Advancement of additive manufacturing technology in the development of personalized in vivo and in vitro prosthetic implants

2.1 FDM

FDM is a type of 3D printing technology involving layer-by-layer thermoplastic material deposition to create a 3D object. Polymeric materials are commonly used in AM, and ME techniques are ideal for them; one of the most common methods is FDM (Figure 1a). Scott Crump invented the fused deposition process in 1988. It was then patented by a 3D printing company Stratasys. Later, in 2014, the company introduced the world’s first 3D printer based on the fused deposition process. This process involves depositing layers of polymers that have been heated to a certain temperature and used to mold plastic components. Due to their low melting point, thermoplastic polymers are ideal for this type of application. It involves transporting a thermoplastic wire to a heated extruder. The wire is then fed through a feed unit, which is controlled by the temperature of the heated part. After heating the part to a certain temperature, it is extruded. Once the first cross-sectional layer has been formed, the worktable slopes down. A second layer is then formed on the resulting section and repeated until the part is made. This process is commonly used in developing bone engineering components in the biomedical field [37]. They can be used safely and effectively in offices, schools, and laboratories [21]. In addition to the common printers, multiple heads can be used in a single process to create different materials with varying properties. One of the main advantages of this process is that it does not utilize a laser. This means that it has a low manufacturing cost. Apart from the print quality, this process can be used to make various components, such as metal and plastic parts, which can be very cost-effective [38,39].

Figure 1

Schematic representation of various 3D-printing techniques (working procedure [left] and print output [right]). (a) FDM. (b) SLA. (c) SLS. Adapted with permission from [51] Copyright 2020, John Wiley and Sons, [52] Copyright 2018, Taylor and Francis.

2.2 SLS

DTM developed the first laser sintering process in 1987 under the supervision of Dr. Carl Deckard and academic adviser Dr. Joe Beaman at the University of Texas at Austin. The process was patented in 1988. In 1992, the Sinterstation was released by the DTM Company. It was based on the SLS process [40]. The usual laser for this process is CO₂. The polymers absorb CO₂ better at this wavelength. The process works by having two cylinders, one for powder and one for molding, in a closed mold chamber. Powder materials are then heated to a temperature below the sintering point. The first step in forming is the movement of the powder-feeding cylinder’s piston. This causes the powder to spread on the forming surface evenly. The laser beam then scans the first layer of the materials. The powder is then solidified into a sheet with a given thickness after being swept by the laser beam. The un-sintered powder supports and helps form the first layer of the part. The second layer is then formed by scanning the laser beam (Figure 1c). This process results in a 3D solid part built by stacking the layers [41,42]. Unlike the SLA process, this process uses a powder material instead of a liquid resin. It is made smooth by a temperature-controlled roller optimized to ensure that the powder’s fluidity is maintained. The chamber’s heat is also controlled to ensure that the bond is firm. The metal powder with a high melting point is then bonded to the polymer. The binder is then removed using a degreasing process, which leaves many holes in the resulting material. This process can be utilized to make functional scaffolds for bone regeneration [43]. SLS is a process that can be used to process various materials. It allows for a short production cycle.

2.3 SLM

SLM is an AM technique that can produce a part with almost full-scale density using a high-energy source. It is similar to SLS but with a layer-wise structure. Through a computer-controlled model, it can make components that are based on a 3D CAD. SLM systems utilize a laser beam as an energy source to melt the part’s powder material [44]. A computer then controls the beam and makes it focus on the part’s powder bed. The part’s processing chamber is then filled with an inert atmosphere, usually Argon. This prevents the parts from getting damaged. Various materials, such as metals and alloys, have been used to make components [45]. Compared to traditional methods, SLM-produced components with complex or solid scaffolds exhibit better mechanical properties. Lasers are commonly used in SLM to melt metal powders. This process is commonly utilized in biomedical materials such as titanium, stainless steel, and cobalt-chromium [46]. Most of the materials were considered based on the following parameters: high biocompatibility, corrosion resistance, and mechanical strength [46]. This process can make various metal parts with compact and high-quality structures. A study conducted by Tonelli et al. [47] revealed that they could achieve the melting of various Co-28Cr–6Mo samples with SLM technology. They also optimized the LED window for these materials for biomedical applications. The researchers then studied the various process conditions involved in producing the parts using SLM technology. They discovered that the nickel-titanium alloy exhibited a significant bulk density after cooling [48]. Titanium and its alloys are widely used for dental and orthopedic implants, while Co-Cr alloys are popular for developing orthopedic implants and dental prostheses. Stainless steel is a popular choice for developing cardiovascular implants [49]. In the biomedical field, SLM has significantly influenced the development of medical implants, dental prostheses, and surgical tools. SLM has enabled the production of highly customized and patient-specific implants with superior mechanical properties, biocompatibility, and osseointegration. SLM has also been used to produce dental prostheses, surgical implants like joint replacement implants, and cranial implants with excellent precision, aesthetics, and durability. Additionally, SLM has been used to produce surgical tools, such as forceps and bone drills, with complex geometries and reduced weight. SLM has revolutionized the manufacturing of medical implants and devices, allowing for greater flexibility, accuracy, and customization and improved patient outcomes [50].

