Collagen–cellulose composite thin films that mimic soft-tissue and allow stem-cell orientation

  • Terry W. J. Steele
  • Charlotte L. Huang
  • Evelyne Nguyen
  • Udi Sarig
  • Saranya Kumar
  • Effendi Widjaja
  • Joachim S. C. Loo
  • Marcelle Machluf
  • Freddy Boey
  • Zlata Vukadinovic
  • Andreas Hilfiker
  • Subbu S. Venkatraman


Mechanical properties of collagen films are less than ideal for biomaterial development towards musculoskeletal repair or cardiovascular applications. Herein, we present a collagen–cellulose composite film (CCCF) compared against swine small intestine submucosa in regards to mechanical properties, cell growth, and histological analysis. CCCF was additionally characterized by FE-SEM, NMR, mass spectrometry, and Raman Microscopy to elucidate its physical structure, collagen–cellulose composition, and structure activity relationships. Mechanical properties of the CCCF were tested in both wet and dry environments, with anisotropic stress–strain curves that mimicked soft-tissue. Mesenchymal stem cells, human umbilical vein endothelial cells, and human coronary artery smooth muscle cells were able to proliferate on the collagen films with specific cell orientation. Mesenchymal stem cells had a higher proliferation index and were able to infiltrate CCCF to a higher degree than small intestine submucosa. With the underlying biological properties, we present a collagen–cellulose composite film towards forthcoming biomaterial-related applications.

Graphical Abstract


Mesenchymal Stem Cell Human Umbilical Vein Endothelial Cell Small Intestine Submucosa Fluorescein Diacetate Methyl Stearate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors acknowledge and appreciate the help and support rendered by Final Year Project Student, Wang Qianying Dione. This research was most generously supported by the Singapore National Research Foundation under parts of the following programs: NRF2010NRF-POC002-019, NRF 2007 NRF-CRP 002-12, and the CREATE program: The Regenerative Medicine Initiative in Cardiac Restoration Therapy Research.


No competing financial interests exist.

Supplementary material

10856_2013_4940_MOESM1_ESM.tif (205 kb)
Fig. S1 1H-NMR of D2O rinse from CCCF. Glycerol (3.7-3.4 ppm) and benzene (7.35 ppm, internal standard) are labeled.. Right inset: Magnified view from 2.2-1.0 ppm, displaying CH2 peaks from fatty acid(s) or ester(s) present. (TIFF 205 kb)
10856_2013_4940_MOESM2_ESM.tif (53 kb)
Fig. S2 Macrophage stimulating assay. PLGA: Poly-L-Lactic-co- Glycolic-acid (85 %:15 %); LPS: Lipopolysaccharide from Pseudomonas aeruginosa, 1 μg/mL. * CCCF and PLGA were non-significantly different from one another P < 0.05, ** Basal NO secretion was significantly lower (P < 0.01) than all tested groups. (TIFF 52 kb)


