Page 270 - IJB-10-3

International Journal of Bioprinting 3D bioscaffolds with SR1 for vasculogenesis

1. Introduction by directly binding to and inhibiting aryl hydrocarbon
receptor (AhR) signaling, which plays a role in the
The treatment of critical-sized defects caused by serious regulation of pluripotency and stemness of hematopoietic
injury is often rendered unsuccessful due to the inherent stem cells under normal condition. 19-21 A previous study
limitations of bone grafting, despite the excellent healing demonstrated a 50-fold increase in CD34 cells in human
+
capacity of bones. Therefore, there is an increasing cord blood CD34 cell-transplanted immunodeficient
1
+
demand for bone-repairing implants to circumvent the mice. Many studies using CD34 cells have shown a
19
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limitations of bone grafting, which is generally used to successful promotion of angiogenesis and osteogenesis.
11
treat extensive bone loss. Other than the traditional However, the number of CD34 cells available for
1
+
methods, three-dimensional (3D) bioprinting can be therapeutic purposes is often limited, particularly in adult
used as a manufacturing technique to produce bone- tissues. Therefore, evaluating the ability of SR1 to expand
repairing implants with structural flexibility from a range the CD34 cell population in vivo is required, to allow
+
of applicable materials. Several 3D-bioprinted bone further studies examining the development of clinical
2,3
scaffolds have been developed using various materials to therapies targeting CD34 cells.
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enhance osteogenesis in previous studies. However, the
4,5
failure to promote angiogenesis, an essential step in the In the early stages of 3D-printed bone scaffold
repair and regeneration of damaged bone, remains a weak development, some scaffolds were printed with bioink
point for 3D-printed bone scaffolds. Without angiogenesis, that was directly mixed with growth factors, such as
bone healing would fail due to a lack of essential nutrients the vascular endothelial growth factor (VEGF) or
6
and oxygen. Therefore, promoting local vascularization fibroblast growth factor. Recently, scaffolds capable
is a crucial step for the successful healing of extensive of sustained release were developed to circumvent
the limitations of the early-stage scaffolds, which
bone loss.
7
have short half-life and subject to swift loss of
Endothelial progenitor cells (EPCs) play an important growth factors. 22,23 In this study, mesoporous silica
role in the early stages of vascularization. During the nanoparticles (MSNs) were added to a 3D-printed
8
healing process, bone marrow-derived EPCs circulating scaffold to enable the sustained local release of SR1.
in the peripheral blood are recruited to injured areas. The The components of the bone scaffold were selected
recruited EPCs then form new vessels by differentiating considering the advantages of the polymers. Recently,
into endothelial cells (ECs). Asahara et al. were the first natural polymers have been recognized as promising
9
to identify EPCs that can differentiate into ECs. Notably, materials for constructing bone scaffolds because of
10
CD34 cells have received considerable attention because of their favorable biocompatibility, biodegradability, and
+
24
their neovascularization potential. Previous studies have osteoconductivity. On the other hand, harboring
11
demonstrated increased vascularization in myocardial the capacities to form extracellular matrix and create
25
ischemia models and human clinical trials using CD34 porous structures, collagen can be used to manufacture
+
cells. 12-14 Additionally, CD34 cells play an important role scaffolds, i.e., collagen-based scaffolds, which possess
+
in bone regeneration because of their ability to promote the desirable characteristics, such as cell attachment and
+
vascularization. Previous studies have shown that CD34 osteogenic differentiation. 26-28 Although existing results
cells contribute not only to vascularization, but also to indicate that SR1 is a promising material for promoting
bone healing, as demonstrated by in vivo experiments angiogenesis in vitro, the lack of in vivo studies remains
that locally supplied CD34 cells in rat models of critical- a challenge in demonstrating the clinical efficacy of

+
sized femoral defect. 15-18 Many studies have underscored SR1. Therefore, we aimed to address this gap in the
the potential of CD34 cells in promoting vascularization, literature by examining whether the sustained release of
+
signifying that this cell type can be used as an endothelial SR1 from collagen scaffolds promoted angiogenesis and
cell source for bone scaffold construction. Therefore, ultimately increased bone healing using in vivo studies.
3D-printed bone scaffolds incorporating an angiogenic
factor that can enhance CD34 populations may lead to 2. Materials and methods
+
successful bone healing in critical defects. StemRegenin-1 2.1. In vitro studies
(SR1), a purine derivative molecule promoting CD34 + In the in vitro studies, the cells were divided into three
cell expansion, was first identified by Boitano et al. Co- groups: (i) negative control (CT) group, in which no
19
culturing of monoclonal peripheral blood cells with SR1 treatment was given; (ii) SR1 nanoparticle (SNP) group,
+
led to a significant increase in CD34 hematopoietic stem in which the cells were treated with SR1 nanoparticles
and progenitor cell populations under ex vivo conditions (final concentration = 1 µM); and (iii) blank nanoparticle
Volume 10 Issue 3 (2024) 262 doi: 10.36922/ijb.1931