Three Dimensional Bioprinting: Emerging materials,

technique and applications in drug delivery and biomedical

fields.

A CAPSTONE PROJECT REPORT

Submitted To The
Department of Pharmaceutical Sciences
In Partial Fulfillment of
Requirement for the

Degree of

Bachelor of Pharmacy
Submitted By
SOYEB KHAN (12112163)
COURSE CODE: BP706PS
Under the Guidance of
DR. MOHHAMMAD RAMZAN
Associate Professor

School of Pharmaceutical Science

Lovely Professional University,
Phagwara, Punjab-144411
 STATEMENT BY THE CANDIDATE

I hereby declare that this written submission, part of my project report titled " Three Dimensional
Bioprinting: Emerging materials, technique and applications in drug delivery and
biomedical field," reflects myoriginal thoughts articulated in my own language. In instances
where I have incorporated the ideas or expressions of others, I have properly cited and referenced
the original sources. Furthermore, I affirm my adherence to the principles of academic honesty and
integrity, ensuring that I have not misrepresented, fabricated, or falsified any ideas, data, facts, or
sources in this submission. I acknowledge that any breach of these principles may result in
disciplinary measures from the institution and could also lead to legal repercussions from the
original sources that have not been appropriately cited or from whom permission has not been
obtained when necessary.

I have reviewed any relevant patents concerning active pharmaceutical ingredients (API),
processes, products, methods, and equipment to ensure that my work does not infringe upon
existing patents.

This thesis contains information generated through my experimental work conducted at the
institute. I take full responsibility for its authenticity.

Forwarded Through Soyeb Khan

Dr. Mohhammad Ramzan
Professor
School of Pharmaceutical Science,
Lovely Professional University, Punjab.

2
 CERTIFICATE BY SUPERVISOR

I hereby confirm that the project report titled " Three Dimensional Bioprinting:
Emerging materials, technique and applications in drug delivery and biomedical field"
has been conducted by Soyeb Khan under my guidance. I certify that this work is his
genuine effort. The research presented is original and has not been submitted for any
academic degree at this or any other University.

Date: 29th November 2024 Dr. Mohhammad Ramzan

Place: School of Pharmaceutical Science, Professor
Professor Lovely Professional University, Punjab
 CERTIFICATE BY SCHOOL

This is to certify that the project report titled " Three Dimensional Bioprinting: Emerging materials,
technique and applications in drug delivery and biomedical field " has been conducted by Soyeb Khan
under the supervision of Dr. Mohhammad Ramzan at the School of Pharmaceutical Sciences, Lovely
Professional University, Punjab.

HOD

School of Pharmaceutical Sciences,

Lovely Professional University, Punjab

4
5
 ACKNOWLEDGMENT

The realization of a long-held aspiration has finally materialized. I have successfully completed
my project, and it is now imperative to extend my heartfelt gratitude to all those who have
contributed, whether directly or indirectly, to my journey. I offer my deepest thanks to the divine,
who has been a constant source of strength throughout my life.
The first individual who comes to mind is my esteemed Professor, Dr. Mohammad Ramzan,
Assistant Professor at the School of Pharmaceutical Sciences, Lovely Professional University. His
guidance has been instrumental in shaping my innovative ideas, and words cannot adequately
convey his dedication and support.
I would also like to express my sincere appreciation to Dr. Monica Gulati, Senior Dean of the
School of Pharmaceutical Sciences at Lovely Professional University, for her unwavering support
throughout the project’s completion.

Furthermore, I am deeply grateful to my parents and friends for their companionship and
encouragement during this endeavor.
This project is dedicated to my parents and to the divine. Their encouragement and patience have
been pivotal in my journey thus far. My words fall short of capturing the depth of my emotions,
including my profound gratitude towards my loving parents, family members, and relatives, who
have sacrificed for my future. Their boundless love, continuous inspiration, and support have
empowered me to embrace challenges with courage.

