Microsystem Technologies

, Volume 25, Issue 9, pp 3339–3355 | Cite as

Fabrication of three-dimensional mPEG-PCL-mPEG scaffolds combined with cell-laden gelatin methacrylate (GelMA) hydrogels using thermal extrusion coupled with photo curable technique

  • Jianghui Dong
  • Yu-Da Yang
  • Liping WangEmail author
  • Cho-Pei JiangEmail author
Technical Paper


It has remained a great challenge to design a tissue engineering scaffold for tissue regeneration, which should be suitable for cell adhesion, proliferation and differentiation. One possible solution may be to fabricate the scaffolds with the stable mechanical property, controllable pore size and good interconnectivity, and allowing homogenous cell distribution. This study described the key technology of fabricating three-dimensional (3D) mPEG-PCL-mPEG scaffolds combined with cell-laden gelatin methacrylate (GelMA) hydrogels. Firstly, a dual-nozzle 3D printing system was successfully developed using thermal extrusion coupled with a photo curable technique. Then, the triblock material mPEG-PCL-mPEG was synthesized and evaluated. Subsequently, the fabricated 3D mPEG-PCL-mPEG scaffolds were injected with cell-laden GelMA hydrogels. Finally, the mPEG-PCL-mPEG scaffolds were evaluated. The evaluation results showed that this 3D mPEG-PCL-mPEG scaffolds technology is a potentially powerful approach, which may be used in a variety of tissue engineering applications.



This work was supported by MOST of Taiwan grant (106-2221-E-150-001) and NSFC (Natural Science Foundation of China) project grant (No.81671928). LPW is supported by National Health and Medical Research Council (NHMRC) Fellowship (No. APP1158402), Channel 7 Children’s Research Foundation grant (No.181662), and NSFC (No.81671928).