2.4 EBM

Like the SLM process, EBM involves using an electron beam to melt metal powder particles. This method can also process various materials, such as titanium and stainless steel. This implies that EBM techniques utilize a processing mechanism similar to SLM methods. Both methods can produce almost full-density components. However, EBM utilizes an electron beam as its source for melting the powder. Before a component can be made, a vacuum is created in the building to prevent the materials from getting damaged. A powder layer thickness of around 20–100 mm for EBM systems is typical. The substrate plate must be heated to around 700°C to reduce the residual stresses between the finished product and the substrate [53]. This process can also help prevent powder smoking. Numerous studies have been conducted on the performance and processing of EBM-produced components [54]. Most of these studies focused on metals. Due to the advantages of EBM technology, medical applications such as knee and hip replacements are being made using it. Titanium is one of the most common materials used in the process [55]. This is a widely used metal for the manufacture of bone implants. In a study conducted by Aziziderouei et al. [56], the influence of the build direction and lack of fusion on the Charpy impact Energy of Ti–6 Al–4V during the EBM procedure were determined. They found that the three factors influencing the IE are the angle between the notch and the construction direction, the difference in microstructure, and the lack of fusion. Although both EBM and SLM can be utilized to process metallic substances, the former is usually preferred when producing porous materials such as titanium [57]. SLM can also process non-metal degradable materials, such as iron and magnesium. Compared to SLM, EBM has fewer applications. It is commonly used in biomedical industries to process medical metals such as tantalum [57].

2.5 SLA

The earliest practical application of 3D printing technology is the SLA apparatus, developed by Charles Hull in 1984. In 1986, Charles Hull established the first commercial 3D printing system. The SLA-250 was the world’s first 3D printer [16,17]. The fundamental idea of SLA is that a layer of powder is laid flat on a part’s upper surface, which then gets heated to a temperature below its un-sintered point. The control system for SLA uses laser beam scanning to inspect the powder layer’s cross-section outline. Once the powder reaches its melting point, it undergoes sintering and bonding. After the first layer has been laid flat, the workbenches will reduce the layer’s thickness. They then spread a thick and uniform powder layer on it. They will also sinter the new section until the entire process is completed. The basic composition of SLA is shown in Figure 1b. It includes various materials such as ultraviolet laser, photosensitive resin, and liquid horizon [58]. This technology is commonly used to produce orthopedic and tissue engineering parts. The SLA apparatus is characterized by its stable operation and high-quality printed parts. However, its large equipment makes achieving the ideal optical pixel size for the plane’s microstructure difficult. The low penetration level of ultraviolet light restricts SLA technology. A new economical and innovative 3D printing process can produce light centers capable of curing polymers. This method involves the use of NaYF4 microcrystals [59]. This process has demonstrated the ability to achieve high up-conversion emission through microcrystals. This method can make large-scale structures using a low-cost semiconductor laser. SLA has significantly impacted biomedical engineering and has been used to create a wide range of medical devices and models. This makes it ideal for creating custom implants, prosthetics, and other medical devices that fit perfectly and perform specific functions [60]. Another area where SLA has had an impact is in drug delivery. It has been used to create microfluidic devices that can precisely control the flow and delivery of drugs, allowing for targeted and personalized treatment [61].

3.1 Biomedical polymer materials

The earliest biomedicine-related materials are biomedical polymers. These are widely used in various fields of medicine. There are two types of biomedical polymers: nondegradable and degradable. The Nondegradable polymer materials include polyformaldehyde, polyethylene, and polypropylene [69]. These polymers can endure various environmental conditions due to their good physical properties. Some degradable biological materials include collagen, chitin, and cellulose [70]. Due to the degradation caused by the environment, some of the degraded products can be partially eliminated through the body’s normal metabolism. This makes biomedical polymers ideal for the repair of various tissues, soft tissues, hard tissues [71], scaffold fabrication [72], and cardiovascular stents [73]. Polymer materials have become increasingly important in biomedical engineering due to their unique properties and ability to be customized for specific applications. One of the key advantages of biomedical polymers is their biocompatibility, meaning they are non-toxic and non-immunogenic to living tissues [74]. This allows for their use in direct contact with human tissue and implantable devices without causing an adverse immune response. Examples of biocompatible polymers include polyethylene glycol (PEG), poly(lactic-co-glycolic acid), and PU [74]. Another important property of biomedical polymers is their ability to degrade and be absorbed by the body over time. This makes them useful in drug delivery systems and tissue engineering scaffolds, where they can be designed to release drugs or encourage tissue growth before gradually being absorbed by the body. Examples of biodegradable polymers include polycaprolactone (PCL), polyglycolic acid (PGA), and polylactic acid (PLA) [75]. The properties with the influence of polymers in the biomedical field are tabulated in Table 2. Polymer materials can also be engineered to have specific mechanical properties, such as stiffness, flexibility, and strength, making them ideal for use in various medical devices and implants. For example, ultra-high molecular weight polyethylene [76] is commonly used in orthopedic implants due to its high strength and wear resistance. In contrast, due to its flexibility and durability, silicone is used in medical devices such as catheters and implants.

3.2 Biomedical metal materials

When referring to biomedical materials, such as those used in surgical implants, the term “biomedical metal” is often used to refer to those materials [11]. Various biomedical materials, such as titanium and stainless steel, are commonly used in healthcare applications. Other common medical metals include medical precious metals and cobalt chromium. This material exhibits high mechanical strength and fatigue resistance [2]. It also has good corrosion resistance and biocompatibility. Titanium alloys are widely used in orthopedic implants due to their high strength, biocompatibility, and corrosion resistance [77]. Cobalt-chromium alloys are often used in dental implants and cardiovascular devices due to their high strength, wear resistance, and biocompatibility. This type of material is commonly used in various healthcare applications, such as joint and bone substitutes [77]. Table 3 comprehensively summarizes frequently utilized metal biomaterials in AM and their corresponding advantages, limitations, and applications in bone tissue engineering. By examining the properties and potential uses of materials and their research developments, I will gain a deeper understanding of the potential of metal biomaterials in AM for bone tissue engineering.