Date: 29th November 2024

Place: Lovely Professional University Soyeb Khan

Phagwara (Punjab) 144001

6
 INDEX

S. No. Title Page No.

1. INTRODUCTION 8

2 REVIEW OF LITERATURE
2.1 OVERVIEW OF 3D BIO PRINTING 9

2.2 MATERIAL DESIGN FOR 3D BIO PRINTING 9

2.3 DRUG DELIVERY MECHANISMS IN BIO PRINTED 10

CONSTRUCTS
2.4 INNOVATIONS IN 3D BIO PRINTING FOR DRUG 12
DELIVERY
3 CONCLUSION
4 REFERENCES

7
 [1]
INTRODUCTION

The convergence of 3D bioprinting and drug delivery systems signifies a groundbreaking advancement
in contemporary medicine, heralding a new era of therapeutic possibilities. This innovative domain
seamlessly integrates state-of-the-art technologies with biological sciences, providing unparalleled
accuracy in the design and administration of therapeutic interventions. By leveraging the capabilities of 3D
bioprinting, researchers and clinicians can create highly customized solutions that cater to the unique needs
of individual patients, thereby enhancing the efficacy of treatments. Central to this progress is the creation
of sophisticated bioprinting materials, which play a pivotal role in the success of these advanced systems.
These materials encompass a diverse range of natural biomolecules, such as collagen and alginate, known
for their biocompatibility and ability to support cell growth.

Additionally, synthetic polymers like poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol
(PEG) are utilized, as they can be engineered to possess specific properties that enhance cell compatibility,
maintain structural integrity, and facilitate effective drug release. The bioprinting process itself involves
the meticulous layer-by-layer construction of intricate structures, often incorporating therapeutic agents
directly within the matrix. This method allows for the precise spatial arrangement of cells and drugs,
optimizing their interactions and enhancing therapeutic outcomes. This fusion of scientific inquiry and
technological advancement seeks to address critical issues that have long plagued traditional drug delivery
methods, including drug stability, targeted delivery, and controlled release mechanisms. By overcoming
these challenges, 3D bioprinting and drug delivery systems can significantly improve the therapeutic index
of various treatments. The prospective applications of this technology are vast and varied, encompassing
several key areas:

• Personalized Medicine: This approach utilizes patient-specific scaffolds for localized

treatment, ensuring that therapies are tailored to the individual’s unique biological makeup.
By creating customized drug delivery systems, healthcare providers can enhance treatment
efficacy while minimizing side effects.

• Cancer Therapy: The ability to enable precise administration of drug doses directly at
tumor sites represents a significant advancement in oncology. This targeted approach not
only maximizes the therapeutic effect on cancer cells but also reduces the impact on
surrounding healthy tissues, thereby improving patient outcomes.
• Regenerative Medicine: The integration of drug delivery with tissue scaffolding opens
new avenues for repairing or replacing damaged tissues and organs. By delivering growth
factors or other therapeutic agents in conjunction with bioprinted scaffolds, it is possible
to promote tissue regeneration and healing in a controlled manner.

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OVERVIEW OF 3D BIOPRINTING
3D bioprinting is a cutting-edge technology that blends principles of biology, materials science,
and engineering to fabricate complex biological structures. It allows the precise layer-by-layer
assembly of biomaterials, cells, and therapeutic agents, creating constructs that mimic the
architecture and functionality of natural tissues. This technology has gained significant attention
in fields like regenerative medicine, tissue engineering, and drug delivery due to its ability to
produce customized and biologically relevant structures.
At its core, 3D bioprinting leverages computer-aided design (CAD) and advanced printing
techniques to achieve high precision and reproducibility. Several bioprinting techniques are
employed depending on the application and material properties. Inkjet-based bioprinting, for
instance, involves the deposition of bio-ink droplets onto a substrate, making it suitable for high-
throughput applications like drug testing. Extrusion-based bioprinting, on the other hand, uses
continuous extrusion of bio-inks to fabricate large, complex scaffolds, ideal for tissue regeneration.
Laser-assisted bioprinting provides unparalleled precision by using laser pulses to deposit
biomaterials, making it particularly useful for high-resolution constructs in localized drug delivery.
The success of 3D bioprinting largely depends on its key components, particularly bio-inks and
bioprinters. Bio-inks are typically composed of natural or synthetic polymers, with or without
embedded cells or drugs, to achieve desired structural and biological properties. Natural polymers
like alginate and collagen offer excellent biocompatibility, while synthetic polymers such as PEG
and PLGA allow customization for specific mechanical and degradation requirements. Composite
materials, which combine the strengths of both, are increasingly used to overcome the limitations
of single-material systems. The bioprinters themselves integrate sophisticated hardware and
software to ensure precise deposition, resolution, and scalability of the constructs. With its
versatility and ability to bridge the gap between biological sciences and engineering, 3D
bioprinting continues to revolutionize drug delivery systems, enabling the development of patient-
specific solutions with controlled release properties. Its potential for innovation extends beyond
healthcare, offering transformative applications in various scientific domains.

