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Biomedical subjects

Ho-Wook Jun

Publications and source records attributed to Ho-Wook Jun.

6 recordsLinked to original sources

Self-assembly of peptide-amphiphile nanofibers: the roles of hydrogen bonding and amphiphilic packing.

The role of hydrogen bonding and amphiphilic packing in the self-assembly of peptide-amphiphiles (PAs) was investigated using a series of 26 PA derivatives, including 19 N-methylated variants and 7 alanine mutants. These were studied by circular dichroism spectroscopy, a variety of Fourier transform infrared spectroscopies, rheology, and vitreous ice cryo-transmission electron microscopy. From these studies, we have been able to determine which amino acids are critical for the self-assembly of PAs into nanofibers, why the nanofiber is favored over other possible nanostructures, the orientation of hydrogen bonding with respect to the nanofiber axis, and the constraints placed upon the portion of the peptide most intimately associated with the biological environment. Furthermore, by selectively eliminating key hydrogen bonds, we are able to completely change the nanostructure resulting from self-assembly in addition to modifying the macroscopic mechanical properties associated with the assembled gel. This study helps to clarify the mechanism of self-assembly for peptide amphiphiles and will thereby help in the design of future generations of PAs.

Amino Acid Sequence↗

Modulation of peptide-amphiphile nanofibers via phospholipid inclusions.

In this communication, we illustrate a new method to modulate the chemical and mechanical properties of peptide-amphiphile nanofibers. Hydrogels containing a mixture of peptide-amphiphile and phospholipid were prepared and evaluated for their mechanical properties, peptide conformation, and nanostructure. It was found that the storage modulus achieved a maximum at 5 mol % phospholipid and that this coincided with the maximum beta sheet signal as observed by circular dichroism. Throughout the ratios of peptide-amphiphile to phospholipid tested, the storage modulus and peptide secondary structure were closely correlated indicating the coupling between molecular structure and macroscopic properties. The nanostructure of the composite fibers was assessed by vitreous ice cryo-TEM and found to be largely independent of the mixture ratio. These new findings will enhance the versatility of peptide-amphiphiles in nanostructured tissue engineering and drug delivery applications.

Cryoelectron Microscopy↗

Modification of polyurethaneurea with PEG and YIGSR peptide to enhance endothelialization without platelet adhesion.

Improved endothelialization without platelet adhesion is essential to enhance the long-term patency of synthetic vascular grafts and other blood-contacting devices. We have developed a dually modified polyurethaneurea by incorporating endothelial cell adhesive YIGSR peptide sequences as chain extenders and nonthrombogenic PEG as a soft segment (PUUYIGSR-PEG) in the polymer backbone. PUUYIGSR-PEG was successfully synthesized and characterized by proton NMR, FTIR, GPC, DSC, ESCA, and contact angle measurement. Despite having similar molecular weight, the peptide/PEG-modified polyurethaneurea (PUUYIGSR-PEG) showed superior mechanical properties compared to the control PEG-modified polyurethaneurea (PUUPPD-PEG). Virtually no platelet adhesion was observed on PUUYIGSR-PEG, while endothelial cell adhesion, spreading, and migration were significantly greater on PUUYIGSR-PEG compared to PUUPPD-PEG. Thus, this bioactive polymer may be an appropriate biomaterial for small diameter vascular grafts.

Amino Acid Sequence↗

Development of a YIGSR-peptide-modified polyurethaneurea to enhance endothelialization.

Polyurethanes have been investigated for use as vascular grafts due to their excellent mechanical properties and relatively good biocompatibility. However, poor retention of endothelial cells and thrombogenicity in vivo remain problematic for vascular graft applications. The peptide YIGSR has been shown to increase endothelial cell adhesion but not attachment of platelets, suggesting its possible utility for vascular graft applications. In this study, a bioactive polyurethaneurea has been synthesized by incorporating GGGYIGSRGGGK peptide sequences into the polymer backbone. Successful incorporation of the peptides was confirmed by NMR, contact angle measurement and ESCA. Uniform distribution of peptides on the surface was observed using a fluorescent probe capable of reacting with tyrosine residues on the peptides. Hard segment domains were visualized using tapping mode AFM. Endothelial cell adhesion, spreading, proliferation, migration and extra-cellular matrix production were improved on bioactive polyurethaneurea compared to control polyurethaneurea. Competitive inhibition of endothelial cell attachment and spreading by soluble YIGSR peptides indicated that cell adhesion and spreading were specifically mediated by YIGSR-sensitive cell adhesion receptor, not just by changed surface properties. There was no significant difference in the number of adherent platelets. Therefore, this bioactive polyurethanurea may improve vascular graft endothelialization without increasing thrombogenicity.

4-Chloro-7-nitrobenzofurazan↗

Nitric oxide-producing polyurethanes.

Thrombus formation and eventual intimal hyperplasia are the leading causes of small-diameter synthetic vascular graft failure. To combat these issues, we have incorporated a diazeniumdiolate-modified nitric oxide (NO)-producing peptide into a polyurethane to improve the thromboresistance of this biocompatible polymer. NO production by polyurethane films occurred for approximately 2 months under physiological conditions, and mechanical properties of the material were suitable for vascular graft applications. Platelet adhesion to NO-releasing polyurethane was dramatically decreased compared to control polyurethane. Furthermore, endothelial cell growth was stimulated in the presence of the NO-releasing polyurethane, while smooth muscle cell growth was greatly inhibited. The ability of this bioactive material to inhibit platelet adhesion and smooth muscle cell proliferation while encouraging endothelialization suggests that this NO-generating polyurethane may be suitable as a candidate material for small-diameter vascular grafts.

Animals↗