Cardiovascular
diseases remain the leading cause of death worldwide.
Patency rates of clinically utilized small diameter synthetic vascular
grafts, such as Dacron and expanded polytetrafluoroethylene (ePTFE),
to treat cardiovascular disease are inadequate because of the lack
of endothelialization. Sodium trimetaphosphate (STMP) cross-linked
poly(vinyl alcohol) (PVA) could be potentially employed as blood-compatible
small diameter vascular graft for the treatment of cardiovascular
disease. However, PVA severely lacks cell adhesion properties, and
the efforts to endothelialize STMP-PVA have been insufficient to produce
a functioning endothelium. To this end, we developed a one-pot method
to conjugate cell-adhesive protein via hydroxyl-to-amine coupling
using carbonyldiimidazole by targeting residual hydroxyl groups on
cross-linked STMP-PVA hydrogel. Primary human umbilical vascular endothelial
cells (HUVECs) demonstrated significantly improved cells adhesion,
viability, and spreading on modified PVA. Cells formed a confluent
endothelial monolayer, and expressed vinculin focal adhesions, cell–cell
junction protein zonula occludens 1 (ZO1), and vascular endothelial
cadherin (VE-Cadherin). Extensive characterization of the blood-compatibility
was performed on modified PVA hydrogel by examining platelet activation,
platelet microparticle formation, platelet CD61 and CD62P expression,
and thrombin generation, which showed that the modified PVA was blood-compatible.
Additionally, grafts were tested under whole, flowing blood without
any anticoagulants in a nonhuman primate, arteriovenous shunt model.
No differences were seen in platelet or fibrin accumulation between
the modified-PVA, unmodified PVA, or clinical, ePTFE controls. This
study presents a significant step in the modification of PVA for the
development of next generation in situ endothelialized synthetic vascular
grafts.
Hydrogel has been an attractive biomaterial for tissue engineering, drug delivery, wound healing, and contact lens materials, due to its outstanding properties, including high water content, transparency, biocompatibility, tissue mechanical matching, and low toxicity. As hydrogel commonly possesses high surface hydrophilicity, chemical modifications have been applied to achieve the optimal surface properties to improve the performance of hydrogels for specific applications. Ideally, the effects of surface modifications would be stable, and the modification would not affect the inherent hydrogel properties. In recent years, a new type of surface modification has been discovered to be able to alter hydrogel properties by physically patterning the hydrogel surfaces with topographies. Such physical patterning methods can also affect hydrogel surface chemical properties, such as protein adsorption, microbial adhesion, and cell response. This review will first summarize the works on developing hydrogel surface patterning methods. The influence of surface topography on interfacial energy and the subsequent effects on protein adsorption, microbial, and cell interactions with patterned hydrogel, with specific examples in biomedical applications, will be discussed. Finally, current problems and future challenges on topographical modification of hydrogels will also be discussed.
Poly(vinyl alcohol) (PVA) is a water-soluble polymer and forms a hydrogel that has been studied as a potential small-diameter (<6 mm) vascular graft implant. The PVA hydrogel crosslinked using sodium trimetaphosphate (STMP) has been shown to have many beneficial properties such as bioinert, low-thrombogenicity, and easy surface modification. Compared to conventional synthetic vascular graft materials, PVA has also shown to possess better mechanical properties; however, the compliance and other mechanical properties of PVA grafts are yet to be optimized to be comparable with native blood vessels. Mechanical compliance has been an important parameter to be studied for small-diameter vascular grafts, as compliance has been proposed to play an important role in intimal hyperplasia formation. PVA grafts are made using dip-casting a cylindrical mold into crosslinking solution. The number of dipping can be used to control the wall thickness of the resulting PVA grafts. In this study, we hypothesized that the number of dip layers, chemical and physical crosslinking, and interlayer adhesion strength could be important parameters in the fabrication process that would affect compliance. This work provides the relationship between the wall thickness, burst pressure, and compliance of PVA. Furthermore, our data showed that interlayer adhesion as well as chemical and physical crosslinking density can increase the compliance of PVA grafts.
Nonviral direct neuronal reprogramming holds significant potential in the fields of tissue engineering and regenerative medicine. However, the issue of low reprogramming efficiency poses a major barrier to its application....
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.