Scope

High-throughput and combinatorial research on biomaterials aims at the rapid development of new materials and the establishment of structure–function relationships. Therefore, knowledge of the chemistry of each material and its impact on physical properties is essential to understand the effect on its function as a biomaterial. A tutorial on basic physical and chemical properties of (polymeric) materials highlights these features and can be found in the first part of this chapter. The second part gives an overview of relevant techniques that can be used to screen these material properties in high throughput. In addition, several examples are described in which these methods are used to develop structure–function relationships between material properties and biological performance.

Basic principles: physical and chemical properties of polymeric biomaterials

Chemistry is a constant factor from which the performance of most (polymeric) biomaterials can be predicted, but this extrapolation becomes less obvious when numerous materials are mixed in huge combinatorial libraries. Therefore, researchers are becoming increasingly involved in high-throughput material research when successful correlations between biological performance and physico-chemical material properties are to be made. This accelerating trend can be extracted from many studies where high-throughput technologies are successfully applied to measure physical properties and biological performance of many different polymeric biomaterials. Physical properties such as hardness, topography and hydrophilicity are known to be important parameters in the biological evaluation of materials, because they allow or block the adhesion of biological compounds which is required to allow cell-spreading, migration, proliferation and differentiation. These properties are naturally different for every material or combination of materials, and relate primarily to the variable properties on the chemical level (molecular structure, functional groups and degradation). Therefore, the chemistry of a biomaterial directly contributes to its interaction with biological environments.

Scope

High-throughput screening (HTS) is carried out on two- (2D) and three-dimensional (3D) materials, with hundreds to thousands of conditions at various size scales. When hits are successfully found in HTS systems, upscaling to clinically relevant surfaces needs to be performed to validate whether the identified material and functionality can be replicated on the macroscale. In doing so, parameters such as surface chemistry, topography and sample dispensing must be controlled to maintain reproducibility. Here, we discuss the methods harnessed to replicate chemical and topographical features from the nano- to the macroscale in 2D and 3D systems. Technologies to control cell adhesion and 3D scaffold fabrication are introduced and discussed in terms of their potential for HTS.

Basic upscaling principles

HTS is a highly automated process that tests small amounts of large numbers of compounds for a desired function. In the previous chapters of this book, the general principles behind material chemistry and resulting physico-chemical properties, combinatorial chemistry, microfabrication technologies and development of tools to perform biological assays on HTS platforms have been described. These elements partly return here, where basic principles of polymer chemistry and surface topographies are introduced in the context of facing the technological challenges to upscale selected candidates to larger surfaces or medical devices with complex curved shapes. In addition, the basic principles behind implant fabrication technologies and precise cell deposition are discussed to illustrate the steps required to assimilate HTS into clinically relevant 3D systems.

Scope

Combinatorial chemistry and high-throughput synthesis of novel materials warrant a paradigm shift in current methods to analyse biological responses. This chapter will provide an overview on bioassay development and how novel assays amenable to high-throughput screening platforms can be adapted to more complex systems. Special emphasis will be devoted to the development of assays that can be used in platforms that closely mimic the in vivo complexity of tissues and organs. In that respect, assays that can cope with co-culture systems as well as 3D environments will be discussed. Moreover, modifications or development of new assays and techniques will be described as well as their respective advantages and disadvantages.

Basic principles of assay development

The ability to measure the speed of light changed the field of physics and the world. Chemical reactions led to the Big Bang and the creation of the Universe, but the ability to measure and control those reactions changed the face of the Earth. We can surely say that the need to see more, and in more detail, led to the development of technologies that made that possible and ultimately contributed to the advance of science and society.

Introduction to materiomics

The ability to regenerate and repair tissues and organs – using science and engineering to supplement biology – continuously intrigues and inspires those hoping that the frailty of our bodies can be ultimately avoided. From ancient times, a surprising range of unnatural materials have been used to (partially) substitute human tissues for medicinal purposes. For example, in the era of the Incas (c. 1500), moulded materials such as gold and silver were used for the ‘surgical’ repair of cranial defects. In addition, archaeological findings reveal a wide range of materials, such as bronze, wood and leather, being used to replace and repair parts of the human body. Continuous refinement led to the first evidence of materials successfully implanted inside the body, reportedly used to repair a bone defect in the seventeenth century (see Further Reading).

Even earlier than this, the relationships between anatomy (i.e. structure) and function of living systems had been explored by Leonardo da Vinci and Galileo Galilei, who were among the first few to apply fundamental science to biological systems. In the current age of technology, new materials for biomedical and clinical application have undergone a modern Renaissance, resulting in a surge in design and successful application (1–5). The concepts of tissue repair and substitution are constantly improving and becoming more accessible, as proven for example by the widespread occurrence (and popular approval) of total hip and knee replacements. But rather than replacement with synthetic analogues, can biological tissue(s) be directly engineered?