  1. Abbott A (2003) Cell culture: biology’s new dimension. Nature 424:870–872CrossRefGoogle Scholar
  2. Agarwal R, García AJ (2015) Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair. Adv Drug Deliv Rev 94:53–62CrossRefGoogle Scholar
  3. Baker BM, Chen CS (2012) Deconstructing the third dimension–how 3D culture microenvironments alter cellular cues. J Cell Sci 125(13):3015–3024CrossRefGoogle Scholar
  4. Bernardin JD, Mudawar I, Walsh CB, Franses EI (1997) Contact angle temperature dependence for water droplets on practical aluminum surfaces. Int J Heat Mass Transf 40(5):1017–1033CrossRefGoogle Scholar
  5. Bertol LS, Schabbach R, dos Santos LAL (2017) Different post-processing conditions for 3D bioprinted α-tricalcium phosphate scaffolds. J Mater Sci Mater Med 28(10):168CrossRefGoogle Scholar
  6. Bose S, Vahabzadeh S, Bandyopadhyay A (2013) Bone tissue engineering using 3D printing. Mater Today 16(12):496–504CrossRefGoogle Scholar
  7. Brydone A, Meek D, Maclaine S (2010) Bone grafting, orthopaedic biomaterials, and the clinical need for bone engineering. Proc Inst Mech Eng Part H J Eng Med 224(12):1329–1343CrossRefGoogle Scholar
  8. Cohen DL, Lo W, Tsavaris A, Peng D, Lipson H, Bonassar LJ (2010) Increased mixing improves hydrogel homogeneity and quality of three-dimensional printed constructs. Tissue Eng Part C Methods 17(2):239–248CrossRefGoogle Scholar
  9. Cuadros TR, Erices AA, Aguilera JM (2015) Porous matrix of calcium alginate/gelatin with enhanced properties as scaffold for cell culture. J Mech Behav Biomed Mater 46:331–342CrossRefGoogle Scholar
  10. Do AV, Khorsand B, Geary SM, Salem AK (2015) 3D printing of scaffolds for tissue regeneration applications. Adv Healthcare Mater 4(12):1742–1762CrossRefGoogle Scholar
  11. Doblaré M, Garcıa J, Gómez M (2004) Modelling bone tissue fracture and healing: a review. Eng Fract Mech 71(13–14):1809–1840CrossRefGoogle Scholar
  12. E ISO 10993-5 (2009) Biological evaluation of medical devices. Part 5: tests for in vitro cytotoxicity. International Organization for Standardization, GenevaGoogle Scholar
  13. Edep ME, Shirani J, Wolf P, Brown DL (2000) Matrix metalloproteinase expression in nonrheumatic aortic stenosis. Cardiovasc Pathol 9(5):281–286CrossRefGoogle Scholar
  14. Erdemli Ö, Usanmaz A, Keskin D, Tezcaner A (2014) Characteristics and release profiles of MPEG-PCL-MPEG microspheres containing immunoglobulin G. Colloids Surf B Biointerfaces 117:487–496CrossRefGoogle Scholar
  15. Fillingham Y, Jacobs J (2016) Bone grafts and their substitutes. Bone Joint J 98(1 Supple A):6–9CrossRefGoogle Scholar
  16. Florencio-Silva R, Sasso GRDS, Sasso-Cerri E, Simões MJ, Cerri PS (2015) Biology of bone tissue: structure, function, and factors that influence bone cells. BioMed Res Int 2015:421746CrossRefGoogle Scholar
  17. Fu S, Ni P, Wang B, Chu B, Zheng L, Luo F, Luo J, Qian Z (2012) Injectable and thermo-sensitive PEG-PCL-PEG copolymer/collagen/n-HA hydrogel composite for guided bone regeneration. Biomaterials 33(19):4801–4809CrossRefGoogle Scholar
  18. Gibbs DM, Vaezi M, Yang S, Oreffo RO (2014) Hope versus hype: what can additive manufacturing realistically offer trauma and orthopedic surgery? Regen Med 9(4):535–549CrossRefGoogle Scholar
  19. Gruskin E, Doll BA, Futrell FW, Schmitz JP, Hollinger JO (2012) Demineralized bone matrix in bone repair: history and use. Adv Drug Deliv Rev 64(12):1063–1077CrossRefGoogle Scholar
  20. Guillotin B, Guillemot F (2011) Cell patterning technologies for organotypic tissue fabrication. Trends Biotechnol 29(4):183–190CrossRefGoogle Scholar
  21. Hollister SJ (2005) Porous scaffold design for tissue engineering. Nat Mater 4(7):518CrossRefGoogle Scholar
  22. Holzwarth JM, Ma PX (2011) 3D nanofibrous scaffolds for tissue engineering. J Mater Chem 21(28):10243–10251CrossRefGoogle Scholar
  23. Jiang CP, Chen YY, Hsieh MF (2013a) Biofabrication and in vitro study of hydroxyapatite/mPEG–PCL–mPEG scaffolds for bone tissue engineering using air pressure-aided deposition technology. Mater Sci Eng C 33(2):680–690CrossRefGoogle Scholar
  24. Jiang CP, Chen YY, Hsieh MF, Lee HM (2013b) Solid freeform fabrication and in vitro response of osteoblast cells of mPEG-PCL-mPEG bone scaffolds. Biomed Microdevice 15(2):369–379CrossRefGoogle Scholar
  25. Jiankang H, Dichen L, Yaxiong L, Bo Y, Hanxiang Z, Qin L, Bingheng L, Yi L (2009) Preparation of chitosan–gelatin hybrid scaffolds with well-organized microstructures for hepatic tissue engineering. Acta Biomater 5(1):453–461CrossRefGoogle Scholar
  26. Kricheldorf HR, Kreiser-Saunders I, Boettcher C (1995) Polylactones: 31. Sn (II) octoate-initiated polymerization of l-lactide: a mechanistic study. Polymer 36(6):1253–1259CrossRefGoogle Scholar
  27. Lietman SA, Tomford WW, Gebhardt MC, Springfield DS, Mankin HJ (2000) Complications of irradiated allografts in orthopaedic tumor surgery. Clin Orthop Relat Res 375:214–217CrossRefGoogle Scholar
