biocybernetics and biomedical engineering 40 (2020) 624–638

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Review Article

A review of fabrication polymer scaffolds for

biomedical applications using additive
manufacturing techniques

Patrycja Szymczyk-Ziólkowska a, Magdalena Beata Labowska b,

Jerzy Detyna b,*, Izabela Michalak c, Piotr Gruber a
a
Centre for Advanced Manufacturing Technologies (CAMT/FPC), Faculty of Mechanical Engineering,
Wroclaw University of Science and Technology, Wroclaw, Poland
b
Department of Mechanics, Materials and Biomedical Engineering, Faculty of Mechanical Engineering,
Wroclaw University of Science and Technology, Wroclaw, Poland
c
Department of Advanced Material Technologies, Faculty of Chemistry, Wroclaw University of Science
and Technology, Wroclaw, Poland

article info abstract

Article history: This paper presents the current state-of-the art of additive manufacturing (AM) applications
Received 22 November 2019 in the biomedical field, especially in tissue engineering. Multiple advantages of additive
Received in revised form manufacturing allow to precise three-dimensional objects fabrication with complex struc-
18 January 2020 ture using various materials. Depending on the purpose of the manufactured part, different
Accepted 24 January 2020 AM technologies are implemented, in which a specific material can be utilized. In the
Available online 20 February 2020 biomedical field, there are used several techniques such as: Binder Jetting, Material Extru-
sion, Material Jetting, Powder Bed Fusion, Sheet Lamination, Vat Polymerization. This article
Keywords: focuses on the utilization of polymer materials (natural and synthetic) taking into account
Additive manufacturing hydrogels in scaffolds fabrication. Assessment of polymer scaffolds mechanical properties
3D printing enables personalized patient care, as well as prevents damage after implantation in human
Biomaterials body. By controlling process parameters it is possible to obtain optimised mechanical
Scaffolds properties of manufactured parts.
Properties © 2020 Nalecz Institute of Biocybernetics and Biomedical Engineering of the Polish
Applications Academy of Sciences. Published by Elsevier B.V. All rights reserved.

structures from digital data (3D model) by adding material

1. Introduction
layer-by-layer manner. This technological process is also called
three-dimensional (3D) printing and has been introduced by
Additive manufacturing (AM) or rapid prototyping (RP) is Charles W. Hull in 1986 [1–3]. To produce physical 3D objects in
a technology which allows to build three-dimensional AM technology it is necessary to use CAD 3D software or scanner

