Page 93 - IJB-10-5

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

In another study, researchers proposed that antimicrobial sterilization is difficult to remove and may
healthy regeneration of cartilage relies on dynamic affect cell behavior. 193,194 Addressing the immunogenicity
multidimensional microenvironment regulation. They of dECM, researchers have proposed a series of measures
developed a microenvironment-optimized scaffold by such as crosslinked antigen masking and genome editing.
115
using 3D printing inks (i.e., containing cdECM, GelMA, Nevertheless, there remains a need for extensive research
and TGF-β3-embedded microspheres) and PCL. The to explore suitable sterilization and decellularization
sustained release of TGF-β3 from the scaffold facilitates protocols tailored to different dECM bioinks.
cell migration and differentiation, promotes cartilage
formation, and demonstrates effective repair in sheep 7.2. Improvement of mechanical properties
animal models (Figure 9D). However, there is limited and printability
research on the regulatory processes and regulators of the Researchers have investigated various techniques to
cartilage repair process, with current research only focusing improve the mechanical properties of dECM bioinks,
38
on promoting cartilage differentiation and regeneration. 186 including adding support materials (e.g., PEVA scaffolds,
PCL ) or crosslinking with other molecules (e.g., vitamin
39
68
147
7. Challenges and future perspectives B2, GelMA ). Furthermore, the high miscibility
of bioinks allows for the incorporation of various
Based on the biocompatibility of dECM and similarity nanoparticles, such as hydroxyapatite, GO, cells, GFs,
40
41
131
in composition to natural tissues, dECM-based bioinks and more, into dECM bioinks through covalent bonding,
have demonstrated outstanding potential in TE of hydrophobic, and hydrophilic interactions, resulting
musculoskeletal tissues. Despite advancements in this in enhanced mechanical and biological characteristics.
field, significant challenges and limitations persist that Ongoing research has successfully achieved stable 3D
need to be addressed to facilitate their widespread structures. However, challenges still exist in addressing
clinical application. 1,140,145,187,188 issues such as vascularization, recovery of soft and hard
7.1. Optimization of decellularized extracellular interface partitions, and the precise arrangement of
matrix-based bioinks preparation process muscle fibers when repairing and regenerating large
178,195–197
Both decellularization and solubilization processes damage musculoskeletal tissue defects.
the ultrastructure of the native ECM, significantly reducing The regulation of ECM scaffold degradation remains a
its mechanical properties 92,116 and increasing its sensitivity significant challenge. Rapid degradation can lead to tissue
to toxicity and adverse reactions. 25,189 Heterologous collapse and hinder regeneration. Given the unique nature
dECM contains a variety of bioactive components. of the musculoskeletal system, implants are susceptible to
However, during the decellularization process, residual degradation and failure, especially under prolonged fatigue
cell components, nucleic acids, and decellularizing stress conditions like exercise. Ongoing research has
8
reagents may cause adverse immune reactions and successfully decreased the degradation rate of dECM by
damage the ECM ultrastructure, resulting in local/ crosslinking it with other substances. 25,178,198 Future studies
systemic reactions. 99,109,115 Conversely, maximum removal should focus on extrapolating the findings from implanted
of antigens will inevitably lead to ultrastructural damage scaffolds by assessing the degradation rate of the scaffold
of the ECM, and the inflammatory response triggered by over time for further improvement.
cell residues, within a certain range, can accelerate tissue To enhance the printability of bioinks, researchers
repair. Therefore, decellularization techniques should be can alter their rheological properties by increasing the
187
carefully selected and refined. This involves understanding dECM concentration or through chemical modification.
the composition and structural properties of ECM However, higher bioink viscosity can reduce cell activity
from different tissue sources, striking a balance between due to low oxygen permeability and high shear stress.
187
removing cellular components and preserving the ECM Therefore, some researchers have explored gelatinized
structure, and developing standardized decellularization dECM with tissue-specific rheology adjustment,
evaluation criteria. 187,190 maintaining its flexibility while ensuring printability
In addition, allogically derived dECMs must be sterilized and shape fidelity. Future research should explore new
199
to avoid adverse immune responses, but inappropriate composite materials to balance the above conflicting needs.
sterilization methods can affect the nature of dECMs, In addition to improving bioinks, some researchers have
disrupting the structure of tissues and scaffolds. 139,191 also made advancements in printing techniques and have
For example, ethylene oxide can affect the mechanical employed dynamic photoinitiation systems to enhance the
properties of dECM and is harmful to cells, while printability of low-concentration bioinks. 200
192

Volume 10 Issue 5 (2024) 85 doi: 10.36922/ijb.3418