Journal of Materials Science

, Volume 54, Issue 9, pp 7180–7197 | Cite as

Preparation of polycarbonate/gelatine microspheres using a high-voltage electrostatic technique for enhancing the adhesion and proliferation of mesenchymal stem cells

  • Chunxu Li
  • Linlong Li
  • Rui Ma
  • Zongliang Wang
  • Xincui Shi
  • Xiaoyu YangEmail author
  • Yu WangEmail author
  • Peibiao ZhangEmail author
Materials for life sciences


In this study, a high-voltage electrostatic technique is introduced to prepare polycarbonate (PC) microspheres in order to design an expansion strategy for the bone marrow mesenchymal stem cells (BMMSCs). The effects of the solution concentration, temperature, nozzle specification and voltage on the sphericity, homogeneity, diameter and sedimentation velocities of the microspheres are investigated. By optimising the preparation parameters, PC microspheres with a diameter of 316.39 μm ± 14.75 μm and porous surface were prepared. The gelatine-modified PC (GEL-PC) microspheres exhibited better hydrophilicity and protein adsorption ability than PC microspheres. Enhancement of the adhesion and proliferation of the BMMSCs can be observed on GEL-PC microspheres after 7 days. Therefore, this study demonstrates that employing a dynamic culture using GEL-PC microspheres is a promising method for deriving BMMSCs.



This research was financially supported by the National Natural Science Foundation of China (Project Nos. 51673186, 51203152, 8167090834 and 51473164), the Program of Scientific Development of Jilin Province (20170520121JH and 20170520141JH), the joint funded program of Chinese Academy of Sciences and Japan Society for the Promotion of Science (GJHZ1519) and the Special Fund for Industrialization of Science and Technology Cooperation between Jilin Province and Chinese Academy of Science (2017SYHZ0021). We thank youdao ( for its linguistic assistance during the preparation of this manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10853_2018_3200_MOESM1_ESM.mpg (746 kb)
Supplementary material 1 (MPG 745 kb)


