Page 144 - IJB-9-4

International Journal of Bioprinting 3D-printed scaffolds for osteochondral defects

widely used in cartilage regeneration [70,71] . However, the There have been many attempts to use highly
BMSCs also shows certain limitations. Their tendency to differentiated embryonic stem cells in articular cartilage
differentiate toward chondrocyte phenotype on the growth repair. Wakitani et al. successfully repaired cartilage
[79]
plate in vitro or in vivo results in chondrocyte hypertrophy damage in the knee joint of mice using a combination
or death and endochondral bone formation, ultimately of chondrocytes differentiated from embryonic stem
affecting the articular cartilage regeneration . A series of cells and hyaluronic acid-based hydrogel. McKee et al.
[72]
[80]
recent studies have used different approaches to improve successfully induced the differentiation of embryonic
the ability of BMSCs to differentiate into chondrocytes. stem cells into chondrocytes on a 3D scaffold material
Studies have shown that the addition of stimulating under stress-stimulated conditions. However, embryonic
factors, such as insulin-like growth factor 1 (IGF-1) and stem cells have many limitations, including the risk of
bone morphogenetic protein (BMP)-7, can promote the tumorigenicity, disease transmission, immune rejection,
differentiation of BMSCs into chondrocytes, maintain and ethical issues, all of which restrict their widespread
the target phenotype, and inhibit the hypertrophic use to some extent. Nevertheless, an in-depth exploration
phenotype . In addition, due to its advantages of natural of the mechanisms of articular cartilage repair during the
[73]
components and the unique structure of cartilage matrix fetal period may provide valuable information for chondral
and good biocompatibility, the decellularized cartilage regenerative repair.
matrix could significantly promote the BMSCs maintenance
and differentiation . BMSCs have been widely used in The presence of skeletal stem cells was first confirmed
[74]
[81]
the articular osteochondral tissue engineering, but further by Chan et al. in mice. Unlike conventional MSCs,
research is needed to improve their application effects. these stem cells merely differentiate into osteoblasts,
chondrocytes, and stromal cells, but not into adipocytes,
Adipose stem cells are MSCs of adipose origin. They hematopoietic cells, or myoblasts. Murphy et al.
[82]
are easy to obtain and have broad sources and good demonstrated that one of the main mechanisms of cartilage
immunomodulatory properties, while being less invasive repair of microfracture techniques is the proliferation
to the donor, having fewer postoperative complications and of skeletal stem cells. In addition, BMP and vascular
possessing the potential to be seed cells for osteochondral endothelial growth factor (VEGF) inhibitors were used
tissue engineering. Studies have shown significant to induce differentiation of skeletal stem cells into hyaline
improvements in clinical symptoms and imaging in cartilage tissue, which was comparable to the native tissue
patients with OA following implantation of adipose stem in terms of mechanical properties, composition, and
cells alone or in combination with a scaffold . Although degree of integration with the surrounding tissue.
[75]
studies have shown positive short-term effects, the long-
term recovery and histological regeneration characteristics 3.4. Monophasic and biphasic scaffolds
after use of adipose stem cells in cartilage defects need to Monophasic scaffolds use a homogeneous single material
be further investigated. or composite to repair the entire articular osteochondral
defects. This means that the scaffold needs to meet the
Chondral progenitors/stem cells are found in the
superficial layer of the articular cartilage, which account structural and functional requirements of each of these
tissue areas with the same porosity and mechanical
for 0.1%–1% of the total articular cartilage tissue. These properties. Studies have been reported on the preparation
cells are capable of self-renewal in vitro and maintain the of single-phase scaffolds using a range of materials and
potential to differentiate into osteoblasts, chondrocytes bio-fabrication techniques, including ES based on ZnO–
and adipocyte lines even after 60 generations of PCL composites and ME based on bio-ceramics [83,84] .
expansion . They play an important role in the Herein, the material solution concentration and its surface
[76]
formation, growth and maturation of articular cartilage, characteristics are optimized and modified to enhance
and also respond to chondral damage by migrating to chondrogenic or osteogenic differentiation potential of
the injury site and proliferating and differentiating to cells. Furthermore, confocal laser scanning microscope
repair the defect . Compared to MSCs, chondrocytes (CLSM) images display that micro/nanostructured
[77]
derived from chondrogenic stem/progenitor cells are more surface significantly promoted the attachment of both
likely to maintain their phenotype rather than progress chondrocytes and rBMSCs. Most importantly, the in vivo
to chondrocyte hypertrophy and calcification . These study has shown that the micro/nanostructures on the
[78]
results show the possible prospect of chondrogenic stem/ surface of the 3D-printed scaffolds significantly promote
progenitor cells as a source of chondral tissue-engineered the regeneration of cartilage and subchondral bone tissues
seed cells, but the limitations of their scarcity and safety (Figure 3C). However, monophasic scaffolds cannot mimic
issues of aberrant karyotypes after many passages need to the biological microenvironment well due to the lack of
be further investigated.

Volume 9 Issue 4 (2023) 136 https://doi.org/10.18063/ijb.724