MATERIAL DESIGN FOR 3D BIOPRINTING

The success of 3D bioprinting relies heavily on the careful selection and design of materials, often
referred to as bio-inks, which must meet stringent criteria to ensure functionality and
biocompatibility. These materials serve as the structural and functional foundation for bioprinted
constructs, influencing the mechanical properties, cellular interactions, and drug delivery
capabilities of the final product. A well-designed bio-ink should exhibit properties such as
printability, structural stability, and the ability to encapsulate and release therapeutic agents in a
controlled manner.

Bio-inks can be broadly classified into three categories: natural polymers, synthetic polymers,
and composite materials. Natural polymers, such as alginate, collagen, and gelatin, are widely
used for their excellent biocompatibility and ability to mimic the extracellular matrix. These
materials provide a conducive environment for cellular growth and proliferation. However, they
often lack the mechanical strength required for certain applications, making them less suitable for
load-bearing structures. Synthetic polymers like poly(ethylene glycol) (PEG), poly(lactic-co-
glycolic acid) (PLGA), and poly caprolactone (PCL) address this limitation by offering
9
customizable mechanical and degradation properties. They can be engineered to provide precise
control over structural integrity and degradation rates, making them ideal for drug delivery systems
and scaffolds requiring prolonged stability.

Composite materials combine the strengths of both natural and synthetic polymers to create bio-
inks with enhanced properties. These stimuli-responsive materials enable the creation of smart
drug delivery systems that release therapeutics in a controlled and targeted manner. The design of
bio- inks also takes into account the specific requirements of the bioprinting process. For instance,
the viscosity of the material must be optimized to ensure smooth extrusion or deposition during
printing while maintaining the structural fidelity of the construct. Crosslinking mechanisms, such
as ionic, thermal, or photo-crosslinking, are often employed to stabilize the printed structure. These
mechanisms allow for rapid solidification after deposition, enabling the construct to retain its shape
and functionality.

Material design in 3D bioprinting is further driven by advancements in computational modeling

and machine learning, which help optimize bio-ink formulations for specific applications. For
example, computational tools can predict the printability and degradation behavior of a material,
reducing trial-and-error experimentation. This approach facilitates the development of tailored bio-
inks that meet the unique demands of applications such as drug delivery, tissue engineering, and
organ printing.

Ultimately, the thoughtful design of materials for 3D bioprinting not only enhances the functional
capabilities of bioprinted constructs but also drives innovation in biomedical research. By
addressing the challenges of biocompatibility, mechanical stability, and drug delivery efficiency,
material design plays a pivotal role in realizing the full potential of 3D bioprinting in medicine and
beyond.

DRUG DELIVERY MECHANISMS IN BIOPRINTED CONSTRUCTS

Bioprinted constructs provide a highly customizable platform for controlled drug delivery,
offering spatial precision, temporal control, and the ability to integrate multiple therapeutic agents
within a single structure. These mechanisms are engineered based on material properties, construct
architecture, and specific therapeutic requirements. By leveraging the unique capabilities of 3D
bioprinting, researchers can design drug delivery systems that release drugs in a targeted,
sustained, or stimuli-responsive manner, improving therapeutic outcomes and reducing side
effects.

