Typical research and application areas of polymeric biomaterials include tissue re­placement, tissue augmentation, tissue support, and drug delivery. In many cases, the body needs only the temporary presence of a device/biomaterial, in which in­stantly biodegradable and certain partially biodegradable polymeric materials are used. Recent treatment concepts of scaffold based on tissue engineering principles differ from those based on standard tissue replacement and drug therapies, as the en­gineered tissue aims not only to repair but also to regenerate the target tissue. Cells have been cultured outside the body for many years; however, it has only recently become possible for scientists and engineers to grow complex three-dimensional tissue grafts to meet clinical needs. New generations of scaffolds based on synthetic and natural polymers are being developed and evaluated at rapid pace, aimed at mimicking the structural characteristics of the natural extracellular matrix.122 The natural abundance and biodegradability of cellulose, together with its ability to pro­vide unique properties through diversification of cellulosic structures determine a wide range of biomedical applications. In their native form, cellulosic materials have been widely used in the manufacture of optical products, such as hard contact lenses, due to their excellent clarity, good wettability and high gas permeability, textile fibers, molding powder sheets, optical membranes, etc. In addition, cellulose derivatives evidence excellent properties. Usually, these materials are molded and extruded into various consumer products, such as brush handles, tool handles, toys, steering wheels, or other items.

In view of a direct contact of the biomaterial with blood, a clear understanding of their interactions is a prerequisite. First of all, the material interacts instanta­neously with blood constituents, which is critical in determining their potential side effects on the circulatory system and, eventually, on the whole organism.123 124 Sec­ondly, the interactions with blood can affect the in-vivo pharmacokinetic behaviors of the polymers and their ability to leave the blood compartment and enter other tissues. Blood has important physiological functions and a complex composition, being divided into two compartments, namely plasma — which contains proteins, lipids, salts — and specific cells, including red blood cells, white blood cells, and platelets, as well.

The artificial surfaces interact with blood platelets, initially causing platelet ad­herence and aggregation; when such foreign surfaces are placed in contact with the circulating blood, this interaction is believed to lead to thrombosis and thromboem­bolism, and to the removal of platelets from the circulation.125 The surface charac­teristics of biomaterials, such as the hydrophilicity/hydrophobicity, roughness, and flexibility affect the cell-surface interactions, protein adsorption, behavior of cells adhesion and proliferation, and the host response, too. Therefore, cellular adhesion has a direct bearing on the thrombogenicity and immunogenicity of a specific mate­rial, predicting its blood compatibility and deciding the long-term use for a blood­contacting materials application.

On the other hand, adhesion of red blood cells, platelets or water to the cellulose derivative substrate plays an important role in biomedicine. For analyzing biocom­patibility, the relations between the physicochemical properties of material surface and the adhesion of blood components should be known. Surface wettability, which is associated with surface free energy, has been often related to cell adhesion phe­nomena. In order to study the red blood cells, platelets, or water adhesion as a func­tion of the substitution degree, it is preferable to compare a chemically — homolo­gous series of polymers, for minimizing the contribution of specific interactions between the adherent cells and the chemical groups at the solid surface.

Cellulose derivatives compatibility with blood can be established by equation 12, where Wsw, Ws, rbc, Ws, p, Ws, f, Wsa, and Ws, IgG describe the work of spreading of water, red blood cells, platelets, fibrinogen, albumin, and immunoglobulin G, respectively:78,79,126

where superscripts “d” and “p” indicate the disperse and polar component of the

film surface tension obtained from the Y electron-donor and Y electron-accep­tor interactions, while Ysi indicates the solid-liquid interfacial tension.

When the solid-liquid interfacial tension, Ysl, takes negative values (Fig. 3.41), the interfacial free energy, AGsls, has positive values (Eq. (17), Fig. 3.41) and re­jection between the two surfaces of the same polymer, s, immersed in liquid, along with attraction of the liquid occurs:

The hydrophilic/hydrophobic balance of the polymers can be described by the work of spreading of water, over the considered surface. In addition, when blood

