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

functional groups on the surface of a material, and it has did not directly confirm the precise mechanism by which
been proposed that treating the PCL surface with sodium the E7 peptide recruits bone marrow-derived mesenchymal
hydroxide could break the PCL ester bond, resulting in stem cells (BMSCs), Shao et al. indirectly evidenced that
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the production of more hydroxyl and carboxyl groups cells bound to the E7 peptide express elevated levels of
on the surface. However, this also accelerates the CD44, CD90, and CD105. Remarkably, these markers are
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degradation of PCL and reduces its physical properties. also highly expressed in BMSCs, suggesting that the E7
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In recent years, polydopamine (PDA) has been proposed peptide may selectively recruit mesenchymal stem cell-like
as an effective surface adhesion modifier that not only cells within the bone marrow.
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decreases the hydrophilicity of the material surface and In the present study, the PCL@SS31@E7 group
makes it easy for cells to attach but also enables bioactive
factors to be anchored to the polymer via its abundant showed significant advantages over the other three
amino functional groups. In this study, we effectively groups with respect to cell adhesion, cell migration,
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increased the hydrophilicity of the materials by utilizing modulation of mitochondrial function in high-glucose
PDA as a surface adhesive. In addition, sulfo-succinimide microenvironment, and promotion of osteogenic
hexamethylene carbonate (sulfo-SMCC) was used as a differentiation of BMSCs. In addition, we observed the
crosslinking agent such that its N-hydroxysuccinimide release of SS31 and E7 peptides on PCL porous scaffolds;
reactive ester group reacted specifically with the abundant a cumulative release of 65.8% was achieved in PBS at 37°C
amino group on PDA to form an amide bond, whereas the for 21 days, demonstrating that slow-release therapy could
maleimide group reacted with the modified sulfhydryl be achieved. Therefore, optimizing the performance of
group (-SH) at the peptide tail to form a thioether bond. scaffold materials through peptide modification is a highly
This ultimately led to the peptides being successfully promising tissue engineering technique that provides us
grafted onto the surface of the PCL porous scaffold. with new methods and ideas for the design of this system.
SS31 is a mitochondria-targeted peptide with Electrons leaking from mitochondria can combine
antioxidant properties. It has attracted increasing attention with oxygen molecules to generate oxygen radicals and
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because of its ability to promote cellular uptake, along promote ROS expression. Through the OCR assay, we
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with good biosafety. In this study, we modified the SS31 found that when BMSCs were cultured in a high-glucose
peptide on the surface of PCL porous scaffolds by linking environment, intracellular mitochondrial respiration
it with sulfo-SMCC. Some previous studies have shown was significantly inhibited, followed by a decrease in
that the EPLQLKM (E7) peptide can specifically recruit ATP production and an increase in proton leakage in
BMSCs in vitro and in vivo. Thus, it is possible to shorten mitochondria, which ultimately caused mitochondrial
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the time required for bone regenerative repair by stem cell dysfunction; however, after co-culture with PCL@SS31@
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recruitment. Shao et al. also reported that the E7 peptide E7 porous scaffolds, the cellular respiratory function of
could effectively promote the adhesion of BMSCs to an BMSCs was close to the normal level. Our in vivo study
electrospinning network and induced less inflammatory showed that the PCL@SS31@E7 porous scaffold system
cell development—and hence less inflammatory damage— had significant therapeutic effects on bone defects in
than the RGD peptide. In addition, the E7 peptide diabetic rats. Moreover, the abilities of PCL@SS31 and
synergized with the SS31 peptide to improve intracellular PCL@E7 to promote bone differentiation and bone
mitochondrial function while recruiting BMSCs, regeneration were different from those of PCL@SS31@E7
contributing to the normalization of cellular respiration, in vitro and in vivo.
increased oxygen and glucose consumption, scavenging Although the PCL@SS31@E7 porous scaffold system
of ROS, and lowering of blood glucose levels and developed in this study is a promising treatment for
ultimately correcting the hyperglycemic and inflammatory diabetic bone defects, the following points remain to be
microenvironment. Zhang et al. concluded that SS31 explored for future research:
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effectively prevents excessive entry of mitochondrial
protons and restores mitochondrial function by directly (i) In clinical practice, diabetic critical bone defects
binding to ANT1 and maintaining the stability of ATP are mostly open fractures, and bone defect repair
synthase. In the present work, according to the results is limited by multiple factors. These factors, which
of mitochondrial membrane potential assay, the inner affect bone regeneration, include a high-glucose
membranes of cellular mitochondria were depolarized microenvironment, local blood supply disruption,
after high-glucose drying, and the potential was restored and infection. In the present study, we focused on
to normal level after treatment with PCL@SS31@E7, which the effects of a single factor—the high-glucose
improved electron transfer in the MRC. While our study microenvironment—on the process of bone

Volume 10 Issue 4 (2024) 218 doi: 10.36922/ijb.2379