Printing Technologies for Medical Applications

doi:10.1016/j.molmed.2016.01.003

Trends in Molecular Medicine

Volume 22, Issue 3, March 2016, Pages 254-265

https://doi.org/10.1016/j.molmed.2016.01.003 Get rights and content

Trends

3D printing is a versatile emerging technology that is finding its way through all aspects of human life, and the unique potential of 3D printers can be exploited in different areas of medicine, such as fundamental research, drug delivery, and testing, as well as in clinical practice.

Nearly all current medical non-biological implants, such as ear prostheses or human mandibular replacements, are manufactured at predetermined sizes and configurations that are widely used for patients. 3D printing allows more accurate personalized manufacturing of devices created to the patient's own specifications; a process which is often aided by 3D imaging software.

Surgical planning with 3D printing is already showing promise. As an example, living-donor liver transplantation surgery for patients with end-stage organ disease is complex and can be life-threatening. The use of 3D printed surgical models has been shown to help shorten operative time and decrease donor risk, thereby boosting surgical outcomes.

Bioprinting is being used to create more accurate non-biologic and biologic research models for research purposes in wide variety of applications, including spatial and temporal trauma in cancer research.

3D printing is being increasingly used for the design and manufacturing of living tissues and organs that may one day be implanted into patients.

Over the past 15 years, printers have been increasingly utilized for biomedical applications in various areas of medicine and tissue engineering. This review discusses the current and future applications of 3D bioprinting. Several 3D printing tools with broad applications from surgical planning to 3D models are being created, such as liver replicas and intermediate splints. Numerous researchers are exploring this technique to pattern cells or fabricate several different tissues and organs, such as blood vessels or cardiac patches. Current investigations in bioprinting applications are yielding further advances. As one of the fastest areas of industry expansion, 3D additive manufacturing will change techniques across biomedical applications, from research and testing models to surgical planning, device manufacturing, and tissue or organ replacement.

Section snippets

The Basics of Bioprinting

Generally, bioprinting includes three sets of steps; pre-bioprinting, bioprinting, and post-bioprinting activities. Pre-bioprinting involves imaging and digital design in addition to material selection [13]. Computed tomography (CT) and magnetic resonance imaging (MRI) are considered the two most common imaging technologies for medically applied bioprinting. After medical imaging, tomographic reconstruction is performed to achieve segmental 2D images for the layer-by-layer fabrication process

Biomedical Printing Applications

Bioprinting has been utilized for drug screening and delivery (Box 2), personalized medicine (Box 3), and fabrication and modeling of living organs for medical applications, as discussed below.

Ears

Congenital deformities such as microtia and anotia in addition to accidents or disease can cause ear damage or loss 22, 23. The most common treatment is to replace the damaged ear with a prosthesis or a sculpted rib cartilage 22, 23, 24. However, these conventional techniques are not ideal. The manufacture of a silicone ear is expensive and involves several hospital visits for customization [24]. Costal cartilage is difficult to design and cut to the appropriate shape [22]. Both options may

Livers

The limited number of cadaveric livers cannot meet the growing need for liver transplantation. Consequently, increasing numbers of patients are undergoing transplantation of a liver lobe from a healthy donor [18]. However, this method is prone to some risks and donors may incur blood loss, injury to surrounding tissues or organs, and even death. Furthermore, it is important to predict the volume of the transplanted liver to avoid large/small-for-size syndromes [36]. 3D imaging, such as CT and

Bioprinting for Cancer Applications

Traditional 2D cultures are restricted in many aspects as in vitro models 16, 59, 60, 61 and have a limited level of complexity. Therefore, a 3D model may be necessary to examine the interactions among cells and their environment (e.g. ECM, mechanical stimulation, other cells) 16, 59, 60. A suitable 3D in vitro replica for cancer research must mimic the invasive behavior of tumors as well as tumor–stromal cell interactions with sophisticated design principles [62]. Hence, cancer studies should

Concluding Remarks

Since the beginning of the 21st century, 2D and 3D printing technologies are dramatically impacting on medicine. Today, printing is being recognized as a versatile manufacturing technology. The patterning capabilities, precise manufacturing, diverse printable materials, extensive choices of substrates, and overall cost-effectiveness of bioprinters are increasing exponentially. Printers have been used largely to pattern cells; to make tissues, organs, and medical devices; to construct surgical

