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IPCME 2021 IOP Publishing
IOP Conf. Series: Materials Science and Engineering 1078 (2021) 012007 doi:10.1088/1757-899X/1078/1/012007

Additive manufacturing in medical applications: A brief

review

Bo Sun1,2,*, Quanjin Ma1,2, Xinfu Wang1, Jinyan Liu3 and M R M Rejab1,2

1
School of Mechanical Engineering, Ningxia University, 750021 Yinchuan, China
2
Structural Performance Materials Engineering (SUPREME) Focus Group, Faculty of
Mechanical & Automotive Engineering Technology, Universiti Malaysia Pahang,
26600 Pekan, Pahang, Malaysia
3
School of Fine Arts, Shandong Yingcai University, 370115, Shandong, China

*Corresponding author’s email: [email protected]

Abstract. In the medical field, due to the obvious individual differences between patients, the
complexity of human tissues and the fact that patients are too price-sensitive, it is desperate to
search for a new biological material adjuvant therapy, which far more closely matches the
pathological characteristics of patients. It is noted that additive manufacturing has the ability to
overcome those limitations by virtue of its exclusive characteristics of personalized
customization, small-scale production and high precision. This paper aims to summarize the
characteristics and applications of 3D printing technology used at four levels in the medical field,
including adjuvant therapy and anatomical model, implants and scaffolds, biological 3D printing,
and pharmaceuticals, as well as, to present the recent innovation and discuss existing issues with
3D printing that related to medical applications. It is highlighted that 3D printing technology will
be further built on medical application.

Keyword: Additive Manufacturing; Adjuvant Therapy; Implants; Biological Material;

Pharmaceutical.

1. Introduction
3D printing technology used to be born in the 1990s and has been extensively used in a variety of fields
such as industry, pharmacy, architecture, clothes, training [1-4]. Thanks to its blessings of precision,
quick prototyping and customization, it is now increasingly imperative to realize an individualized and
accurate therapeutic cure [5, 6]. This technology separates a 3D model into multiple layers of slices
alongside a certain set path and types a 3D object by layer by layer creation and layer by layer stacking.
Its specific flow includes acquisition of statistics, image analysis and development of models [7].
Current research on 3D printing technology for medical purposes concentrates on the following four
important areas: 1. Study on personalized manufacturing of bioactive permanent prosthesis implants and
scaffolds; 2. Study on manufacturing pathological organ models to assist preoperative planning and
surgical treatment analysis [8]; 3. Study on directly printing tissues and organs with complete life
functions [9-11]; 4. Study on versatile platform for drug delivery [12]. Although such applications
remain a long way from widespread clinical applications as several key technical and fundamental
scientific issues that are yet to be overcome, notable scientific advancements and applications have been
achieved in these areas.

Content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution
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IPCME 2021 IOP Publishing
IOP Conf. Series: Materials Science and Engineering 1078 (2021) 012007 doi:10.1088/1757-899X/1078/1/012007

2. 3D printing fundamentals

2.1. 3D printing technology

3D printing technology is known to be an Additive Manufacturing (AM) technique used for the
manufacture of products in a consecutive layering series. Normally, this technology is categorized into
solid, liquid and power-based approaches based entirely on input materials [13]. The solid-based pattern
is Fused Deposition Modeling (FDM), the power-based pattern is composed of Selective Laser Sintering
(SLS) and Selective Laser Melting (SLM). Liquid-based trends include Stereolithography (SLA),
Optical Light Processing (DLP), Direct Ink Writing (DIW), and Inkjet [14, 15].

2.2. 3D printed medical model methods

There are forms of 3D part printing processes [16-18]. All these processes in 3D solid object printing,
using the aggregation layer-by-layer technique and reducing manufacturing costs and improving the
printing precision and efficiency of 3D printers, 3D printing technology allows significant advancements
in medical equipment, implant material and cell printing [19], the processes of 3D medical models by
additive manufacturing.: 1. Creating a 3D CAD model of the individual patient by the use of Computed
Tomography (CT), Magnetic Resonance Imaging (MRI), 3D scanner or any design software; 2.
Converting Digital Imaging and Communications in Medicine (DICOM)/3D CAD generated from these
scanning technologies into STL format; 3. Printing of patient-specific implants vie using AM
technologies; 4. Post-processing of implants; 5. Testing of implants; 6. Final implementation of the
implant in the patient body [20]. Figure 1 indicates the method of 3D printing techniques to create an
anthropomorphic thorax phantom for clinical imaging purposes.