  1. 1.
    Brusselaers N, Pirayesh A, Hoeksema H, Richters CD, Verbelen J, Beele H, et al. Skin replacement in burn wounds. J Trauma. 2010;68(2):490–501. doi: 10.1097/TA.0b013e3181c9c074.CrossRefGoogle Scholar
  2. 2.
    Filova E, Straka F, Mirejovsky T, Masin J, Bacakova L. Tissue-engineered heart valves. Physiol Res. 2009;58(Suppl 2):S141–58. doi: 931919.Google Scholar
  3. 3.
    Chajra H, Rousseau CF, Cortial D, Ronziere MC, Herbage D, Mallein-Gerin F, et al. Collagen-based biomaterials and cartilage engineering. Application to osteochondral defects. Biomed Mater Eng. 2008;18(1 Suppl):S33–45.Google Scholar
  4. 4.
    Galois L, Freyria AM, Grossin L, Hubert P, Mainard D, Herbage D, et al. Cartilage repair: surgical techniques and tissue engineering using polysaccharide- and collagen-based biomaterials. Biorheology. 2004;41(3–4):433–43.Google Scholar
  5. 5.
    Isenberg BC, Williams C, Tranquillo RT. Small-diameter artificial arteries engineered in vitro. Circ Res. 2006;98(1):25–35. doi: 10.1161/01.RES.0000196867.12470.84.CrossRefGoogle Scholar
  6. 6.
    L’Heureux N, Paquet S, Labbe R, Germain L, Auger FA. A completely biological tissue-engineered human blood vessel. FASEB J. 1998;12(1):47–56.Google Scholar
  7. 7.
    Hirai J, Matsuda T. Venous reconstruction using hybrid vascular tissue composed of vascular cells and collagen: tissue regeneration process. Cell Transplant. 1996;5(1):93–105. doi: 0963689795020020.CrossRefGoogle Scholar
  8. 8.
    Mitchell SL, Niklason LE. Requirements for growing tissue-engineered vascular grafts. Cardiovasc Pathol. 2003;12(2):59–64. doi: S1054880702001837.CrossRefGoogle Scholar
  9. 9.
    Canham PB, Talman EA, Finlay HM, Dixon JG. Medial collagen organization in human arteries of the heart and brain by polarized light microscopy. Connect Tissue Res. 1991;26(1–2):121–34.CrossRefGoogle Scholar
  10. 10.
    Tranquillo RT. The tissue-engineered small-diameter artery. Ann N Y Acad Sci. 2002;961:251–4.CrossRefGoogle Scholar
  11. 11.
    Venkatraman S, Boey F, Lao LL. Implanted cardiovascular polymers: natural, synthetic and bio-inspired. Prog Polym Sci. 2008;33(9):853–74.CrossRefGoogle Scholar
  12. 12.
    Weinberg CB, Bell E. A blood vessel model constructed from collagen and cultured vascular cells. Science. 1986;231(4736):397–400.CrossRefGoogle Scholar
  13. 13.
    Floren MG, Gunther RW, Schmitz-Rode T. Noninvasive inductive stent heating: alternative approach to prevent instant restenosis? Invest Radiol. 2004;39(5):264–70. doi: 00004424-200405000-00004.CrossRefGoogle Scholar
  14. 14.
    Punchard MA, O’Cearbhaill ED, Mackle JN, McHugh PE, Smith TJ, Stenson-Cox C, et al. Evaluation of human endothelial cells post stent deployment in a cardiovascular simulator in vitro. Ann Biomed Eng. 2009;37(7):1322–30. doi: 10.1007/s10439-009-9701-6.CrossRefGoogle Scholar
  15. 15.
    Yazdani SK, Berry JL. Development of an in vitro system to assess stent-induced smooth muscle cell proliferation: a feasibility study. J Vasc Interv Radiol. 2009;20(1):101–6. doi: 10.1016/j.jvir.2008.09.025.CrossRefGoogle Scholar
  16. 16.
    Pinnel SR, Murad S, Darr D. Induction of collagen synthesis by ascorbic acid. A possible mechanism. Arch Dermatol. 1987;123(12):1684–6.CrossRefGoogle Scholar
  17. 17.
    Chan D, Lamande SR, Cole WG, Bateman JF. Regulation of procollagen synthesis and processing during ascorbate-induced extracellular matrix accumulation in vitro. Biochem J. 1990;269(1):175–81.Google Scholar
  18. 18.
    Schulz JT 3rd, Tompkins RG, Burke JF. Artificial skin. Annu Rev Med. 2000;51:231–44. doi: 10.1146/ Scholar
  19. 19.