* Corresponding author at: Department of Mechanics, Materials and Biomedical Engineering, Faculty of Mechanical Engineering,
Wroclaw University of Science and Technology, Smoluchowskiego 25, 50-370 Wroclaw, Poland.
E-mail address: jerzy.detyna@pwr.edu.pl (J. Detyna).
https://doi.org/10.1016/j.bbe.2020.01.015
0208-5216/© 2020 Nalecz Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of Sciences. Published by Elsevier
B.V. All rights reserved.
 biocybernetics and biomedical engineering 40 (2020) 624–638
(i.e., computerized tomography (CT), micro-CT, magnetic reso-
nance 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 consecu-
tively layer upon layer a portion of material [3,6–11]. 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 [6,12–17]. Men-
tioned 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]. Gener-
ally, 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) [20–24].
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 nanomater-
ials (e.g., carbon nanofibers, carbon nanotubes, graphene))
[4,12,25,26]. Manufacturing complex structure while maintain-
Fig. 1 – Example of: a) customized jaw implant for oncological treatment [31]; b) patient-specific acetabular hip implants
(Materialise, Belgium).
625
ing 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), pharmaceuti-
cals (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–
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, attach-
ment, 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, thermo-
plastic 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
626 biocybernetics and biomedical engineering 40 (2020) 624–638
Fig. 2 – Examples of 3D scaffold structures manufactured
using AM technology (own source).
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 technol-
ogies 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.
2. 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 pro-
duced with the same precision using traditional production
methods. CAD software enables designing shape and geometry,
which can be produced accurately and reproducible without
resigning of customization [20,33,37]. Moreover, there is a
possibility of combining multi-component pharmaceuticals
and medication carriers, in which controlled release of the drug
depends on applied materials (e.g., tablets). In the biomedical
field there are used AM techniques such as: Material Extrusion
(e.g., Fused Deposition Modeling (FDM), Gel or paste extrusion),
Vat Polymerization (e.g., Stereolithography (SLA), Digital Light
Projection (DLP)), Powder Bed Fusion (e.g., Selective Laser
Sintering (SLS)), Binder Jetting (e.g., Powder Bed Inkjet printing),
Material Jetting (e.g., Inkjet printing, Polyjet), Sheet Lamination
(e.g., Laminated Object Manufacturing), as it is shown in
Table 1. Each of the mentioned AM technology methods uses a
different material that is bonded differently (e.g., by various
energy sources, different physical state of the material).
Desirable pharmaceuticals and medical facilities can be
produced in this way. Early stages of AM technology allowed
to make a product prototype in a short manufacturing time and
cost-effectively. Nowadays, in comparison to the traditional
manufacturing method, AM technology typically has advan-
tage in lower cost of the material used (e.g., material saving)
[38]. It is also an example of the elimination of the large-scale
manufacture systems due to the compact size of the device
used in AM technology [20].
As a result of the technological progress many methods
have been developed in additive technologies. Unfortunately,
only few are utilised in biomedical field, mainly due to more
restrictive material requirements and the process conditions.
Some manufacturing methods operate at high temperatures
that could damage used material or additives (such as drug)
[3,20]. In the Table 2, commonly used Additive Manufacturing
methods applied in the biomedical field, such as FDM, binder
jet printing, SLA, SLS with details about materials and their
limitations have been gathered. Each technique of additive
manufacturing has both benefits and disadvantages, not all
types of materials can be used by each method, especially in
the biomedical field, where used materials must be biocom-
patible and biofunctional [3].
2.1. Fused deposition modelling
Fused Deposition Modelling (FDM) is a widely propagated
method of additive manufacturing technology, in which
thermoplastic polymer in shape of wire (called filament) is
melted and extruded through the nozzle with fine diameter.
Processed material, in semi-liquid state, is added layer-by-
layer. Each cross section is formed due to print-head move-
ment (in X and Y axis). Recursive process results in building
geometry based on three dimensional computer aided design
(3D CAD) model [4,6,66]. In Fig. 3 scheme of this method is
shown. FDM has many advantages, such as good efficiency,
easy material replacement and its low costs of operation and
implementation, furthermore, building process is automated
and does not require the use of any tooling. FDM has also
several limitations such as narrow selection of possible to
process biomedical materials. Mechanical properties of ther-
moplastics processed using FDM in comparison to traditional
manufacturing technologies are characterized by lower pa-
rameters, which results in a shorter lifetime of such products
[6,34–36].
Due to poor surface finish, this method is not preferred for
biomedical implants. The way to refine the surface roughness
and to improve the mechanical properties is to lower layer
 biocybernetics and biomedical engineering 40 (2020) 624–638 627

Table 1 – Applications of AM techniques in biomedical field.

Method Principle of technology Drug formulation References
Material Extrusion
Fused Deposition Selective extrusion of wire * Tablets [21–29]
Modeling (FDM) shaped thermopolymer * Oral dispersible films
* Capsules
* Customized medicine for drug delivery
* Dental fixtures, bridges and crowns
* Customized patient specific implants and prostheses
* Surgical models for perioperative surgical preparations
* Scaffolds (tissue engineering, regenerative medicine)

Gel or paste Selective extrusion of gel/paste [37,40,41]

extrusion * Scaffolds for regeneration (bone, aortic valve, vasculature
microfabrication, cartilage, neuronal, skeletal muscle, organ)
* Cell cultures
* Live tissue
* Tablets (drug delivery models: immediate-release tablet,
gastro-floating tablet, bilayer tablet, polypills)

Vat Polymerization
Stereolithography Polymerization of photocurable [7,39,42–44]
(SLA) liquid resin initiated by laser * Tablets
* Personalised scaffolds
* Drug-loaded scaffolds
* Implantable devices
* Cell-containing hydrogels

Digital Light Solidification of photosensitive [45,46]

Projection (DLP) material by UV light modulated * Spatially patterned tissue engineering scaffolds
by several millions of * Complex organ structures (ear auricle, the cerebral sulcus and
micromirrors grooves, the heart with aorta and pulmonary artery/vein, the
lung with thoracic cavity and the vascular network structures)