Figure 1. Overview of 3D printing/molding process [21].

2.3. 3D printed material types

Additive Manufacturing (AM) presents flexibility for the production of any shape, and must therefore
be one of the main innovations that lead to medical therapy and the coming industrial revolution [22].
Additive Manufacturing (AM) makes precise versions of patient-specific software for complex
procedures. Exclusive heart valves and scaffolds are used in cardiology and are also useful for
preoperative planning [23]. This will manufacture surgical instruments at a reduced cost relative to
traditional technology. It creates personalized prostheses that are effortless to adjust and match the

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IPCME 2021 IOP Publishing
IOP Conf. Series: Materials Science and Engineering 1078 (2021) 012007 doi:10.1088/1757-899X/1078/1/012007

wearer [24]. Additive Manufacturing (AM) technology helps to enhance human life by removing the
human organ, making artificial organs, surgical instruments and accelerating surgery. Efficient contact
and substances are required in the field of medical treatment [25]. This technology is used for bioprinting
of suitable medical material. A living cell and synthetic living tissue can be developed for the medical
laboratory [26]. This makes it easier to build a surgical mesh that protects tissues and organs during
surgery. In short, a vast range of materials are used to build 3D models for the medical industry. The
various types of materials used in AM technologies are shown in table 1.
Table 1. The summary of materials used by Additive Manufacturing in the medical field.

No Materials Application Refs

1 Silicone • Medical implants like tracheal scaffolds [18, 27]
• Single-use and reusable components, diagnostic
instruments and other surgical tools
• Medical wires and cable components
2 Plastic • Thin tube which helps to unblock blood vessels [28, 29]
• Heart valve, intravenous blood bags, disposable
syringes, eyeglass frame and lenses
3 Metal • Metals implants to fix of a fractured bone [30-32]
• Artificial joints, scaffolds, plate, screw and valves
• Long term implantable devices
4 Tissue and cell • Improving whole organ/damaged tissue [33-35]
• Creating desired cell type
• Organs for transplantation, Human tissue repair
products
• Improving damaged tissue and whole organs
5 Polylactic-acid • Tissue engineering application like bone [36-38]
(PLA) • Wound management of dental extraction, surgical
sutures and preventing postoperative adhesions
• Scaffolds
6 Carbon Fiber • Patient's lost limb, Medical tools [39, 40]
7 Powder • Presurgical planning for complex surgery [41, 42]
• Education of the medical student
8 Nitinol • Medical implants, Personalization [43, 44]

3. Medical applications

3.1. Bioactive permanent prosthesis implants and scaffolds

At present, prosthesis implantation is frequently used in orthopedics and dentistry [45], which requires
that the prosthesis has a desirable biocompatibility, that it does not biodegrade in the human body and
that it may exist for a long time to take over the previous body tissue to function, and that the related
technology is relatively mature at present. In comparison to traditional manufacturing techniques, 3D
printing allows for the custom production of goods in a limited period and is used to the manufacture of
implantable prostheses of ideal scale, form and mechanical properties.
Permanent implants can replace human body parts and play a parallel function in the rest of the
patient's life, such as in hip joint, knee joint, shoulder joint, elbow joint or wrist prostheses [46]. Titanium
has a high strength/weight ratio, non-magnetic and high corrosion resistance due to the dense titanium
oxide (TiO2) protective film on its surface, so permanent bone tissue prostheses are usually made of
metallic titanium or other materials with a gel coating on their surface, which are enable to enhance
biocompatibility, promote cell growth around the implant prosthesis and reduce the risk of inflammation
and infection that may be caused by titanium or other permanent materials.