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Studying liver anatomy can be challenging for medical students and surgical residents due to its complexity. Three-dimensional visualization technology (3DVT) allows for a clearer and more precise view of liver anatomy. We sought to assess how 3DVT can assist students and surgical residents comprehend liver anatomy.
Data from 5 patients who underwent liver resection for malignancy at our institution between September 2020 and April 2022 were retrospectively reviewed and selected following consensus among the investigators. Participants were required to complete an online survey to investigate their understanding of tumor characteristics and vascular variations based on patients’ computed tomography (CT) and 3DVT.
The study was carried out at the General and Hepato-Biliary Surgery Department of the University of Verona.
Among 32 participants, 13 (40.6%) were medical students, and 19 (59.4%) were surgical residents.
Among 5 patients with intrahepatic lesions, 4 patients (80.0%) had at least 1 vascular variation. Participants identified number and location of lesions more correctly when evaluating the 3DVT (84.6% and 80.9%, respectively) compared with CT scans (61.1% and 64.8%, respectively) (both p ≤ 0.001). The identification of any vascular variations was more challenging using the CT scans, with only 50.6% of correct answers compared with 3DVT (72.2%) (p < 0.001). Compared with CT scans, 3DVT led to a 23.5%, 16.1%, and 21.6% increase in the correct definition of number and location of lesions, and vascular variations, respectively. 3DVT allowed for a decrease of 50.8 seconds (95% CI 23.6-78.0) in the time needed to answer the questions. All participants agreed on the usefulness of 3DVT in hepatobiliary surgery.
The 3DVT facilitated a more precise preoperative understanding of liver anatomy, tumor location and characteristics.
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Glioblastoma multiforme is a highly malignant brain tumor with significant intra- and intertumoral heterogeneity known for its aggressive nature and poor prognosis. The complex signaling cascade that regulates this heterogeneity makes targeted drug therapy ineffective. The development of an optimal preclinical model is crucial for the comprehension of molecular heterogeneity and enhancing therapeutic efficacy. The ideal model should establish a relationship between various oncogenes and their corresponding responses. This review presents an analysis of preclinical in vivo and in vitro models that have contributed to the advancement of knowledge in model development. The experimental designs utilized in vivo models consisting of both immunodeficient and immunocompetent mice induced with intracranial glioma. The transgenic model was generated using various techniques, like the viral vector delivery system, transposon system, Cre-LoxP model, and CRISPR-Cas9 approaches. The utilization of the patient-derived xenograft model in glioma research is valuable because it closely replicates the human glioma microenvironment, providing evidence of tumor heterogeneity. The utilization of in vitro techniques in the initial stages of research facilitated the comprehension of molecular interactions. However, these techniques are inadequate in reproducing the interactions between cells and extracellular matrix (ECM). As a result, bioengineered 3D-in vitro models, including spheroids, scaffolds, and brain organoids, were developed to cultivate glioma cells in a three-dimensional environment. These models have enabled researchers to understand the influence of ECM on the invasive nature of tumors. Collectively, these preclinical models effectively depict the molecular pathways and facilitate the evaluation of multiple molecules while tailoring drug therapy.
3D printing of biologics—what has been accomplished to date?
2024, Drug Discovery Today
Three-dimensional (3D) printing is a promising approach for the stabilization and delivery of non-living biologics. This versatile tool builds complex structures and customized resolutions, and has significant potential in various industries, especially pharmaceutics and biopharmaceutics. Biologics have become increasingly prevalent in the field of medicine due to their diverse applications and benefits. Stability is the main attribute that must be achieved during the development of biologic formulations. 3D printing could help to stabilize biologics by entrapment, support binding, or crosslinking. Furthermore, gene fragments could be transited into cells during co-printing, when the pores on the membrane are enlarged. This review provides: (i) an introduction to 3D printing technologies and biologics, covering genetic elements, therapeutic proteins, antibodies, and bacteriophages; (ii) an overview of the applications of 3D printing of biologics, including regenerative medicine, gene therapy, and personalized treatments; (iii) information on how 3D printing could help to stabilize and deliver biologics; and (iv) discussion on regulations, challenges, and future directions, including microneedle vaccines, novel 3D printing technologies and artificial-intelligence-facilitated research and product development. Overall, the 3D printing of biologics holds great promise for enhancing human health by providing extended longevity and enhanced quality of life, making it an exciting area in the rapidly evolving field of biomedicine.
Inkjet printing technique for membrane fabrication and modification: A review
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Recently, inkjet printing technology has received increasing interests for membrane fabrication and modification. It offers various advantages such as the facile and fast process, minimal chemical consumption and precise chemical deposition. It is essential to have a holistic understanding of the inkjet printing technique used for different kinds for membranes, not only to further accelerate its application in membrane field, but also to prepare more advanced membranes with excellent performance. This review paper introduced the basic inkjet printer types used for membrane preparation such as thermal and piezoelectric drop-on-demand (DOD) inkjet printers. It also provided a comprehensive review of the detailed inkjet printing assisted membrane fabrication and modification processes and their applications in different membrane areas including the membrane-based separation (e.g., reverse osmosis (RO), nanofiltration (NF), organic solvent nanofiltration (OSN), gas separation membranes, and oil/water separation membranes) and fuel cell applications.
3D Printed Larynx as a Novel Simulation Tool for Window Elaboration in Medialization Laryngoplasty
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Surgical simulation training in residents has declined due to the limited exposure to cadaveric specimens. Three-dimensional (3D)-printing technology is rapidly taking an important role in different medical areas, especially in surgical specialties. It provides an alternative for resident simulation practices and for developing surgical skills before exposure to real settings. The elaboration of the thyroid window in the medialization laryngoplasty procedure requires high technical precision and experience for better outcomes.
The computer-based 3D reconstruction model was created using computed tomograph scan images from a standard larynx. The final model was created using a deposition modeling 3D printing technique with polylactic acid filament. The model was tested for surgical simulation practice in three otolaryngology residency programs in Bogotá, Colombia.
The model had similar anatomic detail and it was considered very useful, safe, and relevant for surgical simulation.
3D printed models are a cost-effective alternative for resident training.
Application of additive manufacturing in the biomedical field- A review
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Three dimensional (3D) bioprinting is a rapidly developing and emerging field in medicine and engineering. It allows for the production of three-dimensional structures that mimic body tissue function, which can be used in drug delivery and medical research such as cancer studies. In addition, bioprinting can provide patients with specific, controlled microstructures that mimic their natural geometries, increasing the rate of take-up with tissue implants and ongoing success. Towards that, a comprehensive review on the development of biomaterials, osseous tissues, bone and the vascular tissue bioprinting was conducted. These provide an insight into the latest research trends, difficulties, and understanding of the technologies used. Before implementation to replicate a human organ, there are variety of limitations to overcome together with the questions of ethics. Though bioprinting is still in its infancy period, it can play a vital role in tissue engineering in near future.