3.3 Biomedical ceramic materials

In addition to being biomedical materials, biomedical ceramics are also inorganic nonmetal materials. They were first used as biomedical materials during the eighteenth century. They were then applied in China during the 1970s. There are various types of biomedical ceramics, such as biologically inert, biodegradable, and biologically active [89]. Ceramic materials used for biomedical applications include carbon, alumina, and zirconia. These are characterized by their high strength, stability, and abrasion resistance. Bioactive ceramics are composed of either tricalcium phosphate or Bioglass, which can form strong chemical bonds when exposed to the body’s chemical reactions [90]. Bioactive and biodegradable ceramics can stimulate the growth of new bone by allowing the body to absorb them. In clinical applications, the strength and toughness of biomedical ceramics are the main issues they face. Recently, ceramic nanomaterials have gained significant interest in biomedical applications due to their unique physical, chemical, and biological properties [91]. This review provides a comprehensive overview of the current state-of-the-art in the use of ceramic nanomaterials in biomedical applications. One of the most important properties of ceramic nanomaterials is their high surface area-to-volume ratio, which makes them suitable for drug delivery, biosensing, and tissue engineering [91,92]. In drug delivery applications, ceramic nanomaterials can be used to encapsulate and release drugs in a controlled manner. The high surface area of the nanomaterials allows for a high drug-loading capacity and the ability to target specific cells or tissues. Ceramic nanomaterials also have excellent biocompatibility and can be used as scaffolds for tissue engineering. They can mimic the structure of natural bone and promote cell attachment, proliferation, and differentiation. In addition, ceramic nanomaterials can be used to create coatings on medical implants, improving their biocompatibility and reducing the risk of implant rejection [91]. Another important application of ceramic nanomaterials is biosensing. They can be biosensors for detecting biological molecules, such as proteins and DNA, with high sensitivity and specificity [93]. However, there are also challenges associated with the use of ceramic nanomaterials in biomedical applications. One of the major challenges is their potential toxicity [94], as some ceramic nanomaterials have been shown to induce inflammation and cell death [95]. Another challenge is controlling their synthesis and tailoring their properties for specific applications.

3.4 Biomedical composite materials

A biomedical composite material is composed of several different materials. Due to its unique properties, it can improve a certain material’s performance significantly. This type of material also has a wide variety of applications. Although it can benefit the human body, a biomedical composite material should also meet certain biocompatibility and mechanical properties requirements. Composite materials can be used to create bone regeneration scaffolds that mimic bone tissue’s natural structure and composition [96]. For example, composite materials made of hydroxyapatite and collagen can be used to create scaffolds that have both the mechanical strength of hydroxyapatite and the biological activity of collagen. Another application of biomedical composite materials is in dental restorative materials. Composite materials made of resin and ceramic particles are commonly used in dental fillings and crowns due to their aesthetics and mechanical properties [97]. Various biomedical materials such as nano-phosphoric lime, bone cement, and coating materials produce artificial organs and tissues [96,98]. They can also be utilized to replace or repair human organs and tissues.

3.5 Derived materials

Bio-renewable materials are those that are derived from natural sources. They are usually formed through special processing. Due to how their biological counterparts lose their vitality after treatment, biologically-based materials are considered inanimate objects. Compared to their biological counterparts, bio-based materials offer similar functions and configurations. They are vital in maintaining and replacing human dynamic processes [99]. Bio-based materials are commonly used in various applications, such as artificial heart valves and skin masks [73]. Despite the technological advancements in 3D printing, biomedical 3D printing is still in its early stages of development. Numerous achievements have been made in this field, such as developing tissue engineering scaffolds. There are still many challenges that need to be overcome to realize this technology’s full potential. In addition to 3D printing, various mechanical metamaterials can also be utilized in the development of tissue engineering [100]. These include super-hard and auxiliary materials, programmable and self-assembled materials, and hyper-elastic materials [101]. Biomimetic materials are created using natural resources such as buildings. Metamaterials start with porous implants [100,101]. Using mechanical metamaterials can lead to novel designs for developing functional tissue scaffolds, such as orthopedic implants and bone tissue regeneration. Due to their ability to retain their shape memory effect, intelligent materials are regarded as remarkable engineering materials. Some of these include the Shape-memory polymer (SMP), which is a type of Shape-memory material generally classified as SMP, Shape-memory ceramics, Shape-memory alloys, and Shape-memory hydrogels; out of which, SMP became a more notable and researchable class, intelligent materials to open up further the possibility of more bone regeneration [102,103,104].

3.6 Life expectancy of implant materials and the influence of fabrication technologies

Bertol et al. [105] studied the use of direct metal laser sintering to fabricate Ti alloy implants. Emphasis is on customization, durability, and the impact of manufacturing technology on implant longevity. Campbell et al. [106] focused on the clinical factors influencing removable partial dentures’ lifespan. Technological advancements in design and fabrication are highlighted as key to improving longevity. Bokros [107] reviewed the use of carbon materials in biomedical implants, examining long-term stability, biocompatibility, and systemic effects. Morgan [108] explored nitinol-based implants, their mechanical properties, and how fabrication techniques enhance the longevity and reliability of medical devices. Teo et al. [109] reviewed advancements in implant polymeric materials, highlighting manufacturing processes like extrusion and injection molding that improve device performance and lifespan. Chan et al. [110] focused on AM techniques such as EBM for Ti implants, analyzing their impact on fatigue life and overall performance. Geetha et al. [111] reviewed Ti-based biomaterials for orthopedic use, emphasizing mechanical properties, biocompatibility, and the role of AM processes in enhancing lifespan. Li et al. [112] highlighted the innovations in biodegradable implants, focusing on material design and the clinical outcomes of using advanced manufacturing techniques.