  28. Lin RZ, Chen YC, Moreno-Luna R, Khademhosseini A, Melero-Martin JM (2013) Transdermal regulation of vascular network bioengineering using a photopolymerizable methacrylated gelatin hydrogel. Biomaterials 34(28):6785–6796CrossRefGoogle Scholar
  29. Liu X, Smith LA, Hu J, Ma PX (2009) Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering. Biomaterials 30(12):2252–2258CrossRefGoogle Scholar
  30. Martin I, Wendt D, Heberer M (2004) The role of bioreactors in tissue engineering. Trends Biotechnol 22(2):80–86CrossRefGoogle Scholar
  31. Mouriño V, Boccaccini AR (2010) Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds. J R Soc Interface 7(43):209–227CrossRefGoogle Scholar
  32. Murphy SV, Atala A (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32(8):773CrossRefGoogle Scholar
  33. Neufurth M, Wang X, Wang S, Steffen R, Ackermann M, Haep ND, Schröder HC, Müller WEG (2017) 3D printing of hybrid biomaterials for bone tissue engineering: calcium-polyphosphate microparticles encapsulated by polycaprolactone. Acta Biomater 64:377–388CrossRefGoogle Scholar
  34. Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A (2010) Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 31(21):5536–5544CrossRefGoogle Scholar
  35. Nijenhuis A, Grijpma D, Pennings A (1992) Lewis acid catalyzed polymerization of l-lactide. Kinetics and mechanism of the bulk polymerization. Macromolecules 25(24):6419–6424CrossRefGoogle Scholar
  36. Occhetta P, Visone R, Russo L, Cipolla L, Moretti M, Rasponi M (2015) VA-086 methacrylate gelatine photopolymerizable hydrogels: a parametric study for highly biocompatible 3D cell embedding. J Biomed Mater Res Part A 103(6):2109–2117CrossRefGoogle Scholar
  37. Sachlos E, Reis N, Ainsley C, Derby B, Czernuszka J (2003) Novel collagen scaffolds with predefined internal morphology made by solid freeform fabrication. Biomaterials 24(8):1487–1497CrossRefGoogle Scholar
  38. Schneider OD, Weber F, Brunner TJ, Loher S, Ehrbar M, Schmidlin PR, Stark WJ (2009) In vivo and in vitro evaluation of flexible, cottonwool-like nanocomposites as bone substitute material for complex defects. Acta Biomater 5(5):1775–1784CrossRefGoogle Scholar
  39. Smith IO, McCabe LR, Baumann MJ (2006) MC3T3-E1 osteoblast attachment and proliferation on porous hydroxyapatite scaffolds fabricated with nanophase powder. Int J Nanomed 1(2):189CrossRefGoogle Scholar
  40. Stephens J, Cooper JA, Phelan F, Dunkers JP (2007) Perfusion flow bioreactor for 3D in situ imaging: investigating cell/biomaterials interactions. Biotechnol Bioeng 97(4):952–961CrossRefGoogle Scholar
  41. Strong DM, Friedlaender GE, Tomford WW, Springfield DS, Shives TC, Burchardt H, Enneking W, Mankin HJ (1996) Immunologic responses in human recipients of osseous and osteochondral allografts. Clin Orthop Relat Res 326:107–114CrossRefGoogle Scholar
  42. Subia B, Kundu J, Kundu S (2010) Biomaterial scaffold fabrication techniques for potential tissue engineering applications. Tissue engineering. InTech2010, LondonGoogle Scholar
  43. Tang D, Tare RS, Yang LY, Williams DF, Ou KL, Oreffo ROC (2016) Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration. Biomaterials 83:363–382CrossRefGoogle Scholar
  44. Ullah F, Othman MBH, Javed F, Ahmad Z, Akil HM (2015) Classification, processing and application of hydrogels: a review. Mater Sci Eng C 57:414–433CrossRefGoogle Scholar
  45. Van Den Bulcke AI, Bogdanov B, De Rooze N, Schacht EH, Cornelissen M, Berghmans H (2000) Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromol 1(1):31–38CrossRefGoogle Scholar
  46. Yao X, Panichpisal K, Kurtzman N, Nugent K (2007) Cisplatin nephrotoxicity: a review. Am J Med Sci 334(2):115–124CrossRefGoogle Scholar
  47. Yaszemski MJ, Payne RG, Hayes WC, Langer R, Mikos AG (1996) Evolution of bone transplantation: molecular, cellular and tissue strategies to engineer human bone. Biomaterials 17(2):175–185CrossRefGoogle Scholar
  48. Yuan Y, Lee TR (2013) Contact angle and wetting properties, surface science techniques. Springer, Berlin, pp 3–34Google Scholar
  49. Zhu N, Chen X (2013) Biofabrication of tissue scaffolds. Advances in biomaterials science and biomedical applications. InTech2013, LondonGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Hand Surgery, Department of Plastic Reconstructive SurgeryNingbo No.6 HospitalNingboChina
  2. 2.School of Pharmacy and Medical Sciences, and UniSA Cancer Research InstituteUniversity of South AustraliaAdelaideAustralia
  3. 3.Department of Power Mechanical Engineering, Institution of Mechanical and Electro-Mechanical EngineeringNational Formosa UniversityYunlinTaiwan
  4. 4.Department of Mechanical EngineeringNational Taipei University of TechnologyTaipeiTaiwan

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