Powder Bed Fusion

Selective Laser Sintering or melting of a [7,39,42,47–58]
Sintering (SLS) powder polymer with laser * Orodispersible tablets
* Oral drug delivery systems
* Accelerated release formulations
* Dental parts
* Medical parts
* Scaffolds

Binder Jetting
Powder Bed Inkjet Bonding of a powder material [47–49,51,58–60]
printing with selectively jetted liquid * Reconstructive models
binder * Surgical templates
* Drug delivery devices (implantable/subdermal)
* Oral dosage forms
* Resorbable devices

Material Jetting
Inkjet printing Deposing micro-droplets of [42,61]
liquid materials at high speed * Tablets
* Controlled drug delivery device
* Oral films and orally dispersible formulations
* Microdots
* Films

Polyjet Solidification of liquid [37,62,63]

photopolymers by UV light * Anatomical models for surgical planning and pre-operative
source simulations (intrahepatic vessel models, liver models)
* Solid dosage forms
* Dental delivery trays
* Surgical orthopaedic guides
* Hearing aids materials

Sheet Lamination
Laminated Object Lamination of sheet [37,64,65]
Manufacturing photopolymer material in a * Anatomical models
layer-by-layer by laser * Models of soft tissue
628 biocybernetics and biomedical engineering 40 (2020) 624–638

Table 2 – Methods of addition manufacture used in biomedical field.

Method Materials Limitations Benefits References
Fused Deposition Continuous filaments of * Limited selection of [3,6,33,35,44,115]
Modeling (FDM) thermoplastics: materials used in  Diverse range of geometries
 ABS biomedical field  Complex structures and shape
* Thermoplastic polymer  Readily available filaments
 nylon used in this method  Time of manufacturing objects
 PC cause shorter lifetime  Affordability
 PCL and poor mechanical
 PLA characteristics
 PLLA * Poor surface quality of
 PLGA printed objects
 PET-G * Not preferred for
 TPC biomedical implants
 TPS * Complications with
incorporation of cells or
bioactive molecules
into filament

Stereolithography (SLA) [3,6,19,76]

 PCL * Limited number of  High dimensional accuracy
 PEGDA materials (necessity of a  Intricate details
 PDL photocrosslinkable  Smooth surface finish
 PDLLA material)
 PPF * Limited number of
potential materials
(toxic substances during
photopolimerisation)

Selective Laser Sintering [3,4,6,7,33,55]

(SLS)  Polymers powders: * Using high temperature  Fast process
 PEEK/HA energy source  Manufacturing large and
 PCL * Expensive technique complex parts (irregular
 PCL/HA * Large dimension of SLS shapes and structures)
 PDLLA device  Material versatility
 PEEK * Resolution dependent  Small series produced in one
 PLGA upon powder manufacturing process
 PVA microstructure and the  High part accuracy
spot size of the laser

Binder Jetting [3,4,6,47]

Bioprinting  carbohydrates * Poor adhesion between  The cheapest and fastest
 polyvinyls layers method
 silica * Poor surface quality  Wide range of used materials
 sucrose * Low mechanical  High precision of
 enable incorporation of properties manufactured objects
biomolecules and drug
PC - polycarbonate, PLLA - Poly (L-lactic acid), PPF - poly (propylene fumarate), TPS - thermoplastic starch.