  1. 1.
    Freimark D, Pino-Grace P, Pohl S, Weber C, Wallrapp C, Geigle P, Poertner R, Czermaka P (2010) Use of encapsulated stem cells to overcome the bottleneck of cell availability for cell therapy approaches. Transfus Med Hemother 37(2):66–73Google Scholar
  2. 2.
    Escacena N, Quesada-Hernandez E, Capilla-Gonzalez V, Soria B, Hmadcha A (2015) Bottlenecks in the efficient use of advanced therapy medicinal products based on mesenchymal stromal cells. In: Stem cells international, Article ID 895714Google Scholar
  3. 3.
    Carlsson P-O, Schwarcz E, Korsgren O, Le Blanc K (2015) Preserved beta-cell function in type 1 diabetes by mesenchymal stromal cells. Diabetes 64(2):587–592Google Scholar
  4. 4.
    Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentis J, Sanchez A, Garcia-Sancho J (2013) Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation 95(12):1535–1541Google Scholar
  5. 5.
    Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, Du MQ, Luan SL, Altmann DR, Thompson AJ, Compston A (2012) Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol 11(2):150–156Google Scholar
  6. 6.
    Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363(9419):1439–1441Google Scholar
  7. 7.
    Lee JW, Lee SH, Youn YJ, Ahn MS, Kim JY, Yoo BS, Yoon J, Kwon W, Hong IS, Lee K, Kwan J (2014) A randomized, open-label, multicenter trial for the safety and efficacy of adult mesenchymal stem cells after acute myocardial infarction. J Korean Med Sci 29(1):23–31Google Scholar
  8. 8.
    Dhere T, Copland I, Garcia M, Chiang KY, Chinnadurai R, Prasad M, Galipeau J, Kugathasan S (2016) The safety of autologous and metabolically fit bone marrow mesenchymal stromal cells in medically refractory Crohn’s disease—a phase 1 trial with three doses. Aliment Pharmacol Ther 44(5):471–481Google Scholar
  9. 9.
    Godara P, McFarland CD, Nordon RE (2008) Design of bioreactors for mesenchymal stem cell tissue engineering. J Chem Technol Biotechnol 83(4):408–420Google Scholar
  10. 10.
    King JA, Miller WM (2007) Bioreactor development for stem cell expansion and controlled differentiation. Curr Opin Chem Biol 11(4):394–398Google Scholar
  11. 11.
    Sun LY, Lin SZ, Li YS, Harn HJ, Chiou TW (2011) Functional cells cultured on microcarriers for use in regenerative medicine research. Cell Transplant 20(1):49–62Google Scholar
  12. 12.
    Rodrigues CAV, Fernandes TG, Diogo MM, da Silva CL, Cabral JMS (2011) Stem cell cultivation in bioreactors. Biotechnol Adv 29(6):815–829Google Scholar
  13. 13.
    Frauenschuh S, Reichmann E, Ibold Y, Goetz PM, Sittinger M, Ringe J (2007) A microcarrier-based cultivation system for expansion of primary mesenchymal stem cells. Biotechnol Prog 23(1):187–193Google Scholar
  14. 14.
    Schop D, Janssen FW, Borgart E, de Bruijn JD, van Dijkhuizen-Radersma R (2008) Expansion of mesenchymal stem cells using a microcarrier-based cultivation system: growth and metabolism. J Tissue Eng Regen Med 2(2–3):126–135Google Scholar
  15. 15.
    Schop D, van Dijkhuizen-Radersma R, Borgart E, Janssen FW, Rozemuller H, Prins HJ, de Bruijn JD (2010) Expansion of human mesenchymal stromal cells on microcarriers: growth and metabolism. J Tissue Eng Regen Med 4(2):131–140Google Scholar
  16. 16.
    dos Santos F, Andrade PZ, Abecasis MM, Gimble JM, Chase LG, Campbell AM, Boucher S, Vemuri MC, da Silva CL, Cabral JMS (2011) Toward a clinical-grade expansion of mesenchymal stem cells from human sources: a microcarrier-based culture system under xeno-free conditions. Tissue Eng Part C Methods 17(12):1201–1210Google Scholar
  17. 17.
    Eibes G, dos Santos F, Andrade PZ, Boura JS, Abecasis MMA, da Silva CL, Cabral JMS (2010) Maximizing the ex vivo expansion of human mesenchymal stem cells using a microcarrier–based stirred culture system. J Biotechnol 146(4):194–197Google Scholar
  18. 18.
    Sun LY, Hsieh DK, Syu WS, Li YS, Chiu HT, Chiou TW (2010) Cell proliferation of human bone marrow mesenchymal stem cells on biodegradable microcarriers enhances in vitro differentiation potential. Cell Prolif 43(5):445–456Google Scholar
  19. 19.
    Liu X, Feng X, Xu X, Wang F, Wang Y (2018) Sol-assisted spray-drying synthesis of porous Li3V2(PO4)(3)/C microspheres as high-activity cathode materials for lithium-ion batteries. J Sol Gel Sci Technol 86(2):343–350Google Scholar
  20. 20.
    Eskandarloo H, Zaferani M, Kierulf A, Abbaspourrad A (2018) Shape–controlled fabrication of TiO2 hollow shells toward photocatalytic application. Appl Catal B Environ 227:519–529Google Scholar
  21. 21.
    Li BZ, Xian XQ, Wang Y, Adhikari B, Chen D (2018) Production of recrystallized starch microspheres using water-in-water emulsion and multiple recycling of polyethylene glycol solution. LWT Food Sci Technol 97:76–82Google Scholar
  22. 22.
    Li C, He M, Tong Z, Li Y, Sheng W, Luo L, Tong Y, Yu H, Huselstein C, Chen Y (2016) Construction of biocompatible regenerated cellulose/SPI composite beads using high-voltage electrostatic technique. Rsc Adv 6(58):52528–52538Google Scholar
