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

Edney P E Silva,Ali Aldalbahi,Boyang Huang,Gabriela C C Albiazetti,Paulo R L Nalesso,Maraiara A De Oliveira,Guilherme F Caetano,Leonardo Bagne,Fernanda A S Mendonça,Mohamed El-Newehy,Júlia V Helaehil,Paulo Bártolo,Milton Santamaria-Jr

doi:10.1007/s42242-020-00116-1

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.

Highlights

Edney P. e Silva, Boyang Huang have contributed .Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Successful bone reconstruction requires osteoproduction, osteoinduction, osteoconduction and vascularization [1]
There is an increasing trend of the connective tissue formation with the increase in multi-walled carbon nanotubes (MWCNTs) concentration and the use of electrical stimulation, there is no significant difference between the groups with and without ES except for the PCL group and natural bone group with ES
It is possible to observe that by increasing the MWCNTs’ concentration, the percentage of connective tissue decreases while the mineralized tissue increases, implying that the addition of MWCNTs promotes the transition of mature bone tissues from fibrous tissues

Summary

Introduction

Edney P. e Silva, Boyang Huang have contributed . Successful bone reconstruction requires osteoproduction, osteoinduction, osteoconduction and vascularization [1]. Current clinical strategies to treat bone defects including autografts, allografts and xenografts present several major limitations such as shortage of donations, potential transmission of disease, risk of rejection and immunogenicity issues [2]. In particular the scaffold-based strategy, is a promising approach for bone tissue regeneration which can overcome these limitations [3,4,5]. Additive manufacturing techniques combined with active biomaterials have been recognized as an effective way to produce porous 3D bone scaffolds with predefined internal shape and morphology, allowing better control of pore size and distribution [4]

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Discussion

Conclusion