4.1 Planning for patient-specific implants

Increasing the time involved in surgery can lead to an increased operation risk. This is why researchers are looking for ways to reduce the operation time. Through the use of 3D printing, it is now possible to reduce the time involved in surgery. This new technique can be used to create a detailed model of a fractured bone [114]. Studies have shown that 3D-printed fractured bone models can improve orthopedic procedures’ success rate [115,116]. The data collected from MRI or CT scans can then be used to create a 3D model of the patient’s fractured bone (Figure 2). The 3D model can then be used to create a detailed plan of the operation, such as the size of the incision and the position of the screws [117]. According to You et al. [118], a study conducted on the use of 3D printing technology for the treatment of patients with a proximal humeral bone fracture demonstrated clinical feasibility. The model could show the structure and morphology of the fractured bone, which was very important for determining the degree of the fracture and its classification. The treatment strategy could then be modified to reduce the risk of an intraoperative fracture. The researchers developed a method that can improve the accuracy of the insertion of the screws using 3D printing [119]. They used three types of templates to determine the position of the screws. They simulated the procedure with the templates and selected ten patients for the operation. The study results showed that the method can help reduce the time it takes to perform the procedure.

Figure 2

Flowchart of the activities carried out for the process from 3D modeling (DICOM - 3D model) to post-processing through 3D printing [113].

5.1 Bone tissue engineering

Understanding natural bone’s structural properties is important to create high-quality implants. There are two main types of bone tissues: cortical and cancellous. The porosity of cortical is less than 10%, while that of cancellous is around 50–90 vol% [121]. Ideally, the goal of a bone replacement implant should be to have a structure that resembles that of natural bone. Through 3D printing, medical professionals can now create complex and personalized structures that can be used to design and construct bone replacement implants. These structures can be made using a variety of materials and techniques. A bio-friendly environment can be created inside the implant by using porous structures, which can mimic the properties of real bone. In addition, this type of structure can improve the bio-transport capabilities of the implant material. Various metals, such as titanium and its variants, are commonly used in 3D printing. The properties of porous Ti-6Al-4V frameworks have been studied in order to improve their biocompatibility and processing. In a study conducted by Li et al. [122], they found that the Ti-6Al-4V cells exhibited a good linear relationship. In a study conducted on the properties of porous titanium alloy materials, Li and colleagues compared the two methods [122]. The researchers noted that the microstructures exhibited by the two types of 3D-printed materials differed due to the varying processing temperatures. Compared to the SLM-produced materials, the EBM ones exhibited higher relative densities. This helps in limiting the influence of compressive testing on their results. The researchers noted that the fatigue life of the SLM-produced materials was affected by the defects in the inner structure of the component. A 3D-printed cage made from Ti-24Nb-Zr-8Sn exhibited superior osseointegration properties and mechanical stability compared to traditional polyether ether cages. Shokouhimehr et al. [123] explored using 3D bioprinting technology to fabricate a hyper-elastic bone scaffold with bacteriostatic properties. The scaffold is designed to promote damage-specific bone regeneration and enhance the overall healing process. The article highlights the significant challenges associated with conventional bone tissue engineering methods, such as low cell viability, insufficient mechanical strength, and limited capability for bone regeneration. The article discusses the potential of 3D bioprinting technology in overcoming these challenges by providing a platform for precise control of scaffold architecture, pore size, and mechanical properties [123]. He concludes the study on a 3D bio-printed scaffold made from a combination of nanoparticles and a complex structure. They are used as a 3D model for analyzing and treating large bone fractures (Figure 3). They can also be used as a therapeutic tool for tissue regeneration. The ability to customize bio-printed implants for different soft and hard tissues could be used for various applications. In vitro and in vivo studies conducted by their team demonstrate the precision and efficacy of this approach, which highlights how bio-fabrication, nanoscience, and bioengineering could work together to develop new regenerative medicines. The study examines the concentration of superparamagnetic iron oxide nanoparticles found in the bio-printed scaffolds that fall outside the two tested groups. It is important to note that varying the particle concentrations in the constructs could affect the regenerative function of the bio-printed tissue.

Figure 3

Schematic summary of the experimental method used in this study (a–e), surgical procedure (f–o), material characterization analysis (p–s), and scout views and µCT axial CUTS of the rat femur (I–VIII). Adapted with permission from [123] Copyright 2021, materials, MDPI.

5.2 Vascular stents

Coronary artery disease is a type of cardiovascular disease that affects the heart valves, myocardium, and blood vessels. The morbidity and mortality rates are gradually increasing. Every year, around the world, millions of people die due to cardiovascular disease [124]. It is regarded as the leading cause of death among people. Due to the increasing number of people suffering from cardiovascular diseases, the treatment of these conditions has become the focus of various academic institutions. Some procedures commonly used to treat these conditions include drug therapy, vascular stenting, and external surgical procedures [125,126]. One of the major concerns regarding the use of drugs for treating cardiovascular diseases is their potential to cause secondary injuries. After the surgery, the recovery period can last for a long time. A minimally invasive procedure known as vascular stenting can be performed to treat various types of cardiovascular diseases. It can reduce the pain and minimize the trauma that occurs after the operation. The process of preparing a blood vessel stent using different types of 3D printing technology is shown in Figure 4. To make the scaffolds for the procedure more flexible, Flege et al. [127] utilized a SLM technique. They then coated the surface of the scaffold with a protective dip coating. The researchers demonstrated the biocompatibility of the 3D printing process and the materials used to make the scaffolds in an experiment.

