A multi-layered vascular scaffold with symmetrical structure by bi-directional gradient electrospinningby Tong Wu, Chen Huang, Dawei Li, Anlin Yin, Wei Liu, Jing Wang, Jianfeng Chen, Hany EI-Hamshary, Salem S. Al-Deyab, Xiumei Mo

Colloids and Surfaces B: Biointerfaces

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Title: A multi-layered vascular scaffold with symmetrical structure by bi-directional gradient electrospinning

Author: Tong Wu Chen Huang Dawei Li Anlin Yin Wei Liu

Jing Wang Jianfeng Chen Hany EI-Hamshary Salem S.

Al-Deyab Xiumei Mo

PII: S0927-7765(15)00361-6

DOI: http://dx.doi.org/doi:10.1016/j.colsurfb.2015.05.048

Reference: COLSUB 7121

To appear in: Colloids and Surfaces B: Biointerfaces

Received date: 21-1-2015

Revised date: 2-5-2015

Accepted date: 29-5-2015

Please cite this article as: T. Wu, C. Huang, D. Li, A. Yin, W. Liu, J. Wang, J.

Chen, H. EI-Hamshary, S.S. Al-Deyab, X. Mo,A multi-layered vascular scaffold with symmetrical structure by bi-directional gradient electrospinning, Colloids and Surfaces

B: Biointerfaces (2015), http://dx.doi.org/10.1016/j.colsurfb.2015.05.048

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Ac ce pte d M an us cri pt 1 A multi-layered vascular scaffold with symmetrical structure was developed by bi-directional 1 gradient electrospinning;2 In comparison to the blended scaffold, the multi-layered scaffold showed better elasticity and a 3 controllable biodegradability under the same proportion of raw materials;4 Growth of endothelial cells and human smooth muscle cells on the multi-layered scaffold was 5 accelerated on the bioactive surface made of natural materials only.6 7

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Ac ce pte d M an us cri pt 2

A multi-layered vascular scaffold with symmetrical structure by 1 bi-directional gradient electrospinning2

Tong Wua, Chen Huangb, Dawei Lib, Anlin Yina, Wei Liuc, Jing Wanga, Jianfeng Chenc, Hany EI-Hamsharyd,e, 3

Salem S. Al-Deyabd, Xiumei Mo*a,c4 a State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering 5 and Biotechnology, Donghua University, Shanghai 201620, China 6 b Engineering Research Center of Technical Textiles, Ministry of Education, College of Textiles, Donghua University, Shanghai 7 201620, China8 c College of Material Science and Engineering, Donghua University, Shanghai 201620, China9 d Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Kindom of Saudi Arabia10 e Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt11 * Corresponding Author: Phone: +86 02167792653; E-mail: xmm@dhu.edu.cn12 13

Multi-layered scaffolds are advantageous in vascular tissue engineering, in consideration of better combination of biomechanics, 14 biocompatibility and biodegradability than the scaffolds with single structure. In this study, a bi-directional gradient 15 electrospinning method was developed to fabricate Poly(L-lactide-co-caprolactone) (P(LLA-CL)), collagen and chitosan based 16 tubular scaffold with multi-layered symmetrical structure. The multi-layered composite scaffold showed improved mechanical 17 property and biocompatibility, in comparison to the blended scaffold using the same proportion of raw materials.18

Endothelialization on the multi-layered scaffold was accelerated owing to the bioactive surface made of pure natural materials. 19 hSMCs growth showed the similar results because of its better biocompatibility. Additionally, fibers morphology change, pH value 20 balance and long term mechanical support results showed that the gradient structure effectively improved biodegradability. 21 22

Key words: Electrospinning, multi-layered vascular scaffolds, P(LLA-CL), collagen, chitosan, tissue engineering 23 24

Introduction25

Clinically accredited vascular prostheses are increasingly desired as alternatives to autologous arterial or venous vascular substitutes because 26 of the high mortality and disability caused by cardiovascular diseases. Although autograft is usually the most effective way , it has been often 27 limited by the shortage of donors.[1] Besides, the acute thrombosis and subsequent occlusion often lead to the failure of the transplantation 28 when commercialized Dacron or e-PTFE vascular grafts were used for small-diameter blood vessels.[2] In this regard, the unmet need drives 29 the research into alternative tissue engineered vascular grafts for small diameter vessels.[3] Tissue engineered scaffolds aim at mimicking the 30 natural extracellular matrix (ECM) both structurally and functionally to provide a suitable biophysiological microenvironment for tissue 31 regeneration. As reported, ECM in native cardiovascular tissue plays a critical role for cells proliferation, motility and intercellular signaling, 32 and the protein fibers along with other components in the ECM confer the structural integrity and mechanical support of blood vessels.[4]33

Therefore, choosing effective molding technologies and ECM-mimicking biomaterials is of great importance for designing bionic tissue 34 engineered grafts. 35

Electrospinning is now a commonly utilized fabrication technique to prepare ultrafine fibers and fibrous scaffolds.[5, 6] Electrospun 36 scaffolds could offer more cues for cell growth because of the high surface area and porosity. Since the morphology and diameter of 37 electrospun fibers depend on material and processing parameters, through regulating these interrelated variables (i.e. spinneret design, 38 electric field intensity, auxiliary electric/magnetic field, applied voltage, flow rate, collection distance, solution conductivity, solution 39 conductivity), fibers morphology can be well controlled.[7]40

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Ac ce pte d M an us cri pt 3

A wide variety of natural and synthetic polymers have been electrospun for tissue engineered tubular scaffolds, including collagen, elastin, 1 chitosan, polylactic acid (PLA), poly(ε-caprolactone) (PCL), poly (glycolic acid) (PGA), Poly(L-lactide-co-caprolactone) (P(LLA-CL)), 2 etc.[4, 8-13] Natural materials usually have better biocompatibility and lower thrombogenicity, while synthetic biomaterials could provide 3 suitable mechanical support.[14] Collagen, as the primary structural component of natural ECM, could modulate the mechanical property of 4 tissue engineered scaffolds and regulate cell adhesion, proliferation, etc.[4, 15-18] Chitosan is a biomimetic, amino cationic polysaccharide 5 derived by deacetylation of chitin, which could emulate ECM glycosaminoglycan molecules and amplify the number of amine reaction sites 6 and form an ionic complex with collagen that may result in enhanced stability.[19-21] Our previous efforts[8, 22-24] suggested that, for 7 electrospun collagen and chitosan scaffolds, optimal mechanical property and biocompatibility could be achieved when the blending ratio of 8 collagen and chitosan was 4:1 (w/w). P(LLA-CL) was further mixed with collagen and chitosan blend as the reinforcement. When the ratio 9 of P(LLA-CL)/collagen/chitosan was 75:20:5, the multicomponent nanofibrous scaffolds demonstrated good endothelial cell proliferation 10 and mechanical support.[13] However, for blended scaffolds, direct contact of synthetic material with tissues could not be avoided, which 11 often results in a relatively slow cell growth than natural scaffolds.12