Page 255 - IJB-8-3

Li, et al.
proven to be potentially effective in the connection 4.5. Vascularized bone
between artificial vascular networks in liver with human
vasculature. Before the 3D printing, details in dimensions As the highest biological strength of tissue in the human
of the donor livers, recipient socket, and diameters body, bone is a flinty composition of hydroxyapatite and
collagen with naturally balanced intensity and elasticity
of connecting vessels should be precisely recorded
with micro-scanning technology . The outcome modulus. To maintain proper elasticity and avoid brittle
[10]
demonstrated that the artificial liver holds some value in fracture, the blood vessels in the bone tissue are abundant
clinical applications. to maintain high level of metabolic activity and maintain
the balance of bone resorption and bone reconstruction.
4.4. Pancreas The cortical bone has 10 – 30% porosity, meanwhile,
the cancellous bone has 30 – 90% porosity [118] . The
Anatomically, pancreas is a large elongated glandular organ, porous structure enables an active vascularized system to
situated behind the stomach, that secretes insulin, glucagon, maintain the normal function of bone metabolism [119,120] .
and somatostatin into the blood stream, and pancreatic The distance between the intraosseous blood vessels
juice (including digestive enzymes) into the duodenum [117] . and the nearest capillaries is within 100 μm in case of
In diabetes, the body produces insufficient insulin. Some ischemic necrosis. Besides, the intravascular system
people are genetically predisposed to diabetes. In certain provides advanced functions to maintain bone integrity,
patients, diabetes is caused by a fault in the insulin such as bone reconstruction, development, and fracture
production. Diabetics have long been considered to be repair [121] .
particularly prone to infection. A possible way to control In traditional clinical application, typical bone graft
juvenile-onset diabetes is through pancreas transplant. models have been expected to have many characteristics,
However, the number of donors is extremely limited.
The first 3D-printed vascularized pancreas was including osseointegration, [122] bone conduction,
reported in 2010 in Professor Wang’s laboratory using her osteoinduction, and osteogenesis . Since 3D printing
home-made double-nozzle 3D bioprinter . In this study, technology has been regarded as an excellent alternative
[99]
to traditional bone graft manufacturing, vascularization
ASCs in a gelatin-based hydrogel, that is, gelatin/alginate/
fibrin, were assembled and induced to differentiate in 3D bone printing has become the focus of researchers.
into two target cell types, that is, adipocytes and ECs, Therefore, angiogenesis has become the essential
based on their positions within an orderly arranged process that must be considered in the design of 3D
3D construct; pancreatic islets were then implanted at bone substitutes. Wang et al. described the process of
designated locations and constituted adipoinsular axis vascularized osteogenesis using viral activated matrix
with adipocytes. Analysis of the factors involved in and arginine glycine aspartate peptide phage nanofibers
[120]
energy metabolic showed that the system captured more combined with 3D printing . The scaffolds sowed with
physiological and pathophysiological features of energy bone marrow mesenchymal stem cell were used as bone
metabolic in vivo (Figure 10). defect fillers, which proved effectively, generate new
Notably, after pre-cultured with high glucose, the blood vessels and increase osteogenesis. Temple et al.
glucose-induced insulin secretion peak of the assembled generated vascularized bone grafts using polycaprolactone
β-cells was delayed compared to normal controls, this (PCL) in 3D printing system [122] . The biodegradable PCL
delay could be revised by nateglinide. After long-term and the utilization of human ASCs enable the vascular
exposure to high glucose, adipocytes became obese and network to be automatically modified when it was fused
secreted more free fatty acids, leptin, and resistin, which with recipient’s vessels. Furthermore, PCL was proved to
actively involved in crosstalk with β-cell, decreased and be deferoxamine sustained releasing. Yan et al. believed
delayed the insulin secretion peak value of β-cell. ECs that the PCL-based bone scaffolds are the ideal material
form vascular wall-like structure, which serves as the for promoting vascularization and osteogenesis [123] .
endothelial barrier between the adipocytes and β-cells A biologically inspired nano coating technique was
in vivo. Drugs known to have effects on metabolic integrated into a 3D printing scaffold to achieve intelligent
syndrome showed accordant effect in the system. delivery of dual growth factors (BMP-2 and VEGF) and
This technique is automatic, versatile, rapid, and release them in a spatiotemporal coordinated order. [124]
highly productive, it has significant potentials in high- In another study, the authors combined the advances of
content drug screening areas. Construction of such a dual 3D printing and regional immobilization strategy
multicellular system can help us to better understand of bioactive factors for complex vascularized bone
pathogenesis of metabolic syndrome, develop new regeneration. [125,126] The combination of hard PLA scaffolds
technologies for drug discovery and metabolomic and soft gelatin vessels provides a promising platform for
profiling. Nevertheless, more than 10 years have passed obtaining hierarchical bionic structures with multiphasic
since then. No further literature was reported in this area. features and vascular networks [127-129] .

International Journal of Bioprinting (2022)–Volume 8, Issue 3 247