a) Title

A Special Study of 3D Bioprinting using Machine Learning.

b) Rationale and Gap Analysis

3D Bioprinting is a technology that uses cells and other biocompatible materials as ink (also
known as bioink) to print living structures that can be implanted into the human body. It is a
form of additive manufacturing that layer-by-layer prints a structure that can imitate the behavior
of natural living systems. This technology can be used in medical applications like 3D printed
skin grafts, bone grafts, implants, and even organs.

The process of 3D bioprinting starts with a model of a structure that is recreated layer-by-layer
out of bioink that is either mixed with living cells or seeded with cells after the completion of the
print. The 3D model is then fed into a slicer i.e. a specialized computer program that analyzes the
geometry of the model and generates a series of thin layers, or slices that then take the shape of
the original model when stacked vertically. Once a model is sliced, the slices are then
transformed into path data, stored as a g-code file, that can be sent to a 3D bioprinter for printing.
The bioprinter then follows the instructions in the g-code file sequentially, including instructions
to control the temperature of the extruders, extrusion pressure, bedplate temperature, crosslinking
intensity and frequency, and lastly the 3D movement path generated by the slicer. Once all of the
g-code commands are executed, the print is completed and can be cultured or seeded with cells.

The current system of transplanting involves a long list of people waiting for organs and not
enough donors. And the patients who do get transplants end up suffering from chronic problems
due to long term damaging effects of post transplant immunosuppression. Thus, this technology
is of significant importance as it provides an alternative to the transplanting system.

Sr. Title Authors Year of Findings

No Publishing

1. A Perspective on Using
Machine Learning in 3D
Bioprinting
Chunling Yu, Jingchao Jiang 2020
The authors reviewed machine
learning methods used in 3D
printing and provided a
perspective on how machine
learning can benefit 3D
bioprinting.

2. Machine learning-based Jooyoung Lee, Seung Ja Oh, 2020 The authors developed a
design strategy for 3D Sang Hyun An, Wan-Doo machine learning-based
printable bioink: elastic Kim and Sang-Heon Kim. method to design a
modulus and yield stress 3D-printable bioink using a
 determine printability model system with naturally
derived biomaterials.

3. A Review on Development of Ansheed A. Raheem, 2021 The authors provided evidence

Bio-Inspired Implants Using Pearlin Hameed, Ruban supporting use of biomimetics
3D Printing Whenish, Renold S. Elsen, to 3D print ceramic, polymer,
Aswin G, Amit Kumar and metal implants with
Jaiswal, Konda Gokuldoss resemblance to natural tissue.
Prashanth and Geetha
Manivasagam

4. Coupling machine learning
with 3D bioprinting to fast
track optimization of
extrusion printing
Kalani Ruberu, Manisha
Senadeera, Santu Rana,
Sunil Gupta, Johnson
Chung, Zhilian Yue, Svetha
Venkatesh, Gordon Wallace
2021 The authors explore machine
learning as a tool to evaluate
printability, quantitatively and
to fast track optimization of
extrusion printing in achieving
a reproducible 3D scaffold.

c) Objectives

● The printability of the biomaterials is directed by a heap of factors, for example, bioink
properties, printer boundaries and post print restoring, and the streamlining.
● Machine learning strategies will speed up the exploratory plan process.
● It will help in making data sets from Big Data curation and building advanced twins of
human organs with cellular resolution and properties.
● An astute framework which will diminish the material wastage and the energy cost
positively.
● It will assist with overseeing the item quality and the throughput of the assembling plant.

d) Hypothesis

● In this research, the regular course of development will be projected into a computational
system using ML to study bioinspired various leveled structures. Normal materials,
which should get by with the material constituents accessible in their environmental
factors, impel novel material reactions without presenting new materials by utilizing
various leveled gatherings.
● Accordingly, we propose this ML-based worldview of savvy added substance producing,
while at the same time exhibiting its capacities of finding new material plans with
significant degrees of speedup contrasted with traditional strategies.
 e) Research Design and Methods/ Research Methodology