1. CONTROLLED RELEASE MECHANISMS

Bioprinted constructs facilitate controlled drug release by regulating how drugs diffuse through
the material matrix or degrade within it. Key controlled release mechanisms include:

1.1 Diffusion-Controlled Release

In this mechanism, drugs diffuse out of the bioprinted scaffold into the surrounding tissue. The
rate of release depends on the material's porosity, the size of the drug molecules, and the gradient
of drug concentration. Porous hydrogels and polymeric matrices are commonly used to achieve
sustained release over time, ensuring a steady therapeutic effect.

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1.2 Degradation-Controlled Release

Here, the material itself degrades over time, releasing the embedded drugs. Biodegradable
polymers like PLGA and PCL are ideal for this approach, as their degradation can be tuned by
modifying their composition. This method is particularly useful for long-term therapies, where
drugs need to be released over weeks or months.

1.3 Swelling-Controlled Release

Certain materials swell in the presence of water or bodily fluids, increasing their porosity and
allowing drug molecules to diffuse out. Hydrogels, such as alginate or gelatin, are often used for
this purpose due to their high water absorption capacity and biocompatibility.

2. STIMULI-RESPONSIVE DRUG DELIVERY

Stimuli-responsive systems are designed to release drugs in response to specific triggers, such as
changes in pH, temperature, or external signals like light or ultrasound. These "smart" systems
enhance targeted delivery and reduce off-target effects.

2.1 pH-Responsive Systems

These constructs are tailored to release drugs in environments with specific pH levels, such as the
acidic microenvironment of a tumor or the neutral pH of healthy tissues. Materials like chitosan
and polyacrylic acid are commonly used for pH-responsive systems.

2.2 Temperatures-Responsive Systems

Thermo-responsive materials release drugs when exposed to a certain temperature range. For
example, poly (N-isopropyl acrylamide) (PNIPAAm) hydrogels can transition between solid and
liquid phases, enabling controlled drug release.

2.3 Light or Ultrasound-Responsive Systems

Light-sensitive materials use photochemical reactions to release drugs on demand, while
ultrasound-sensitive systems leverage acoustic waves to disrupt the construct and trigger drug
release. These mechanisms allow precise spatial and temporal control over drug delivery.

3. MULTI-DRUG DELIVERY SYSTEMS

Bioprinted constructs can be designed to deliver multiple drugs simultaneously or sequentially.
This is particularly beneficial for complex conditions like cancer or infections, where different
drugs target various pathways or pathogens. Multi-material bioprinting enables the creation of
layers or compartments, each loaded with a specific drug, allowing distinct release profiles for
each therapeutic agent.

4. ROLE OF 3D ARCHITECTURE IN DRUG DELIVERY

The 3D architecture of bioprinted constructs significantly impacts drug delivery efficiency. By
designing constructs with specific porosities, micro channels, or gradients, researchers can control
the diffusion and localization of drugs. For example:
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 • Porous scaffolds enhance nutrient and drug diffusion.
• Layered structures allow sequential drug release.
• Microchannels can direct drugs to specific regions, enabling targeted therapies.

5. APPLICATIONS IN DRUG DELIVERY

5.1 Tumor-Targeted Drug Delivery

Bioprinted scaffolds can localize anti-cancer drugs at tumor sites, minimizing systemic toxicity.
Constructs designed with pH-sensitive materials can release chemotherapeutics in the acidic
tumor microenvironment.

5.2 Wound Healing

Bioprinted skin patches loaded with antibiotics or growth factors can promote faster wound healing
and prevent infections. Hydrogels are often used for their moisture-retaining and biocompatible
properties.
5.3 Regenerative Medicine
Bioprinted scaffolds used in tissue engineering often incorporate growth factors or drugs to
enhance cell proliferation and differentiation, facilitating tissue repair and regeneration.