thickness, but it increases production time and costs. Smooth
surface finish of manufactured parts may be achieved by
additional processes, like mechanical and chemical finishing
[12,35]. In order to extend the applications of FDM technology,
it is necessary to improve properties of processed material,
processability and reliability, but also the functionality of
produced components [36]. In Fig. 4 examples of parts
fabricated using FDM method are shown.
Materials mainly used in Fused Deposition Modelling are
acrylonitrile butadiene styrene (ABS), polylactic acid (PLA),
polycaprolactone (PCL), polyethylene terephthalate glycol
(PET-G), tricalcium phosphate (TCP), nylon [33,66]. Unfortu-
nately, there is a problem with incorporation of cells or
bioactive molecules into filament at the stage of the produc-
tion or this is usually inefficient process [6].
2.2. Selective laser sintering/melting
Selective Laser Sintering/Melting (SLS/SLM) is one of the
powder bed fusion technologies. Process of SLS is shown in
Fig. 5. It uses heater, which preheats applied layer of powder
material into build cavity (mainly metals and polymers, but
also glass, ceramics) and laser radiation as a heating source for
fusing (melting or sintering) desired cross sections. Layer-by-
layer process of melting and subsequent solidification allows
joining of individual layers, which results in three dimensional
object, as shown in Fig. 6 [3,4,70]. It is worth mentioning that
using material in the powder form, allows to obtain/receive
higher geometrical freedom of manufacturing.
In comparison with other processes, such as SLA or FDM,
SLS bioprints usually exhibit better accurate detail and sharp
 biocybernetics and biomedical engineering 40 (2020) 624–638
Fig. 3 – Scheme of Fused Deposition Modeling system (own
source).
reproduction. Accuracy is dependent upon the powder
morphology (its flow behaviour, fluidization, particle shape
and surface, particle size distribution) and upon the spot size
of the laser, layer thickness, material shrinkage [3,4]. On the
other hand, SLS bioprints exhibit excellent mechanical
properties [6].
Significant disadvantage of this method is the use of high
temperatures, especially instant high temperature due to laser
radiation, which limits the number of materials that can be
applied in bioengineering [33]. Materials used in SLS technol-
ogy are mainly polymers but also ceramics. Tissue engineering
scaffolds are produced most commonly using polymeric
biomaterials and their composites (e.g., pure PCL, poly(D,L-
lactide) (PDLLA), poly(ether-etherketone) (PEEK), poly(lactic-
co-glycolic acid) (PLGA), poly(vinyl alcohol) (PVA), composite of
polycaprolactone/hydroxyapatite (PCL/HA) or poly(ether-
etherketone)/hydroxyapatite (PEEK/HA)) [3,4].
2.3. Stereolithography
Stereolithography (SLA) is the oldest process of AM technolo-
gy, patented in 1986 by Charles Hull. SLA is one of vat
Fig. 4 – Examples of objects manufactured in FMD technique: a) cranial segment [67]; b) tablets [68]; c) dental model [69].
629
Fig. 5 – Diagram of Selective Laser Sintering process (own
source).
photopolymerization methods, which uses ultraviolet laser to
cure photopolymer resin. UV laser spot traces desired cross
section starting a photopolymerization process, in which
liquid material (resin) is solidified. System of SLA is shown in
Fig. 7 [4,72]. Since only one material at time can be used,
support structures are made of model material, and have to be
manually removed after the process [4,73].
Significant disadvantage of using stereolithography in tissue
engineering is the limited number of potential materials due to
free radicals formation during photopolymerization process,
which can damage cell membrane, protein, and nucleic acids
[33]. Many researchers have carried out investigation with
biomaterials to find a cytocompatible photo-initiator for SLA
method [4]. For the production of porous 3D scaffolds, Elomaa
et al. [74] used three-armed polycaprolactone (PCL) oligomers
synthesized and end-functionalized with methacrylic anhy-
dride. Hydrogel based polyethylene glycol (PEG) is used to create
3D structure of liver aggregates and microperfusion flow within
the open channels of this structure [75]. For vascular applica-
tions, based on cell-laden hydrogel by poly-D-lysine (PDL),
Elomaa et al. [74] used poly(ethylene glycol-co-depsipeptide)
macromer. It is also possible to create cells-encapsulated
hydrogel in complex 3D structure by using photopolymerizable
poly(ethylene glycol) diacrylate (PEGDA) [76].
2.4. Binder Jetting
Binder Jetting is a method, which uses a liquid bonding agent
and a powder-based material for manufacturing of object.
630 biocybernetics and biomedical engineering 40 (2020) 624–638
Fig. 6 – Scaffolds manufactured by SLM method [71].
Fig. 7 – Process of Stereolithography method (own source).
Three dimensional objects are built using print-head, which
selectively jets liquid agent according to the desired cross
section which glues powder material [4]. Likewise in SLS
technology, not bound powder material acts as a support
structure, which allows to produce more complex geometries.
That is why Binder Jetting can be used in tissue engineering in
order to produce advanced and complex scaffold structures.
Devices are inexpensive, moreover, unused powder can be
used in the next process [3]. However, the lack of adhesion
between layers and print resolution (range of 20–100 mm) in
this technique is a challenges for the future [3,6].
This process can print a plurality of powder materials such
as ceramics, metals, sand and polymers [4]. In the biomedical
field, it is possible to process cells and hydrogel with the
incorporation of biomolecules or drugs. Exemplary biomater-
ials used in this method are carbohydrates (e.g., sucrose),
polyvinyls, silica [4,77]. Examples of manufactured objects in
Binder Jetting are shown in Fig. 8.
3. 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 mm due to
