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International Journal of Bioprinting 3D-Printed scaffolds for diabetic bone defects

Keywords: 3D printing; Stem cell recruitment; Mitochondrial respiratory chain; Diabetic bone defects; Bone regeneration

1. Introduction bone defects, suffers from a reduction in BMSC cellular
respiratory capacity, a precursor causing a drop in BMSCs
Diabetes mellitus is among the most common chronic migration and osteogenesis that lowers bone regeneration
diseases seen in clinical practice, with a prevalence of capacity. These factors give rise to two major problems:
approximately 451 million globally in 2017, which is decreased quality (impaired cellular respiratory function
1,2
expected to increase to 693 million by 2045. People with of BMSCs) and quantity (decreased migration and
diabetes mellitus face an increased risk of fracture, are proliferation of BMSCs) of new bone tissues in patients
prone to delayed fracture healing and bone nonunion, and with diabetic bone defects.
eventually develop osteonecrosis and bone defects. Thus,
3
bone defects due to fractures in diabetic patients stand as Therefore, bone repair materials capable of both stem
a serious public health problem. Studies have shown that cell recruitment and cellular respiration regulation are
the mechanisms affecting bone regeneration in diabetic warranted for promoting bone tissue regeneration, and
patients include inhibition of osteoblast differentiation their preparation is the aim of the present study.
by the high-glucose environment, as well as impaired In recent years, three-dimensional (3D) printing
4,5
cellular mitochondrial electron transport function and technology has emerged as an innovative method of material
decreased cell migration and recruitment caused by high- processing, and 3D-printed materials have been widely used
glucose microenvironment. In addition, new bone tissue in biological tissue engineering. 3D printing technology can
6
of diabetic patients is characterized by poor bone matrix accurately control the mechanical structure of the material
calcification status, low bone cortical thickness, and and endow it with unique biological properties, giving it a
diminished formation of new bone trabeculae. Autologous clear advantage in bone tissue engineering regeneration. 16,17
7,8
and allogeneic bone grafting is the prevailing treatment of Polycaprolactone (PCL) is often used as a 3D-printed material
diabetic bone defects. However, autologous bone grafting for bone repair, as it has the benefit of a highly controllable
gives traumatic experiences to the recipients and causes structure that facilitates the customization of personalized
them substantial postoperative pain, whereas allogeneic scaffolds. However, PCL lacks bioactive groups to improve
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bone grafts lack biological activity, increasing the risk of cellular respiratory function and needs to be modified
postoperative infection and immune rejection. Therefore, for better function. The SS31 peptide (elamipretide) is an
9,10
it is of utmost significance to develop biomaterials that can antioxidant peptide with a mitochondria-targeting function.
effectively promote regeneration of normal bone tissue in SS31 reduces reactive oxygen species (ROS) production by
bone defect areas in diabetic patients. improving bending of mitochondrial endosomal membrane
Cellular respiration refers to the oxidative cristae and restoring the role of the mitochondrial electron
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decomposition of organic matter in cells to provide transport chain. SS31 has been shown to directly interact
energy, a primary element for cell survival and biological with the adenine nucleotide transporter ANT1 to prevent
functions. In diabetes mellitus, the physiological process proton leakage, thereby rejuvenating the mitochondrial
11
20
of cellular respiration is inhibited owing to uncontrolled electron transport chain in aging cardiomyocytes.
blood glucose levels, disruption of microcirculation in Moreover, it reduces inflammation and oxidative stress
bone defect areas, increased mitochondrial permeability, (ROS) levels in diabetic patients by increasing SIRT1
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decreased efficiency of the electron transport chain, expression. In addition, some researchers have screened
increased levels of reactive oxygen species (ROS), and peptide E7 with amino acid sequence EPLQLKM by phage
decreased antioxidant capacity; these effects jointly lead screening technology and found that it can specifically
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to weakening of the cellular energy supply and, ultimately, recruit BMSCs. Therefore, we constructed a functionalized
inhibition of bone regeneration. 12,13 In addition, the SS31/E7-peptide-modified 3D-printed PCL bioscaffold
migration and proliferation of bone marrow mesenchymal (PCL@SS31@E7) that could recruit and improve cellular
stem cells (BMSCs) are reduced in diabetes mellitus, respiratory function in diabetic pathology, promoting the
and cell senescence and apoptosis are increased. 14,15 regeneration of normal bone tissue.
Effective recruitment of BMSCs to bone defect regions In this study, we prepared PCL bone repair scaffolds
and promotion of their osteogenic differentiation are with a biomimetic porous structure (the microporous
central factors in accelerating bone defect regeneration. diameter of the scaffolds was 400 μm) by 3D fused
We postulate that high-glucose microenvironment, deposition modeling (FDM) printing, using sulfo-
which is a pathological hallmark of patients with diabetic SMCC as a crosslinking agent and grafting SS31 and E7

Volume 10 Issue 4 (2024) 205 doi: 10.36922/ijb.2379