4D Printing: The Dawn of “Smart” Drug Delivery Systems and Biomedical Applications

With the approval of first 3D printed drug “spritam” by USFDA, 3D printing is gaining acceptance in healthcare, engineering and other aspects of life. Taking 3D printing towards the next step gives birth to what is referred to as “4D printing”. The full credit behind the unveiling of 4D printing technology in front of the world goes to Massachusetts Institute of Technology (MIT), who revealed “time” in this technology as the fourth dimension. 4D printing is a renovation of 3D printing wherein special materials (referred to as smart materials) are incorporated which change their morphology post printing in response to a stimulus. Depending upon the applicability of this technology, there may be a variety of stimuli, most common among them being pH, water, heat, wind and other forms of energy. The upper hand of 4D printing over 3D printing is that 3D printed structures are generally immobile, rigid and inanimate whereas 4D printed structures are flexible, mobile and able to interact with the surrounding environment based on the stimulus. This capability of 4D printing to transform 3D structures into smart structures in response to various stimuli promises a great potential for biomedical and bioengineering applications. The potential of 4D printing in developing pre-programmed biomaterials that can undergo transformations lays new foundations for enabling smart pharmacology, personalized medicine, and smart drug delivery, all of which can help in combating diseases in a smarter way. Hence, the theme of this paper is about the potential of 4D printing in creating smart drug delivery, smart pharmacology, targeted drug delivery and better patient compliance. The paper highlights the recent advancements of 4D printing in healthcare sector and ways by which 4D printing is doing wonders in creating smart drug delivery and tailored medicine. The major constraints in the approach have also been highlighted. Keywords: 4D printing, smart, drug delivery system, patient compliance, biomaterials, tailored medicine

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Chemotaxis-based smart drug delivery of epirubicin using a 3D printed microfluidic chip

Journal of Chromatography B ◽

10.1016/j.jchromb.2020.122456 ◽

2021 ◽

Vol 1162 ◽

pp. 122456

Author(s):

Kolsoum Dalvand ◽

A. Ghiasvand ◽

Vipul Gupta ◽

Brett Paull

Keyword(s):

Drug Delivery ◽

Microfluidic Chip ◽

3D Printed ◽

Smart Drug ◽

Smart Drug Delivery

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Smart drug delivery systems: from fundamentals to the clinic

Chemical Communications ◽

10.1039/c4cc01429d ◽

2014 ◽

Vol 50 (58) ◽

pp. 7743-7765 ◽

Cited By ~ 210

Author(s):

Carmen Alvarez-Lorenzo ◽

Angel Concheiro

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Medical Devices ◽

Smart Materials ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Smart Drug ◽

Smart Drug Delivery

Smart materials can endow implantable depots, targetable nanocarriers and insertable medical devices with activation-modulated and feedback-regulated control of drug release.

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3D and 4D Printing of Multistable Structures

Applied Sciences ◽

10.3390/app10207254 ◽

2020 ◽

Vol 10 (20) ◽

pp. 7254

Author(s):

Hoon Yeub Jeong ◽

Soo-Chan An ◽

Yeonsoo Lim ◽

Min Ji Jeong ◽

Namhun Kim ◽

...

Keyword(s):

3D Printing ◽

Smart Materials ◽

Compliant Mechanisms ◽

Three Dimensional ◽

4D Printing ◽

New Paradigm ◽

Strained Layers ◽

Three Dimensional Printing ◽

Mechanical Metamaterials ◽

3D Printed

Three-dimensional (3D) printing is a new paradigm in customized manufacturing and allows the fabrication of complex structures that are difficult to realize with other conventional methods. Four-dimensional (4D) printing adds active, responsive functions to 3D-printed components, which can respond to various environmental stimuli. This review introduces recent ideas in 3D and 4D printing of mechanical multistable structures. Three-dimensional printing of multistable structures can enable highly reconfigurable components, which can bring many new breakthroughs to 3D printing. By adopting smart materials in multistable structures, more advanced functionalities and enhanced controllability can also be obtained in 4D printing. This could be useful for various smart and programmable actuators. In this review, we first introduce three representative approaches for 3D printing of multistable structures: strained layers, compliant mechanisms, and mechanical metamaterials. Then, we discuss 4D printing of multistable structures that can help overcome the limitation of conventional 4D printing research. Lastly, we conclude with future prospects.

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Review of Polymeric Materials in 4D Printing Biomedical Applications

Polymers ◽

10.3390/polym11111864 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1864 ◽

Cited By ~ 14

Author(s):

Ming-You Shie ◽

Yu-Fang Shen ◽

Suryani Dyah Astuti ◽

Alvin Kai-Xing Lee ◽

Shu-Hsien Lin ◽

...