Figure 4

Schematic representation of various AM technologies used for developing personalized polymeric stents and their applications: (a) Powder bed fusion (PBF) process for fabricating polymer stents using a laser beam; (b) Material jetting process using photocurable polymer droplets and UV curing; (c) Binder jetting process depositing binder droplets onto a powder bed; (d.i–ii) Vat photopolymerization approaches using a digital micromirror device for light projection, including conventional resin tank (i) and oxygen-permeable window system (ii); (e.i) Material extrusion 3D printing (FDM) using polymer filaments; (e.ii) Rotating mandrel-assisted FDM for creating cylindrical stent geometries; (e.iii) Rotating mandrel-assisted extrusion using solvent-based inks. Adapted with permission from [128] Copyright 2017, John Wiley and Sons, [129] Copyright 2022, Elsevier.

According to Kaesemeyer et al. [130], the vRSF system’s vascular stent can be biodegradable. It was constructed using a combination of different polymers such as lactide, glycolide, lovastatin, and -caprolactone. Besides being able to provide a supporting function, the vascular stent also releases drugs into the body to treat damaged endothelium. The researchers then created a spiral bioabsorbable vascular stent using 3D printing. The drug coating of the polymers was then placed inside the body using ultrasonic atomization. The continuous curve of the vascular intimal growth rate and the release of the drug Rolimus were observed after the procedure [131]. In order to create a bio-absorbable vascular stent [132], the researchers utilized the 3D printing technique of micro-liquid interface production. They then created a customized vascular scaffold using a combination of graphene nanoflakes and biodegradable polymers. Both foreign and domestic research organizations have acknowledged the potential of 3D printing technology to produce vascular stents. However, its use in this field is still in its early stages. Unfortunately, the development of 3D-printed vascular stents has been hampered by various factors. One is the lack of mechanical properties of the scaffolds made from biodegradable polymers. This issue could prevent them from being used effectively in treating vascular diseases.

5.3 Prosthetic valve

3D printing technology has shown great potential in developing prosthetic valves. However, it is important to note that a 3D-printed prosthetic valve is not a commonly used solution for valve replacement. The heart has four valves: the aortic valve, the mitral valve, the tricuspid valve, and the pulmonary valve. Each valve has a different structure and function; therefore, designing a 3D-printed prosthetic valve requires a deep understanding of the anatomy and physiology of the specific valve (Figure 5). A heart valve is a device that helps the blood flow in the right direction. If it gets damaged, it can lead to various health conditions. Due to the aging process, heart valve disease and myocardial infarction are common in older adults [133]. Also, chronic kidney disease and hypertension can damage a heart valve. In modern medicine, heart valve disease is one of the most common types of heart disease. It can lead to damage of the heart’s function and cause heart failure.

Figure 5

Custom 3D printed prosthetic valves. (i) Various valve sections printed with different reinforcement patterns. (ii) Complete heart valve replacement system (leaflets and synthetic aortic root). (iii) Comparing heart valve designs hemodynamic performance. (a) Pulse duplication system illustrating valve closure at different time points (t₁–t₄); (b) Computational flow simulations across the valve leaflets at various cardiac cycle stages; (c) Valve performance graphs showing pressure and flow characteristics for non-reinforced and fiber-reinforced valves; (d) Geometric orifice area (GOA) plotted over the cardiac cycle for the different valve designs. Adapted with permission from [134] Copyright 2019, Elsevier.

Different types of treatment methods are available for heart valve disease. One is external surgical therapy, which involves a heart valve replacement procedure [135,136]. This is a radical treatment that can cure heart valve disease. Through the use of 3D printing technology, a customized heart valve can be created for different patients. One of the main advantages of 3D printing technology is the ability to customize the prosthetic valve based on the patient’s unique anatomy. This can improve the fit and function of the valve, potentially reducing the risk of complications and improving the patient’s quality of life. However, there are also several challenges associated with 3D printing prosthetic valves. One of the main challenges is ensuring that the valve is durable and can withstand the pressures and stresses of the cardiovascular system. In addition, the materials used in 3D printing must be biocompatible and be able to integrate with the surrounding tissues. This can help improve its stability and accuracy and reduce the rejection rate. Artificial heart valves have been developed through different stages, such as mechanical, biological, and tissue-based valves [137].

5.4 Orthopedic implants

The human body comprises various tissues and organs, one of which is bone tissue. It is an incredibly important body component, and it can regenerate and repair itself. When a bone defect develops at a certain level, it will not be possible for the bone tissue to repair itself. This condition has a significant impact on the growth of non-bone tissues. Due to the increasing number of bone defects, the demand for bone implant procedures is increasing [138]. Various procedures, such as autologous and allografts, are available to treat bone defects. In order to perform an autologous procedure, two operations are required. The patient’s pain is usually severe due to insufficient autologous bone resources. This limitation prevents the body from supplying enough bone for all its needs. Allografts can be used to treat bone disorders, but they can also carry the risk that they might cause an immunological rejection and expose the recipient to infectious diseases [139]. Due to these issues, various academic institutions are conducting research on artificial bone repair. Traditional methods used to prepare artificial bone scaffolds, such as gas foaming, fiber bonding, phase separation, and freeze drying, do not allow the desired cell pore size and shape to be precisely controlled. This makes the artificial scaffolds perform poorly. In the past few years, 3D printing technology has become a preferred method for creating artificial bone scaffolds [57].

