A novel technique for the production of electrospun scaffolds with tailored three-dimensional micro-patterns employing additive manufacturing

Electrospinning is a common technique used to fabricate fibrous scaffolds for tissue engineering applications. There is now growing interest in assessing the ability of collector plate design to influence the patterning of the fibres during the electrospinning process. In this study, we investigate a novel method to generate hybrid electrospun scaffolds consisting of both random fibres and a defined three-dimensional (3D) micro-topography at the surface, using patterned resin formers produced by rapid prototyping (RP). Poly(D,L-lactide-co-glycolide) was electrospun onto the engineered RP surfaces and the ability of these formers to influence microfibre patterning in the resulting scaffolds visualized by scanning electron microscopy. Electrospun scaffolds with patterns mirroring the microstructures of the formers were successfully fabricated. The effect of the resulting fibre patterns and 3D geometries on mammalian cell adhesion and proliferation was investigated by seeding enhanced green fluorescent protein labelled 3T3 fibroblasts onto the scaffolds. Following 24 h and four days of culture, the seeded scaffolds were visually assessed by confocal macro- and microscopy. The patterning of the fibres guided initial cell adhesion to the scaffold with subsequent proliferation over the geometry resulting in the cells being held in a 3D micro-topography. Such patterning could be designed to replicate a specific in vivo structure; we use the dermal papillae as an exemplar here. In conclusion, a novel, versatile and scalable method to produce hybrid electrospun scaffolds has been developed. The 3D directional cues of the patterned fibres have been shown to influence cell behaviour and could be used to culture cells within a similar 3D micro-topography as experienced in vivo.

[1]  Meifang Zhu,et al.  Bionic electrospun ultrafine fibrous poly(L-lactic acid) scaffolds with a multi-scale structure , 2009, Biomedical materials.

[2]  R. Reis,et al.  Patterning of polymer nanofiber meshes by electrospinning for biomedical applications , 2007, International journal of nanomedicine.

[3]  Frank Ko,et al.  Melt-electrospinning. part I: processing parameters and geometric properties , 2004 .

[4]  D. Reneker,et al.  Nanometre diameter fibres of polymer, produced by electrospinning , 1996 .

[5]  Dietmar Pum,et al.  Reassembly of S-layer proteins , 2014, Nanotechnology.

[6]  Jiang Chang,et al.  Patterning of Electrospun Fibers Using Electroconductive Templates , 2007 .

[7]  Milica Radisic,et al.  Biomaterial based cardiac tissue engineering and its applications , 2015, Biomedical materials.

[8]  C. Prinz,et al.  Interactions between semiconductor nanowires and living cells , 2015, Journal of physics. Condensed matter : an Institute of Physics journal.

[9]  A. Bruinink,et al.  The effect of topographic characteristics on cell migration velocity. , 2006, Biomaterials.

[10]  H. Craighead,et al.  Control of an electrospinning jet using electric focusing and jet-steering fields , 2006 .

[11]  常江,et al.  Electrospinning of Three-Dimensional Nanofibrous Tubes with Controllable Architectures , 2008 .

[12]  Seeram Ramakrishna,et al.  Technological advances in electrospinning of nanofibers , 2011 .

[13]  A F von Recum,et al.  Quantitative analysis of fibroblast morphology on microgrooved surfaces with various groove and ridge dimensions. , 1996, Biomaterials.

[14]  Younan Xia,et al.  Electrospinning Nanofibers as Uniaxially Aligned Arrays and Layer‐by‐Layer Stacked Films , 2004 .

[15]  K. Shakesheff,et al.  Directed differentiation of human embryonic stem cells to interrogate the cardiac gene regulatory network. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[16]  Giuseppino Fortunato,et al.  Anisotropically oriented electrospun matrices with an imprinted periodic micropattern: a new scaffold for engineered muscle constructs , 2013, Biomedical materials.

[17]  Dietmar W Hutmacher,et al.  Electrospinning and additive manufacturing: converging technologies. , 2013, Biomaterials science.

[18]  Younan Xia,et al.  Collecting electrospun nanofibers with patterned electrodes. , 2005, Nano letters.

[19]  M. Hussain,et al.  Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold. , 2007, Biomaterials.

[20]  Andrea Bagno,et al.  Electrospun scaffolds of self-assembling peptides with poly(ethylene oxide) for bone tissue engineering. , 2011, Acta biomaterialia.

[21]  Dietmar W Hutmacher,et al.  Direct Writing By Way of Melt Electrospinning , 2011, Advanced materials.

[22]  C. Vaquette,et al.  Increasing electrospun scaffold pore size with tailored collectors for improved cell penetration. , 2011, Acta biomaterialia.

[23]  Younan Xia,et al.  Radially aligned, electrospun nanofibers as dural substitutes for wound closure and tissue regeneration applications. , 2010, ACS nano.

[24]  R. Clark,et al.  Template-assisted assembly of electrospun fibers , 2010 .

[25]  J M Polak,et al.  Scaffolds and biomaterials for tissue engineering: a review of clinical applications. , 2003, Clinical otolaryngology and allied sciences.

[26]  Younan Xia,et al.  Electrospinning of polymeric and ceramic nanofibers as uniaxially aligned arrays , 2003 .

[27]  D. Cho,et al.  Fabrication of patterned nanofibrous mats using direct-write electrospinning. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[28]  Cellular Incorporation Into Electrospun Nanofibers: Retained Viability, Proliferation, and Function in Fibroblasts , 2008, Annals of plastic surgery.

[29]  Seajin Oh,et al.  Controlled continuous patterning of polymeric nanofibers on three-dimensional substrates using low-voltage near-field electrospinning. , 2011, Nano letters.

[30]  Liwei Lin,et al.  Continuous near-field electrospinning for large area deposition of orderly nanofiber patterns , 2008 .

[31]  Hirofumi Hidai,et al.  The effect of micronscale anisotropic cross patterns on fibroblast migration. , 2010, Biomaterials.

[32]  A Curtis,et al.  Topographical control of cells. , 1997, Biomaterials.

[33]  Xingyu Jiang,et al.  Fabrication of Aligned Fibrous Arrays by Magnetic Electrospinning , 2007 .

[34]  Choongsoo S. Shin,et al.  Current approaches to electrospun nanofibers for tissue engineering , 2013, Biomedical materials.