The case study prioritizes on explaining the role

of biomaterials in the field of medical

applications. Biomaterial can be defined as a
material intended to interface with biological
system to evaluate or treat any tissue, organ or
function of the body. The idea of using materials
in medical field is not new. Teeth implants made
of gold were used by Egyptians, in India sutures
were used by Sushruta followed using metallic
sutures in Greek era & contact lenses in late
1500s. Currently various type of material are
being used in medical department.
Some of these discoveries have been accidental.
Two such examples are explained here. First is
the use of acrylic polymer,
polymethylmethacrylate or different kinds of
hydrogen materials for contact lenses. The credit
goes to great ophthalmologist, Sir Harold Ridley
who discovered that when the spit fighters had
their windshields broken and the pieces went
inside the eyes of the pilot, they did not get any
inflammation or infection as it was made of the
polymer, polymethylmethacrylate instead of
glass which led to its pre dominant use for
manufacturing artificial ocular lenses. Second is
the discovery of metallic implants by Professor
Branemark which was also a serendipity. He
wanted to study the blood circulation in bone
and how the bone healing takes place. He
performed in vivo experiments in which he
implanted two chambers side by side one made
of titanium, & the other of steel into a rabbit
bone. After some days as he tried to retrieve the
metal parts, he somehow managed to retrieve
the stainless steel but the titanium was so fixed
that it was inseparable without fracturing the
bone. As he investigated more, he surprisingly
found that the titanium chambers screwed into
rabbit fibulas got permanently incorporated with
the bone. This led to its use as a primary metal
for medical implants in the field of dentistry and
orthopedics. Currently a wide range of materials
are used in human body starting from dental to
craniofacial plates, silicon implants for breast,
orthopedic implants are sometimes made of
combination of different materials such as
plastic, hydroxyapatite, ceramic & metallic alloys.
Stents are used widely for correcting the teeth
impressions or as a temporary closure to relieve
obstruction are made of a specialized alloy,
nitinol. Looking at these dimensions a huge
number of medical devices are used inside
human body. The industry now stands at 100
billion and with time the numbers are expanding
all over the world. But there are certain
limitations such as these implants have a fixed
lifetime after that it needs to be replaced or the
patient may get infections if they are allergic, so
this is not a perfect solution. For e.g., Hip & Knee
prostheses have a 10-15 yr. lifetime which needs
replacement, catheters used in patients often
results to thrombosis and infection, contact lens
used provide discomfort and thus are not
preferable. This is where biomaterials come in as
it brings in expertise from all domains combined
to refine these materials ,make them
biocompatible and effective in a long term.
Biomaterial was first defined in 1970s, though
many new definitions were proposed in following
years, but the fundamental concept remained
same i.e.it facilitates the healing after injury or
disease. Some of the properties we look for
when we select a biomaterial is high level of
strength when it comes to orthopedic implants
for e.g., metals are preferrable. Flexibility is also
an important property which can be worked on
using polymers. Ceramics can be used where we
need to enhance the biological activity.
Composites are used when a single material
doesn’t show all the properties required to meet
the requirements. Different kinds of biological
material like collagen or materials derived from
animals such as chitosan, alginate is currently in
use for human applications. A biomaterial is
chosen from a plethora of materials based on
the ideal properties such as ability to direct
cellular behavior i.e.material should be non-toxic
& adapt to microenvironment in which it is
implanted. Moreover, the mechanical property
of the material should match the structure of the
replaced tissue and its functionality. However,
this becomes crucial if the material is resorbable
as when it resorbs/ degrades integration should
happen at the same rate as regeneration of the
tissue is. Again, for the material to be accepted
widely it should be economically viable and
comply with regulatory bodies such as FDA, ISO
etc. These are some of the prerequisites to select
a biomaterial precisely.
Biomaterials are used in bioprinting in two kinds
of approaches- one is cell free or acellular
approach, and the other is cell laden or
bioprinting approach. Acellular printing mainly
prints a scaffold, but cells are not incorporated so
ceramics or hard polymers like silica, PLA
(Pluronic Acid), polyurethane etc. are added as
they are easily printable whereas in cell laden
approach, cells & material are mixed and soft
materials like cellulose, gelatin etc. are used
irrespective of their origin (i.e., can both natural
and synthetic) in bigger proportion for
bioprinting. These methods help us to picture
how the scaffolds are manufactured and cells are
positioned in 3D. In traditional tissue
engineering, some cells are taken from primary
donor and expanded in a culture, after that they
are sieved on a suitable scaffold with certain
growth factors eventually it is put in the
bioreactor to attain maturity and then its
implanted in the damaged site. But for the entire
process to be accurate, the mentioned
prerequisites are to be followed whether its
cellular or acellular.
In cell laden approach or bioprinting use of
hydrogels is appreciable as it is a 3D network of
hydrophilic polymers that swell and hold a large
amount of water due to physical/chemical
crosslinking of individual polymer chains as a
result helps maintain the structural framework
like ECM (extracellular matrix) that surrounds the
cell. As the hydrogel is mainly composed of water
it is very soft and flexible it supports cellular
survival while the printing process is carried out
i.e., it is biocompatible. Hydrogel system can be
broadly classified into three types, there’s ECM
derived hydrogels like collagen, fibrin etc.
Synthetic hydrogels are also synthesized in the
labs using various molecules like peptide based,
PEG (Polyethylene Glycol) based hydrogel
systems etc. Non- mammalian hydrogels like
agarose, chitosan which are natural are also
present that can be used as bio ink.
Bio ink is rarely composed of cells alone, a
substance can be properly defined as a bio ink
when the cells and biomaterial are combined. A
bio ink can be classified as natural or synthetic
depending on the source of the biomaterial with
the choice of the cells. There are certain
prerequisites for bio inks and the primary one is
biocompatibility i.e., cell should be able to
survive within the hydrogel system and in
addition, attain the strength required for a tissue
we are interested in. They should also exhibit a
shear thinning behavior to obtain required
thickness for its efficient use in extrusion based
bioprinting. Some of these properties are well
shown by synthetic materials which becomes a
limitation for natural ones as they have least
control on molecular mechanics. Bio inks should
be able to gel at physiological conditions (pH
around 7, temperature about 37 degrees
centigrade). Another parameter is shape fidelity
which means they should be able to hold
various range of complex shapes. To summarize,
once we can achieve these requirements, we can
call the hydrogel as bio ink but not every
hydrogel should be necessarily printable, that’s
justifies the statement that “Every hydrogel is
not a bio ink”. Basically, this case study enriched
our level of understanding of biomaterials and
the prerequisites of bioprinting & how they are
tailored to meet bio-engineering applications.