Several types of orthopedic implants are designed for a specific purpose. Joint replacement implants are used to replace damaged or diseased joints. In contrast, spinal implants stabilize the spine and relieve pain caused by spinal injuries or conditions like scoliosis. Similarly, hip, knee, or shoulder implants were widely used worldwide. Fracture fixation implants, such as screws, plates, and nails, are used to hold broken bones in place while they heal. Ortho-biologics are implants made from biological materials, such as bone grafts or artificial bone substitutes, and are used to promote bone growth and repair. Other types of orthopedic implants include screws, plates, nails, wires, and orthopedic implants made from metal or bioresorbable materials. The type of implant used will depend on the specific condition being treated and the patient’s needs and circumstances (Figure 6). These implants are typically made from titanium or other metals that are strong and lightweight, allowing for easy movement while the bone heals. While orthopedic implants can be highly effective in treating various medical conditions, they come with certain risks and potential complications. These can include infection, implant failure, and allergic reactions to the materials used in the implant. As such, patients need to work closely with their healthcare providers to determine if an orthopedic implant is the right treatment option for their specific needs.

Figure 6

The medical applications of 3D printing in custom implants in a human body. (a) maxillofacial, dental, (b) foot, (c) shoulder-rib, (d) shoulder, (e) finger, (f) femur, (g) rib cage, (h) cranial, (i) pelvis, (j) hip, (k) tibia, and (l) spinal implants. Adapted with permission from [140] copyright 2023, Elsevier.

5.5 Artificial joint prostheses

Osteoarthritis is a type of arthritis that affects the cartilage in the joint. It eventually leads to the development of a degenerative joint disease. Joint replacement surgery, a more complex operation performed in orthopedics, can treat the dysfunctional joint. It involves the use of a metal or artificial hip prosthesis. A metal or artificial hip prosthesis can be used for people with old or fresh femoral neck fractures or those suffering from severe osteoarthritis.

5.5.1 Total hip arthroplasty

Total hip replacement is a procedure that can improve a patient’s quality of life and prevent them from experiencing pain. It can also reduce the risk of developing arthritis. A total hip replacement is usually performed using a modular implant system. During the procedure, the surgeon uses a combination of instruments and techniques to visualize and assess the patient’s anatomical landmarks. One main strategy for a traditional total hip replacement is a cemented or uncemented fixation technique [141]. Despite the advantages of using either method, many surgeons are still considering using patient-specific instruments (PSIs) for total hip replacement [142]. One of the most common reasons for revision surgery after a total hip replacement is the mispositioning of the acetabular cup. Using an accurate acetabular cup positioning technique can reduce the risk of dislocation and decrease the implant wear rate and pain. An accurate acetabular cup positioning technique can be performed using PSIs in total hip replacement procedures [142]. In total hip replacement procedures, computer-assisted planning software allows the surgeon to plan the procedure and create PSIs. The temporary acetabular cup is placed inside and around the patient’s acetabulum. A guide wire is drilled through the acetabular cup to guide the reaming process. After removing the temporary guide wire, a permanent acetabular component is inserted using the residual guide wire. The design of the prosthetic instruments is based on the scans and MRI images taken of the patient’s hip. They are also made to accommodate the unique features of the patient’s pelvis. This method of total hip replacement significantly reduces the chances of errors associated with the conventional method of performing the procedure. It also eliminates the need for the surgeon’s exposure, patient positioning, and pelvis orientation to be considered (Figure 7) [143].

Figure 7

Total hip implant system (a). Adapted with permission from [144] copyright 2022, MDPI. (b) 3D printed implants with three different lattice structures. Adapted with permission from [145] copyright 2020, MDPI. (c) The plaster and resin models of the 3D printed implant. Adapted with permission from [146] copyright 2021, frontiers. (d) 3D printed prosthesis in a pelvis before implantation. Adapted with permission from [147] copyright 2019, Elsevier. (e) 3D printed pelvic model and acetabulum prosthesis with lattice structures for implantation. Adapted with permission from [148] copyright 2017, Exp Ther Med.

Studies have shown that these instruments are more accurate than the conventional method when positioning the implants. Using PSIs in total hip replacement could also benefit patients with certain morphologies or high body mass index. A study on the malposition of the acetabular cup in patients with high body mass index (BMI) revealed no difference in the positioning of the implants compared to those with low BMI [149,150]. The traditional method of performing total hip replacement is also affected by various factors such as the degree of pathology, patient positioning, and soft tissue [151]. The imaging technology known as the patient specific implant system for total hip arthroplasty mainly focuses on providing objective measurements and customization [152]. Despite the positive effects of these imaging technologies in total hip replacement, long-term studies are still needed to confirm the safety and effectiveness of these instruments.

5.5.2 Total knee arthroplasty (TKA)

The increasing popularity of TKA has led to the development of new methods to improve the accuracy and efficacy of these procedures [153,154]. This field of research is vital to developing new treatment options for patients. One of the most important factors a successful TKA should consider is the alignment of the implant component [155]. When a patient’s natural knee anatomy is misaligned, this can lead to various problems, such as knee instability, pain, and decreased function. These issues can also cause the component to wear and tear. The alignment of the implant component can help improve a patient’s knee function and prevent them from experiencing pain and other issues. It can also help them recover faster and maintain their quality of life.

