Effects of electromagnetic fields treatment on rat critical-sized calvarial defects with a 3D-printed composite scaffold

Chang Tu,Weigang Li,Chunwei Huang,Jiyuan Yan,Yongzhuang Ma,Chaoxu Liu,Jingyuan Chen,Hao Li,Xiangyu Tang,Hua Wu,Yifan Xiao

doi:10.1186/s13287-020-01954-7

Abstract

BackgroundCurrent strategies for craniofacial defect are faced with unmet outcome. Combining 3D-printing with safe, noninvasive magnetic therapy could be a promising breakthrough.MethodsIn this study, polylactic acid/hydroxyapatite (PLA/HA) composite scaffold was fabricated. After seeding rat bone marrow mesenchymal stem cells (BMSCs) on scaffolds, the effects of electromagnetic fields (EMF) on the proliferation and osteogenic differentiation capacity of BMSCs were investigated. Additionally, 6-mm critical-sized calvarial defect was created in rats. BMSC-laden scaffolds were implanted into the defects with or without EMF treatment.ResultsOur results showed that PLA/HA composite scaffolds exhibited uniform porous structure, high porosity (~ 70%), suitable compression strength (31.18 ± 4.86 MPa), modulus of elasticity (10.12 ± 1.24 GPa), and excellent cyto-compatibility. The proliferation and osteogenic differentiation capacity of BMSCs cultured on the scaffolds were enhanced with EMF treatment. Mechanistically, EMF exposure functioned partly by activating mitogen-activated protein kinase (MAPK) or MAPK-associated ERK and JNK pathways. In vivo, significantly higher new bone formation and vascularization were observed in groups involving scaffold, BMSCs, and EMF treatment, compared to scaffold alone. Furthermore, after 12 weeks of implanting, craniums in groups including scaffold, BMSCs, and EMF exposure showed the greatest biomechanical properties.ConclusionIn conclusion, EMF treatment combined with 3D-printed scaffold has great potential applications in craniofacial regeneration.

Highlights

Current strategies for craniofacial defect are faced with unmet outcome
Characterization of 3D-printed Polylactic acid (PLA)/HA composite scaffolds In our study, the 3D-printed polylactic acid/hydroxyapatite (PLA/HA) composite scaffolds showed an interconnected network of macropores with a porosity of 70 ± 2.23% (Fig. 3g)
Our in vitro results proved that Electromagnetic fields (EMF) promoted the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells (BMSCs) cultured on scaffolds and functioned partly by activating the mitogen-activated protein kinase (MAPK) or MAPK-associated ERK and JNK pathways

Summary

Introduction

Current strategies for craniofacial defect are faced with unmet outcome. Combining 3D-printing with safe, noninvasive magnetic therapy could be a promising breakthrough. Craniofacial defect caused by trauma, disease, congenital malformation, or surgery remains a challenge for surgeons [1, 2]. Autologous bone grafts, allografts, and xenografts are widely used for craniofacial defect regeneration [3, 4]. Hydroxyapatite (HA), as the major mineral constituent of the bone matrix, exhibits suitable mechanical properties. In contrast to PLA alone, combination of PLA and HA can improve the biocompatibility and the osteoconductivity of the scaffold [13]. It has been reported that scaffolds fabricated by different proportions of PLA and HA showed promising effects in bone tissue engineering [13,14,15]. Incorporation of HA can markedly improve the hydroscopicity of PLA, promoting the swelling properties of scaffold. Among various PLA to HA weight ratio for manufacturing implants by supercritical CO2, the PLA/HA (4:1) exhibited the optimal property [16]

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