Effect of hyaluronic acid incorporation method on the stability and biological properties of polyurethane-hyaluronic acid biomaterials.

The high failure rate of small diameter vascular grafts continues to drive the development of new materials and modification strategies that address this clinical problem, with biomolecule incorporation typically achieved via surface-based modification of various biomaterials. In this work, we examined whether the method of biomolecule incorporation (i.e., bulk versus surface modification) into a polyurethane (PU) polymer impacted biomaterial performance in the context of vascular applications. Specifically, hyaluronic acid (HA) was incorporated into a poly(ether urethane) via bulk copolymerization or covalent surface tethering, and the resulting PU-HA materials characterized with respect to both physical and biological properties. Modification of PU with HA by either surface or bulk methods yielded materials that, when tested under static conditions, possessed no significant differences in their ability to resist protein adsorption, platelet adhesion, and bacterial adhesion, while supporting endothelial cell culture. However, only bulk-modified PU-HA materials were able to fully retain these characteristics following material exposure to flow, demonstrating a superior ability to retain the incorporated HA and minimize enzymatic degradation, protein adsorption, platelet adhesion, and bacterial adhesion. Thus, despite bulk methods rarely being implemented in the context of biomolecule attachment, these results demonstrate improved performance of PU-HA upon bulk, rather than surface, incorporation of HA. Although explored only in the context of PU-HA, the findings revealed by these experiments have broader implications for the design and evaluation of vascular graft modification strategies.

Differential support of cell adhesion and growth by copolymers of polyurethane with hyaluronic acid.

Mechanical mismatch, along with inadequate hemocompatibility and endothelialization, contribute to the high failure rate of many synthetic vascular grafts. However, due to the dueling nature of these requirements (i.e., inhibiting platelet adhesion frequently means inhibiting endothelial cell (EC) adhesion), the creation of materials that simultaneously satisfy the mechanical and biological design criteria needed for small diameter vascular grafts has been an elusive goal. In this work, we demonstrate the ability of polyurethane (PU) containing hyaluronic acid (HA) in its backbone structure to reduce protein adsorption, platelet and bacterial adhesion, and fibroblast and macrophage proliferation while allowing the retention of both ECs and vascular-appropriate mechanics. Irrespective of HA molecular weight (MW), PU-HA materials selectively supported the growth of ECs relative to fibroblasts, reduced platelet adhesion, and performed comparably to negative controls with respect to bactericidal activity. The extent of EC growth on the PU-HA materials did differ with HA MW, with a lower HA MW yielding improved EC growth in both two-dimensional (2-D) films and 3-D electrospun fibrous scaffolds. These findings illustrate that HA incorporated into the backbone of a synthetic polymer structure can retain bioactivity, with subtle differences in HA MW significantly impacting the physical and biological properties of the biomaterial; in particular, PU modified with low-MW HA appears promising for vascular graft applications.

Polyurethane/dermatan sulfate copolymers as hemocompatible, non-biofouling materials.

The range of application of polyurethanes has been limited by their poor hemocompatibility and inability to resist non-specific binding of biomolecules and cells. In this work, a non-adhesive PU-based material was synthesized via the copolymerization of PU with dermatan sulfate. Incorporation of DS into the PU backbone dramatically increased material hydrophilicity and decreased protein adsorption. The in vitro adhesion of several cell types, including platelets, also significantly decreased with increasing DS content. Both the physical and biological properties of the DS contributed to the anti-adhesive properties of the PU/DS copolymer, and this anti-adhesive nature of PU/DS renders this new biomaterial attractive for blood-contacting or non-fouling applications.