Requirements of, scaffolds

Another peculiarity of this type of scaffolds is their high specific surface originating from the small thickness of the microfibrils (around 1 pm. Table 17.3). In other words, this type of scaffold meets some of the basic requirements of scaffolding materials, namely their high porosity and as high as possible specific surface. Regardless of these obvious... 

The integration of combinatorial chemistry, structure-based library design and virtual screening [268, 269] also resulted in successful applications [270, 271]. It ultimately should result in broader SAR information about directionality and physicochemical requirements of acceptable building blocks. This concept is based on feasible scaffolds for exploring protein subsites using parallel or combinatorial synthesis. 

The varying hit rates commonly seen in HTS screens combined with the individual requirements of the project team (stringent or relaxed physiochemical properties, specific scaffolds that represent uninteresting inhibitor classes, and so forth) demand an approach to hit selection that is customizable. This is not true for the Top X method but has been shown clearly here for the current method applied to three very diverse projects with hit rates varying by an order of magnitude (1.3 to 14.6%). 

Another controversial aspect is the durability of the system. It has become common to find researchers who focus their attention on so-called biodegradable scaffolds. We have chosen as a design requirement of our hypothetical device to focus on so-called biodurability. This is not simply a construct for this example. It is a viable alternative that should be explored and will be discussed elsewhere. 

In this chapter and the one that follows, we will review the research concerning the uses of polyurethanes in biomedical applications. Such uses range from topical application of hydrophilic polyurethane pads to the implantation of scaffolds of reticulated foam as organ-assist devices. The range of applications is broad and each use requires that specific problems associated be addressed. This chapter begins with a discussion of biocompatibility — a broad concept ranging from the simple nonir-ritating characteristics required for topical applications to the complex type of compatibility (hemocompatibility) that allows use with whole blood. 

The most advanced technology is the extracorporeal hollow fiber reactor. It is currently in Phase III trial and achieved a good Phase II record to support it. Other techniques including a polyurethane system devised in Japan and encapsulated hepatocytes from UCLA are or were in large animal trials. Whether a device is extracorporeal or is intended for implantation, clinical significance requires a suitable scaffold to support a sufficiently large colony of hepatic cells. For both extracorporeal and implant use, the physical structure of the scaffold must meet certain requirements of strength, void volume, biocompatibility, and other parameters. 

The knowledge gained from this novel cell transplantation device will allow us to expand the technology to other organs and systems, for example, an artilicial pancreas, kidney, or extracorporeal bone marrow system. Nevertheless, Yuang offers a glimpse of what would be required of a scaffold for use in a cell transplant device. 

The binding process may exert a profound effect on cell function. It is well known that hepatic cells do not function when cultured on a flat plate. This reason may be partially explained by the binding-spreading phenomenon. It therefore follows that an ideal scaffold would minimize the spreading effect. Inasmuch as hepatic cells are our primary interest, a scaffold that best approaches the native shapes of the cells would appear to be the best. It is equally clear that this shape must be optimized against additional requirements of void volume and mass transport. Nevertheless, an ideal scaffold would be more curvilinear than flat. 

The properties of peptide fibers formed by ionic complementary peptides may need some tailoring to meet the different requirements for scaffolds and materials for drug delivery. Flowever, these roles could be quite complementary. It is easy to envisage that mixtures of peptide fibers with different stabilities could be used to simultaneously stimulate and support the growth of soft tissues. 

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