A Critical Review on the Production of Electrospun Nanofibres for Guided
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nanomaterials Review A Critical Review on the Production of Electrospun Nanofibres for Guided Bone Regeneration in Oral Surgery Federico Berton * , Davide Porrelli , Roberto Di Lenarda and Gianluca Turco Clinical Department of Medical, Surgical and Health Sciences, University of Trieste, 34100 Trieste, Italy; [email protected] (D.P.); [email protected] (R.D.L.); [email protected] (G.T.) * Correspondence: [email protected]; Tel.: +39-0403992020 Received: 3 November 2019; Accepted: 16 December 2019; Published: 19 December 2019 Abstract: Nanofibre-based membranes or scaffolds exhibit high surface-to-volume ratio, which allows an improved cell adhesion, representing an attractive subgroup of biomaterials due to their unique properties. Among several techniques of nanofiber production, electrospinning is a cost-effective technique that has been, to date, attractive for several medical applications. Among these, guided bone regeneration is a surgical procedure in which bone regeneration, due to bone atrophy following tooth loss, is “guided” by an occlusive barrier. The membrane should protect the initial blood clot from any compression, shielding the bone matrix during maturation from infiltration of soft tissues cells. This review will focus its attention on the application of electrospinning (ELS) in oral surgery bone regeneration. Despite the abundance of published papers related to the electrospinning technique applied in the field of bone regeneration of the jaws, to the authors’ knowledge, no articles report clinical application of these structures. Moreover, only a few records can be found with in vivo application. Therefore, no human studies have to date been detectable. New approaches such as multifunctional multilayering and coupling with bone promoting factors or antimicrobial agents, makes this technology very attractive. However, greater efforts should be made by researchers and companies to turn these results into clinical practice. Keywords: electrospinning; guided bone regeneration; oral surgery; membranes; scaffolds 1. Introduction Nanofibres in tissue Eegineering (TE) represent an extremely attractive subgroup of biomaterials due to their unique intrinsic features. Nanofibre-based membranes or scaffolds exhibit high surface-to-volume ratio, which allows an improved cell adhesion. Moreover, these structures can be implemented with proteins, drugs and ligands. The mechanical and morphological properties of these structures are even more promising thanks to the customizable dimensions, orientation, packing, porosity and density of the fibres. Finally, the resulting three-dimensional structure of the obtained nanostructured material mimics the morphology of the extracellular matrix, which consists predominantly of collagen fibrils, coupled with elastin and other macromolecules such as glycoproteins [1]. Furthermore, nanofibres can promote specific cellular functions such as adhesion, proliferation, differentiation, and can modulate stem cell behavior [2,3]. Several techniques have been proposed in literature to fabricate nanofibres: phase separation technique [4], self-assembly fibres [5], template synthesis [6] and electrospinning (ELS) [7] to name some. Among these techniques, electrospinning is a cost-effective technique that can be used to prepare nanofibres. The ELS technique has risen its popularity since its early development in the 1930s [8] along with the refinements of its basic components and setup. Nanomaterials 2020, 10, 16; doi:10.3390/nano10010016 www.mdpi.com/journal/nanomaterials Nanomaterials 2020, 10, x FOR PEER REVIEW 2 of 16 NanomaterialsThis technique2020, 10, 16 is used for polymeric solutions that can be modified and enriched with bioactive2 of 17 molecules. Electrospun fibres are to date, attractive for several medical applications such as, wound dressings,This techniquedrug delivery is used and for scaffolds polymeric for tissue solutions engineering that can [9]. be modifiedThanks to and their enriched features, with electrospun bioactive nanofibresmolecules. have Electrospun been attractive fibres are also to date,in the attractive dental field: for several periodontal medical regenerat applicationsion [10], such coatings as, wound for cariesdressings, prevention drug delivery [11], enrichment and scaff oldsof resin for tissuecomposites engineering [12], implant [9]. Thanks surface to modification their features, [13], electrospun wound healingnanofibres of mucosa have been [14], attractivedrug-releasing also in systems the dental [15] field:and bone periodontal regeneration regeneration [16] are the [10 ],main coatings topic forof basiccaries research. prevention Guided [11], enrichmentbone regeneration of resin (GBR) composites is