Review ArticleA review of fabrication polymer scaffolds for biomedical applications using additive manufacturing techniques
Introduction
Additive manufacturing (AM) or rapid prototyping (RP) is a technology which allows to build three-dimensional structures from digital data (3D model) by adding material layer-by-layer manner. This technological process is also called three-dimensional (3D) printing and has been introduced by Charles W. Hull in 1986 [[1], [2], [3]]. To produce physical 3D objects in AM technology it is necessary to use CAD 3D software or scanner (i.e., computerized tomography (CT), micro-CT, magnetic resonance imaging (MRI)) and then, create digital design file in CAD file [4,5]. In opposite to subtractive manufacturing technology to produce an object, AM technology depends on adding consecutively layer upon layer a portion of material [3,[6], [7], [8], [9], [10], [11]]. In contrast to conventional manufacturing technologies advantages of additive manufacturing can be acknowledged. Technological progress in this area allowed to eliminate several limitations in manufacturing and enabled to obtain product more precisely with controlled dimension and more complex geometry without using traditional tools, with low manufacturing costs, in faster time and with minimum human intervention [6,[12], [13], [14], [15], [16], [17]]. Mentioned strengths indicate that AM technologies show high potential of providing a cost-effective method of aiding or changing supply chain of complex and personalized medical products. Moreover there is a noticeable growth of medical industry driven by population ageing, increasing number of chronic diseases as well as dynamic development in emerging markets [18]. In 2018 size of AM global healthcare was estimated at USD 951.2 million and is expected to grow with a CAGR (Compound Annual Growth Rate) of 20.8% [19].
Under the term of 3D printing, different manufacturing methods can be distinguished, such as: Binder Jetting (e.g., Powder Bed Inkjet printing, S-printing, M-printing, ZipDose®), Directed Energy Deposition (e.g., Be Additive Manufacturing (BeAM), Direct Metal Tooling (DTM), Electron Beam Direct Manufacturing), Material Extrusion (e.g., Fused Deposition Modelling (FDM), gel or paste extrusion), Material Jetting (e.g., Inkjet printing, Polyjet), Powder Bed Fusion (e.g., Direct Metal Laser Sintering (DMLS), Selective Laser Sintering (SLS), Selective Metal Sintering (SLM)), Sheet Lamination (e.g., Laminated Object Manufacturing) and Vat Polymerization (e.g., Digital Light Projection (DLP), Stereolithography (SLA)) [4,6,20]. Generally, mentioned methods differ from each other by device construction and selection of suitable material for each method, layer bonding methods, efficiency of production, but also characteristic of the obtained object (e.g., geometric accuracy, surface finish, structure, mechanical properties) [[20], [21], [22], [23], [24]].
Depending on the type of method, it is possible to implement manufactured elements in various sectors of industry (i.e., aerospace parts, automobiles, art, construction, cosmetic industry, food industry, medicine, textile, toys, sport accessories) by using different materials (i.e., polymers (natural and synthetic), metal, ceramic, resins, or even living cells, but also merger of basic materials with additions like nanomaterials (e.g., carbon nanofibers, carbon nanotubes, graphene)) [4,12,25,26]. Manufacturing complex structure while maintaining dimensional precision is one of the advantages in 3D printing applications, especially in bioengineering. Continuous technical development and research in material engineering provides opportunity to utilize improved biomaterials in medical field [27]. The recent expansion of AM technologies has provided personalized patient care (e.g., possibility of a precise dose of the drug) [20,25]. Medical application of 3D printing is the most commonly used as an anatomical model (e.g., surgical planning tools used for training and education), in dentistry (e.g., braces, bridges, dentures, dental crowns bridges, prostheses, surgical guides), medical devices (e.g., implants, prostheses and orthoses, surgical instruments), pharmaceuticals (e.g., drug with controlled release, personalized medicines), organs, tissue and models (e.g., disease models and drug testing, tissue analogues for implantation, scaffolds) [20,25,[28], [29], [30]]. In Fig. 1, an example of custom-made implants is shown.