View all citing articles on Scopus

View full text

Trends in Molecular Medicine

ReviewPrinting Technologies for Medical Applications

Trends

Section snippets

The Basics of Bioprinting

Biomedical Printing Applications

Ears

Livers

Bioprinting for Cancer Applications

Concluding Remarks

Fabrication and processing of polymer solar cells: a review of printing and coating techniques

Solar Energy Mater. Solar Cells

Biofabrication: an overview of the approaches used for printing of living cells

Appl. Microbiol. Biotechnol.

Fabrication of organic solar cells based on a blend of poly (3-octylthiophene-2,5-diyl) and fullerene derivative using inkjet printing technique

Proc. SPIE

Fabrication of organic solar cells based on a blend of donor-acceptor molecules by inkjet printing technique

A novel RGB multicolor light-emitting polymer display

Synth. Met.

Inkjet printing of polymer thin film transistors

Thin Solid Films

Structural, optical and electrical properties of fluorine doped tin oxide thin films deposited using inkjet printing technique

Sains Malaysiana

Preparation nanostructure thin films of fluorine doped tin oxide by inkjet printing technique

Transparent conducting thin films of fluoro doped tin oxide (FTO) deposited using inkjet printing technique

Transparent conductive electrode of fluorine doped tin oxide prepared by inkjet printing technique

Mater. Sci. Forum

Biomaterials for integration with 3-D bioprinting

Ann. Biomed. Eng.

3D bioprinting of tissues and organs

Nat. Biotechnol.

Tailoring controlled-release oral dosage forms by combining inkjet and flexographic printing techniques

Eur. J. Pharm. Sci.

Scaffold-free vascular tissue engineering using bioprinting

Biomaterials

Three-dimensional printing of Hela cells for cervical tumor model in vitro

Biofabrication

Hydrogel templates for rapid manufacturing of bioactive fibers and 3D constructs

Adv. Healthc. Mater.

Three-dimensional print of a liver for preoperative planning in living donor liver transplantation

Liver Transpl.

Post-deposition bioink self-assembly: a quantitative study

Biofabrication

Bioprinting of nerve

Predictive modeling of post bioprinting structure formation

Soft Matter

High-fidelity tissue engineering of patient-specific auricles for reconstruction of pediatric microtia and other auricular deformities

PLoS ONE

3D printing of composite tissue with complex shape applied to ear regeneration

Biofabrication

Fabrication of low cost soft tissue prostheses with the desktop 3D printer

Sci. Rep.

Complete integration of technology for improved reproduction of auricular prostheses

J. Prosthet. Dent.

Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing

Biofabrication

Accommodation-dependent model of the human eye with aspherics

J. Opt. Soc. Am. A.

Application of 3-dimensional printing technology to construct an eye model for fundus viewing study

PLoS ONE

Accuracy of three-dimensional, paper-based models generated using a low-cost, three-dimensional printer

J. Craniomaxillofac. Surg.

Accuracy of upper jaw positioning with intermediate splint fabrication after virtual planning in bimaxillary orthognathic surgery

J. Craniofac. Surg.

RapidSplint: virtual splint generation for orthognathic surgery – results of a pilot series

Comput. Aided Surg.

Manufacturing splints for orthognathic surgery using a three-dimensional printer

Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod.

Mandibular reconstruction using stereolithographic 3-dimensional printing modeling technology

Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod.

Customized biomimetic scaffolds created by indirect three-dimensional printing for tissue engineering

Biofabrication

Scaffold fabrication by indirect three-dimensional printing

Biomaterials

Transplantation: 3D printing of the liver in living donor liver transplantation

Nat. Rev. Gastroenterol. Hepatol.

Application of a three-dimensional print of a liver in hepatectomy for small tumors invisible by intraoperative ultrasonography: preliminary experience

World J. Surg.

Current progress in 3D printing for cardiovascular tissue engineering

Biomed. Mater.

Review
Printing Technologies for Medical Applications