Page 349 - IJB-10-5

International Journal of Bioprinting Printing organoids in peptide matrices

1. Introduction vitro is challenged by the involvement of multiple cell
types and their organized 3D architecture. Like normal
Colorectal cancer (CRC) is a prevalent type of cancer that
affects either the colon or rectum. CRC is the third most tissue, CRC organoids comprise different cell types, such
commonly diagnosed cancer worldwide and ranks as the as epithelial stem cells, enteroendocrine cells, and goblet
15
most diagnosed cancer among males and the second most cells. Epithelial stem cells in lower gut crypts (or buds)
common among females in Saudi Arabia. In 2012, CRC will proliferate and differentiate into specialized cells in
1,2
16
was reportedly the third leading cause of cancer death for higher locations outside the crypts. Overall, organoids
3
females and the fourth for males. In 2020, CRC became can emulate key tissue features in vivo, from genetic to
the second leading cause of cancer death (9.4%) after lung functional aspects, making them a potential and efficient
4
cancer (18%), with over a million newly diagnosed CRC CRC in vitro model. 17
cases and over 576,000 global mortalities. Its prevalence A standardized platform is urgently required to facilitate
is exceptionally high and keeps increasing in developing the scalability and manipulation of organoids. Bioprinting
countries. Recently, CRC has become a more common organoids represent an emerging field, characterized
5
disease among the younger population. Notably, the risk by two approaches, either bioprinting undifferentiated
of CRC disease is related to gender and age, with men pluripotent stem cells or printing differentiated stem cells
and older people at greater risk. Consequently, as the 18
6
population grows and ages, CRC may become a more or fully formed organoids. Current bioprinting methods
pressing concern. predominantly rely on permissive extracellular matrices
(ECMs), such as Matrigel and collagen I. However,
19
Hereditary and epigenetic abnormalities in colon synthetic bioinks offer promising alternatives, characterized
epithelial cells contribute to CRC. Both environmental by chemical precision, tunability, and reproducibility.
5,7
and genetic variables influence CRC development, Synthetic bioinks allow for the integration of functional
complicating its diagnosis and treatment. Various factors, chemical groups, including bioactive molecules, owing
8,9
including dietary (red meat, processed meat, alcohol to the abundance of available groups in the polymer.
20
consumption, and obesity), non-dietary (smoking, chronic Nonetheless, synthesizing polymeric synthetic bioinks is
use of non-steroidal anti-inflammatory drugs, and other often challenging and substantially costly. Additionally,
diseases), and genetic factors (polyposis or nonpolyposis crosslinking methods employed with polymeric bioinks,
syndromes), can increase the risk of CRC. 9,10
such as ultraviolet (UV) light exposure, may adversely
Addressing this major public health burden necessitates impact cell viability. Furthermore, polymeric bioinks tend
21
the urgent development of efficient medical tools and better to form covalent bonds, hindering self-healing capabilities,
therapies for CRC. Several methods have been developed and complicating remodeling unless cleavage systems
for drug screening and therapy development, such as cell are integrated.
lines, animal models, and patient xenografts on animals. 11,12
However, these models have a limited predictive capacity. Ultrashort self-assembling peptide (USAP) scaffolds
For instance, cell lines with controlled 2D morphologies are supramolecular structures governed by hydrophobic
respond differently to chemotherapy. Animal models and effects, electrostatic interactions, and stacking forces.
11
patient xenografts also have limited value in predicting The weak interactions between residues facilitate the
therapeutic results. Besides being labor-intensive and self-assembly of peptides into stable 3D nanofibers. 22–24
unsuited for high-throughput drug screening applications, Peptide-based nanofibers are relatively similar to fibers
these models pose significant physiological, genetic, and found in tissue ECMs, and they are non-immunogenic
environmental differences between humans and other with a tunable sequence, which can be utilized in several
animals. In addition, there are ethical concerns about applications. 25–31 These fiber-forming USAPs have also
13
using animals for research. 14 demonstrated potential for stem cell cultures and have
Alternatively, 3D-cultured organoids are a promising been used to generate a multicellular disease model for
32
substitute for cell lines, animal models, and patient hematological malignancies. These materials have been
xenografts to mimic human cells’ biological properties proven to recapitulate the cellular microenvironment,
in vivo while avoiding ethical dilemmas. The most maintaining the pluripotency of encapsulated stem
commonly used 3D matrix for developing CRC organoids cells in long-term cultures for over 30 passages without
is Matrigel. Nonetheless, batch-to-batch variation and major chromosomal mutations. 33–36 We have previously
non-human tissue origin limit its use, especially in developed a USAP-derived peptide containing the
developing organoids for assessing the efficiency of IKVAV sequence, a motif that contains cell-adhesive and
immunotherapy. The development of a CRC model in self-assembling properties. 37

Volume 10 Issue 5 (2024) 341 doi: 10.36922/ijb.3033