Self‐Assembled Heterojunction Carbon Nanotubes Synergizing with Photoimmobilized IGF‐1 Inhibit Cellular Senescence

Abstract

Synthesis of artificial and functional structures for bone tissue engineering has been well recognized but the associated cell senescence issue remains much less concerned so far. In this work, surface-modified polycaprolactone-polylactic acid scaffolds using self-assembled heterojunction carbon nanotubes (sh-CNTs) combined with insulin-like growth factor-1 are synthesized and a series of structural and biological characterizations are carried out, with particular attention to cell senescence mechanism. It is revealed that the modified scaffolds can up-regulate the expressions of alkaline phosphates and bone morphogenetic proteins while down-regulate the expressions of senescence-related proteins in mesenchymal stem cells, demonstrating the highly preferred anti-senescence functionality of the sh-CNTs modified scaffolds in bone tissue engineering. Furthermore, it is also found that with sh-CNTs, scaffolds can accelerate bone healing with extremely low toxicity in vivo.

Mesenchymal Stem/Stromal Cell Senescence: Hallmarks, Mechanisms, and Combating Strategies

“… 162 , 163 Studies found that insulin receptor (IR) blockage, deletion of insulin receptor substrate 1 (IRS1), and/or IRS2 contribute to inhibiting MSC senescence or functional restoration of aging MSCs. 164 , 165 As for the TGF-β signaling, members of the TGF-β family ligands are key components of the stem cell niche and orchestrate diverse responses in different types of stem cells, including MSCs. 166 Transforming growth factor-β has been shown to accelerate aging by activating p16 INK4A and p21 CIP1/WAF1 .…”

Carbon based nanomaterials for tissue engineering of bone: Building new bone on small black scaffolds: A review

“…Chen et al synthesized surface-modified PCL-PLA acid scaffolds using a combination of self-assembled heterojunction CNTs and insulin-like growth factor-1 (IGF1). They investigated cellular senescence and the possible underlying mechanism by characterizing the functionality and cell biology features of these scaffolds and demonstrated the anti-senescence functionality of the self-assembled heterojunction CNT-modified scaffolds in bone tissue engineering, being able to accelerate bone healing with extremely low in vivo toxicity [82]. Park et al suggested a new method for the biosynthesis of a CNT-based 3D scaffold by in situ hybridizing CNTs with bacterial cellulose (BC).…”

Bone Tissue Engineering via Carbon‐Based Nanomaterials

“…Aside from composited with polymers, CNTs were also directly coated onto polymer scaffold in which osteogenic differentiation was accelerated while cell senescence was reduced. The CNTs‐coated polymer scaffold, in conjunction with insulin‐like growth factor‐1 (IGF‐1) and MSCs, were able to repair bone defects efficiently and normally ( Figure ) …”

“…C) X‐ray assay exhibiting bones healing with different scaffolds after 28 days of implantation. Reproduced with permission . Copyright 2016, Wiley‐VCH.…”