Despite the importance of proper implant alignment, conventional surgical techniques can lead to malalignment [1]. This issue is associated with a higher incidence of implant malalignment than other procedures. One of the main goals of the design of prosthetic systems is to reduce the incidence of malalignment. This can be achieved through the use of a combination of surgical techniques and software. A patient-centered PSI of TKA utilizes a combination of imaging and software to visualize the complete joint space. This procedure can help guide the surgeon’s decisions regarding the treatment plan. The ideal joint alignment can be achieved by combining the patient’s mechanical leg axis, the femoral component, the tibia, and the sagittal and femoral components [160,161]. This technique can also be performed with the help of the patient’s three-dimensional anatomic model. It can visualize the various cutting planes’ shapes and sizes [162]. The program can also warn the surgeon about the possible consequences of a cutting plane if it can cause a problem. After the patient’s preoperative plan is reviewed, custom-made jigs are then made based on the plan’s bone resections (Figure 8). These jigs can be used to guide the surgeon in making the appropriate bone resections. They can also help prevent the patient from experiencing painful conditions after the surgery. Although 3D printing has been widely used in joint replacement, the innovation of the process and material still needs to be improved to make the prosthesis more effective and stable [162].

Figure 8

Schematic illustration of the TKA model: (i) Model alignment in neutral positions. Adapted with permission from [156] copyright 2021, Springer Nature. (ii) Isometric view assembly of all the components with scaffolded femoral knee build of CO-29CR-6MO BY EBM. Adapted with permission from [157] copyright 2012, Hindawi. (iii) Comparison of knee implant, (a) conventional TKA, and (b) customized TKA for (a) femur; (b) tibia. Adapted with permission from [158] copyright 2020, MDPI. (iv) Three implant designs: GMK primary posterior stabilized (top), sphere (middle), and primary ultra-congruent design (bottom). Adapted with permission from [159] copyright 2019, frontiers.

5.5.3 Bone plates

Custom 3D-printed bone plates are highly specialized medical devices that have revolutionized how bone fractures and defects are repaired. These plates are designed and created using a 3D printer, which allows for a precise and personalized fit that traditional bone plates cannot achieve [163]. Custom 3D-printed bone plates have many applications in the medical field, including orthopedic surgery, maxillofacial surgery, dental implants, and spinal surgery [164,165]. By providing a tailored and accurate fit, these bone plates can provide better support and stability, reducing the risk of complications and improving patient outcomes (Figure 9).

Figure 9

Design and development stages of the personalized bone plate. (a) patient with foot drop of both feet, (b) scanned image, (c) ankle model based on CT image, (d) designed plate was matching to the bone surfaces and fixing the screws on locking holes, (e) loading conditions for finite element simulations, (f) printed plate and matching with model, and (g) postoperative X-ray image. Adapted with permission from [166] copyright 2021, Elsevier.

Custom 3D-printed bone plates are an exciting development in medical technology, and their continued use and refinement will undoubtedly lead to further advancements in orthopedic surgery and beyond. In treating corrective bone disorders, such as those involving a correctional procedure. 3D bone models are used to create a simulation of the operation. This method can be performed by manipulating the virtual models in a computer. Through the simulation, the researchers can create a customized cutting guide and a plate to stabilize the healing process after the procedure [164]. The accuracy of the reconstruction in the preoperative phase is very important for patients who have undergone a correctional osteotomy. Over-correction or under-correction can lead to muscle weakness and loss of range of motion. Due to the increasing popularity of computerized modeling and planning, orthopedic implants have also gained popularity. Studies conducted on the accuracy of patient-specific guides have shown that the simulations generated by the computer can reduce the residual errors compared to the traditional methods. The average error patients experience during a standard corrective osteotomy is around four [167]. However, as with other procedures, such as joint arthroplasties, further studies are required to justify the increased cost of these procedures.

5.6 Comparison of 3D printed and conventional implants

Custom 3D-printed implants offer several advantages over conventional implants. First, custom 3D-printed implants can be designed to match the exact specifications of the patient’s anatomy, ensuring a precise fit that can lead to better patient outcomes. Custom 3D-printed implants can be manufactured and delivered quickly, reducing surgery time and minimizing the risk of infection or other complications. The precise fit of custom 3D-printed implants can also reduce the risk of implant failure due to misalignment or instability. Finally, custom 3D printed implants can be less expensive than conventional implants, as they can be manufactured using less material and with fewer manufacturing steps. However, conventional implants offer proven reliability and have been used successfully for many years. Conventional implants are manufactured using standardized manufacturing processes, which ensures consistent quality and reliability. Additionally, conventional implants have a track record of success and are well-understood by medical professionals. Conventional implants may be the better choice for patients who need implants but do not require a custom fit due to their reliability and familiarity. Another advantage of custom 3D-printed implants is that they offer greater flexibility in terms of design. With 3D printing technology, implants can be designed with complex geometries and internal structures that may not be possible with conventional manufacturing methods. This can lead to improved functionality and performance of the implant, especially in cases where the implant needs to mimic the natural anatomy of the body. On the other hand, one disadvantage of custom 3D printed implants is that they may require more specialized expertise and equipment to design and manufacture. This can lead to higher costs for the patient or the healthcare system. Custom 3D-printed implants may also require additional regulatory approvals and quality control measures to ensure safety and efficacy. However, the choice between custom 3D-printed implants and conventional implants depends on the patient’s specific needs and the medical team’s expertise. Custom 3D printed implants offer several advantages in terms of precise fit, reduced surgery time, reduced implant failure, lower cost, and flexibility in design. However, conventional implants offer proven reliability and are well-understood by medical professionals. Ultimately, the choice between the two should be made based on a thorough evaluation of the patient’s needs and circumstances.