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IPCME 2021 IOP Publishing
IOP Conf. Series: Materials Science and Engineering 1078 (2021) 012007 doi:10.1088/1757-899X/1078/1/012007

Winder et al [47]. combined CT imaging and 3D printing technology to achieve a customized

titanium plate by making the patient's 3D-printed skull model in order to repair the patient's skull defect.
The tailored titanium plate was better fitted to the skull and enhanced the fitting effect. Figure 2 shows
a customized cranial titanium (Ti) implant and Ti hip implant for an Australian patient using selective
laser melting (SLM). Scaffolding is an integral aspect of tissue engineering. The advance of the scaffold
helps the weakened regions of the human body to be repaired as an alternative rather than removed,
which not only fixes the issue of inadequate transplant donors, it also avoids the incompatibility of
immune rejection of grafts.
In clinical practice, non-permanent scaffolding is more difficult to incorporate than permanent
implants. In particular, it should not only conform with the requirements of mechanical and structural
properties, but also enable the materials used to be degradable, capable of providing a surface
environment for the attachment and spread of living cells, providing a pore network for survival
conditions, and also directing cells via growth factors to divide into certain lines.
Lee et al. [48] used indirect 3D printing to use gelatin particles to print the mold with the desired
shapes using gelatin shapes, and then a scaffold was generated from the printing. In addition, the
polycaprolactone and chitosan were used to accurately control the internal morphology of the scaffold,
and the inert 3D printing material applied to the scaffold was modified with a bioactive apatite coating.
The scaffold was used to simulate the human mandibular condyle. The prepared scaffold material
therefore had strong cell compatibility, and after surface treatment, its bioactivity was further increased.
While several similar research and clinical implementations have been performed on scaffolds, complex
organs with more specific multicellular structures involving vascular networks are still difficult to
produce.

Figure 2. (a) Stereolithographic resin model of a full skull with a custom Ti plate
in place; (b) Hip implant fabricated by SLM Solutions in Germany [47].

3.2. Pathological organ models to assist preoperative planning and surgical treatment analysis
For clinical treatment and preoperative planning, high-fidelity physical organ models are of significant
importance, and can also be used in medical education in colleges and universities, offering more
intuitive stereoscopic vision and tactile sensation for students [49]. The patient condition can only be
understood from the 2D plane by means of magnetic resonance imaging (MRI) or computed tomography
(CT) technologies due to the individual variations between patients, which cannot provide more accurate
preoperative guidance for surgery, whereas the traditional model production procedure is not only
difficult, but also not appropriate for rapid prototype modeling.
Whereas the advent of 3D printing can overcome these problems easily, prior to surgery, physicians
are able to conduct surgery preparation and diagnosis using 3D printed models. In addition, these 3D
printed models include procedure repeatability, automate steps and make the whole operation phase
more precise, thus reducing the operation's anesthesia time and infection risk and eventually improving
the operation's success rate. Cardiovascular disease is a chronic and regularly occurring disease in
hospitals, with elevated clinical death and injury rates. Having a proper diagnosis of coronary disease
prompt and reliable is conducive to effective management of the disease, thus reducing the mortality

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IOP Conf. Series: Materials Science and Engineering 1078 (2021) 012007 doi:10.1088/1757-899X/1078/1/012007

risk of the disease.

Farooqi et al. [50] conducted a cardiac magnetic resonance imaging of a woman with tricuspid valve
hypoplasia, and printed a 3D model on this basis. They could quickly and plainly view the severely
dilated and deformed right ventricular from the outside of the 3D printed model, and the tricuspid valve
leaflet could be seen to be relocated from the inside to the right ventricular outflow, which was useful
in preparing the positioning of inflow and outflow sleeves for ventricular assistance systems. Figure 3
displays the left and right ventricles models of the heart, the myocardial models, the cardiac fibrous
skeleton and the various solid valve models created by 3D printing.

Figure 3. 3D printed models of heart: (a) The left and right ventricles models of the
heart and myocardial models; (b) The cardiac fibrous skeleton and various valve solid
models; (c) The assembly of components [51].