is exposed to a biomaterial surface, the life of the implanted biomaterials is de­cided by adhesion/cohesion of cells. Cellular adhesion to biomaterial surfaces could activate coagulation and the immunological cascades. Therefore, cellular adhesion has a direct bearing on the thrombogenicity and immunogenicity of a biomaterial, thus dictating its blood compatibility. The materials, which exhibit a lower work of adhesion, would show a lower extent of cell adhesion than those with a higher work of adhesion. Polymer interaction with red blood cells is mediated mostly by the hydrophobic interaction with the lipid bilayer (the red blood cell hydrophobic layer containing transmembrane proteins), the electrostatic interaction with the sur­face charges or/and the direct interaction with membrane proteins, depending on polymer characteristics. Figure 3.41 shows generally positive values for the work of spreading of red blood cells, Ws, Ac, and negative values for the work of spreading of platelets, Ws, p, suggesting a higher work of adhesion, comparatively with that of cohesion for the red blood cells, but a lower work of adhesion, comparatively with the work of cohesion for platelets. Blood platelets are essential in maintain­ing hemostasis, being very sensitive to changes in the blood microenvironment. Platelet aggregation is used as a marker for materials’ thrombogenic properties, the polymer-platelet interaction being an important step for understanding their hemato — compatibility.135136 Therefore, considering the exposure to blood platelets, the nega­tive values of spreading work indicate that all compositions of cellulose derivative blends evidence cohesion; this result suggests that polymer blends do not interact with platelets, thus preventing activation of coagulation at the blood/biomaterial interface.

Also, an important problem in the evaluation of biocompatibility refers to the analysis of the competitive or selective adsorption of blood proteins at the biomate­rial surface; predictions about these interactions can be formulated only by knowing exactly the structure of the biomaterial. Initially, the surface of an implanted mate­rial is mainly coated with albumin, immunoglobulins (especially immunoglobulin G (IgG)), and fibrinogen from plasma. These sanguine plasma proteins were selected for the study of the affinity of polymer blends towards physiological fluid media, due to their presence in the biological events from blood. Hence, Fig. 3.41 exhibits negative values of spreading work for all three plasma proteins, revealing that co­hesion prevails, thus favoring a nonadsorbent behavior at the interface, as required by bio-applications. Also, all samples exhibit lower values of spreading work for albumin that, along with the rejection of platelets, emphasizes the important role they play in material-host interactions. On the other hand, CAP/HPC blends may be considered as being compatible with certain elements from the physiological environment (i. e., tissue, cells), since their interaction with the studied biological materials would cause no damage of the blood cells or change in the structure of plasma proteins. All these properties, along with the special microarchitecture of the CAP/HPC blends, recommend them as proper candidates for applications in cellular and tissue engineering.

Another significant observation relates to the interesting combination of CAP/ HPC blends properties, such as suitable cohesion with sanguine plasma proteins and platelets, and small adhesion with red blood cells; these results show them as prom­ising materials for blood-contacting devices (including vascular grafts, stents, pace­makers, extracorporeal circuits, etc.), even if long-term biocompatibility requires, however, administration of anticoagulant drugs (i. e., warfarin, heparin). At the same time, the studies performed have made possible the production of blood-compatible polymeric materials by preparing heparin-containing blends for biomedical fields.

The results reveal that, for tissue engineering, obtaining of some porous and interconnected 3D polymer networks is recommended. Thus, CAP/HPC blends can be used to accomplish the required properties for specific applications making them good tissue-engineered candidates. As a result, considering the traditional processes and the recently developed techniques, the improved ability to control the poros­ity and molecular microarchitecture of the CAP/HPC hydrophobic membranes will drive the research closer to its proposed goals.

This type of membranes — with surface topography and roughness as important factors in determining the response of cells to a foreign material — represents an excellent scaffold for applications in cellular and tissue engineering.137 138 Mention should be made of the fact that fibroblasts and chondrocyte cells were shown to grow well in a 3D porous membrane, evidencing superior properties (specific molecular microarchitecture and controlled porosity) for tissue regeneration applications.

With these techniques, it is possible not only to specifically control individual and group pore architecture, but also to take the next step, namely to create micro­vascular features to improve integration within host tissues. Nevertheless, structural improvement and increased pore interconnectivity of porous scaffolds is claimed for the development of artificial blood vessels or peripheral nerve growth.

3.4 CONCLUSIONS

The chapter reviews especially our recent studies on the modification and applica­tions of some cellulose derivatives from a nanotechnology consideration, involv­ing biomedical applications. Generally, the information for each type of cellulose derivative includes aspects of synthesis, processing and properties in solid state and in solution, thus illustrating a variety of research directions. In this context, stud­ies contribute to a better knowledge of the specific interactions that generate and modify the properties of cellulose derivatives, required by the applications in differ­ent domains. Information regarding the influence hydrogen bonding on properties of cellulose derivative in solvent/nonsolvent mixtures — over a large concentration domain, microstructures and appearance of lyotropic liquid crystal phases and bio­compatibility, reveal important aspects necessary to diversify domain of their ap­plications.

3.5 ACKNOWLEDGEMENT

This work was supported by a grant of the Romanian National Authority for Sci­entific Research, CNCS — UEFISCDI, project number PN-n-RU-TE-2012-3-143 (stage 2013).

KEYWORDS

• Biocompatibility

• Blends

• Cellulose Derivatives

• Hydroxypropylcellulose (HPC)

• Liquid Crystals

• Lyotropic Liquid Crystal

• Nano-Particles