Page 141 - IJB-9-4

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

2.2.1. Cartilage degeneration in OA to release various enzymes that break down collagen
Although many tissue cells are involved in the pathological and glycoproteins, thereby destroying the tissue [36,37] .
process of OA, chondrocytes are thought to be a key factor In addition, helper T cells (Th17) and regulatory T cells
in the development and progression. Aging of articular (Tregs) are related T cells. Th17 are able to release pro-
chondrocytes causes impaired synthesis and secretion of inflammatory cytokines, which further activate immune
type II collagen and proteoglycan, and imbalances in the cells and induce inflammation. In contrast, regulatory T
anabolic and catabolic processes of the extracellular matrix cells secrete immunosuppressive cytokines that effectively
(ECM). This can cause further cartilage degradation and suppress the activity of T cells and other immune cells.
destruction, ultimately leading to the onset of OA [23-25] . Studies have shown that decreased Tregs function in RA
patients induces the initiation of harmful autoimmunity by
It was found that the number of senescent [38,39]
chondrocytes in OA cartilage was significantly higher than Th1 cells, which further leads to chronic inflammation .
in healthy control cartilage of the same age [26-28] . Senescent 2.2.3. Mechanical abrasion in sports injury
chondrocytes are predominantly located around damaged Traumatic osteochondral lesions are related to the
cartilage in OA and are rarely detected in intact cartilage, high-intensity violence to bones, including bone
further suggesting an intrinsic link between chondrocyte bruises, cartilage fractures, subchondral fractures, and
senescence and OA [27,29] . Senescent chondrocytes secrete osteochondral fractures. Traumatic osteochondral lesions
senescence-associated secretory phenotype (SASP) factors are “outside-in” lesions that affect articular cartilage first
that inhibit ECM synthesis and activate matrix protein and then destroy the subchondral bone when sufficient
hydrolases to promote the development of OA . Notably, force is applied. Articular cartilage provides a smooth
[30]
although the accumulation of senescent chondrocytes and load-bearing surface. Synovial fluid in the joint
(chronic cellular senescence) can lead to joint tissue cavity contains hyaluronic acid and lubricating hormones
dysfunction and OA, acute cellular senescence plays secreted by superficial chondrocytes , which lubricate
[40]
a positive role in embryonic development and tissue the cartilage surface. The synovial fluid is one of nutrition
regeneration . For example, senescent cells derived from sources for chondrocytes and contains electrolytes, oxygen
[31]
the wound can release platelet-derived growth factor and glucose. Due to the lack of directly nourishing blood
AA (PDGF-AA) to promote wound healing . Research vessels and nerves in the cartilage, its nutrition source
[32]
shows that PDGF-AA promotes chondrocyte proteoglycan is mainly derived through matrix penetration of the
secretion and cartilage repair, and that PDGF-AA from subchondral bone vessels. Therefore, articular cartilage has
subchondral bone can alleviate cartilage degeneration in a limited ability to repair itself. Studies have shown that
[33]
an OA mouse model . the cartilage tissue surrounding the damaged area has a
2.2.2. Inflammatory erosion in rheumatoid arthritis lower cell density compared to healthy tissue in articular
Inflammation, one of the most remarkable pathological osteochondral lesions. The animal model of osteochondral
features of rheumatoid arthritis, plays a crucial role in its lesions further demonstrates that a decrease in cell
development. Macrophages are the main cells that promote density within 100 μm of the defect edge can be observed
the inflammatory response in RA. A large number of for weeks and even months after surgical treatment.
macrophages have been found in the cartilage and synovial Some chondrocytes undergo apoptosis, with the highest
[41]
tissue of patients with rheumatoid arthritis . The study apoptosis rate on day 4 after trauma .
[34]
found that the synovial macrophage activation caused
overexpression of major histocompatibility complex II 2.3. Restoration mechanisms
(MHC II) molecules, chemokines, and inflammatory Mature articular cartilage will make some attempts to repair
factors, and that the number of macrophages and the levels itself when damaged, although the ultimate effect is rather
of interleukin (IL)-1β and tumor necrosis factor alpha limited. When articular cartilage is impaired by factors
(TNF-α) correlated with the degree of joint damage and such as trauma or repeated abrasion, the repair mechanism
[35]
clinical symptoms in patients . varies depending on the lesion category. The cartilage tissue
at the edge of the lesion is barely capable of repairing itself
On the other hand, T cells play a crucial part in the when the lesion depth does not reach the subchondral bone
development of RA. Its development is caused by the level. Although a few fibroblasts and mesenchymal stem
interplay of CD4 cells and antigen-presenting cells cells (MSCs) from the synovium or synovial fluid migrate
+
(APCs). The binding of T cells with MHC II and antigenic to the lesion site, this is not sufficient to repair the cartilage
peptides activates macrophages to release inflammatory defect , whereas in complete lesions (when the lesion
[42]
cytokines including TNF-α and IL-1. These cytokines reaches the level of subchondral bone), a large amount of
further stimulate chondrocytes and synovial fibroblasts blood and even bone marrow will rush into the defect and

Volume 9 Issue 4 (2023) 133 https://doi.org/10.18063/ijb.724