Hybrid polycaprolactone/hydrogel scaffold fabrication and in-process plasma treatment using PABS

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Fengyuan Liu, Hussein Mishbak, Paulo jorge dasilva Bartolo


challenge for tissue engineering is to produce synthetic scaffolds of adequate chemical, physical, and biological cues effectively. Due to the hydrophobicity of the commonly used synthetic polymers, the printed scaffolds are limited in cell-seeding and proliferation efficiency. Furthermore, non-uniform cell distribution along the scaffolds with rare cell attachment in the core region is a common problem. There are no available commercial systems able to produce multi-type material and gradient scaffolds which could mimic the nature tissues. This paper describes a plasma-assisted bio-extrusion system (PABS) to overcome the above limitations and capable of producing functional-gradient scaffolds; it comprises pressure-assisted and screw-assisted extruders and plasma jets. A hybrid scaffold consisting of synthetic biopolymer and natural hybrid hydrogel alginate-gelatin (Alg-Gel) methacrylate anhydride, and full-layer N2 plasma modification scaffolds were produced using PABS. Water contact angle and in vitro biological tests confirm that the plasma modification alters the hydrophilicity properties of synthetic polymers and promotes proliferation of cells, leading to homogeneous cell colonization. The results confirm the printing capability for soft hard material integration of PABS and suggest that it is promising for producing functional gradient scaffolds of biomaterials.


Tissue engineering; hybrid scaffold; PABS; in-process plasma modification; functional gradient scaffold

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Pereira R F, Sousa A, Barrias C C, et al., 2017, Advances in

bioprinted cell-laden hydrogels for skin tissue engineering.

Biomanuf Rev, 2(1): 1. https://doi.org/10.1007/s40898-017-


Melchels F P, Domingos M A, Klein T J, et al., 2012,

Additive manufacturing of tissues and organs. Prog

Polym Sci, 37(8): 1079-1104. https://doi.org/10.1016/j.


Vyas C, Pereira R, Huang B, et al., 2017, Engineering the

vasculature with additive manufacturing. Curr Opin Biomed

Eng, 2: 1-13. https://doi.org/10.1016/j.cobme.2017.05.008.

Rahman S, Carter P, Bhattarai N, 2017, Aloe vera for tissue

engineering applications. J Funct Biomater, 8(1): 6. https://


Maldonado M A, Bonham A J, 2017, Conductive gel

polymers as an extracellular matrix mimic and cell vehicle

for cardiac tissue engineering. FASEB J, 31(1_supplement):


Black C R, Goriainov V, Gibbs D, et al., 2015, Bone tissue

engineering. Curr Mol Biol Rep, 1(3): 132-140. https://doi.


Asghari F, Samiei M, Adibkia K, et al., 2017, Biodegradable

and biocompatible polymers for tissue engineering application: A review. Artif Cells Nanomed Biotechnol, 45(2):185-192. https://doi.org/10.3109/21691401.2016.1146731.

Trombetta R, Inzana J A, Schwarz E M, et al., 2017, 3D printing

of calcium phosphate ceramics for bone tissue engineering

and drug delivery. Ann Biomed Eng, 45(1): 23-44. https://doi.


Vacanti J P, Langer R, 1999, Tissue engineering: The design

and fabrication of living replacement devices for surgical

reconstruction and transplantation. Lancet, 354: S32-S34.


Mohanty A K, Misra M, Hinrichsen G, 2000, Biofibres,

biodegradable polymers and biocomposites: An

overview. Macromol Mater Eng, 276(1): 1-24. https://doi.


Kumar A, Mandal S, Barui S, et al., 2016, Low temperature

additive manufacturing of three dimensional scaffolds for

bone-tissue engineering applications: Processing related

challenges and property assessment. Mater Sci Eng Rep, 103:

-39. https://doi.org/10.1016/j.mser.2016.01.001.

Forrestal D P, Klein T J, Woodruff M A, 2017, Challenges

in engineering large customized bone constructs. Biotechnol

Bioeng, 114(6): 1129-1139. https://doi.org/10.1002/bit.26222.

Bártolo P, Chua C, Almeida H, et al., 2009,

Biomanufacturing for tissue engineering: Present and future

trends. Virtual Phys Prototyp, 4(4): 203-216. https://doi.


Bártolo P J, Domingos M, Patrício T, et al., 2011,

Biofabrication strategies for tissue engineering. Adv Model

Tissue Eng, 11: 137-176. https://doi.org/10.1007/978-94-


Bartolo P, Kruth J P, Silva J, et al., 2012, Biomedical production

of implants by additive electro-chemical and physical

processes. CIRP Ann Manuf Technol, 61(2): 635-655. https://


Rutz A L, Hyland K E, Jakus A E, et al., 2015, A multimaterial

bioink method for 3D printing tunable, cell-compatible

hydrogels. Adv Mater, 27(9): 1607-1614. https://doi.


