Blood‐Compatible Materials: Vascular Endothelium‐Mimetic Surfaces that Mitigate Multiple Cell‐Material Interactions

Abstract

When flowing whole blood contacts medical device surfaces, the most common blood–material interactions result in coagulation, inflammation, and infection. Many new blood‐contacting biomaterials have been proposed based on strategies that address just one of these common modes of failure. This study proposes to mitigate unfavorable biological reactions that occur with blood‐contacting medical devices by designing multifunctional surfaces, with features optimized to meet multiple performance criteria. These multifunctional surfaces incorporate the release of the small molecule hormone nitric oxide (NO) with surface chemistry and nanotopography that mimic features of the vascular endothelial glycocalyx. These multifunctional surfaces have features that interact with coagulation components, inflammatory cells, and bacterial cells. While a single surface feature alone may not be sufficient to achieve multiple functions, the release of NO from the surfaces along with their modification to mimic the endothelial glycocalyx synergistically improves platelet‐, leukocyte‐, and bacteria‐surface interactions. This work demonstrates that new blood‐compatible materials should be designed with multiple features, to better address the multiple modes of failure of blood‐contacting medical devices.

Enzymatic Degradation of Glycosaminoglycans and Proteoglycan-Mimetic Materials in Solution and on Polyelectrolyte Multilayer Surfaces

“…Polyelectrolyte complex nanoparticles (PCNs) were prepared as previously described. ,,, Briefly, CHI (1 mg/mL), HEP (1.5 mg/mL), and CS (2.8 mg/mL) solutions were prepared in an acetate buffer solution (0.2 M sodium acetate and acetic acid at pH 5.0). Solutions were filtered using 0.22 μm PDVF syringe filters.…”

“…PEMs were prepared as previously described. , Briefly, chitosan (CHI) (1 mg/mL) and HA (0.5 mg/mL) solutions were prepared with acetate buffer (0.2 sodium acetate and acetic acid at pH 5.0). Solutions were stirred for at least 2 h at room temperature and were then filtered through 2.0 um PDVF syringe filters.…”

“…They also integrated these mimics into cartilage tissues by injection . Nanoparticles that consist of an outer layer of GAGs may mimic the chemistry and approximate size of PGs, resulting in favorable material properties. ,,,− Polymer-GAG complexes may not have the same chemical composition as PGs, but they can still mimic some key functions of PGs in the ECM. − Regardless of the approach, all PG mimics should be designed to be biodegradable, biocompatible, and effective for their specific application.…”

“…Polyelectrolyte complex nanoparticles (PCNs) were made to mimic the relative size and charge of dense PG clusters while also presenting GAG chemistries . We have shown that these particles mimic the size, composition, and biochemical activity of the PGs including aggregan. , Polyelectrolyte complex nanoparticles on surfaces can inhibit bacterial attachment, some immune responses, platelet adhesion, protein attachment, and polymerization and can stabilize and deliver growth factors. ,,,, We have referred to PCN materials as PG mimics, glycocalyx mimics, and aggrecan mimics depending on their intended application. ,,,, PCNs are stabilized through simple electrostatic interactions between polyanions and polycations, which makes them easy to synthesize but which does not allow for tunability of specific properties. Our lab has also developed a family of PG-mimetic graft copolymers (GCs) with tunable graft density.…”

Ex vivo evaluation of blood coagulation on endothelial glycocalyx-inspired surfaces using thromboelastography

“…Additionally, the nitrosation process may disturb the surface layer of heparin and cause polysaccharides to disperse into solution. This physically changes the surface roughness and might further affect the coagulation cascade [47].…”