the cell size, migration requirements and transport. Pore size
higher than 300 mm is recommended in terms of enhanced
new bone formation and the formation of capillaries [33,78,79].
Scaffolds structures can be implemented in the clinical uses
such as bone grafts and substitute of bone material, growth
factors, free fibrous transplantation and the incorporation of
metalwork to aid bone stability, restoration, regeneration or
replacement of injured or defective living tissue, cartilage and
organs [4,26,80].
Open porosity is an important factor in designing and
producing scaffolds. It ensures flow of the culture medium or
blood and therefore continuous nutrients and metabolites
supply, but also oxygen transport. Moreover, porous scaffolds
enable tissue growth and ensure appropriate mechanical
strength for transplantation and implantation in the human
body, what contributes to the healing of complex tissue
[3,4,33]. By production of biocompatible and biodegradable
scaffolds it is possible to prepare implants out of cells procured
from cell culture, which can be replaced after their dissolution
by the natural tissue [33]. In this way, by integrating scaffolds
into biomaterials design, tissue engineers could unlock
cellular mechanisms, improve the reaction and regeneration
of native tissues and contribute to the healing function [3].
In tissue engineering and regenerative medicine, 3D
structures from biomaterials are often applied to basically
all tissues in human body (e.g., blood vessels, bones, ears) and
they are used to manufacture whole organs [2,12]. Initial
scaffolds production methods were based on traditional
manufacturing techniques, such as electrospinning, fiber-
bonding, melt molding, membrane lamination, particulate
leaching, solvent casting and particulate leaching, thermally
induced phase separation, and gas foaming [3,81]. In this way
it was possible to achieve architectural miscellaneous in
produced scaffolds due to the lack of the full control of the
pores geometry. Nowadays, these complex and porous 3D
structures are mainly produced using additive manufacturing
(example in Fig. 9), which enables to eliminate traditional
production methods' limitations. Precisely, by checking the
geometry of the pores, their connections and sizes, it is
possible to increase repeatability, better detail reproduction
and provide more effective personalisation of the manufac-
tured scaffolds [3,12].
During polymer scaffolds manufacturing in tissue engi-
neering it is important to take a suitable material into
consideration, which will degrade and resorb in a controlled
manner making place for new cells to form [83]. Bružauskaite
et al. [84] showed that the number of cells is dependent on the
pore size. Physical properties of the bioresorbable scaffold
should be retained until ingrowth tissue will be sufficiently
strong and stiff to match the properties of the host tissue as
closely as possible. Gradually disappearing scaffold matrix will
 biocybernetics and biomedical engineering 40 (2020) 624–638
Fig. 8 – Objects manufactured in Binder Jetting technique: a) heart model; b) backbone [59].
Fig. 9 – Example of polymer 3D scaffold manufactured in AM
technology [82].
start losing its mechanical properties and ought to be absorbed
by the body without a foreign body reaction within a
predetermined period of time [83,84].
Scaffold's material is required to be biocompatible, because
in contact with human tissue it cannot induce inflammatory
reactions and exhibit immunogenicity or cytotoxicity. Another
feature to be implemented is its biodegradability, to allow
development and growth of natural support structure after its
degradation. In addition, scaffold's materials are supposed to
be readily available and easy to manufacture. Moreover, to
prevent infection, tissue scaffolds should be easily sterilizable
Fig. 10 – Bioprinted 3D hydrogel constructions [87,88].
631
[33,78,85]. Scaffolds used in the biomedical field, especially in
tissue engineering, are manufactured from natural or syn-
thetic polymers (e.g., hydrogels, proteins, thermoplastic
elastomers and chemically cross-linked elastomers), bioactive
ceramics (e.g., bioactive glasses, glass ceramics and calcium
phosphates), ceramic and polymers composites and metallic
materials (e.g., magnesium and titanium alloys) [4,32].
Mentioned biomaterials have some disadvantages: natural
polymers may be characterized by poor mechanical properties,
not all synthetic polymers are degradable and ceramics are too
stiff. Unfortunately, there are only few biomaterials fulfilling
all the requirements for scaffolds. To achieve functions and
develop perfect biomaterial for bioengineering applications it
is necessary to find the most appropriate combination of
materials of different origins [84,86]. The selection of suitable
biomaterial in scaffolds production is very important since in
certain processes bioactive molecules and living cells are
incorporated into biomaterials (e.g., hydrogels, which example
is shown in Fig. 10) [4].
Mechanical properties are one of the major requirements
for scaffolds designing. Mechanical functionality and stability
of this structure must be adequate to avoid structural damage
during early postoperative function under physiologic loading
conditions and patient's normal activities [78,85]. It is
significant to keep the shape of scaffolds pores during the
cell growth, which also requires a certain mechanical strength
of the structure [4]. According to the mechanical strength,
scaffolds can be classified as soft and hard tissues. Soft tissues
(hydrogels) have a very high water content, they are flexible
and it is possible to incorporate cells into hydrogels. Hard
tissues (e.g., bones, teeth) are mineralized tissue and have a
firm intercellular matrix. They are also known as calcified
tissues [33].
632 biocybernetics and biomedical engineering 40 (2020) 624–638