Jakus A E, Shah R N, 2017, Multi and mixed 3D-printing of

graphene-hydroxyapatite hybrid materials for complex tissue

engineering. J Biomed Mater Res Part A, 105(1): 274-283.


Hoque M E, Chuan Y L, Pashby I, 2012, Extrusion based

rapid prototyping technique: An advanced platform for tissue

engineering scaffold fabrication. Biopolymers, 97(2): 83-93.

Bellini A, 2002, Fused Deposition of Ceramics: A

Comprehensive Experimental, Analytical and Computational

Study of Material Behavior, Fabrication Process and

equipment Desig. Philadelphia, PA: Drexel University.

Almeida H, Bartolo P, Mota C, et al., 2010, Process equipment

for rapid bioextrusion fabrication. Portuguese Patent Appl,

, 247.

Zhang L G, Fisher J P, Leong K, 2015, 3D Bioprinting and

Nanotechnology in Tissue Engineering and Regenerative

Medicine. London: Academic Press.

Giannitelli S, Mozetic P, Trombetta M, et al., 2015,

Combined additive manufacturing approaches in tissue

engineering. Acta Biomater, 24: 1-11. https://doi.org/10.1016/j.


Sobral J M, Caridade S G, Sousa R A, et al., 2011, Threedimensional

plotted scaffolds with controlled pore size

gradients: Effect of scaffold geometry on mechanical

performance and cell seeding efficiency. Acta Biomater, 7(3):

-1018. https://doi.org/10.1016/j.actbio.2010.11.003.

Oh S H, Lee J H, 2013, Hydrophilization of synthetic

biodegradable polymer scaffolds for improved cell/tissue

compatibility. Biomed Mater, 8(1): 014101. https://doi.


Yang J, Wan Y, Yang J, et al., 2003, Plasma-treated, collagenanchored

polylactone: Its cell affinity evaluation under shear

or shear-free conditions. J Biomed Mater Res Part A, 67(4):

-1147. https://doi.org/10.1002/jbm.a.10034.

Ozbolat I T, Chen H, Yu Y, 2014, Development of ‘multiarm

bioprinter’for hybrid biofabrication of tissue engineering

constructs. Robot Comput Integr Manuf, 30(3): 295-304.


Intranuovo F, Gristina R, Brun F, et al., 2014, Plasma

modification of PCL porous scaffolds fabricated by solventcasting/

particulate-leaching for tissue engineering. Plasma

Process Polym, 11(2): 184-195. https://doi.org/10.1002/


Intranuovo F, Gristina R, Fracassi L, et al., 2016, Plasma

processing of scaffolds for tissue engineering and regenerative

medicine. Plasma Chem Plasma Process, 36(1): 269-280.


Jeon O, Bouhadir K H, Mansour J M, et al., 2009,

Photocrosslinked alginate hydrogels with tunable biodegradation

rates and mechanical properties. Biomaterials, 30(14): 2724-


Liu F, Hinduja S, Bartolo P, 2018, User interface tool for a

novel plasma-assisted bio-additive extrusion system. Rapid

Prototyp, 10: 1108.https://doi.org/10.1108/RPJ-07-2016-0115.

Park K, Ju Y M, Son J S, et al., 2007, Surface modification of biodegradable electrospun nanofiber scaffolds and their

interaction with fibroblasts. J Biomater Sci Polym , 18(4):

-382. https://doi.org/10.1163/156856207780424997.

Thakur S, Neogi S, 2015, Tailoring the adhesion of polymers using

plasma for biomedical applications: A critical review. Rev Adhes

Adhes, 3(1): 53-97. https://doi.org/10.7569/RAA.2015.097303.

Gross M, Zhao X, Mascarenhas V, et al., 2016, Effects of the

surface physico-chemical properties and the surface textures

on the initial colonization and the attached growth in algal

biofilm. Biotechnol Biofuel, 9(1): 38. https://doi.org/10.1186/


Hashimoto M, Hossain S, Masumura S, 1999, Effect of aging

on plasma membrane fluidity of rat aortic endothelial cells-.☆

Exp Gerontol, 34(5): 687-698. https://doi.org/10.1016/


Wavhal D S, Fisher E R, 2002, Hydrophilic modification of

polyethersulfone membranes by low temperature plasmainduced

graft polymerization. J Membr Sci, 209(1): 255-269.


Pappa A M, Karagkiozaki V, Krol S, et al., 2015, Oxygenplasma-

modified biomimetic nanofibrous scaffolds for

enhanced compatibility of cardiovascular implants. Beilstein

J Nanotechnol, 6: 254. https://doi.org/10.3762/bjnano.6.24.

Sousa I, Mendes A, Pereira R F, et al., 2014, Collagen surface

modified poly (ε-caprolactone) scaffolds with improved

hydrophilicity and cell adhesion properties. Mater Lett, 134:

-267. https://doi.org/10.1016/j.matlet.2014.06.132.

DOI: http://dx.doi.org/10.18063/ijb.v5i1.174


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