In vivo study of conductive 3D printed PCL/MWCNTs scaffolds with electrical stimulation for bone tissue engineering

Abstract

Critical bone defects are considered one of the major clinical challenges in reconstructive bone surgery. The combination of 3D printed conductive scaffolds and exogenous electrical stimulation (ES) is a potential favorable approach for bone tissue repair. In this study, 3D conductive scaffolds made with biocompatible and biodegradable polycaprolactone (PCL) and multi-walled carbon nanotubes (MWCNTs) were produced using the extrusion-based additive manufacturing to treat large calvary bone defects in rats. Histology results show that the use of PCL/MWCNTs scaffolds and ES contributes to thicker and increased bone tissue formation within the bone defect. Angiogenesis and mineralization are also significantly promoted using high concentration of MWCNTs (3 wt%) and ES. Moreover, scaffolds favor the tartrate-resistant acid phosphatase (TRAP) positive cell formation, while the addition of MWCNTs seems to inhibit the osteoclastogenesis but present limited effects on the osteoclast functionalities (receptor activator of nuclear factor κβ ligand (RANKL) and osteoprotegerin (OPG) expressions). The use of ES promotes the osteoclastogenesis and RANKL expressions, showing a dominant effect in the bone remodeling process. These results indicate that the combination of 3D printed conductive PCL/MWCNTs scaffold and ES is a promising strategy to treat critical bone defects and provide a cue to establish an optimal protocol to use conductive scaffolds and ES for bone tissue engineering.

Conductive Scaffolds for Bone Tissue Engineering: Current State and Future Outlook

“…However, poor administration of growth factors (i.e., uncontrolled release from scaffolds) can lead to ectopic bone growth [ 114 ]. Alternatively, recent studies have shown that biophysical cues, particularly scaffold conductivity, in conjunction with electrical stimulation (ES) can better aid in the generation of healthy bone tissue without the need for additional growth factors [ 18 , 115 ]. Furthermore, by employing stimuli-responsive (i.e., piezoelectric) materials as scaffolds for BTE applications, cells can convert scaffold generated stimuli into biochemical signals that illicit changes to other cellular signaling events, potentially providing scaffolds that closely approximate natural bone tissue.…”

“…These conductive scaffolds can then be divided into two distinct categories based on their composition, conductive polymer-based scaffolds and conductive nanomaterial-based scaffolds. Conductive bone scaffolds have the ability to transfer both electrical and electromechanical signals directly to targeted cells; showing the ability to improve proliferation and osteogenic differentiation in vitro, as well as bone formation in vivo, as presented in several studies [ 22 , 77 , 104 , 115 , 138 ]. Through this, conductive scaffolds can be seen as a way to not only decrease healing times associated with traumatic injuries, but also improve tissue repair overall.…”

“…By incorporating conductive nanomaterials into scaffolding matrices, particularly CNTs, a variety of structural scaffolding characteristics (i.e., strength and flexibility) can be improved as well as the induction of angiogenesis, the reduction of thrombosis and the manipulation of gene expression for tissue repair [ 171 ]. Furthermore, studies have shown that by increasing the percentage of CNTs in scaffolding, bone scaffolds can achieve a significantly higher compressive modulus, while also improving bone formation in vivo with exogenous ES [ 115 , 172 ].…”

Advances in Use of Nanomaterials for Musculoskeletal Regeneration

“…The tartrate-resistant acid phosphatase positive cell formation was promoted. While the osteoclastogenesis was inhibited using MWCNTs, the use of ES promoted it [133]. Similarly, a 3D printed porous scaffold with aligned MWCNTs and nHA was prepared by Huang et al [134].…”

Co‐Axial Gyro‐Spinning of PCL/PVA/HA Core‐Sheath Fibrous Scaffolds for Bone Tissue Engineering

“…[ 3 ] Large bone defects require bone fixation through autografts or allografts for complete healing to be achieved. [ 4,5 ] The autografts and allografts techniques are considered to be a gold‐standard treatment for large bone defects but they suffer from limitations such as multiple surgeries, potential morbidity, immunogenic responses, infection, and pathogen transmissions. [ 6 ] Bone tissue engineering emerged as an alternative approach and efficient methodology to heal, repair, and reconstruct large bone defects and tissues, and has generated substantial development in bone‐regeneration thus eliminating the drawbacks pertaining to autografts and allografts.…”