a surgical [12], implant procedure surface in which modification bone regeneration, [13], wound duehealing to bone of mucosa atrophy [ 14following], drug-releasing tooth loss, systems is “guided” [15] and by an bone occlusive regeneration barrier. [16 The] are membrane the main topicshould of maintainbasic research. the shape Guided of the bone defect regeneration in which the (GBR) bone isis astimulated surgical procedure to regenerate. in which The memb bone regeneration,rane should alsodue protect to bone the atrophy initial followingblood clot tooth from loss,any compression, is “guided” by shielding an occlusive the bone barrier. matrix The during membrane maturation should frommaintain infiltration the shape of of soft the defecttissues in whichcells. Therefore, the bone is stimulatedthese membranes to regenerate. should The maintain membrane suitable should mechanicalalso protect properties the initial bloodat least clot for from three any months compression, of permanence shielding exhibiting the bone at matrix the same during time maturation a proper biofrom-degradability infiltration of which soft tissues avoids cells. second Therefore, surgery these for membranes patients [17,18 should]. maintainThis review suitable will mechanical focus its attentionproperties on at the least production for three months of ELS of membranes permanence for exhibiting bone regeneration at the same timein oral a proper surgery bio-degradability of ELS in oral surgerywhich avoids bone regeneration. second surgery Hereafter, for patients the [ 17production,18]. This reviewof both willscaffolds focus and its attention membranes on the by production means of ELSof ELS is discussed membranes in view for bone of regenerating regeneration alveolar in oral bone surgery defects of ELS. [19,20], in oral prior surgery to implant bone regeneration. insertion in theHereafter, atrophic the jaws production [21]. of both scaffolds and membranes by means of ELS is discussed in view of regenerating alveolar bone defects. [19,20], prior to implant insertion in the atrophic jaws [21]. 2. Principles of the Electrospinning (ELS) Technique 2. PrinciplesThis technique of the was Electrospinning firstly applied (ELS) in 1934 Technique by Anton Formhals and represents a combination of two techniquesThis technique which was are firstly the appliedelectrospray in 1934 and by Antonthe spinning Formhals of andfibres represents [22]. A high a combination electric field of two is appliedtechniques to both which the are syringe the electrospray needle, which and contains the spinning a po oflymeric fibres solution, [22]. A high and electric to the collector field is applied (Figure to 1).both the syringe needle, which contains a polymeric solution, and to the collector (Figure1). Figure 1. Schematic representation of the essential set-up of an electrospinning (ELS) device. Figure 1. Schematic representation of the essential set-up of an electrospinning (ELS) device. The collector and the syringe needle are kept at the proper distance one from the other. MetallicThe collector plates, aluminumand the syringe foils needle and rotating are kept drums at the proper can be distance used as one target from for the the other. collection Metallic of plates,nanofibres aluminum during foils the electrospinningand rotating drums process. can be The used potential as target di ffforerence the collection is, hence, of able nanofibres to overcome during the thesurface electrospinning tension electrostatic process. The forces potential of the polymeric difference solutionis, hence ejected, able to from overcome the needle the surface tip and tension assume electrostaticthe so called forces “Taylor of cone”the polymeric configuration solution [23 ]ejected (Figure from2). This the process needle shapestip and the assume polymeric the so solution called “Taylor cone” configuration [23] (Figure 2). This process shapes the polymeric solution into a jet of Nanomaterials 2020, 10, 16 3 of 17 Nanomaterials 2020, 10, x FOR PEER REVIEW 3 of 16 into a jet of charged fluid that is electrostatically attracted by the collector. The solvent evaporates charged fluid that is electrostatically attracted by the collector. The solvent evaporates during this during this transit from the needle to the collector allowing for the accumulation of dry fibres on it. transit from the needle to the collector allowing for the accumulation of dry fibres on it. Figure 2.2. Taylor conecone obtainedobtained withwith thethe followingfollowing parameters:parameters: a solution of polycaprolactone (PCL) 12%12% ww/v/v inin dichloromethanedichloromethane/dimethylformamide/dimethylformamide (DCM(DCM/DMF)/DMF) 7:3 applying 17 kV of potentialpotential and 0.6 mL//hh ofof flowflow raterate andand usingusing aa 2525 GG needle.needle. NikonNikon D3500,D3500, macro 105105 SigmaSigma tamrontamron