5.7 Human organs

Various applications of 3D printing include the creation of functional tissues, such as liver, kidney, and skin. These can be used to replace damaged or diseased organs or tissues. For patients with end-stage renal failure, kidney transplantation is the best option. Unfortunately, there are only so many kidney donors available. Due to the limited number of donors, 3D printing has been used to create artificial kidneys that can be used for surgery. In order to create the first fully-cell kidney tissue, Organovo utilized 3D printing technology. King and colleagues then created an in vitro proximal tubule model using the same process. This led to the development of a new strategy for kidney regeneration and organ transplantation. In 2011, Anthony Atala, a professor at Wake Forest University, showed how 3D printing could be used to create artificial kidneys [168]. The technology of 3D printing kidney organs is being used to create functional tissues and organs that function properly. With the continuous development of this technology and the field of materials science, it is predicted that the artificial kidney made using this process will be able to meet the needs of patients and improve their lives. One of the most important organs in the body, the liver, is complex. It regenerates at a fast pace compared to the other organs. Due to the limited number of liver donors and the long recovery time of its organs, 3D printing liver organs has been considered the most effective method to address the issue.

In 2013, Zeni and colleagues 3D printed a transparent human liver. In 2014, Zein and Alkhouri utilized the same process to create a miniature liver, which can be used to treat patients with end-stage liver failure [169]. With this technology’s help, Organovo could 3D print a miniature liver in 2013. It can be used for skin transplantation in facial burns patients. In addition to being able to create 3D-printed human skin tissues, the technology is also expected to be used to develop personalized orthopedic implants. These could treat various conditions, such as bone defects and cardiovascular diseases. Despite the technological advancements that have been made in 3D printing, various challenges remain to be resolved [170,171]. One of these is the accuracy of the printed product. Another challenge that remains to be resolved is the availability of suitable materials for 3D printing. This long-term process involves identifying the right properties for the printed product. Besides the availability of suitable materials, other factors, such as the requirements for the manufacturing process and the biological prerequisites of the product, are also considered to determine the success of 3D printing in the field (Figure 10).

Figure 10

3D printed full-size segment of the coronary artery (A) 3D model of the human heart, (b) coronary artery in the image file, (c) 3D fresh printed in alginate, (d) coronary artery segment after perfusion with red glycerol; (B) alginate heart model stained with alizarin red and a printing needle in the foreground for scale, (b) alginate heart, (c) half print of the alginate heart done to show the internal structure, (d) zoomed parts are arranged in order. Adapted with permission from [172] copyright 2020, ACS. (C) 3D printed liver model. Adapted with permission from [173] copyright 2019, Springer Nature. (D) Silicone ear, ear cast with polished mold. Adapted with permission from [174] copyright 2014, Springer Nature.

5.8 Rehabilitation equipment

3D printing technology in the rehabilitation industry is mainly concentrated in orthopedics, hearing aids, prosthetic limbs, and exoskeletons [175,176]. Various types of 3D printing technology are used in orthosis manufacturing. These include SLS, material spraying, photopolymerization, and melting deposition molding. Regardless of the type of 3D printing process used, it can be lightweight and customizable. This type of technology is commonly used to make parts using nylon materials for orthosis.

A 3D print foot orthosis by SLS features integrated functions, such as a geometric structure and an annular sealing system. It was created using a multi-functional spraying process. The orthosis used an integrated structure with numerous hollows in its main body. It can also boast good ventilation and be lightweight. These can provide better stability and support during the rehabilitation process. In addition, 3D printing technology can also be used to create a customized upper limb prosthesis [180,181]. For instance, a biomimetic EMG hand can be customized using this technology. 3D printing technology for creating lower limb prostheses has led to the development of shell and cavity-based designs. In the twenty-first century, 3D printing technology has mass-produced customized hearing aid shells. These are made using a process known as photopolymerization. In order to improve the strength and volume of the shell, a combination of titanium alloy and SLM is used.

5.9 Organ-on-a-chip

The concept of organ-on-chip refers to a new technology that enables scientists to analyze and detect biological and chemical substances on a miniature chip [182]. In 2010, 3D printing technology was first used to produce microchips indirectly. In 2011, the direct manufacturing of such devices started. The image shows the various 3D printing techniques used for making microchips. One of these is using a 3D printing process to make a chip that can detect the hepatitis B virus [183]. This new technology significantly improved the performance of the existing blood screening method. A biosensor made using 3D printing technology can detect the presence of metallothionein in a tumor. This new method could help in the diagnosis of cancer (Figures 11 and 12).

Figure 11

Examples of organ-on-a-chip (a) preclinical models used in biomedical research. Adapted with permission from [184] copyright 2021, MDPI. (b) Kidney-on-a-chip. (c) lung-on-a-chip: (i) Microfluidic model of human lung-on-a-chip and (ii) protocol for the surface treatment of the 3D printed resin mold. Adapted with permission from [185] copyright 2016, Elsevier.

Figure 12

3D Printed custom orthoses and prostheses (a) alex, the new arm light exoskeleton. Adapted with permission from [177] Copyright 2016, Springer Nature. (b) Examples of 3D-printed orthotics are (i) forearm static fixation, (ii) cyborg beast hand prosthesis, (iii) spinal brace, and (iv) ankle-foot orthosis. Adapted with permission from [178] copyright 2020, MDPI. (c) Examples of orthosis and prosthesis fabricated using AM: Ankle-foot orthosis and foot orthosis. (d) Prosthetic hand and prosthetic ankle. Adapted with permission from [179] Copyright 2016, Elsevier.

Lab-on-chip 3D printing technology is still in its early stages of development [186]. Its applications include chip design verification and chip development. Integrating 3D printing technology into the miniaturization and production of biosensors and other small devices is expected to be significant.