Page 86 - IJB-9-1

International Journal of Bioprinting Progress in bioprinting of bone

of trabecular bone (metaphysis). Microscopically, bone 2. Consideration of bioprinting a bone
lamella, which is composed of mineralized collagen fibers,
exhibits a planar arrangement with a width of 3 – 7 μm . The conventional tissue engineering strategy is to
[4]
In cortical bone, osteons (or Haversian systems) are formed seed cells onto scaffolds, which can then direct cell
proliferation and differentiation into three-dimensional
by concentric layers of lamellae wrapped around a central (3D) functioning tissues and organs. Although significant
canal. On the other hand, the arrangement of mineral
platelets in the trabecular bone is different, in which the success has been achieved in the past decades both in
[10]
[2]
mineral platelets are aligned with the collagen fibers . research and clinical applications , it is obvious that
complex 3D tissues require more precise multicellular
Furthermore, lamellae, which are considered the basic structures, which cannot be fulfilled by traditional
building blocks of bone, contain mineralized collagen methods. Bioprinting offers a controllable fabrication
fibrils (~100 nm in diameter). Collagen type I (COL-I) process, which allows precise spatial placement of
is the primary organic component of the matrix, which various biomaterials and/or cell types simultaneously
is secreted by osteoblasts followed by self-assembling. mimicking the target natural tissue or organ .
[11]
Apatite crystals distribute discretely along the collagen Complementing the existing review articles about
fibrils. The lamellae and collagen fibers of bone are bioprinting and its applications [12-14] , this review focuses
organized in a way that prevents crack propagation and on 3D bioprinting of bone, which is rapidly advancing in
increases bone toughness . As for the composition of the field of regenerative medicine. This article discusses
[5]
bone, hydroxyapatite (HAp, 60%) and collagen-I (20%) the up-to-date progress in 3D bioprinting technologies
are the major substances. Besides, there are several types of for bone reconstruction by integrating knowledge from
impurities in bone, including sodium (Na ), magnesium in vitro and in vivo studies. Bioprinting approaches and
+
(Mg ), and potassium (K ), as well as proteins, such other major considerations are carefully evaluated, such as
+
2+
as osteocalcin (OCN), osteonectin, and sialoprotein . bioprinting apparatus, biomaterials, bone vascularization,
[6]
Osteoblasts, osteocytes, osteoclasts, and bone lining cell source, differentiation factors, mechanical properties
cells are the four types of cellular components of bone and reinforcement, hypoxic environment, and dynamic
that are embedded in the extracellular matrix (ECM). culture. This review outlines the latest advancement in
Osteoblasts, the bone-forming cells, consist of 4 – 6% of bioprinting of bone and aims to assist the researchers to
the total number of bone cells. ECM is synthesized by gain insights into the reconstruction of clinically relevant
osteoblasts in a two-step process involving the deposition bone tissues with appropriate mechanical properties and
of organic matrix followed by mineralization . During precisely regulated biological behaviors.
[7]
the calcification process, osteoblasts transform into In this review, studies based on conventional 3D
osteocytes, which distribute in the ECM and act as stress printing, in which acellular scaffolds are fabricated followed
sensors in the bone. In some cases, osteoblasts stay on by cell-seeding, are excluded from the study. Studies on the
the top of new bone and protect the bone underneath, topic of bone bioprinting, in which cellular components
hence the term lining cells. A bone osteoclast is a very are manipulated together with bioink deposition without
large, multinucleate cell that absorbs bone matrix, in subsequent manual cell-seeding process, are carefully
which function is critical in the maintenance, repair, and selected and reviewed. From the viewpoint of the authors,
remodeling of bone.
the selected studies are innovative in certain aspects such
Bone plays an essential role in providing the body as bioink preparation, bioprinting process, or construct
with mechanical support. Calcium phosphate provides design and represent the state-of-the-art progress in
mechanical durability and high resistance to compression this field. When discussing about bone bioprinting, the
of bone, whereas collagen is responsible for bone’s following questions should be kept in mind (Figure 1):
elasticity and resistance to tension and stretching. Young’s (i) What printing processes and structure designs
modulus is approximately GPa for native bone, and tensile can facilitate micro-/macroscale vascularization of
and compressive strengths are approximately MPa, which bioprinted bone?
are determined by the location of the bone in the body (ii) What is the optimal bioink formula for derive
or by the specific location within the bone. Compared the greatest benefits from natural and synthetic
with cancellous bone, cortical bone exhibits much higher biomaterials?
Young’s modulus (7 – 30 GPa vs. 50 – 500 MPa), tensile (iii) What are the best combinations of cell types for bone
strength (50 – 150 MPa vs. 1.2 – 20 MPa), compressive bioprinting? When multiple cell types are loaded in the
strength (167 – 193 MPa vs. 1.9 – 10 MPa), and strain to bioink, how do they interact and promote osteogenesis
failure (1 – 3% vs. 5 – 7%) in the longitudinal direction [8,9] . of stem cells and the formation of vasculature?

Volume 9 Issue 1 (2023) 78 https://doi.org/10.18063/ijb.v9i1.628