This research paper will revolve around two main concepts, they are machine learning and 3D-
bioprinting. Our qualitative data revolves around the utilization of machine learning in the field
of science. From each process to living tissues, cells, organs creation through 3D-bioprinting.
We will be covering everything from the optimization process which includes predictions from
datasets, after our input of datasets; we move on to a mathematical model, which gives us a
mathematical interpretation providing us with a requisite amount of prediction for all the inputs.
So, the whole objective of the optimization is to control and adjust the variables along with
different environments. That’s how we can increase our efficiency and performance, and that’s
how optimization in machine learning works.
The inputs or the variables they use here are bioink properties, printer parameters, post-print
curing, etc., combining all these variables setting them in different scenarios, and getting their
predictions through machine learning optimization makes it easier to test.
Next, we have material property prediction which uses hierarchical methods. Every time we train
our machine learning model with a huge mass of data with a lot of outcomes based on finite
element analysis (how a thing reacts to physical properties), it is done by using experimentation
and additive manufacturing. In recent years, they have also done coarse-graining analysis
(Coarse-graining is done by condensing a collection of elements into a single cell unit) and
designing material without the use of microstructural data.
Here, the property plays a very important role, every step is based on the element’s property and
how it reacts when merged with other elements in an environment, making up a new whole
equation, every time we introduce new elements. Rather than experimenting, ML makes our
work much easier.
Manufacturing defects, in 3D bioprinting Machine learning, can be used to detect defects in any
layer or any error at any level in the fabrication process (3D bioprinting involves fabricating
tissue, organs, and biomedical parts that imitate natural tissue architecture). Here, CNN
(convolutional neural network) is used to detect defects or errors in 3D bioprinting.
Dimensional accuracy analysis has also reached a major level in machine learning. A machine
learning model can even predict accurate distortions even at a minor level. In 3D bioprinting,
Machine learning can predict any slight error during additive manufacturing, and the predictions
are very much accurate.
Machine learning has not been fully used in 3d bioprinting, but yes. Soon it will reach its full
efficiency. We might even be able to solve the complexity of creating a heart and other organs.
Till now we have successfully managed to make miniature organs, different tissues, and blood
cells. The biggest challenge they faced was keeping the blood flowing through the network of
arteries.
We strongly believe through this new approach of tissue engineering along with Machine
learning, would definitely solve the problem of shortage of organs for transplants, and people
don’t have to be on the waiting list anymore.

f) Preliminary Work/Survey

3D Bioprinting uses 3D printing-like technologies to fabricate biomedical parts that consist of

biomaterials, growth factors, and cells with the aim of supremely emulating natural tissue
characteristics The fabrication process of bioprinting is similar to 3D printing that deposits
materials layer by layer. In this additive process it adds materials gradually until the whole part is
completed. With the help of bioink tissue-like structures can be created that can be used as
implants. Some of the major types of bioprinting techniques available include,
stereolithography-based, inkjet, extrusion-based and laser-assisted bioprinting. Amidst them,
extrusion-based bioprinting is the most common technique. The three extrusion-based
bioprinting processes are pneumatic dispensing ( uses air pressure), piston-driven dispensing (
uses direct force ), and screw-driven dispensing (uses rotation).

Another key element of 3D bioprinting is the bioink, it was originally introduced with the rise of
the organ printing concept. Bioinks not only guides the enclosed living cells and molecules to
build complex 3D structures but also provides an environment for controlling cell activities.
Hence, bioinks basic requirement is appropriate physical and biological properties. The physical
properties of a bioink include tunable viscosity that can be modified to different 3D bioprinting
techniques, shear-thinning rheological behavior which protects cell viability during the printing
process, acceptable printability enabling efficient fabrication of complex constructs, mild
gelation condition to minimize cell damages, and proper mechanical properties relevant for
biomedical application scenarios. In the view of biological properties, the bioink should be
non-immunogenic when used to build tissue and organ implants, bio-instructive for promoting
the adhesion and migration of residing cells, biodegradable allowing for ECM altering and
controlled release of payloads.

g) Expected Outcomes

Machine learning, an emerging technology, can immensely optimize systems through a smarter
and more effective use of products, materials and services. In the case of the 3D bioprinting
process, machine learning can offer a reduction of fabrication time, minimized cost, and
increased quality. Machine learning, in a very effective way, can improve the predicting process
conditions and optimizing process parameters. It can also be used to detect defects such as wrong
positioned cells, curved layers, and microstructure errors in a fabrication process. In addition to
that, machine learning can analyze the accuracy of fabricated bio-parts and also to design or
analyze material properties in the 3D bioprinting process. Thus, with the help of machine
learning, bio materials and bioprinting techniques can be easily developed.

Image credits:

https://ijb.whioce.com/public/journals/10/cover_article_253_en_US.png

There are multiple machine learning approaches that can be used for 3D bioprinting. In
supervised learning, computer algorithms can inspect the input and output and guess an
approximate function (also called as ML model) between them. The more input and output data
there are, the more accuracy is provided my the ML model. In contrast, in unsupervised learning,
the output is not given, the computer algorithms must figure out the output on its own. This
approach is best for revealing hidden patterns or relationships in data. Similar to supervised ML,
another approach is reinforcement learning in which both the input and output are known, and
the algorithms have to find the function between them, but through a dynamic interaction with
another test algorithm called environment. The environment rewards or punishes the algorithms
trial and error learning so that the ML model becomes more accurate in prediction by maxing the
reward.
h) Benefits to the Society