6. CHALLENGES AND OPPORTUNITIES

While bioprinted drug delivery systems hold immense promise, challenges such as ensuring
uniform drug distribution, achieving precise release profiles, and maintaining drug stability within
the constructs remain. Advances in material science, bioprinting technology, and computational
modeling are key to overcoming these hurdles and unlocking the full potential of bioprinted drug
delivery platforms.
In summary, bioprinted constructs are redefining drug delivery by enabling unparalleled control
over therapeutic release mechanisms. As research progresses, these systems are poised to address
complex medical challenges and revolutionize precision medicine.

INNOVATIONS IN 3D BIOPRINTING FOR DRUG DELIVERY

The field of 3D bioprinting has made remarkable strides in the development of advanced drug
delivery systems, introducing new methods to enhance the precision, efficiency, and
personalization of treatments. These innovations are largely driven by advancements in material
design, printing technologies, and the integration of functional biomaterials, creating opportunities
to improve patient outcomes in areas like cancer treatment, wound healing, and regenerative
medicine. Here are some key innovations shaping the future of 3D bioprinting in drug delivery:

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1. Advanced Bio-Ink Development
The creation of smart bio-inks has been a major innovation in 3D bioprinting for drug delivery.
These inks are designed not only to support cell growth but also to respond to external stimuli such
as temperature, pH, light, or magnetic fields, enabling stimuli-responsive drug release.

• Stimuli-Responsive Materials: New bio-inks, such as thermo responsive polymers (e.g.,

PNIPAAm) or pH-sensitive materials (e.g., chitosan), enable drugs to be released only
when triggered by specific conditions, such as acidic tumor environments or elevated body
temperature.
• Nanomaterial Incorporation: The addition of nanoparticles (e.g., liposomes, gold
nanoparticles) to bio-inks enhances drug encapsulation and offers the potential for targeted
drug delivery, improving drug stability and release control.

2. Multi-Drug Delivery Systems

The ability to deliver multiple drugs simultaneously or sequentially within a single bioprinted
construct is a groundbreaking innovation. By integrating multi-material 3D printing technologies,
bioprinted scaffolds can be designed with compartments that release different drugs at varying
rates, creating highly efficient polytherapy systems.

• Layered Constructs for Sequential Release: Researchers can print scaffolds with
different drug-loaded layers that release drugs at staggered intervals, allowing for
combination therapies or for drugs that need to be released at different stages of treatment.
• Spatially Controlled Drug Release: Multi-compartment systems within a single scaffold
enable localized delivery of drugs to specific areas of a tumor or site of injury, improving
therapeutic efficacy while minimizing systemic side effects.

3. Personalized Drug Delivery

One of the most exciting innovations in 3D bioprinting is its ability to create patient-specific drug
delivery systems. Advances in 3D scanning and imaging technologies enable the creation of
personalized drug delivery devices tailored to an individual’s anatomy and disease profile.

• Customized Scaffolds for Targeted Therapy: Using patient imaging data (e.g., MRI or
CT scans), 3D bioprinting can produce scaffolds that fit precisely to a patient's tissue or
organ, allowing for the targeted release of drugs directly to affected areas, such as tumors
or damaged tissues.
• Organ-on-a-Chip Models: For drug testing and optimization, bioprinted organ-on-a-
chip models that replicate human tissue behavior are being used to evaluate drug
interactions before clinical use. These models provide a more accurate prediction of drug
efficacy and toxicity in humans, reducing the reliance on animal models.

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4. Bioprinted Microstructures for Controlled Release

Innovations in bioprinted micro- and nano-structured materials are enabling the creation of
highly sophisticated drug delivery systems. By manipulating the scale and architecture of the
printed materials, scientists can control the rate and pattern of drug release in ways that were
previously impossible.

