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

that the mechanical strength of dECM bioink is affected promise as an efficient platform for manufacturing
by its concentration and digestion time. Moreover, the tendon tissues. 163
mechanical strength of dECM bioink is reduced at lower
dECM concentrations and longer digestion time at 6.4. Musculoskeletal tissue interfaces
5–10 mg/mL. Researchers have also fabricated tendon The musculoskeletal interface is the transition between
structures from tendon dECM bioinks through a unique bone, cartilage, tendons, ligaments, and muscles. The
process involving piston-driven microcapillary extraction- interface is critical for load absorption or metastasis
extrusion. This process relied on precise control of and is susceptible to musculoskeletal disorders. 164,165
temperature and gelatinization time to achieve rapid gel Traditional treatments to replace or enhance interfaces
kinetics, without the need for cross-linking agents or through autologous or allogeneic tissue transplantation
scaffolds. Despite exhibiting inferior mechanical properties face challenges such as donor scarcity, disease infection,
in comparison to the native tendon tissue, the encapsulated and immune rejection. Therefore, 3D printing TE has the
fibroblasts demonstrated lineage-specific morphology. potential to become a promising and effective alternative
Additionally, it was observed that the application of for interface regeneration. 164,166,167
tendon-derived dECM bioink facilitated the process of The body’s natural ability to self-heal at the bone-
tendon-specific differentiation, subsequently promoting tendon/ligament interface is limited, posing a significant
tendon tissue regeneration. 161 clinical challenge for repairing injuries in this area. To
To enhance the printability of dECM bioink, Zhao address this issue, Liu et al. created a biomimetic composite
et al. investigated the association between the digestion scaffold that mimics the random arrangement of tendons
degree of decellularized tendon ECM (tdECM), obtained in soft tissue–bone junctions. Their research suggests
from porcine tendons, and bioink printability. The results that this scaffold can enhance the expression of cartilage
indicate that the viscosity of tdECM reduces progressively formation and osteogenesis-related genes (e.g., Jmjd1c,
as the digestion time increases. In its less digested form Kdm6b) and promote the formation of both interface
(high-viscosity slurry state), the dECM bioink exhibits bone and fibrocartilage in a rabbit model of anterior
superior shape fidelity, stacking accuracy, printability, and cruciate ligament reconstruction (Figure 7A), highlighting
cell viability compared to the over-digested dECM bioink the potential of dECM in repairing the bone-tendon
168
(low-viscosity slurry). Additionally, the researchers interface. However, the tendon-bone interface (TBI)
126
compared the performance of tdECM bioinks for 3D cell presents structural and compositional gradients through
printing using three common acidic solutions (0.5M acetic fibrocartilage transition, which has unique structural
acid, 0.1M hydrochloric acid, and 0.02M hydrochloric properties. 3D printing technology offers a promising
acid). The results revealed that tdECM hydrogels were solution to customize composite scaffolds for different
softer after hydrolysis with 0.1 M hydrochloric acid, which specific positions within this interface. 166,168,169
was conducive to the spread, proliferation, and tendon Researchers have also used MSC-loaded tdECM and
differentiation of the encapsulated stem cells. However, the bone dECM (bdECM) bioink to create a spatially graded
hydrogels would contract over time and become unstable. 127 TBI patch, which reported significantly accelerated and
166
In another study, Chae et al. used tdECM bioink promoted TBI healing in the rat chronic tear model.
containing MSCs to print implantable tendon structures Chae et al. prepared a heterogeneous structure mimicking
without a supporting frame in a gelatin granule-based TBI to treat rotator cuff (RC) injuries by using pure tdECM,
supporting bath. At in vitro maturation, tissue-specific bdECM, and hybrid bioinks (of pure tdECM and bdECM).
dECM promoted long-term preservation of cell viability After implantation, the complex RC regeneration process
and tendon production by enhancing cellular/structural was observed in vivo in real-time by non-destructive,
anisotropy. The mature 3D-printed tendon tissue structure tissue-targeted near-infrared fluorescence imaging (Figure
exhibited excellent regenerative ability after implantation 7B). The results indicate that the implant facilitates
under the skin in nude mice, and the mechanical properties efficient recuperation of shoulder motor function and
and functions of the new tendon were significantly expedites the healing process of TBI in vivo. Nonetheless,
improved. In another study, researchers proposed a new these studies are constrained by the lack of understanding
162
3D bioprinting method, using human adipose stem cell of the fundamental mechanisms and crucial signaling
(hASC)-laden tdECM bioink, to successfully manufacture pathways of ECM bioink for restoring TBI structure and
cell structures with excellent mechanical stability and function, as well as the absence of in vivo application in
complete arrangement of cells. This advancement holds large animal models. 166,167

Volume 10 Issue 5 (2024) 80 doi: 10.36922/ijb.3418