● By permitting scientists to work with real-time human tissue, it could incredibly

accelerate testing cycles, and produce more reasonable results.
● It could likewise assist with lessening the need to involve lab animals for clinical trials,
just as possibly risky preliminaries on people.
● Bioprinting could replace organ donors.
● Bioprinting could prevent cell rejection.
● The serious level of exactness and accuracy decreases the recurrence of blunders into the
model.
● The interaction can coordinate the speed of the interest where a solitary unit or a group of
units can be fabricated.
● Since 3D printing administration lessens the time and exertion of the maker to make a
model, considerably more accentuation should be possible on the examination and plan
of an item. The makers can focus on making an immaculate item as the creation process
duration is decreased. Various tests can be directed on the model before the real item is
produced. 3D printing prompts a decrease of squanders and along these lines, there is no
prerequisite of lessening, reusing, and reusing the waste materials once in a while. Also,
numerous enterprises like and other people who utilize basic parts that require testing can
utilize this 3D printing innovation to make a functioning model of the part. Because of
the serious level of exactness and accuracy, one can print even the smallest of varieties
perfectly. Hence, these are the manners in which it can help the business that at last
advantages society by either creating quality items or decreasing the cost of the items or
both.

i) Cost Benefit analysis

● 3D printing seems to diminish working room costs auxiliary to shortening system times.
While asset concentrated, 3D printed developments utilized in patients' usable
consideration offers significant downstream benefit to wellbeing frameworks.
● Tissue models can kill the requirement for creature models in drug disclosure and
corrective testing by and large just as abatement preclinical preliminary expenses.
● A 3D bioprinter, that is direct to utilize, versatile, adaptable, and accessible inside a value
scope of ~12,671.85 Indian Rupee, i.e That is super low-estimated.
● ML is an interdisciplinary subject which is a sub-field of AI and promotes low-cost
computing through algorithmic learning.
● Since trial rehearsals are tedious and exorbitant strategies, different procedures have been
applied in this field which are exact and cost effective. Lately, ML has drawn in a great
deal of examination interest in 3D printing because of its prevalent properties.
 j) Future Scope

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https://g.foolcdn.com/image/?url=https%3A%2F%2Fg.foolcdn.com%2Feditorial%2Fimages%2F628450%2Fbiopri
nting-stocks-3d-bioprinting-stocks-list-to-buy-best-2021.jpg&w=1200&h=630&op=resize

Say in robotics, quantum computing, cybersecurity, pharmacy, or biotechnology, machine

learning has its effect in every domain. The emerging scope of Machine Learning involves less
work for humans and gives the best result at minimum cost and time. And in the coming years,
Machine Learning will definitely provide more efficient results in every single field. And also,
the use of Machine Learning is at the scratch level itself, while creating the 3d bioprinters.
During additive manufacturing, we can detect errors or defects at a microstructural level. Also,
we can increase the efficiency of the machine, by incorporating a machine learning model and
training it with a set of datasets.
Soon, we would be able to rectify the complications we are facing in producing vital organs. And
also, will be able to increase the success rates of these organs. Also, with every new prediction as
an outcome, the success rate increases. In the near future, Machine Learning will make a huge
impact in the field of science, by finding new drugs, eradicating all the conventional methods,
and bringing in new, fast and cost-efficient methods.
 k) SWOC Analysis/ Limitations
The machine learning model has to go through a huge amount of historical data. Even if we train
the machine learning model, it's still a machine, there may be times when it cannot give us a
proper reason as to why it has given us a particular outcome. The input we provide should be
clear and crisp, in order for it to grasp and give us the best outcome.
Even if Machine Learning has limitations, it still doesn’t stop there. Machine Learning mainly
gives outcomes on what we feed the model with, if you feed it with poor inputs, we would have
bad/unclear outcomes. Also, as we know the outcomes are in the form of mathematical
interpretations, not everyone can understand. A person who is good at handling statistical data is
the right person for this. This problem is bought in because a machine is basically a device, we
cannot feed it with texts, it needs everything in numbers, we need to convert texts to numbers,
and the outcome it gives is in the same format as what we feed it. Just hoping maybe one day, we
can break down this complexity or find an easier way to learn it.

l) References
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684753/#B28
[2] Yu, Chunling & Jiang, Jingchao. (2020). A Perspective on Using Machine Learning in 3D
Bioprinting. 6. 1-8. 10.18063/ijb.v6i1.253.
[3] Jooyoung Lee et al 2020 Biofabrication 12 035018
[4] Aditya Menon, Barnabás Póczos, Adam W. Feinberg, and Newell R. Washburn.3D Printing
and Additive Manufacturing.Aug 2019.181-189.http://doi.org/10.1089/3dp.2018.0088
[5] https://www.sciencedirect.com/science/article/pii/S2238785421006670