By comparing and studying the cardiac fibrous skeleton and the left and right ventricles of the heart
and their myocardial versions, we can better understand the anatomical configuration of the valve and
its spatial association with the adjacent cardiac chambers. The nervous system comprises primarily the
central nervous system and the peripheral nervous system. There are a host of disorders in the central
nervous system, including multiple pathogenesis. In clinical practice, the occurrence of illness may have
a significant effect on the health of patients and may also jeopardize the wellbeing of patients.
Chen et al. [52] used the photographs collected from magnetic resonance scanning to print the knee
joint disease model in order to provide orthopedic postgraduates with a more vivid and understandable
anatomical type of knee joint events, so that students can not only learn more about the causes, diagnosis
and treatment of the disease, but also better understand the anatomical parts, the spatial arrangement, g.
Around the same time, they can follow the surgical criteria and execute simulation surgery experiments
so that students can discover information that are not technically accessible and improve their knowledge
of the disease and anatomy..
There are some drawbacks with respect to the use of realistic models for adjuvant surgery. Person
refining models have high data quality standards, so hospitals need to configure high-resolution imaging
equipment to collect relevant photographs from patients in order to generate 3D printed models.
Physicians, meanwhile, need to expend a lot of time on simulating and planning surgery before surgery,
which prolongs treatment time and is not appropriate for emergency surgery. Therefore, the
implementation is only at the initial level of discovery.

3.3. Directly printed tissues and organs

In 2000, Professor Thomas Boland of Clemson University, USA, put forward a new idea called 'cell and
organ printing,' which marks the roots of current 3D bioprinting technology. 3D Biological Printing is
a manufacturing process that uses rapid prototyping (RP) for the printing of biomaterials and biological
units individually or in series and directly produces three-dimensional tissues or organs layer by layer
according to the specifications of bionic morphology, biological function, microenvironmental cell
growth, etc. Direct cell printing is an extension of tissue engineering, relative to scaffolding, bioprinting

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IPCME 2021 IOP Publishing
IOP Conf. Series: Materials Science and Engineering 1078 (2021) 012007 doi:10.1088/1757-899X/1078/1/012007

can result in the deposition of various types of cells of different densities at different locations of the
scaffold and directly printing tissues or organs [53, 54].
Bioprinting is generally primarily limited to the printing of blood vessels, skin and organs, although
the complexity of printing tissues and organs focuses mostly on the internal fluid vascular network [19].
Laronda et al. [55] suggested a system for the rehabilitation of ovarian mice using gelatin hydrogel-
printed artificial bio-microporous scaffolding (Figure 4). As a 3D bioprinting hydrogel material, it is
also important to balance its mechanical behavior so that it can fulfill the requirements of both printing
and cell growth. To fix this problem, the team used the partial cross-linking properties of gelatin at a
certain temperature (Figure 4a) to print smooth and continuous hydrogel filaments and completely cross-
linked the hydrogel to the cooling table to accurately print complex microporous scaffolds (Figure 4b)
suitable for follicle growth. The scaffold was used to grow follicles and to further produce the artificial
biological ovaries that could be prepared and inserted in the missing sections of the mice ovaries. This
technology will rebuild the ovaries of the mouse and restore their function (Figure 4c).

Figure 4. Bio-prosthetic ovary created using 3D printed gelatin microporous scaffolds

restores ovarian function in mice [55].

Dolati et al. [56] used MWCNT-reinforced alginate and typical alginate to make vascular catheters
successful. The manufactured vascular catheters have a length of more than 1 m and have a strong
perfusion capacity and high permeability, and can allow the media to diffuse radially, close to natural
blood vessels. Bioprinting remains a cutting-edge approach to the growing international scarcity of
organs, and the opportunity for transplant tissues and organs with a low risk of immune response is
expected.

