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International Journal of Bioprinting 3D bone: Current & future

thereby altering cell metabolism and the secretion of 3.2. Regenerative medicine and bone replacement
ECM components (Table 3). The main factors associated Intensive bone tissue formation stops at the age of 20–25,
with ossification are Runt-related transcription factors after which new bone cells are formed only for renewal and
(RUNX), osterix (OSX), sex-determining region Y (Sry)- regeneration, indicating that the body cannot naturally
related high mobility group (HMG)-related box factors replace a damaged bone in the event of a significant injury.
(SOX), and several other factors responsible for collagen Regenerative medicine repairs damaged tissues and organs
production. 26,27 In primary ossification, the transformation (e.g., from trauma, disease, or congenital problems) through
of MSCs into mature bone tissue consists four main steps: the artificial production (differentiation) and replacement
(i) attachment of MSCs to osteoprogenitor cells; (ii) of cells. The healing process is rapid and biologically similar
proliferation and differentiation of osteoprogenitor cells to natural mechanisms. In addition, it has the advantage
into immature osteoblasts/pre-osteoblasts and subsequent of circumventing the lack of ideal transplant donors and
ECM secretion; (iii) maturation of osteoblasts and ECM can be fully personalized. Some tissues (e.g., skin and liver
mineralization; and (iv) transformation of osteoblasts tissues) are continuously regenerated, and replacing these
into osteocytes and/or lining cells, or apoptotic cell death. tissues could facilitate the healing process. 1,22
These factors can be stimulating or inhibiting at various The production of artificial tissues should
stages. In secondary ossification, cartilage formation also approximate the native tissue or organ in both structural
has its distinct mechanisms: (i) differentiation of MSCs (physicomechanical and chemical properties) and
into chondroprogenitors and subsequent formation of the biological functions. 5,6,31 Biologically functional artificial
cartilage model; (ii) differentiation of chondroprogenitors tissues require cells that can be primary, differentiated,
into chondroblasts and chondrocytes; and (iii) cell swelling or highly potent stem cells. In this regard, hydrogels are
and apoptotic cell death during endochondral ossification. used as an ECM to provide an exceptional environment for
The dead cells are then replaced by MSC-derived bone cells cells, and in some cases, a hard skeleton (e.g., bone) may be
from the initial steps. 28-30 required. 5,32,33 3D scaffolds can be created in several ways
3. Bone deformities and (e.g., casting), but the best method to generate structures
that most closely resemble native tissue is 3D bioprinting
corresponding treatments (tissue printing). 5,6

In the event of injury, disease, or abnormal bone Nonetheless, the performance of 3D bioprinting is
development, bone tissues may need to be replaced. The dpendent on several critical requirements such as good
donor bone tissue may come from another (healthy) biocompatibility, cell dispersion capability, efficient
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part of the individual (autogenous transplantation), nutrient and oxygen diffusion, and suitable material
another human (allogeneic transplantation), or animal printability. For example, a gel must not be too fluid or have
species (xenogeneic transplantation). Alternatively, an inherently cross-linked structure. 3D-bioprinted tissues
1
bone replacement can be performed with non-tissue generally do not have a vascular network in the structures.
bone substitutes of human origin, and these non-tissue Therefore, a crosslinking design should be integrated into
5
substitutes usually contain growth factors and cell- the overall structure prior to 3D bioprinting. 6,31
based bone substitutes. Besides that, bone grafting is a
personalized alternative, and ceramic-based bone grafts 4. 3D bioprinting
are mainly used in dentistry, i.e., to treat traumatic injury,
disease, abnormal development, or dental surgery. 1 3D bioprinting is an additive manufacturing technology
used in tissue engineering to create the most native-
3.1. Bone fractures and injuries like artificial living tissues from a mixture of living cells
In bone fractures and injuries, it is often sufficient to and biomaterial-containing hydrogels, called bioinks.
adequately fix a part of the body while the damaged bone Since organs have a complex structure, spatial location,
regenerates. This is achieved by external non-invasive and cell type presence, imitation of the characteristics of
20
fixation methods or surgically implanting elements to the tissues is essential for appropriate function. In contrast to
bone surface. However, there are cases where bone tissue conventional tissue engineering techniques (e.g., 2D tissue
cannot regenerate or the bones fuse poorly, leading to culture), 3D bioprinting can develop complex tissue-
bone deformation and anatomical dysfunction. In such specific constructs. A general 3D-bioprinted tissue contains
cases, the bone needs to be reshaped with implants or cells and an ECM to provide the cells with a native-like
bone grafts. microenvironment. In addition, different types of tissue-

Volume 10 Issue 3 (2024) 153 doi: 10.36922/ijb.2056