Scaffolds, discussed in this paper and used in biomedical and tissue engineering, are highly porous 3D structures, which are used to replace or regenerate the native tissues in human body functionally and structurally. The aim of scaffolds is to allow cell activity such as migration, proliferation, attachment, and differentiation, even to enable oxygen and nutrients transportation [3,4]. Materials used for scaffolds production have to be biocompatible, easily sterilizable and non-toxic. The most commonly used materials are natural or synthetic polymers (e.g., hydrogels, proteins, thermoplastics, thermoplastic elastomers), metallic materials (e.g., titanium and magnesium alloys), bioactive ceramics and glasses and also composites of polymers and ceramics [32].
Numerous advantages of AM technology make it one of the most adequate methods for the building of complex scaffolds’ architecture [4]. CAD software enables easy customization of applied scaffolds in human body [33]. Examples of additive manufactured 3D structures in form of scaffold are shown in Fig. 2.
Final effect of the manufactured part is influenced by numerous factors, starting with method, material and finally adjustment of process parameters. One of the most important attribute in AM technology is accuracy, which is directly connected to process parameters. It determines quality and usability of final parts and may have an impact on their mechanical properties [34]. Another significant feature of additive manufacture is mechanical characteristics, which determines possible applications. Moreover, mechanical properties depend not only on the chosen material, but also geometry, layer thickness, air gap, fill pattern and temperature during model build process [35,36]. Most of the process parameters can be controlled, which gives the possibility of mechanical properties optimization, where also costs and time of production should be considered [36].
In this section, the general description of AM technology was gathered with its most common techniques and potential applications, notably in the biomedical sector, but also strengths and weaknesses of this technology and important factors to be taken into account during the production process. In the following chapters of this paper particular issues will be extended. The structure of the present paper includes the description of Additive Manufacture techniques used in the biomedical field, especially with polymer scaffolds fabrication, the overview of polymer materials (synthetic and natural), with particular attention to hydrogels. It also contains evaluation of the mechanical properties of polymeric scaffolds with impact on the variability of process parameters during their production.
The aim of this article is to present the currently used manufacturing methods of polymeric scaffolds with an overview of the materials utilized. Application of AM technologies in scaffolds fabrication enables the selection of a wide range of polymeric materials, especially in the form of hydrogels. Potential utilization of scaffolds in biomedical field requires the evaluation of their mechanical properties, especially with implantation in human body. Relevant strength of scaffolds is necessary to sustain structure in their initial shape during the patient's normal activities.
Section snippets
Additive Manufacturing technologies used in biomedical field
The implementation of Additive Manufacturing in medicine allows personalization of the patient care. Promising area is novel drug delivery system, in which it is possible to precisely control the amount of dosed drug (e.g., tablets, pills, capsules) depending on individual patient’s characteristics, disease state, age, gender, lifestyle, genetic profile, etc. In addition, it is possible to build complex geometries and structures, such as implants, prostheses, porous scaffolds, that cannot be
The production of polymer scaffolds with additive manufacturing technologies
Scaffolds are 3D structures mainly utilised in the regeneration and tissue engineering. Porosity and pore size of scaffolds play an important role in biomedical applications. Maximum obtained porosity values range from 50 to 65%, whereas the minimum requirement for pore size is usually 100 μm due to the cell size, migration requirements and transport. Pore size higher than 300 μm is recommended in terms of enhanced new bone formation and the formation of capillaries [33,78,79]. Scaffolds
Conclusions and prospects for the future
Additive Manufacturing enables a wide range of industry applications, especially in the biomedical field [3]. In contrast to traditional methods, AM technologies are relevant in bioengineering, where it is important to produce personalized implants, to manufacture scaffolds with high accuracy and resolution, shape, geometry and complex matrix structure [3,20,33]. The possibility of using several biomaterials simultaneously decreases the production time and enables customization of drug dosage
CRediT authorship contribution statement
Patrycja Szymczyk-Ziółkowska: Conceptualization. Magdalena Beata Łabowska: Writing - original draft, Writing - review & editing. Jerzy Detyna: Conceptualization, Writing - original draft, Writing - review & editing, Project administration. Izabela Michalak: Writing - original draft, Writing - review & editing. Piotr Gruber: Writing - original draft, Writing - review & editing.
Acknowledgment
This work was supported by the National Centre for Research and Development in Poland (Grant No. LIDER/23/0098/L-9/17/NCBR/2018).
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