    Suzuki S, Kawai K, Ashoori F, Morimoto N, Nishimura Y, Ikada Y. Long-term follow-up study of artificial dermis composed of outer silicone layer and inner collagen sponge. Br J Plast Surg. 2000;53(8):659–66. doi: 10.1054/bjps.2000.3426S000712260093426X.CrossRefGoogle Scholar
  20. 20.
    Badylak S, Obermiller J, Geddes L, Matheny R. Extracellular matrix for myocardial repair. Heart Surg Forum. 2003;6(2):E20–6.Google Scholar
  21. 21.
    Badylak S, Kokini K, Tullius B, Simmons-Byrd A, Morff R. Morphologic study of small intestinal submucosa as a body wall repair device. J Surg Res. 2002;103(2):190–202. doi: 10.1006/jsre.2001.6349.CrossRefGoogle Scholar
  22. 22.
    Kakisis JD, Liapis CD, Breuer C, Sumpio BE. Artificial blood vessel: the holy grail of peripheral vascular surgery. J Vasc Surg. 2005;41(2):349–54. doi: 10.1016/j.jvs.2004.12.026.CrossRefGoogle Scholar
  23. 23.
    Campodonico F, Benelli R, Michelazzi A, Ognio E, Toncini C, Maffezzini M. Bladder cell culture on small intestinal submucosa as bioscaffold: experimental study on engineered urothelial grafts. Eur Urol. 2004;46(4):531–7. doi: 10.1016/j.eururo.2004.04.019.CrossRefGoogle Scholar
  24. 24.
    Zhang F, Zhang J, Lin S, Oswald T, Sones W, Cai Z, et al. Small intestinal submucosa in abdominal wall repair after TRAM flap harvesting in a rat model. Plast Reconstr Surg. 2003;112(2):565–70. doi: 10.1097/01.PRS.0000070966.74429.03.CrossRefGoogle Scholar
  25. 25.
    Park SN, Jang HJ, Choi YS, Cha JM, Son SY, Han SH, et al. Preparation and characterization of biodegradable anti-adhesive membrane for peritoneal wound healing. J Mater Sci Mater Med. 2007;18(3):475–82. doi: 10.1007/s10856-007-2007-z.CrossRefGoogle Scholar
  26. 26.
    Chen H, Chen H, Liu L, Yuan P, Zhang Q. The study of improved controlled release of vincristine sulfate from collagen–chitosan complex film. Artif Cells Blood Substit Immobil Biotechnol. 2008;36(4):372–85. doi: 10.1080/10731190802239057.CrossRefGoogle Scholar
  27. 27.
    de Mesquita JP, Patricio PS, Donnici CL, Petri DFS, de Oliveira LCA, Pereira FV. Hybrid layer-by-layer assembly based on animal and vegetable structural materials: multilayered films of collagen and cellulose nanowhiskers. Soft Matter. 2011;7(9):4405.CrossRefGoogle Scholar
  28. 28.
    Luo H, Xiong G, Huang Y, He F, Wang Y, Wan Y. Preparation and characterization of a novel COL/BC composite for potential tissue engineering scaffolds. Mater Chem Phys. 2008;110(2–3):193–6. doi: 10.1016/j.matchemphys.2008.01.040.CrossRefGoogle Scholar
  29. 29.
    Klemm D, Heublein B, Fink HP, Bohn A. Cellulose: fascinating biopolymer and sustainable raw material. Angew Chem Int Ed Engl. 2005;44(22):3358–93. doi: 10.1002/anie.200460587.CrossRefGoogle Scholar
  30. 30.
    Tang S, Yang W, Mao X. Agarose/collagen composite scaffold as an anti-adhesive sheet. Biomed Mater. 2007;2(3):S129–34. doi: 10.1088/1748-6041/2/3/S09.CrossRefGoogle Scholar
  31. 31.
    Hata H, Bär A, Dorfman S, Vukadinovic Z, Sawa Y, Haverich A, et al. Engineering a novel three-dimensional contractile myocardial patch with cell sheets and decellularised matrix. Eur J Cardiothorac Surg. 2010;38(4):450–5. doi: 10.1016/j.ejcts.2010.02.009.CrossRefGoogle Scholar
  32. 32.
    Goren A, Dahan N, Goren E, Baruch L, Machluf M. Encapsulated human mesenchymal stem cells: a unique hypoimmunogenic platform for long-term cellular therapy. FASEB J. 2009;24(1):22–31. doi: 10.1096/fj.09-131888.CrossRefGoogle Scholar
  33. 33.
    Osburn W. Collagen casings. Protein-based films and coatings. Boca Raton: CRC Press; 2002.Google Scholar
  34. 34.
