Page 75 - v11i4

International Journal of Bioprinting Printed organoids for medicine

1. Introduction Bioprinting provides structural fidelity and reproducibility,
while organoids contribute physiological relevance
Organoid technology has emerged as a paradigm-shifting through inherent cellular differentiation programs.
innovation in biomedical research, enabling the in vitro
reconstruction of self-organized three-dimensional (3D) The strategic combination of these modalities creates a
microtissues that recapitulate structural, functional, and transformative framework for precision tissue engineering.
developmental features of native organs. Originating from On that basis, bioprinting can spatially arrange organoid-
1
breakthroughs in stem cell biology and developmental forming progenitors within vascularized scaffolds,
signaling pathways, organoids are typically derived from overcoming the diffusion-limited growth of conventional
9
induced pluripotent stem cells (iPSCs) or various tissue- organoids. Advanced bioinks functionalized with
derived cells, including adult stem cells, differentiated cells, decellularized extracellular matrix (dECM) components
or cancer cells, through spatially controlled differentiation or synthetic mimetic peptides further enhance organoid
protocols. These models have transcended the limitations maturation by replicating tissue-specific biochemical niche.
of conventional two-dimensional (2D) cultures by From a translational perspective, automated bioprinting
preserving cell polarity, cell–cell interactions, and tissue- platforms enable scalable production of standardized
specific functionality, which are critical for modeling organoid arrays, facilitating their integration into high-
organogenesis, disease progression, and therapeutic throughput drug screening pipelines and personalized
responses. Additionally, they are particularly useful in disease modeling. Recent demonstrations include
2,3
cancer research due to their ability to preserve genetic bioprinted hepatorganoids with zonated metabolic activity
and phenotypic stability, as well as their compatibility for toxicity testing, and patient-derived tumor organoids
with cryopreservation techniques. Despite being a incorporating immune cells for immunotherapy evaluation.
4,5
relatively nascent field, organoid technology continues This review examines how the strategic integration of
to face considerable challenges in both construction 3D bioprinting and organoid technologies is redefining the
and cultivation. For instance, the processes of manual frontiers in regenerative medicine and pathophysiological
passaging and cultivation are both labor-intensive and modeling. It analyzes the technological synergies that
6
financially burdensome. Organoids exhibit a lower level resolve historical limitations of both fields: the capacity of
of complexity compared to native tissues, primarily due to bioprinting to impose architectural control on organoid self-
the absence of immune and vascular systems. Meanwhile, organization and the ability of organoids to confer innate
the integration of organoids with tissue engineering biological complexity to bioprinted constructs. Emerging
scaffolds and the mass production of organoids, along with applications in multiscale vascularization, neurovascular
their application in drug development, remains a complex interface engineering, and immune-competent tumor
endeavor. In response to these challenges, researchers have modeling are critically evaluated. By delineating current
been actively exploring various biofabrication techniques, achievements and persistent challenges, this work aims
including 3D bioprinting, to enhance the development to chart a roadmap for next-generation biofabricated
of organoids. organoid systems that bridge the gap between in vitro
Concurrently, 3D bioprinting has evolved from models and clinical translation.
prototyping tools into a sophisticated biofabrication
platform, enabling precise deposition of cell-laden bioinks 2. Functional bioprinted organoids for
with microscale resolution. This technology leverages physiology and regenerative medicine
additive manufacturing principles to construct spatially Bioprinted organoids hold transformative potential for
organized tissues through layer-by-layer assembly of regenerative medicine. However, clinical translation
7,8
living cells, biomaterials, and bioactive cues. Modern requires addressing vascularization deficits, functional
bioprinting modalities, including extrusion-based, laser- maturation, and standardization of bioink formulations.
assisted bioprinting, and digital light processing systems,
offer unparalleled control over tissue architecture, 2.1. Engineered hard-tissue organoids
permitting the engineering of vascular channels, Bone defects are frequently observed in orthopedic clinical
heterogeneous cellular zonation, and mechanically graded research. Traditional treatment strategies often fall short
matrices (Figure 1). Unlike traditional organoid culture, of expectations, due to the distinctive architecture of hard
6
which relies on self-organization within undefined tissue. Bone organoids—3D tissue constructs cultivated in
matrices like Matrigel, bioprinting imposes engineered vitro—aim to mimic the structure and function of native
self-organization, a hybrid approach combining bottom– bone tissue for research and regenerative purposes. The
10
up biological principles with top–down spatial guidance. integration of cutting-edge biomaterials and additive
This synergy addresses critical gaps in organoid technology. manufacturing techniques enables the creation of 3D

Volume 11 Issue 4 (2025) 67 doi: 10.36922/IJB025190184