  23. 23.
    Stojanovic R, Belscak‐Cvitanovic A, Manojlovic V, Komes D, Nedovic V, Bugarski B (2012) Encapsulation of thyme (Thymus serpyllum L.) aqueous extract in calcium alginate beads. J Sci Food Agric 92(3):685–696Google Scholar
  24. 24.
    Shang Y, Ding F, Xiao L, Deng H, Du Y, Shi X (2014) Chitin–based fast responsive pH sensitive microspheres for controlled drug release. Carbohyd Polym 102:413–418Google Scholar
  25. 25.
    Pi C, Yuan J, Liu H, Zuo Y, Feng T, Zhan C, Wu J, Ye Y, Zhao L, Wei Y (2018) In vitro and in vivo evaluation of curcumin loaded hollow microspheres prepared with ethyl cellulose and citric acid. Int J Biol Macromol 115:1046–1054Google Scholar
  26. 26.
    Wu YJ, Chen T, Chen IF, Kuo SM, Chuang CW (2018) Developing highly porous collagen scaffolds by using alginate microsphere porogens for stem cell cultures. Mater Lett 223:120–123Google Scholar
  27. 27.
    Mei S, Han PP, Wu H, Shi JF, Tang L, Jiang ZG (2018) One-pot fabrication of chitin-shellac composite microspheres for efficient enzyme immobilization. J Biotechnol 266:1–8Google Scholar
  28. 28.
    Sart S, Schneider YJ, Agathos SN (2009) Ear mesenchymal stem cells: an efficient adult multipotent cell population fit for rapid and scalable expansion. J Biotechnol 139(4):291–299Google Scholar
  29. 29.
    Sart S, Schneider YJ, Agathos SN (2010) Influence of culture parameters on ear mesenchymal stem cells expanded on microcarriers. J Biotechnol 150(1):149–160Google Scholar
  30. 30.
    Wang JL, Chen Q, Du BB, Cao L, Lin H, Fan ZY, Dong J (2018) Enhanced bone regeneration composite scaffolds of PLLA/beta-TCP matrix grafted with gelatin and HAp. Mater Sci Eng C Mater Biol Appl 87:60–69Google Scholar
  31. 31.
    Li P, Dou X, Feng C, Schoenherr H (2018) Enhanced cell adhesion on a bio-inspired hierarchically structured polyester modified with gelatin-methacrylate. Biomater Sci 6(4):785–792Google Scholar
  32. 32.
    Jahantigh F, Nazirzadeh M (2017) Synthesis and characterization of TiO2 nanoparticles with polycarbonate and investigation of its mechanical properties. Int J Nanosci 16(5–6):1750012Google Scholar
  33. 33.
    Rostamiyan Y, Ferasat A (2017) High-speed impact and mechanical strength of ZrO2/polycarbonate nanocomposite. Int J Damage Mech 26(7):989–1002Google Scholar
  34. 34.
    Kumaraswamy S, Thangasundaralingam SR, Sekar R, Jayakrishnan A (2017) A floating-type dosage form of repaglinide in polycarbonate microspheres. J Drug Deliv Sci Technol 41:99–105Google Scholar
  35. 35.
    Lin YS, Yang CH, Hsu YY, Hsieh CL (2013) Microfluidic synthesis of tail-shaped alginate microparticles using slow sedimentation. Electrophoresis 34(3):425–431Google Scholar
  36. 36.
    Yi W, Sun Y, Wei X, Gu C, Dong X, Kang X, Guo S, Dou K (2010) Proteomic profiling of human bone marrow mesenchymal stem cells under shear stress. Mol Cell Biochem 341(1–2):9–16Google Scholar
  37. 37.
    Knippenberg M, Helder MN, Doulabi BZ, Semeins CM, Wuisman P, Klein-Nulend J (2005) Adipose tissue-derived mesenchymal stem cells acquire bone cell-like responsiveness to fluid shear stress on osteogenic stimulation. Tissue Eng 11(11–12):1780–1788Google Scholar
  38. 38.
    Yourek G, McCormick SM, Mao JJ, Reilly GC (2010) Shear stress induces osteogenic differentiation of human mesenchymal stem cells. Regen Med 5(5):713–724Google Scholar
  39. 39.
    Potier E, Noailly J, Ito K (2010) Directing bone marrow-derived stromal cell function with mechanics. J Biomech 43(5):807–817Google Scholar
  40. 40.
    Olsen JV, Kirkegaard P, Pedersen NJ, Eldrup M (2007) PALM: a new program for the evaluation of positron lifetime spectra. Phys Status Solidi C Curr Top Solid State Phys 4(10):4004–4006Google Scholar
  41. 41.
    Zhu Y, Bhandari B, Prakash S (2018) Tribo-rheometry behaviour and gel strength of κ-carrageenan and gelatin solutions at concentrations, pH and ionic conditions used in dairy products. Food Hydrocolloids 84:292–302Google Scholar
  42. 42.
    Völkl A, Mohr H, Weber G, Fahimi HD (1997) Isolation of rat hepatic peroxisomes by means of immune free flow electrophoresis. Electrophoresis 18(5):774–780Google Scholar
  43. 43.
    Piche-Nicholas NM, Avery LB, King AC, Kavosi M, Wang M, O’Hara DM, Tchistiakova L, Katragadda M (2018) Changes in complementarity-determining regions significantly alter IgG binding to the neonatal Fc receptor (FcRn) and pharmacokinetics. In: MABS-AUSTIN, vol 10, no 1, pp 81–94Google Scholar
  44. 44.
    Wang J, Li D, Li T, Ding J, Liu J, Li B, Chen X (2015) Gelatin tight-coated poly(lactide-co-glycolide) scaffold Incorporating rhBMP-2 for bone tissue engineering. Materials 8(3):1009–1026Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchunChina
  2. 2.Department of Orthopaedics, The Second HospitalJilin UniversityChangchunChina
  3. 3.Xinjiang Laboratory of Phase Transitions and Microstructures in Condensed Matter Physics, College of Physical Science and TechnologyYili Normal UniversityYiningChina

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