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

the tissues are lyophilized with an instrument, followed Therefore, the creation and application of dECM-
by crushing into a powder with a pestle. The final dECM based bioinks have become a significant focus of research.
powder is then dissolved and digested in pepsin or urea These bioinks have demonstrated effective implementation
solution to form a gel for 3D bioprinting. 8,140 Figure 4 in numerous 3D bioprinting applications to produce
illustrates the decellularization of native heart and cartilage tissue and organ substitutes. In this section, we outline
tissues into biocompatible bioinks. the progress and various applications of dECM-based
bioinks, specifically within the field of 3D bioprinting of
Enhancing the functionality of dECM in 3D printing to musculoskeletal tissues.
promote cell function and regeneration involves modifying
the dECM bioink to enhance its mechanical strength and 6.1. Heart tissue
biological activity. This is a primary focus in current 3D The heart is a sophisticated organ with a complex structure
bioprinting research, typically achieved through chemical and regular ejection. In recent years, there has been a
and biological crosslinking methods. Many studies have yearly increase in the incidence of heart attacks and heart
combined dECM bioinks with polymers, such as PCL, failure, significantly affecting patients’ quality of life.
polylactic acid-co-glycolic acid (PLGA), poly-L-lactic Due to the heart’s considerable mechanical strength and
acid (PLLA), and gelatin methacryloyl (GelMA), to create elasticity, traditional surgical treatments often struggle to
bioinks with adjustable mechanical properties, strength, fully restore it to its original state. Therefore, TE and 3D
and structural stability. 132,137,141,142 In a recent study, bioprinting have become the focus of cardiac regeneration,
researchers prepared a bioink composed of polyvinyl as they offer new avenues for repairing damaged
28,144–146
alcohol (PVA) and dECM (PVA/dECM) for meniscal hearts.
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repair. The results indicated an elastic modulus of 0.49 MPa Pati et al. first investigated decellularized heart
and a stress limit of 2.9 MPa. Compared with traditional extracellular matrix (hdECM) hydrogels as a 3D bioprinting
dECM bioinks, the bioink composition exhibited superior bioink that can be printed without a supporting framework.
mechanical properties and printability. GFs (e.g., The expression levels of cardiomyocyte-specific genes, such
137
vascular endothelial growth factor [VEGF]) are added to as fast myosin heavy chain (Myh6) and α-actin (Actn1),
dECM bioinks to enhance cell adhesion and migration, validated the positive effect of the hdECM construct on the
creating an ideal environment for cell proliferation and functional maturation of myoblasts (Figure 5A). However,
differentiation. 36,132 In another study, infrapatellar fat pad due to the inadequate mechanical properties of the
adipose-derived stem cells (IPFP-ADSCs) were extracted, dECM construct for heart tissue applications, researchers
and decellularized cartilage ECM (dcECM) was isolated. have employed chemical crosslinking and polymer
These were then combined with a temperature-responsive blending to enhance the mechanical properties of dECM
120,147,148
hydrogel to create a bioink. Utilizing this 3D dcECM in bioinks. Jang et al. explored the curing of hdECM
bioinks by vitamin B2- and thermal gelation-induced
combination with an IPFP-ADSC-loaded scaffold has been UV-A (UVA)-crosslinking. The findings demonstrated
demonstrated to foster an optimal setting for stem cell that the hardness of the construct was significantly
proliferation and promote chondrogenic differentiation. enhanced by vitamin B2 and UVA irradiation, resulting in
This approach significantly enhanced the effectiveness of a mechanical strength (15.74 kPa) similar to that of actual
repairing cartilage defects in rabbits. 143 heart tissue (10–15 kPa) (Figure 5B). Based on these
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results, researchers created a 3D-printed pre-vascularized
6. Application of decellularized stem cell patch for cardiac repair using dECM bioink
extracellular matrix-based bioinks in the loaded with stem cells. In a rat myocardial infarction
bioprinting of musculoskeletal tissue model, it was observed that this patch facilitated the
growth of new muscles and capillaries, thereby enhancing
The morphogenetic factors, cytokines, and GFs in dECM cardiac function (Figure 5C). Yu et al. used GelMA and
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have important functions in dynamic tissue remodeling. dECM-based bioinks in DLP-based bioprinting to adjust
Moreover, the unique biochemical properties of tissue- their mechanical properties. Through modulation of the
specific dECM make it a highly desirable bioink for the 3D exposure time to UV light, they were able to fabricate a
printing of organs and tissues. This technology presents an heart structure that emulated the mechanical properties of
exciting avenue for tissue and organ regeneration, allowing native heart tissue, demonstrating superior cardiomyocyte
for the reconstruction of natural tissue structures and the maturation in comparison to a collagen/GelMA hydrogel
restoration of physiological function. 116 blend with analogous mechanical properties. 68

Volume 10 Issue 5 (2024) 75 doi: 10.36922/ijb.3418