Page 379 - IJB-9-3

International Journal of Bioprinting 3D-printed anistropic meniscus

Table 2. (Continued)
Strategies combined Materials Methods and process In vitro/ Biological effect References
with 3D printing In vivo of heterogeneity
reconstruction
PCL The 3D-printed PCL scaffold was In vitro Hydrophilic modification of [119]
surface-etched by NaOH. scaffolds could improve the
proliferation and adhesion
of cells.
Bioreactors PCL The dynamic tension-compression In vitro and Anisotropic cell phenotype in [127]
system was designed to in vivo PCL scaffold was successfully
stimulate the biomimetic PCL achieved, and articular
scaffold biomechanically and cartilage was inspiringly
biochemically. protected
Growth factors PCL 3D-printed PCL scaffold was In vitro and BMSCs differentiated [93]
loaded with CTGF in the outer in vivo towards chondrocytes
and TGF-β3 in the inner region. and fibrochondrocytes
heterogeneously.
PCL 3D-printed PCL scaffold was In vivo After 1 year implantation in [132]
loaded with CTGF in the outer sheep knee, f12MRI showed
and TGF-β4 in the inner region. scaffold extrusion.
TEM: Tissue-engineered menisci, PCL: Poly(ε-caprolactone)

systems can quantify stresses and strains on specific tissue formation by inducing the specific differentiation
structures or tissues [119-121] . A model closer to heterogeneity of endogenous stem/progenitor cells. Accordingly,
better explains the biological action patterns. Therefore, growth factors have been utilized in bioengineering to
bioreactors simulating specific microenvironments are promote tissue regeneration. For instance, diverse growth
widely used in bioengineering [122] , among which bioreactors factors have been regionally added to the TEM. Studies
mimicking knee joints have already been studied for have highlighted the importance of CTGF that plays an
meniscus regeneration and biomechanical changes post- indispensable role in the fibrochondrogenic differentiation
meniscectomy [123,124] . Region-dependent mechanical and of stem cells, while TGFβ3 promotes hyaline chondrogenic
chemical stimulations are effective ways to construct differentiation [127-130] .
heterogeneous TEM for meniscal regeneration [125] .
Lee et al. fabricated a 3D-printed PCL scaffold loaded
A dynamic tension-compression system was designed with CTGF in the outer region and TGF-β3 in the inner
for heterogeneous TEM reconstruction. Together with region. By controlling the release of specific growth
the two growth factors, the MSCs in the biomimetic factors, bone marrow-derived MSCs (BMSCs) successfully
PCL scaffold were biomechanically and biochemically differentiate into chondrocytes and fibrochondrocytes
stimulated with the aim of inducing a spatially heterogeneously. They further detected the bioeffect
heterogeneous distribution of chondrocytes. The results in vivo by implanting this heterogeneous TEM into ovine
showed that the anisotropic cell phenotype in the PCL knee joints, showing that significantly increased COL-1
scaffold was successfully achieved, and the knee joint and COL2 levels were successfully induced by CTGF and
cartilage was protected [126] . TGFβ3, respectively [131] . Nakagawa et al. also evaluated
Nonetheless, there is still a long way for TEM from the long-term in vivo effect of loading 3D printing PCL
laboratory to clinic, with obstacles to be removed, such meniscus scaffold loaded with CTGF and TGF- β3 in an
as concise statistics and parameters for bioreactors and ovine knee meniscectomy model for up to 1 year. However,
sophisticated interactions between biomechanical contact MRI showed that most scaffolds were extruded, which may
and cell bioaction [119] . Furthermore, more impactful lead to cartilage degeneration in the treatment group [132] .
research is necessary to gain insight into the criteria and In addition, growth factors, although accelerating the
parameters of bioreactors. development of bioengineering, are still at risk of disease
transmission because of their exogenous characteristics.
3.6. Growth factors applied for 3D-printed Excavation of autologous biomaterials with growth factor-
heterogeneous TEM like functions and low immunogenicity is required. The 3D
Growth factors, recognized as indispensable regulators printing strategies of heterogeneous TEM are summarized
of cell and tissue growth, play a critical role in specific in Table 2.

Volume 9 Issue 3 (2023) 371 https://doi.org/10.18063/ijb.693