Page 291 - IJB-10-6

International Journal of Bioprinting 3D-Printed Zn/MgHA-PCL for angio/osteogenesis

grafting, allogeneic bone transplantation, and artificial to achieve vascularized bone regeneration. Doping
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bone substitutes. Autologous bone grafting, renowned for with divalent or multivalent ions (e.g., Zn - or Si -
2+
4+
1
its high osteoinductivity and osteoconductivity, is regarded doped HA nanoparticles) improves composite material
as the “gold standard” for bone repair. However, its biocompatibility and fosters osteogenic differentiation
21
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applicability is limited due to the scarcity of resources and and tissue-material interface stable bonding. Moreover,
22
2+
2+
the difficulty in precisely matching the size and shape of HA doping ions (e.g., Sr or Mg ) induce BMSCs to
the defect. Allograft bone transplantation carries risks of synthesize and secrete VEGF and other angiogenic
2
immune rejection and even disease transmission, limiting factors, thereby further expediting the induction of
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its clinical use. Consequently, artificial bone grafts, owing vascular regeneration in vitro or in vivo. 24
3
to their wide sourcing and low immunogenicity, have Notably, magnesium, an essential human element,
emerged as a focal point among researchers in bone defect boasts numerous beneficial biological effects and plays
repair. Diverse biomaterials have been engineered for a pivotal role in bone metabolism. Mg deficiency is
25
bone defect repair, including bioactive glasses, porous highly associated with osteoporosis. Additionally,
4,5
26
ceramic scaffolds, metals, hydrogels, polymers, and Mg deficiency upregulates tumor necrosis factor-alpha
6,7
8
1,10
9
their composites. (TNF-α), interleukin-1 beta (IL-1β), and receptor activator
Calcium phosphate (CaP) bioceramics, such as of nuclear factor kappa-B ligand (RANKL) expression
hydroxyapatite (HA), are extensively used for mending and downregulates osteoprotegerin (OPG) expression,
27
skeletal defects across the body due to their chemical hastening bone resorption, and inducing osteoporosis.
similarity to mammalian bones and teeth, as well as their Moreover, Mg could enhance angiogenesis through the
excellent bioadaptability (commonly utilized for filling CGRP-mediated CGRP-FAK-VEGF signaling pathway
1
hard tissue defects and coating implant surfaces). 11,12 to repair critical-sized bone defects. Zinc, also abundant
Among them, HA, the primary inorganic constituent of in bones, is a crucial element in bone metabolism. It
human hard tissues, theoretically appears to be one of the heightens alkaline phosphatase (ALP) activity in BMSCs
most suitable materials for human bone tissue repair. to further induce osteogenic differentiation and stimulate
13
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With its outstanding osteoconductive and osteoinductive bone development and mineralization. Zinc can inhibit
29
properties, HA not only provides a spatial and supportive osteoclasts and accelerate bone healing to some extent.
framework for vascular and new bone ingrowth but also Additionally, zinc exerts antibacterial effects, particularly
induces mesenchymal stem cells to differentiate into against Staphylococcus aureus, Lactobacillus, and Gram-
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osteoblasts; thereby expediting bone reconstruction and positive bacteria, which positively correlates with the Zn
enhancing osteogenic efficiency and the effect of bone doping molar fraction. Compared to single-element (Mg
integration. 14,15 Natural bone HA comprises mixed phases and Zn ions)-doped HA, research on Mg/Zn-co-doped
deviating from the ideal chemical composition (Ca/P = 1.67) HA is relatively scarce. Moreover, some prevalent co-doped
and doped with trace elements. Therefore, synthesizing HA studies mainly investigated physical properties, such as
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HA with the ideal chemical composition is simplistic and lattice and crystal size post-doping, but they are limited
inadequate to meet clinical demands, necessitating diverse in studying the effects on the biological domain (cells,
methods to modify HA to impart requisite biological e.g., osteogenic-related cells). Hence, further research is
functions. Currently, trace element doping stands as warranted to delineate the synergistic effects of Mg/Zn-co-
one of the most common HA modification techniques, doping on angiogenesis and osteogenesis.
broadly classified into cation and anion doping. These Furthermore, the biocompatibility, degradation rate, and
16
trace elements exhibit serval unique biological functions. mechanical properties of bone repair scaffolds must match
For instance, boron ions could upregulate the expression those of natural bone tissue. Traditional HA scaffolds are
of osteogenic differentiation markers (BMP, etc.) in often brittle and lack sufficient mechanical strength, which
MC3T3-E1 cells and induce osteogenic differentiation may result in fractures under load, particularly in areas
of bone marrow mesenchymal stem cells (BMSCs). with significant bone defects. Additionally, their surface
17
Copper ions could stimulate stem cells to secrete VEGF, characteristics, such as porosity and pore size, are often
promoting angiogenesis. Additionally, in a rat cranial inadequate, which can impact nutrient exchange and waste
18
defect model, the Cu-containing group displayed a removal. The optimal pore size for bone repair scaffolds
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significant improvement in bone regeneration, compared ranges from 200 to 350 μm. 3D printing technology
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to the control. Silicon ions could regulate the coupling allows for the precise control of mechanical properties
19
of osteogenesis and angiogenesis and create a beneficial and the adjustment of pore size and porosity to better suit
immune microenvironment at the site of bone defects bone repair requirements. Polycaprolactone (PCL) offers
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Volume 10 Issue 6 (2024) 283 doi: 10.36922/ijb.4243