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International Journal of Bioprinting dECM bioink for 3D musculoskeletal tissue reg.

diseases affect approximately 1.71 billion people globally, which retains the main structure and functionality of
highlighting it as one of the most commonly impacted the native ECM. 24–26 In 2014, Pati et al. demonstrated the
systems in cases of trauma. Musculoskeletal disorders can bioprinting of cell-laden structures using cartilage dECM
significantly impair mobility and flexibility, resulting in bioink. The printed dECM structure exhibited desirable
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decreased fitness levels, premature retirement, and reduced cell viability and functionality. Furthermore, additional
engagement in social activities. Autologous and allogeneic studies have revealed that using dECM bioinks on various
transplantation methods have been widely used to replace tissues, such as the heart, 27,28 muscle, 29,30 cartilage, 31,32
damaged or lost musculoskeletal tissue due to trauma or pancreas, cornea , and skin , yields beneficial effects
8,33
8,34
8,35
other pathologies. However, the utilization of autografts on cell survival, growth, migration, and differentiation.
faces constraints due to issues such as donor site morbidity
and scarcity of donor tissue. Furthermore, autologous However, the decellularization and solubilization
and allogeneic transplantation methods present notable process involved in creating dECM bioink can disrupt the
drawbacks, including donor-related complications, ultrastructure of natural ECM, resulting in a significant
rejection, and the risk of infection. 1,3,4 reduction of ECM components, as well as diminished
mechanical properties and biological activity. 36,37
To address these challenges, tissue engineering (TE) Consequently, the 3D-printed constructs produced with
has garnered considerable attention for its potential to dECM bioinks exhibit inferior mechanical strength
restore the structure and function of tissues and organs compared to native musculoskeletal tissue, potentially
affected by injury or disease. Nevertheless, conventional leading to tissue integrity damage and mechanical
5–9
scaffold-based TE faces limitations in accurately replicating failure. Several studies have incorporated a range
6
the intricate microstructure and natural functions of of polymers, such as poly(ethylene-co-vinyl acetate)
biological tissues. Additionally, it lacks the ability to (PEVA) scaffolds and poly(caprolactone) (PCL), and
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identify specific spatial locations. Advancements in nanoparticles, such as hydroxyapatite and graphene
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3D bioprinting technology offer new opportunities to oxide (GO), into dECM bioinks via covalent bonds, as
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customize personalized TE scaffolds for specific affected well as hydrophobic and hydrophilic interactions. This
areas. Artificial multicellular tissues and organs can be process has improved the mechanical and biological
engineered by precisely organizing cells and biomaterials properties of the bioink, enabling it to achieve strengths
within a 3D structure. 11
comparable to natural tissue and retain a stable 3D
Bioink is a crucial component in bioprinting structure. Nevertheless, there are considerable obstacles to
technology, comprising biological substances (e.g., cells), overcome in the creation of large-scale tissues and organs.
base-building materials, and other essential components. Furthermore, the lack of validation of therapeutic effects
12
Notably, bioinks are typically composed of soft materials, in large animal models hinders the clinical application of
and they are required to have favorable biocompatibility, dECM bioinks.
high porosity, and suitable mechanical qualities, along This review begins with examining the features of dECM
with other biomechanical and biochemical features, for biomaterials, detailing the preparation strategy for these
enhancing organ function and tissue structure. 13,14 For
secure clinical application, bioinks must be biocompatible, biomaterials, and explicating the process of integrating
non-toxic to cells, and avoid triggering a strong immune them into 3D bioprintable bioinks. Following this, the
response. 15,16 Bioinks should also facilitate cell adhesion and review delves into the current progress and applications of
migration, as well as provide biochemical signals necessary dECM bioink in 3D bioprinting of musculoskeletal tissue.
for processes such as differentiation and proliferation. 17–19 Finally, the review addresses current limitations and offers
Simultaneously, bioinks should offer physical support for perspectives on potential directions for future research
cells and possess sufficient mechanical stability for high- and development.
resolution printing. 20,21 As scaffolds degrade, most of the
bioink is replaced by tissue endogenesis, while a portion of 2. Bioprinting technologies for
it can be incorporated into the host tissues. 13,22 decellularized extracellular matrix bioinks
Bioinks are normally composed of a combination of Decellularized ECM (dECM) bioink-based bioprinting
cells, extracellular matrix (ECM) proteins, and growth can be classified according to the working principle into
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factors (GFs). Pati et al. highlighted that many inkjet-based bioprinting, extrusion-based bioprinting,
biomaterials utilized in bioprinting do not fully replicate laser-assisted bioprinting (LAB), and stereolithography
the complexity of the local ECM, thereby failing to maintain apparatus (SLA)/digital light processing (DLP)-based
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natural cellular function and morphology. A highly bioprinting (Figure 2). Each strategy has its advantages,
promising alternative is decellularized ECM (dECM), disadvantages, and limitations (Table 1).
Volume 10 Issue 5 (2024) 69 doi: 10.36922/ijb.3418