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International Journal of Bioprinting Exosome-based bioink for bioprinting

specific structures, and the interactions between cells and and exosomes in tissue engineering, highlighting the
their extracellular matrices (ECMs) [1-3] . representative applications in bone engineering, vascular
Bioprinting has unique advantages for tissue engineering regeneration, nerve repair, and skin regeneration (Figure 1).
and regenerative medicine. Although tissue engineering At the same time, we will provide an outlook on the future
and regenerative medicine are two different research topics, research directions of bioprinting with exosomes.
they share the common goal of generating tissues or organs,
either in vitro (tissue engineering) or in vivo (regenerative 2. Exosomes
medicine). Tissue engineering and regenerative medicine 2.1. The basics of exosomes
usually require the wise combination and organization Exosomes were first discovered in sheep reticulocytes
of biomaterials, cells, and biological factors to fabricate in 1983 but were once thought to be a cellular metabolic
structures to simulate (in tissue engineering) or to replace waste [12-14] . In 2007, Valadi et al. discovered that cells could
(in regenerative medicine) the targeted tissues or organs, exchange genetic materials via RNAs in exosomes , which
[15]
thereby enabling drug testing, disease modeling, trauma ignited public interest in these new genetic information
repair, and reconstruction of tissue functions. The difficulty carriers. The 2013 Nobel Prize in Physiology or Medicine
of these technologies lies in the spatial positioning of was awarded to the discoverers of the intracellular
multiple types of cells and the deposition of different vesicular transport and control mechanism, highlighting
amounts of cells with ECMs or ECM mimics. In contrast, the importance of the studies of exosomes. Since then,
3D bioprinting can precisely regulate the proportions, the researchers have identified a variety of exosomes with
positions, and even the densities of specific types of cells different functions, and a growing number of scholars have
along with biomaterials for tissue reconstruction, fully begun to focus on the enormous potential and values of
demonstrating the advantages of bioprinting in terms of exosomes for tissue development, disease diagnosis, and
directed spatial manipulation and layer-by-layer material therapeutics.
controls . Therefore, bioprinting has been widely used,
[4]
including muscle repair , vascular regeneration , bone Exosomes are membrane vesicles released into the
[5]
[6]
injury treatment , and skin wound healing . ECM by the fusion of intracellular multi-vesicular bodies
[8]
[7]
with the cell membrane. They contain various proteins,
However, current bioprinting strategies still suffer lipids, and RNAs and are widely found in biological
from high costs, inconvenient in vitro cell culture and fluids. Exosomes have important roles in the transmission
storage, as well as problems from multiple perspectives, of materials and information between parent cells and
such as nutritional acquisition, immune rejection, and offspring cells while retaining some of the biological
maladaptation after in vivo implantation [2,9] . To address functions of the parent cells . In addition, exosomes also
[16]
these problems, diverse strategies to fabricate engineered have reduced immunogenicity, enhanced permeability,
ECMs have been developed. One of the practical solutions and good retention effects, enabling them to modulate
comes from the usage of exosomes in bioink. several complex biological activities (Figure 2) .
[17]
Exosomes are natural biological particles that transport
proteins, lipids, or genetic materials to the recipient 2.2. Current applications for exosomes [18]
cells. They come from various sources and have certain Exosomes have various biological functions (Figure 3) .
biological functions of the parent cells, demonstrating It can stimulate anti-tumor immune responses, aid
[17]
potential immune privileges. Exosomes from different angiogenesis in tumor metastasis , and play important
sources have distinct functions, which exhibit good roles in the propagation of misfolded proteins to
potential for adaptation to various situations. At the influence the development of neuroinflammation in
[19]
same time, exosomes are easier to store than cells and neurodegenerative diseases . Exosomes are also rapidly
can be easily applied to multiple systems [10,11] . Compared evolving in the fields of immunomodulation, cancer
to employing living cells, bioprinting with exosomes can therapy, and regenerative medicine.
reduce in vivo rejection, achieve targeted exosome delivery, 2.2.1. Bone tissue engineering
and overcome the regulatory and cost-effectiveness issues, In bone-related disease injuries, exosomes from
thus addressing multiple challenges in tissue engineering. mesenchymal stem cells (MSCs) can mediate cartilage
Therefore, bioprinting with exosomes is expected to repair by enhancing cell proliferation and infiltration,
advance the field of tissue engineering and regenerative reducing apoptosis, and modulating immune responses .
[20]
medicine significantly.
A series of in vivo studies showed that the administration of
In this review, we will discuss the current research exosomes from MSCs effectively reduced the production of
progresses of the combination between bioprinting pro-inflammatory cytokines in chondrocytes, increased the

Volume 9 Issue 6 (2023) 111 https://doi.org/10.36922/ijb.0114