3.1. Hydrogel materials for scaffold

Hydrogels belong to the group of materials, which are used for

biomedical applications, for example in tissue engineering
(bone, cartilage, nerve, muscle, pancreas, and liver repair,
regeneration or replacement), pharmaceutical applications
(delivery of bioactive agents, e.g., drugs, proteins), wound
healing (dressings), in vitro cell culture [89,90]. Hydrogels are
gels formed from networks of hydrophilic, cross-linked
polymer chains that absorb large amounts of water without
dissolving [80,89,91]. There is a wide and diverse range of
natural, biodegradable polymers and their derivatives that
have been used to produce hydrogels, for example (1) anionic
polymers such as hyaluronic acid, alginic acid, carrageenan,
pectin, dextran sulphate, chondroitin sulphate, (2) cationic
polymers such as chitosan and polylysine, (3) neutral poly-
mers such as agarose, dextran and pullulan and amphipathic
polymers such as collagen, fibrin and carboxymethyl chitin
[87,90].
In addition to natural polymers, synthetic polymers can
also be utilised to the synthesis of hydrogels (e.g., poly
(acrylamide) (PAAM), poly(ethylene glycol) (PEG), poly(vinyl
alcohol) (PVA)). Due to the hydrophobic character of synthetic
polymers and their chemical strength, they are characterized
by higher mechanical strength in comparison to natural
polymers, which makes them more durable and slower to
degradation [92,93]. The flexible hydrophilic hydrogel struc-
ture can be produced using many techniques, especially these,
which can be used to create a cross-linked polymer. Water-
soluble linear polymers are cross-linked to form hydrogels in
several ways: physical cross-linking (e.g., by crystallization,
ionic interactions, hydrogen bonds), chemical cross-linking
(e.g., by complementary groups chemical reaction, addition
reactions, condensation reactions, free radical polymerization,
using aldehydes, using enzymes), grafting polymerisation, and
radiation cross-linking. The methods of hydrogel formation
and their modifications can improve mechanical properties
and viscoelasticity [92,94,95]. Examples of cross-linked algi-
nate hydrogels are shown in Fig. 11.
The main advantages of hydrogels are (1) high content of
water — inclusion of growth media allows for cell encapsula-
Fig. 12 – Example of alginate scaffold structure [100].
tion and growth and additionally the aqueous environment
can protect cells and fragile drugs (2) crosslinking enables
modification of mechanical properties, (3) good transport
of nutrient to cells and products from cells, (4) release of drug/
growth factor can be controlled, (5) can be injected in vivo as a
liquid that gels at body temperature, (6) ease of patterning
via 3D printing to mimic tissue microarchitectures, (7) usually
biocompatible [80,90]. Potential restrictions on the use of
hydrogels include (1) difficulties in physical manipulation of
constructs, (2) usually mechanically weak and mechanical
properties can limit use in load bearing constructs, (3) opti-
mising printing conditions for individual hydrogels can be
time consuming, (4) difficulties in loading evenly with cells,
(5) may be difficult to sterilize [80,90].
One of the biomaterials, that have numerous applications
in biomedical science and engineering, is alginate (example of
application in Fig. 12), which is a naturally occurring anionic
copolymer obtained from brown seaweeds. It is composed of
blocks of (1,4)-linked b-D-mannuronate (M) and a-L-guluronate
(G) residues [89]. The physical properties of this polymer and
hydrogels produced from alginate depend on the composition
(e.g., M/G ratio), G-block length, and molecular weight [97].
With the increase of the length of G-block and molecular