• Micro-Channel Systems: Bioprinted micro-channels can direct drug flow within a

scaffold, allowing for spatially controlled drug release. This is particularly useful for
systems that require precision, such as implantable devices for localized cancer treatment
or chronic disease management.
• Gradient Release Systems: 3D bioprinting also allows the creation of scaffolds with drug
release gradients, where drug concentration varies across the construct. This approach is
particularly useful for delivering drugs over an extended period and for treating conditions
where continuous, low-dose release is necessary.

5. 3D Bioprinted Hydrogel Scaffolds for Drug Delivery

Hydrogels have become a popular material in 3D bioprinting for their ability to retain large
amounts of water while maintaining their structural integrity. These properties make hydrogels
ideal for drug delivery applications, particularly in wound healing and tissue regeneration.

• Biocompatible Hydrogels: New hydrogel formulations are being developed that not only
support drug encapsulation but also promote tissue regeneration. For example, hydrogels
loaded with growth factors or stem cells can be bioprinted to deliver both drugs and
regenerative agents simultaneously, accelerating tissue repair.
• Injectable Hydrogel Systems: Advances in injectable hydrogels are enabling the
creation of minimally invasive drug delivery systems that can be injected into the body and
then solidify at the target site, releasing drugs in a controlled manner over time.

6. 3D Bioprinted Drug-Eluting Implants

The development of bioprinted drug-eluting implants represents a significant leap in

implantable drug delivery devices. These implants can be custom-designed to deliver drugs
directly to a specific site over a prolonged period, providing a constant drug concentration that
helps avoid peaks and valleys in drug efficacy.

• Orthopedic and Dental Applications: In orthopedic and dental applications, 3D

bioprinted implants loaded with antibiotics or anti-inflammatory drugs can be implanted
directly into bone or tissue to treat infections or promote healing.
• Cancer Therapy: Bioprinted implants containing anti-cancer agents can be inserted into
or around tumor sites, offering localized and sustained release to minimize damage to
surrounding healthy tissue.

7. Bioprinting with Integrated Vascular Networks for Drug Delivery

One of the most exciting areas of research in 3D bioprinting is the creation of vascularized drug
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delivery systems. Since effective drug delivery depends on the ability to reach target tissues via
the bloodstream, integrating microvascular networks into bioprinted scaffolds is crucial for
improving the efficiency of drug delivery, especially for thick tissues like tumors or organs.

• Vascularized Tumor Models: By printing vascular networks within tumor scaffolds,

researchers can create more realistic models for cancer drug testing and improve the
delivery of therapeutic agents to solid tumors.
• Organ Regeneration: Vascular networks are also critical for regenerating large organs,
allowing nutrients and drugs to be delivered to cells deep within the tissue.

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 [3]

CONCLUSION

3D bioprinting has emerged as a transformative technology in the field of drug delivery, offering
the potential to overcome many limitations of traditional drug delivery systems. By leveraging
precise control over material deposition and structure, bioprinting enables the creation of
sophisticated, personalized drug delivery platforms that can release therapeutic agents in a
controlled, targeted, and sustained manner. The integration of innovative biomaterials, multi- drug
delivery systems, and stimuli-responsive designs has significantly advanced the ability to
customize drug release profiles, improve treatment efficacy, and minimize side effects. As a result,
3D bioprinting is poised to revolutionize personalized medicine, tissue regeneration, and drug
testing.

Despite its remarkable potential, several challenges remain, including the biocompatibility of
materials, the scalability of production, and the complexity of integrating vascularization into
larger constructs. Additionally, regulatory hurdles and the need for standardization of bioprinted
drug delivery systems still pose significant barriers to widespread clinical adoption. Nevertheless,
rapid advances in material science, bioprinting techniques, and computational modeling are
steadily addressing these challenges, bringing the vision of 3D bioprinted drug delivery systems
closer to reality.

The future of 3D bioprinting in drug delivery is bright, with continuous innovations set to improve
patient outcomes through more targeted, effective, and personalized therapies. As research
continues to evolve, 3D bioprinting will likely become a cornerstone of modern healthcare,
enhancing both drug delivery systems and the field of regenerative medicine.

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 [4]
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