Hierarchical multilayer assembly of an ordered nanofibrous scaffold via thermal fusion bonding

A major challenge in muscle tissue engineering is mimicking the ordered nanostructure of native collagen fibrils in muscles. Electrospun nanofiber constructs have been proposed as promising candidate alternatives to natural extracellular matrix. Here, we introduce a novel method to fabricate a two-dimension (2D) sheet-type and three-dimensionally integrated nanofibrous scaffolds by combining electrospinning and rapid prototyping. The aligned 2D nanofiber mats can be processed into different configurations by the CAD/CAM-based deposition of thermally extruded microstructures. We demonstrate the feasibility of these microstructures for application in muscle tissue engineering by culturing C2C12 myoblasts and then evaluating their viability and alignment. Highly aligned cellular morphologies were successfully achieved along the direction of the nanofibers in all types of scaffolds. The hybrid scaffolds provided mechanical support and served as a topographical guide at the nanoscale, exhibiting their potential to meet the requirements for practical use in tissue engineering applications.

[1]  K. Suh,et al.  Hybrid Microfabrication of Nanofiber-Based Sheets and Rods for Tissue Engineering Applications , 2013, Journal of laboratory automation.

[2]  K E Healy,et al.  Ectopic bone formation via rhBMP-2 delivery from porous bioabsorbable polymer scaffolds. , 1998, Journal of biomedical materials research.

[3]  Colleen L Flanagan,et al.  Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. , 2005, Biomaterials.

[4]  K. Leong,et al.  Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. , 2003, Biomaterials.

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

[6]  Margam Chandrasekaran,et al.  Rapid prototyping in tissue engineering: challenges and potential. , 2004, Trends in biotechnology.

[7]  P. Ma,et al.  Polymeric Scaffolds for Bone Tissue Engineering , 2004, Annals of Biomedical Engineering.

[8]  David J Mooney,et al.  Salt fusion: an approach to improve pore interconnectivity within tissue engineering scaffolds. , 2002, Tissue engineering.

[9]  P. Ma,et al.  Biodegradable polymer scaffolds with well-defined interconnected spherical pore network. , 2001, Tissue engineering.

[10]  Cato T. Laurencin,et al.  Electrospun poly(lactic acid-co-glycolic acid) scaffolds for skin tissue engineering. , 2008, Biomaterials.

[11]  C. Bader,et al.  Activation of nicotinic acetylcholine receptors increases the rate of fusion of cultured human myoblasts. , 1995, The Journal of physiology.

[12]  M. Prabhakaran,et al.  Electrospun nanostructured scaffolds for bone tissue engineering. , 2009, Acta biomaterialia.

[13]  F. Marga,et al.  Toward engineering functional organ modules by additive manufacturing , 2012, Biofabrication.

[14]  P. Ma,et al.  Microtubular architecture of biodegradable polymer scaffolds. , 2001, Journal of biomedical materials research.

[15]  Dong-Yol Yang,et al.  Quantitatively controlled fabrication of uniaxially aligned nanofibrous scaffold for cell adhesion , 2011 .

[16]  William P King,et al.  Myoblast alignment and differentiation on cell culture substrates with microscale topography and model chemistries. , 2007, Biomaterials.

[17]  Eyal Zussman,et al.  Electrostatic field-assisted alignment of electrospun nanofibres , 2001 .

[18]  Vladimir Mironov,et al.  Organ printing: computer-aided jet-based 3D tissue engineering. , 2003, Trends in biotechnology.

[19]  Tabatabaei Qomi,et al.  The Design of Scaffolds for Use in Tissue Engineering , 2014 .

[20]  K. Leong,et al.  Scaffold development using selective laser sintering of polyetheretherketone-hydroxyapatite biocomposite blends. , 2003, Biomaterials.

[21]  George J Christ,et al.  The influence of electrospun aligned poly(epsilon-caprolactone)/collagen nanofiber meshes on the formation of self-aligned skeletal muscle myotubes. , 2008, Biomaterials.

[22]  Michael J Yaszemski,et al.  Poly(propylene fumarate) bone tissue engineering scaffold fabrication using stereolithography: effects of resin formulations and laser parameters. , 2007, Biomacromolecules.

[23]  M. Kotaki,et al.  A review on polymer nanofibers by electrospinning and their applications in nanocomposites , 2003 .

[24]  Andre Levchenko,et al.  Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs , 2009, Proceedings of the National Academy of Sciences.

[25]  Benjamin Chu,et al.  Myotube assembly on nanofibrous and micropatterned polymers. , 2006, Nano letters.

[26]  George G. Chase,et al.  Continuous Electrospinning of Aligned Polymer Nanofibers onto a Wire Drum Collector , 2004 .

[27]  K. Leong,et al.  The design of scaffolds for use in tissue engineering. Part II. Rapid prototyping techniques. , 2002, Tissue engineering.

[28]  Ali Khademhosseini,et al.  Directed 3D cell alignment and elongation in microengineered hydrogels. , 2010, Biomaterials.

[29]  Andreas Greiner,et al.  Progress in the Field of Electrospinning for Tissue Engineering Applications , 2009, Advanced materials.

[30]  I. Zein,et al.  Fused deposition modeling of novel scaffold architectures for tissue engineering applications. , 2002, Biomaterials.

[31]  C. V. van Blitterswijk,et al.  Design of porous scaffolds for cartilage tissue engineering using a three-dimensional fiber-deposition technique. , 2004, Biomaterials.

[32]  K. Leong,et al.  The design of scaffolds for use in tissue engineering. Part I. Traditional factors. , 2001, Tissue engineering.

[33]  Dong-Yol Yang,et al.  Development of dual scale scaffolds via direct polymer melt deposition and electrospinning for applications in tissue regeneration. , 2008, Acta biomaterialia.

[34]  Andrés J. García,et al.  Combined microscale mechanical topography and chemical patterns on polymer cell culture substrates. , 2006, Biomaterials.

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

[36]  S. Hollister Porous scaffold design for tissue engineering , 2005, Nature materials.

[37]  Tim R. Dargaville,et al.  Dermal fibroblast infiltration of poly(ε-caprolactone) scaffolds fabricated by melt electrospinning in a direct writing mode , 2013, Biofabrication.

[38]  Nobuyuki Magome,et al.  Electrospun nanofibers as a tool for architecture control in engineered cardiac tissue. , 2011, Biomaterials.

[39]  J. Vacanti,et al.  Contractile cardiac grafts using a novel nanofibrous mesh. , 2004, Biomaterials.

[40]  J. Vacanti,et al.  A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. , 2003, Biomaterials.

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

[42]  Dong-Yol Yang,et al.  Fabrication of aligned electrospun nanofibers by inclined gap method , 2011 .

[43]  Malcolm N. Cooke,et al.  Use of stereolithography to manufacture critical-sized 3D biodegradable scaffolds for bone ingrowth. , 2003, Journal of biomedical materials research. Part B, Applied biomaterials.

[44]  R. Lieber,et al.  Structure and function of the skeletal muscle extracellular matrix , 2011, Muscle & nerve.

[45]  Sook Hee Ku,et al.  Synergic effects of nanofiber alignment and electroactivity on myoblast differentiation. , 2012, Biomaterials.

[46]  R. Langer,et al.  Engineering substrate topography at the micro- and nanoscale to control cell function. , 2009, Angewandte Chemie.