Fig. 11 – Cross-linked alginate hydrogels: a) high-purity; b) low-purity [96].

 biocybernetics and biomedical engineering 40 (2020) 624–638
weight, mechanical properties of alginate gels are enhanced
[89]. Crucial for these properties is also gelation temperature
which influences gelation rate. At lower temperature, the
reactivity of ionic cross-linkers (e.g., calcium ions) is reduced
and the cross-linking is slower and the resulting network
structure has greater order [98]. The main reasons for the
popularity of the alginate as a biomaterial for biomedical
applications are beside simple and fast gelation, low cost and
non-immunogenicity [99].
The main usage of alginate hydrogels includes drug
delivery, wound healing and tissue engineering applications
[87,89]. This is possible due to favourable properties, such as
ease of gelation after addition of for example calcium cations,
biocompatibility and low toxicity [89,101]. The concentration
of Ca(II) ions and sodium alginate in a hydrogel influence its
swelling and mechanical properties [101]. Among mentioned
applications, tissue engineering attracts the attention of
scientists since it enables the manufacture of scaffolds for
tissue/organs. One of the techniques used is 3D bioprinting
with novel compatible biomaterials, including alginate hydro-
gels [4,87,102–104]. Customized-production, rapid-fabrication
and high-precision are the main advantages of 3D bioprinting
[4,102]. 3D bioprinting with alginate hydrogels is a novel
platform which is used to construct complex 3D tissue archi-
tecture that mimic real ones [103]. Alginate-based hydrogels
are known to have tunable mechanical properties (e.g.,
mechanical strength and stiffness) and they can be tailored
to enhance printability and geometric accuracy [91]. There are
two key properties of alginate-based bioink — viscosity and
density that influence its printability [91,102]. Successful
bioprinting of hydrogels depend on geometric accuracy and
cell viability [105]. Some of the examples with a successful
application of alginate-based hydrogels are available in the
literature. For example, Wu et al. [103] developed a hybrid
bioink composed of alginate and cellulose nanocrystals and
used it to print a liver-mimetic honeycomb 3D structure that
contained fibroblast and hepatoma cells. In the work of Yeo
et al. [106], the bioink based on alginate and collagen was used
in the innovative collagen-based cell-printing method to
obtain human adipose stem cell-laden structures. In these
structures, collagen-bioink was in the core region and the pure
alginate in the sheath region to protect the cells in the collagen
during the printing and cross-linking process. Jia et al. [102]
printed alginate solutions with human adipose-derived stem
cells into lattice-structured, cell-laden hydrogels. Di Giuseppe
et al. [91] used alginate-gelatin hydrogels for 3D bioprinting
and tested the viability of encapsulated mesenchymal stem
cells in the bioprinted construct.
3.2. Mechanical properties of AM manufactured scaffolds
Structures built using AM technologies are evaluated in terms
of their features — mechanical properties, e.g., tensile
strength, flexural strength or impact resistance, but also
dimensional and shape accuracy, and economic indicators
such as production time and the amount of material used to
produce the component [34]. Mechanical properties of parts
fabricated using additive technologies are highly influenced by
the used method and its process parameters, but also structure
geometry and chosen material. In order to obtain desired
633
mechanical properties with high quality, it is necessary to
have structured knowledge of correlations between parame-
ters in technological process and mechanical efficiency [35,36].
It is important to verify mechanical properties of the object
manufactured using AM, due to various loads related to
the selected application, like succumbing to deformations,
dynamic stress and vibrations. Is also crucial implantation site
examination. It can help design elements that could substitute
damaged tissue. The most common reason of components
failure is their plasticity under cyclic and dynamic loading
conditions [40,107,108].
Depending on the method used, the mechanical properties
of 3D printed samples may be affected by many factors, such
as layer thickness, fill pattern and air gap between two
adjacent deposited filaments in the same layer, structural
orientation, scan speed and in some methods, the model's
geometry, temperature and laser power [35,109]. Mechanical
response can be influenced also by different defects occuring
during manufacturing processes. This characteristics exhibits
that mechanical response must be anisotropic and display
tension/compression asymmetry [110].
Mohamed et al. [36] have shown, that mechanical response