3.4. Versatile platform for drug delivery

A number of 3D printing technologies are commercially viable, but detailed studies have been
performed showing that Fused Deposition Modeling (FDM) has the greatest potential for the
manufacture of different types of pharmaceutical products due to the large range of polymeric matrices
available [57, 58]. FDM 3D printing can be described as a "flexible-dose dispenser" [59] that permits
the manufacture of dosage forms with varying doses, release profiles ranging from immediate [60] to
continuous [61] and changed release [62] without the need for additional processing, such as coating

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IPCME 2021 IOP Publishing
IOP Conf. Series: Materials Science and Engineering 1078 (2021) 012007 doi:10.1088/1757-899X/1078/1/012007

[63]. This technology therefore provides a more sophisticated method for the engineering of
pharmaceutical devices.
Channeled systems have been investigated to optimize the release of medications from immediate
release formulations (Figure 5a) [64]. By controlling the different aspects of the channels (e.g. width,
length and configuration), the release of drugs could be tailored to meet the required specification. The
development of such complex geometries using traditional manufacturing methods is a challenge.
Similarly, caplets containing internal holes, referred to as gaplets, are developed to facilitate separation
of fast-release tablets and to prevent the need for disintegrants (Figure 5b) [65]. In contrast, 3D printed
networks with controlled release properties and differing densities were also manufactured [66].

Figure 5. Schematic illustration: (a) Channelled caplets; (b) Gaplets prepared using FDM
3D printing [64, 65].

FDM 3D printing technology can also be used to build hollow capsule shells with separate dual
compartments [67]. Each compartment may be constructed of the same or different materials and/or
thicknesses. Since these compartments are precisely sealed, they can be filled with powders or even
liquids [68]. This research is important for the development of personalized drug delivery systems
combining various medications (e.g. metformin and glimepiride [69]) or doses of drugs, in particular
because drugs can be co-formulated even though they are chemically incompatible. In comparison to
traditional manufacturing technologies, FDM 3D printing technology allows on-demand manufacture
of personalized patient-specific dose drug products with reliable dosing, high reproducibility and good
mechanical properties.
In addition, the processing of complex dosage forms may be accomplished, such as through
accommodating a broad variety of polymeric matrices and active ingredients, or through designing
dosage forms that show personalized effects or target particular organs. The technology has further
progressed, making it easier to integrate it with other innovations in order to build more dynamic and
smart distribution mechanisms.

4. Conclusion
Additive Manufacturing (AM) technology is at a flourishing level, and its uses in adjuvant surgery,
permanent prosthesis replacements and rehabilitation medical equipment are becoming more and more
mature. Applying 3D printing to adjuvant therapy can help physicians optimize surgery preparation,
promote diagnostic and preoperative instruction, develop doctor-patient contact, and assist in teaching
research to increase the success rate of surgery. The individualized implant is more consistent with the
initial anatomical form, which increases patient satisfaction and aesthetics following surgery and is
helpful for postoperative rehabilitation. Medical use of direct printing of tissues and organs may resolve
the problems of loss of organ donor and immune rejection.
While 3D printing technology has already been realized in clinical applications, the expense of 3D
printing technology is still limited. The material support is insufficient, the types of printable materials

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IOP Conf. Series: Materials Science and Engineering 1078 (2021) 012007 doi:10.1088/1757-899X/1078/1/012007

are few, the price of biocompatible materials is high, and the price of 3D printing equipment and high-
resolution imaging equipment are equally high, making research and development (R&D) and
verification in clinical applications costly. In comparison, contrary to traditional approaches, there are a
range of relevant comprehensive laws and regulations to guide this technology in getting it closer to the
consumer. In fact, there are still many obstacles in the technological sector, while the cells can be directly
printed at this point, it is still a long way to extend the concept of vitro tissues to clinical applications.
Many similar studies have concentrated on the issue of processing, but there is a lack of breakthrough
in the area of functionalization and implementation, and there is still a bottleneck in the development of
complex organs. As an evolving technology, 3D printing continues to be implemented in the medical
sector and has made a major contribution to clinical work, but there are also many problems that need
to be tackled, such as the ongoing advancement of science and technology, continuous investment in
relevant research, upgrading and changing management and regulatory frameworks, their success and
application in practice.

Acknowledgments
This research work is strongly supported by the Structural Performance Materials Engineering
(SUPREME) Focus Group and the Human Engineering (HEG) Focus Group, Universiti Malaysia
Pahang, and School of Mechanical Engineering, Ningxia University, which provided the research
materials and equipment.

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