactide)s with different molecular weights and a star poly(DL-lactide) initiated by glycerol. In comparison to linear poly(DL-lactide)s, the cholic acid functionalized star poly(DL-lactide) had better wettability and slightly higher surface energy. The cell adhesion and proliferation on different materials were evaluated using two types of cells, 3T3 mouse fibroblasts and ECV304 human endothelial cells. Compared with the linear poly(DL-lactide)s, the cholic acid functionalized star poly(DL-lactide) showed obviously improved property for cell adhesion. The cell proliferation on the cholic acid functionalized star poly(DL-lactide) was also enhanced. The improvement in cell proliferation was not so significant as compared with the improvement in cell adhesion. This modification strategy provides an effective and simple way to promote cell attachment and growth in tissue engineering.

Restoration of functional endothelium is a requirement for preventing late stent thrombosis. We propose a novel method for targeted delivery of stem cells to a site of arterial injury using ultrasound-generated acoustic radiation force. Mesenchymal stem cells (MSCs) were surface-coated electrostatically with cationic gas-filled lipid microbubbles (mb-MSC). mb-MSC was characterized microscopically and by flow cytometry. The effect of ultrasound (5 MHz) on directing mb-MSC movement toward the vessel wall under physiologic flow conditions was tested in vitro in a vessel phantom. In vivo testing of acoustic radiation force-mediated delivery of mb-MSCs to ballooninjured aorta was performed in rabbits using intravascular ultrasound (1.7 MHz) during intra-aortic infusion of mb-MSCs. Application of ultrasound led to marginalization and adhesion of mb-MSCs to the vessel phantom wall, whereas no effect was observed on mb-MSCs in the absence of ultrasound. The effect was maximal when there were 7 -1 microbubbles/cell (n = 6). In rabbits (n = 6), adherent MSCs were observed in the ultrasound-treated aortic segment 20 min after the injection (334 -137 MSCs/cm 2 ), whereas minimal adhesion was observed in control segments not exposed to ultrasound (2 -1 MSCs/cm 2 , p < 0.05). At 24 h after mb-MSC injection and ultrasound treatment, the engrafted MSCs persisted and spread out on the luminal surface of the artery. The data demonstrate proof of principle that acoustic radiation force can target delivery of therapeutic cells to a specific endovascular treatment site. This approach may be used for endoluminal cellular paving and could provide a powerful tool for cell-based re-endothelialization of injured arterial segments.

As a means to stimulate wound healing, a hollow fiber membrane system might be placed within a wound bed to provide local and externally regulated controlled delivery of regenerative factors. After sufficient healing, it would be desirable to triggerably degrade these fibers as opposed to pulling them out. Accordingly, a series of enzymatically degradable thermoplastic elastomers was developed as potential hollow fiber base material. Polyurethane ureas (PUUs) were synthesized based on 1, 4-diisocyanatobutane, polycaprolactone (PCL) diol and polyethylene glycol (PEG) at different molar fractions as soft segments, and collagenase-sensitive peptide GGGLGPAGGK-NH2 as a chain extender (defined as PUU-CLxEGy-peptide, where x and y are the respective molar percents). In these polymers, PEG in the polymer backbone decreased tensile strengths and initial moduli of solvent-cast films in the wet state, while increasing water absorption. Collagenase degradation was observed at 75% relative PEG content in the soft segment. Control PUUs with putrescine or nonsense peptide chain extenders did not degrade acutely in collagenase. Conduits electrospun from PUU-CL25EG75-peptide and PUU-CL50EG50-peptide exhibited appropriate mechanical strength and sustained release of a model protein from the tube lumen for 7 days. Collapse of PUU-CL25EG75-peptide tubes occurred after collagenase degradation for 3 days. In conclusion, through molecular design, synthesis and characterization, a collagenase-labile PUU-CL25EG75-peptide polymer was identified that exhibited the desired traits of triggerable lability, processability, and the capacity to act as a membrane to facilitate controlled protein release.