Keyword(s):

3D Printing ◽

Smart Materials ◽

Biomedical Applications ◽

Polymeric Materials ◽

3D Printer ◽

Future Prospects ◽

4D Printing ◽

Current Application ◽

3D Printed ◽

Over Time

The purpose of 4D printing is to embed a product design into a deformable smart material using a traditional 3D printer. The 3D printed object can be assembled or transformed into intended designs by applying certain conditions or forms of stimulation such as temperature, pressure, humidity, pH, wind, or light. Simply put, 4D printing is a continuum of 3D printing technology that is now able to print objects which change over time. In previous studies, many smart materials were shown to have 4D printing characteristics. In this paper, we specifically review the current application, respective activation methods, characteristics, and future prospects of various polymeric materials in 4D printing, which are expected to contribute to the development of 4D printing polymeric materials and technology.

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Biodegradable 3D Printed Polymer Microneedles for Transdermal Drug Delivery

10.26434/chemrxiv.5851950.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Michael A. Luzuriaga ◽

Danielle R. Berry ◽

John C. Reagan ◽

Ronald A. Smaldone ◽

Jeremiah J. Gassensmith

Keyword(s):

Drug Delivery ◽

3D Printing ◽

Transdermal Drug Delivery ◽

Fused Deposition Modeling ◽

Fused Deposition ◽

Modeling Software ◽

Deposition Modeling ◽

3D Printed ◽

Microfabrication Technique ◽

Mechanical Strengths

Biodegradable polymer microneedle (MN) arrays are an emerging class of transdermal drug delivery devices that promise a painless and sanitary alternative to syringes; however, prototyping bespoke needle architectures is expensive and requires production of new master templates. Here, we present a new microfabrication technique for MNs using fused deposition modeling (FDM) 3D printing using polylactic acid, an FDA approved, renewable, biodegradable, thermoplastic material. We show how this natural degradability can be exploited to overcome a key challenge of FDM 3D printing, in particular the low resolution of these printers. We improved the feature size of the printed parts significantly by developing a post fabrication chemical etching protocol, which allowed us to access tip sizes as small as 1 μm. With 3D modeling software, various MN shapes were designed and printed rapidly with custom needle density, length, and shape. Scanning electron microscopy confirmed that our method resulted in needle tip sizes in the range of 1 – 55 µm, which could successfully penetrate and break off into porcine skin. We have also shown that these MNs have comparable mechanical strengths to currently fabricated MNs and we further demonstrated how the swellability of PLA can be exploited to load small molecule drugs and how its degradability in skin can release those small molecules over time.

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Adult Stem Cells and Biocompatible Scaffolds as Smart Drug Delivery Tools for Cardiac Tissue Repair

Current Medicinal Chemistry ◽

10.2174/09298673113209990032 ◽

2013 ◽

Vol 20 (28) ◽

pp. 3429-3447 ◽

Cited By ~ 9

Author(s):

Stefania Pagliari ◽

Sara Romanazzo ◽

Diogo Mosqueira ◽

Perpetua Pinto-do-O ◽

Takao Aoyagi ◽

...

Keyword(s):

Drug Delivery ◽

Stem Cells ◽

Tissue Repair ◽

Adult Stem Cells ◽

Cardiac Tissue ◽

Smart Drug ◽

Smart Drug Delivery

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Advances in Nanoparticles as Anticancer Drug Delivery Vector: Need of this Century

Current Pharmaceutical Design ◽

10.2174/1381612826666200203124330 ◽

2020 ◽

Vol 26 (15) ◽

pp. 1637-1649 ◽

Cited By ~ 3

Author(s):

Imran Ali ◽

Sofi D. Mukhtar ◽

Heyam S. Ali ◽

Marcus T. Scotti ◽

Luciana Scotti

Keyword(s):

Drug Delivery ◽

Anticancer Drug ◽

Medical Science ◽

Drug Carriers ◽

Anticancer Drug Delivery ◽

Ph Values ◽

Delivery Vector ◽

Future Challenges ◽

Smart Drug ◽

Smart Drug Delivery

Background: Nanotechnology has contributed a great deal to the field of medical science. Smart drugdelivery vectors, combined with stimuli-based characteristics, are becoming increasingly important. The use of external and internal stimulating factors can have enormous benefits and increase the targeting efficiency of nanotechnology platforms. The pH values of tumor vascular tissues are acidic in nature, allowing the improved targeting of anticancer drug payloads using drug-delivery vectors. Nanopolymers are smart drug-delivery vectors that have recently been developed and recommended for use by scientists because of their potential targeting capabilities, non-toxicity and biocompatibility, and make them ideal nanocarriers for personalized drug delivery. Method: The present review article provides an overview of current advances in the use of nanoparticles (NPs) as anticancer drug-delivery vectors. Results: This article reviews the molecular basis for the use of NPs in medicine, including personalized medicine, personalized therapy, emerging vistas in anticancer therapy, nanopolymer targeting, passive and active targeting transports, pH-responsive drug carriers, biological barriers, computer-aided drug design, future challenges and perspectives, biodegradability and safety. Conclusions: This article will benefit academia, researchers, clinicians, and government authorities by providing a basis for further research advancements.

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