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3D/4D Printing in Additive Manufacturing: Process Engineering and Novel Excipients

Christian Muehlenfeld1 and Simon A. Roberts2

1Ashland Industries Deutschland GmbH, Paul-Thomas-Straße 56, 40599 Düsseldorf, Germany

2Ashland Specialties UK Ltd., Vale Industrial Estate, Stourport Road, Kidderminster, Worcestershire, DY11 7QU, UK

1.1 Introduction

In recent years, additive manufacturing, which is more colloquially referred to as three‐dimensional () printing, has seen high‐impact implementation in manufacturing applications in areas such as aeronautics, robotics, electronics, industrial goods, and even the food industry. These wide‐ranging applications have resulted in a change in focus for biomedical research [1]. 3D printing is a generic term that describes various methods of constructing objects in a layer‐by‐layer manner. Although the birth of 3D printing dates back to 1984, when Charles Hull invented the first stereolithographic printer, 3D printing started to increasingly change the way in which manufacturing was performed from the year 2000 onward.

This chapter will introduce the basic concepts of 3D and 4D printing technologies as they pertain to biomedical applications. In particular, 4D printing (printing of objects with the ability to change over time) has a strong potential for biomedical applications. Patient‐specific products such as medical devices, tissue constructs (including muscle structures, bone, and ear tissue), and, eventually, artificial organs may be fabricated using 4D printing [2–6].

1.2 The Process of 3D and 4D Printing Technology

3D printing typically begins with a computer‐aided design () file that describes the geometry and size of the objects to be printed. The object is sliced into a series of digital cross‐sectional layers that are then fabricated by the 3D printer. This process can use many different types of materials such as thermoplastic polymers, powders, metals, and ultraviolet () curable resins.

Four‐dimensional () printing is defined as printing of 3D objects with the ability to change the form or function under the influence of external stimuli over time [7, 8]. A schematic of printing dimensions is shown in Figure 1.1.

Figure 1.1 Schematic of 1D, 2D, 3D, and 4D printing dimensions. In a 4D system, a 3D printed object undergoes time‐dependent deformations when exposed to various stimuli.

The essential difference between 4D printing and 3D printing is the addition of smart design, or responsive materials, that results in a time‐dependent deformation of the object. In order to achieve this goal, the printed material needs to self‐transform in form or function when exposed to an external stimulus such as osmotic pressure, heat, current, ultraviolet light, or another energy source [9]. Incorporating these additional functions poses major challenges to the design process because 4D printed structures must be preprogrammed in detail, based on the transforming mechanism of controllable smart materials that incorporate the requested material deformations. Because most 3D printing materials are designed only to produce rigid, static objects, the choice of materials for 4D printing is significant.

1.3 3D/4D Printing for Biomedical Applications

3D and 4D printing technologies have the potential for great impact in biomedical applications. 3D printing allows printing of biomaterials as well as living cells to build complex tissues and organs, whereas 4D bioprinting is an extension of the process that adds additional value. Different approaches can be used for 4D printing of biomaterials. The first approach strictly follows the original concept of 4D printing, in which a substrate material folds into a predefined 3D configuration upon stimulus. The printed cell or tissue material is incorporated within the device during printing and subsequently follows the folding of the substrate as it forms into a desired shape postimplantation.

The second approach is based on the maturation of engineered tissue constructs after printing and could be considered as a kind of in vivo 4D bioprinting. A 3D printed polymer medical device is implanted first and then accommodates the growth of tissue or organ over the postsurgical period.

1.4 Smart or Responsive Materials for 4D Biomedical Printing

The 3D and 4D printing technologies are classified mainly based on the types of materials used. The selection of materials has a direct influence on mechanical or thermal properties, as well as the transformation stimuli of the finished objects. Although the major difference between 3D and 4D printing is in the materials, the processes used to fabricate printed objects are the same. It should be pointed out that 4D printing is still in its early development stage. Herein, some example applications are presented to demonstrate its potential.

Although numerous materials are available for 3D printing, currently, limited stimuli‐responsive biomaterials are available for 4D printing. At present, researchers are focused on the development of various, novel, smart materials; however, not every smart material can be 3D printed. The most common materials used in 4D printing are biocompatible materials such as hydrogels and polymers. Table 1.1 lists some examples of smart biomaterials intended for biomedical applications based on their stimulus responsiveness. Some of them have already been used for 4D printing, but it is unclear whether others of these materials can be used in 3D/4D printing in the future. The mechanisms facilitating 4D temporal shape transformation of 3D printed materials for biomedical applications range from temperature responsiveness, magnetic field responsiveness, and light responsiveness to humidity responsiveness.

Table 1.1 Examples of smart or responsive materils suitable for biomedical purposes.

Figure 1.2 (A) Schematic diagram illustrating the reversible self‐folding of soft microgrippers in response...