Page 371 - IJB-9-3

International Journal of Bioprinting 3D-printed anistropic meniscus

joint stabilization and cartilage protection [62,63] . In a biomimetic reconstruction of heterogeneous meniscus is
study performed by Moyer et al., the medial-posterior inevitable in TEM.
region was confirmed to have the lowest elastic friction 3D printing, a widely used technique in medical fields
value through indentation, which corresponded to the with the advantages of high efficiency and customizability,
[64]
low GAG intensity . Gonzalesz-leon et al. regionally provides a novel strategy to construct TEM . 3D-printed
[73]
studied meniscus biomechanics in a minipig model that is TEM has achieved eye-catching results. In this review,
biologically similar to a human meniscus. In their research, we systematically summarize the strategies utilized to
the radial Young’s modulus was not significantly different fabricate heterogeneous 3D-printed TEM, focusing on the
between bilateral menisci but was remarkably higher in the manufacturing technique, biomaterial combination, 3D
anterior region than in the posterior region, which may bioprinting, surface functionalization, growth factors, and
explain the relative susceptibility to longitudinal tears of bioreactors.
the posterior meniscus. In addition, the posterior region
was found to have the highest tensile strength in the medial 3.1. Advanced and biomimetic biofabrication
meniscus, whereas no significant difference was found in strategies applied for heterogeneous 3D-printed
the lateral meniscus . scaffolds
[65]
Furthermore, considering that circumferential fibers Diverse biostructures exist in the natural world that
predominate in the meniscus, biomechanical heterogeneity perform their own duties. For instance, the claws
is also exhibited by tensile strength. Research has shown of lobsters, rich in well-organized layers of chitosan
that the circumferential tensile modulus, 75 – 150 MPa, with anisotropic Bouligand structures inlaid, not only
is approximately 10 times higher than the radial tensile exhibit powerful mechanisms but also exhibit high
modulus [42,66] . Excellent tensile strength buffers the loading energy dissipation and impact resistance because of
circumferentially applied to the meniscus and radially the long-term evolution of the structure [74] (Figure 4).
resists outward dislocation. This reminds us that a specific structure is required
The fluid phase is also worthy of attention as another to realize the optimum microenvironment, which is
aspect of anisotropy. The hydraulic permeability ranges also an enlightenment to fabricate TEM with a highly
4
[67]
−14
from 10 −15 to 10 m /N s for confined compression heterogeneous structure.
[68]
4
−15
and 10 to 10 −15 m /N s for indentation . This To realize specific biomechanical heterogeneity in the
hydraulic permeability is of great importance in high meniscus through structural design, Yang et al. combined
levels of load bearing and is also influenced by the fiber a 3D printing technique with carbon nanotubes (CNTs) .
[74]
network. Heterogeneity is also found circumferentially CNTs have great potential in fields such as nanomaterials,
and radially between the pars intermedia and posterior due to their excellent mechanical properties. In their
[69]
horn in the fluid phase . Biomechanical heterogeneity research, with the assistance of electrically assisted additive
plays an essential role in functionalizing the meniscus manufacturing/3D printing technology, a reinforcement
and stabilizing the knee joint. This biomechanical architecture was fabricated with anisotropic layers of
heterogeneity results from the anisotropic alignment aligned surface-modified multi-walled carbon nanotubes
of collagen fibers as well as other ECM components. In (MWCNT-S). Mechanical testing demonstrated that the
return, the variant biomechanical microenvironment augmented circumferential tensile strength improved
also influences cells and the ECM both morphologically energy dissipation and compression resistance regulated
and biochemically. A 5% of biaxial tensile strain at 0.5 Hz through rotation angles, providing a novel method to
increased protein synthesis but did not influence the realize the biomimetic properties of TEM. In addition,
secretion of proteoglycan , while uniaxial tensile strain Bahcecioglu et al. designed a poly(ε-caprolactone) (PCL)/
[70]
promoted COL-1 expression in inner meniscal cells but hydrogel composite scaffold that mimics the structural
[71]
not in outer cells . The precise biomechanical properties organization, biochemistry, and anatomy of the meniscus .
[75]
as well as the interaction between cells and the ECM are The compression strength (380 ± 40 kPa) and tensile
not fully understood, requiring more research on this modulus (18.2 ± 0.9 MPa) were significantly increased
topic. The heterogeneity of the meniscus is summarized by the circumferential collagen strands. Meanwhile, the
in Table 1. proliferation and migration of fibrochondrocytes are
also promoted by circumferentially aligned PCL fibers.
3. 3D printing of heterogeneous TEM Such research has shown the importance of biomimetic

As discussed above, the meniscus shows high heterogeneity design in tissue engineering, particularly for tissues with
in cell type, ECM, and biomechanisms [47,54] . Therefore, mechanical heterogeneity, such as menisci.

Volume 9 Issue 3 (2023) 363 https://doi.org/10.18063/ijb.693