Advanced 3D-Printed Systems and Nanosystems for Drug Delivery and Tissue Engineering

Lisa C. du Toit, Pradeep Kumar, Yahya E. Choonara, Viness Pillay

• Publisher: Woodhead Publishing
• Year: 2020
• Print ISBN: 9780128184714
• eBook ISBN: 9780128184721
• Topic: Technology & Engineering
• Subtopic: Materials Science
• Index: Technology & Engineering

Advanced 3D-Printed Systems and Nanosystems for Drug Delivery and Tissue Engineering explores the intricacies of nanostructures and 3D printed systems in terms of their design as drug delivery or tissue engineering devices, their further evaluations and diverse applications. The book highlights the most recent advances in both nanosystems and 3D-printed systems for both drug delivery and tissue engineering applications. It discusses the convergence of biofabrication with nanotechnology, constructing a directional customizable biomaterial arrangement for promoting tissue regeneration, combined with the potential for controlled bioactive delivery. These discussions provide a new viewpoint for both biomaterials scientists and pharmaceutical scientists.- Shows how nanotechnology and 3D printing are being used to create systems which are intelligent, biomimetic and customizable to the patient- Explores the current generation of nanostructured 3D printed medical devices- Assesses the major challenges of using 3D printed nanosystems for the manufacture of new pharmaceuticals

1

Bioinks for 3D printing of artificial extracellular matrices

Hitesh Chopra ¹ , Sandeep Kumar ² , and Inderbir Singh ^{1 1} Department of Pharmaceutics, Chitkara College of Pharmacy, Chitkara University, Patiala, Punjab, India ² Department of Pharmaceutics, ASBASJSM College of Pharmacy, Ropar, Punjab, India

Abstract

Bioprinting is an additive mechanism–based technology where the living cells are impregnated and the media used for bioprinting is known as bioink. The nature of the material determines the output as well as the process or mechanism to be followed. The science behind the printing needs to be decoded to gain insight into the basic mechanism behind three-dimensional printing. The printing process is controlled via computers so that the minute detailing of the whole process could be controlled. In this chapter, a detailed review about the technologies available for bioprinting of artificial extracellular matrices, along with the bioinks employed for their printing is provided. A detailed review of the bioink materials such as hydrogels, cell aggregates, microcarriers, and decellularized matrix components has been undertaken.

Keywords

Artificial extracellular matrix; Bioink; Biomaterials; Personalized drug delivery; Three-dimensional printing

1. Introduction

The medical field is vast and continually evolving with technological advancements. The past decade has experienced many changes such as the completion of the human genome project in 2003 [1], FDA approval of a new therapy for cystic fibrosis in 2012 for the drug, Kalydco ® [2], and mitochondrial replacement therapy for fatal Leigh syndrome [3], to name a few. The term ‘personalized medicine’ has changed immensely from the 20th to the 21st century, and includes targeted medicines is also used alternatively. Personalized medicine has been described by the National Academy of Sciences as the use of genomic, epigenomic exposure and other data to define individual patterns of disease potentially leading to enhanced individual treatment [4].

Technologies such as pharmacogenetics are gaining momentum, in which researchers are evaluating genes for tailor-made medicines [5], and endeavouring to keep abreast with the genetic issues that cause variation from person to person. Recombinant technology is also at the forefront due to the application of proteins which are readily used as ligands for targeting. Rendering this more effective are hyphenated diagnostic tests already on the market, leading to more targeted therapy [6]. In contrast, formulation scientists are also working on nanotechnology, which is gaining wider acceptance by global researchers. This has led to a novel concept in personalized medicines, which is not only valid to the metabolic diseases or pharmacogenomics.

The latest widely used technology is 3D printing. The use of 3D technology in the field of tissue and organ fabrication, prosthetics, and pharmaceutical dosage forms is already well known. Moreover, in addition to the above applications, it has also shown potential as a candidate for personalized medicines [7].

Presently pharmaceutical companies rely on the fixed dose and dosage regimen. Companies are spending a mammoth amount of money and labor on conventional dosage forms rather than investing in innovative dosage form studies. As a result, the number of research studies underway on novel dosage forms is still very limited [7]. However, new technologies such as 3D printing are moving forward at a rapid pace. With 3D printing technology, technical problems such as dose pliability has been reduced. Moreover, patients may have personalised doses and drug release patterns that render completely tailored dosage forms (Table 1.1).

Table 1.1

Advantages and disadvantages of 3D technology.

Advantages	Disadvantages
Reduced manufacturing cost	Time consuming
Precise control over accuracy	Customized tooling
Waste reduction	Not suitable for most of the bioactives
High accuracy	Not possible to produce big sized models
Resource efficiency	High technical know-how required

2. Printing technologies used in three-dimensional printing

2.1. Inkjet printing

This bioprinter delivers relatively small droplets of 1–100 pL volume with a 10–50 μm diameter. The initial stages of bioprinting were derived from 2D ink-based printers. It was basically a mechanism involving the replacement of the ink in a cartridge with the biological material, which may include cells, and the stage replaced the paper which can be controlled with the computer system attached. Nowadays, inkjet-based bioprinters are specially designed for the customers' need, and they are believed to have increased resolution, precision, and speed. However, the major drawback of the whole method is low encapsulation efficiency [8].

There are three methods used for inkjet printing involving piezoelectric, thermal, and electrohydrodynamic jet bioprinting [8,9]. The piezoelectric printer has crystal inbuilt that helps in the production of acoustic waves that propel the liquid in small doses to ooze out through the nozzle.

While the thermal inkjet system uses the small waves of pressure that cause heating and in turn, the evaporation process begins causing the vaporization of droplets and expulsion of droplets from the printing head. There is a small exposure time of about 2 μs, and such a low exposure time at high temperature causes no damage to cells [9]. The surface tension in the case of liquids is the force or attractive forces existing between the compounds present in the liquid. During the whole process, when the energy is applied in the form of acoustic waves the intermolecular forces between the molecules break or weaken and as a result the droplets are formed. However, the extent of surface tension is inversely proportional to the cell concentration. With an increase in the concentration of cells increased, more cells are adsorbed in the liquid-gas interface, as a result, the total energy of the cell itself is reduced and smaller surface tension is observed. Thereafter the gelation procedure occurs. It may be physical, chemical, or there may be photocrosslinking to ensure the bio-printed constructs are stable [8,9].

However, if gelation of bioink occurs inside the nozzle head, a blockage may occur. Ideally, it must occur after the material exits from the nozzle. Moreover, if the hydrogel formation does not occur in situ, it may happen that bioprinting may not transpire properly. Therefore, for...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Preface
• 1. Bioinks for 3D printing of artificial extracellular matrices
• 2. Applications of 3D printing for the advancement of oral dosage forms
• 3. Recent progress in 3D-printed polymeric scaffolds for bone tissue engineering
• 4. Inorganic additives to augment the mechanical properties of 3D-printed systems
• 5. Cellulosic materials as bioinks for 3D printing applications
• 6. 4D printing and beyond: where to from here?
• 7. Nanomaterials combination for wound healing and skin regeneration
• 8. Nanomedicine advances in cancer therapy
• 9. Nanomaterials for ocular tissue engineering and regeneration
• 10. Nanotechnological paradigms for neurodegenerative disease interventions
• Index