of polylactide (PLA) is better than the other investigated ther-
moplastic polymers and tensile strength of AM manufactured
PLA is anisotropic. It was also presented, that polymers with
low molecular weights achieved the highest tensile strength
[36]. Mechanical properties differ depending on the build
orientation and therefore samples manufactured along Z-axis
have the lowest tensile strength [111]. Ceramic materials are
characterized by a high mechanical strength. Moreover,
researchers were able to produce component of Al2O3/ZrO2
with almost 100% density and flexural strength of more than
500 MPa [112]. In contrary, hydrogels do not provide high
mechanical properties, therefore their application is limited.
Nevertheless, the mechanical properties of hydrogels can be
modified through crosslinking. Moreover, Gu et al. [4] showed
that narrow pore size distribution, with adequate pore inter-
connectivity improved mechanical properties. Metals provide
the highest mechanical properties, which can be favour-
able for slow bone growth applications. Unfortunately, these
materials are not biodegradable and are suspected of releasing
toxic metal ions [80].
The pore diameter and its patterns have strong influence
on the mechanical properties of scaffolds. Compression tests
are carried out to check the strength of manufactured bone
scaffolds [113]. Scaffold produced from sintered CaCO3 and
SiO2 with porosity of up to 71% found maximum scaffold
compressive strength of 28.1 MPa. Akremanite (Ca2MgSi2O7)
with nano-titania particles was used to build a composite
scaffold using SLS, with porosity of up to 58% which exhibited a
maximum compressive strength of 23 MPa [80]. Furthermore,
Zein et al. [81] showed that the fibres orientation in the layer
also influenced mechanical properties of manufactured parts.
They examined the influence of structure (direction of fibres in
layers) and the size of porosity on the mechanical parameters
such as stiffness, yield strength and yield strain [81].
Mechanical properties cannot be controlled by changing
one factor, but it is necessary to control several parameters to
achieve superior effects. Unfortunately, biodegradable mate-
rials tend to be mechanically unstable, thus mechanical
634 biocybernetics and biomedical engineering 40 (2020) 624–638
strength and biodegradability are contradictory to each other
[32]. Nevertheless, finding proper material is still an issue to be
solved by researchers in the future. Connection of higher
porosity and improvement of mechanical properties result
also in higher in vitro cell growth, proliferation and minerali-
zation of scaffold [80].
4. 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 simul-
taneously decreases the production time and enables
customization of drug dosage in a single medication [38].
AM technology also enables the precise manufacturing of the
most important scaffold factor — open porosity, which allows
the flow of nutrients and metabolites, as well as enables tissue
growth and provides appropriate mechanical properties
[3,4,33].
Biomaterials in AM technology, especially used in tissue
engineering, ought to be biocompatible, easy biodegradable
and sterilizable [33,78,85]. The most commonly used materials
in tissue engineering are natural and synthetic polymers.
Not all materials have suitable properties for human body
applications [84].
Assessment of the mechanical properties of scaffolds
implanted into the human body is very important. Damaged
tissue, replaced by implanted tissue should maintain resis-
tance to the load which is adequate to the location of the
scaffold application [36,114]. Hydrogels usually exhibit poor
mechanical properties, nonetheless they can be modified by
crosslinking and provide a good environment for the cell
growth and tissue regeneration [80,90]. By controlling process
parameters in AM technology and proper selection of the
material, it is possible to achieve desired mechanical proper-
ties [25,35,109]. The properties of the implanted scaffold
should be similar to this of the host tissue and should
maintain its mechanical properties until it is replaced by new
growing tissue [83,84].
There are many challenges in the 3D printing to obtain
optimised tissue architecture, biomaterials without defects
and their desirable properties (e.g., biocompatibility, biodeg-
radation, mechanical properties, printability). Research con-
cerning the development of new materials exhibiting relevant
characteristics and their compatible mechanical properties are
the main aims of the modern tissue engineering [25,84].
CRediT authorship contribution statement
Patrycja Szymczyk-Ziólkowska: Conceptualization. Magda-
lena Beata Labowska: 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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