| Part 1 The legacy effects of electromagnetic fields on bone marrow mesenchymal stem cell self-renewal and multiple differentiation potentialBackground: The effects of electromagnetic fields(EMF)on bone nonunion have been reported for many years.Many fundamental studies and randomized controlled trials have demonstrated that EMF exhibited benefits in curing delayed union and nonunion of long bone fractures.Most of them focused on the immediate effects,while the legacy effects of EMF remain poorly investigatedObjective:This study aimed to investigate the legacy effects of EMF on proliferation and multiple differentiation potential of BMSCs in vitro and in vivo.Methods: 1.In this study,rat BMSCs were treated with EMF,and after a period of time the BMSC proliferation and differentiation were detected.2.BMSC sheets with or without EMF pretreatment were transplanted into the rat tibia fracture nonunion models.The bone formation was evaluated 2,4,and 6 weeks post surgery respectively.Results: 1.The proliferation capacity of BMSCs was heightened after EMF pretreatment.Over a period of time of EMF treatment,the capacities of osteogenic and chondrogenic differentiation of BMSCs were enhanced,while adipogenic differentiation was weakened.2.BMSC sheets pretreated with EMF could better promote the healing of tibia fracture in rats,compared to BMSC sheets alone.Furthermore,significantly higher values of radiographic grading scores of rat tibias were observed in the EMF group post operation.Conclusion: 1.EMF has lasting effects on the proliferation and differentiation of BMSCs.2.Combining EMF with cell sheet technology can provide a new method for the treatment of fracture nonunion.Part2Effects of electromagnetic fields treatment on rat critical-sized calvarial defects with a 3D-printed composite scaffold Background: Current strategies for craniofacial defect are faced with unmet outcome.Combining 3D-printing with safe,noninvasive magnetic therapy could be a promising breakthrough.Objective: A BMSCs laden 3D-printed composite scaffold was fabricated and combined with EMF exposure as physical stimulus to repair critical-sized calvarial defects in rats.Methods: 1.PLA/HA composite scaffold was fabricated and the physical properties and cyto-compatibility of the scaffold were evaluated.2.After seeding rat BMSCs on scaffolds,the effects of EMF on the proliferation and osteogenic differentiation capacity of BMSCs were investigated.3.A 6 mm rat critical-sized calvarial defect model was created.4.The rats were randomly allocated to five groups including Control,Scaffold,Scaffold/EMF,Scaffold/BMSCs,and Scaffold/BMSCs/EMF.The bone formation as well as local vascularization of different groups was evaluated at fixed time after surgery.Results: 1.PLA/HA composite scaffolds exhibited uniform porous structure,high porosity(～70%),suitable compression strength(31.18±4.86 MPa)and excellent cyto-compatibility.2.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.3.The 6 mm rat critical-sized calvarial defect model was constructed successfully.All animals survived after surgery and fully recovered after 24 h.4.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.Conclusion: EMF treatment combined with 3D-printed scaffold has great potential applications in craniofacial regeneration. |
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