    Bilbao-Sainz C, Avena-Bustillos RJ, Wood DF, Williams TG, McHugh TH. Composite edible films based on hydroxypropyl methylcellulose reinforced with microcrystalline cellulose nanoparticles. J Agric Food Chem. 2010;58(6):3753–60. doi: 10.1021/jf9033128.CrossRefGoogle Scholar
  35. 35.
    Cellulose Report: STELPRDC5066975. United States Department of Agriculture. 2001. Accessed Oct 1 2010.
  36. 36.
    Hood LL, editor. Collagen in sausage casings. Advances in meat research. New York: Van Nostrand Reinhold; 1987.Google Scholar
  37. 37.
    AOAC International. 2010. Accessed Oct 1 2010.
  38. 38.
    Steele T, Huang C, Widjajab E, Loo J, Venkatraman S. The effect of polyethylene glycol structure on paclitaxel drug release and mechanical properties of PLGA thin films. Acta Biomater. 2011;7(5):1973–83.Google Scholar
  39. 39.
    Widjaja E, Li C, Chew W, Garland M. Band-target entropy minimization. A robust algorithm for pure component spectral recovery. Application to complex randomized mixtures of six components. Anal Chem. 2003;75(17):4499–507.CrossRefGoogle Scholar
  40. 40.
    Widjaja E, Seah RK. Application of Raman microscopy and band-target entropy minimization to identify minor components in model pharmaceutical tablets. J Pharm Biomed Anal. 2008;46(2):274–81. doi: 10.1016/j.jpba.2007.09.023.CrossRefGoogle Scholar
  41. 41.
    Widjaja E, Garland M. Use of Raman microscopy and band-target entropy minimization analysis to identify dyes in a commercial stamp. Implications for authentication and counterfeit detection. Anal Chem. 2008;80(3):729–33. doi: 10.1021/ac701940k.CrossRefGoogle Scholar
  42. 42.
    Seah RK, Garland M, Loo JS, Widjaja E. Use of Raman microscopy and multivariate data analysis to observe the biomimetic growth of carbonated hydroxyapatite on bioactive glass. Anal Chem. 2009;81(4):1442–9. doi: 10.1021/ac802234t10.1021/ac802234t.CrossRefGoogle Scholar
  43. 43.
    Eitan Y, Sarig U, Dahan N, Machluf M. Acellular cardiac extracellular matrix as a scaffold for tissue engineering: in vitro cell support, remodeling, and biocompatibility. Tissue Eng Part C. 2009;16(4):671–83. doi: 10.1089/ten.tec.2009.0111.CrossRefGoogle Scholar
  44. 44.
    Ha TT, Padua GW. Effect of extrusion processing on properties of zein–fatty acids sheets. Am Soc Agric Biol Eng. 2001;44(5):1223–8.Google Scholar
  45. 45.
    Angele P, Abke J, Kujat R, Faltermeier H, Schumann D, Nerlich M, et al. Influence of different collagen species on physico-chemical properties of crosslinked collagen matrices. Biomaterials. 2004;25(14):2831–41. doi: 10.1016/j.biomaterials.2003.09.066S0142961203008081.CrossRefGoogle Scholar
  46. 46.
    Henrickson RL, Ranganayaki MD, Asghar A. Age, species, breed, sex, and nutrition effect on hide collagen. Crit Rev Food Sci Nutr. 1984;20(3):159–72.CrossRefGoogle Scholar
  47. 47.
    Ding Q, Xiao L, Xiong S, Jia Y, Que H, Guo Y, et al. Unmatched masses in peptide mass fingerprints caused by cross-contamination: an updated statistical result. Proteomics. 2003;3(7):1313–7. doi: 10.1002/pmic.200300452.CrossRefGoogle Scholar
  48. 48.
    Xu B, Zhang Y, Zhao Z, Yoshida Y, Magdeldin S, Fujinaka H, et al. Usage of electrostatic eliminator reduces human keratin contamination significantly in gel-based proteomics analysis. J Proteomics. 2011;74(7):1022–9. doi: 10.1016/j.jprot.2011.03.001.CrossRefGoogle Scholar
  49. 49.
    Prendergast PJ, Lally C, Daly S, Reid AJ, Lee TC, Quinn D, et al. Analysis of prolapse in cardiovascular stents: a constitutive equation for vascular tissue and finite-element modelling. J Biomech Eng. 2003;125(5):692–9.CrossRefGoogle Scholar
  50. 50.
    Huang Z, Lui H, McLean DI, Korbelik M, Zeng H. Raman spectroscopy in combination with background near-infrared autofluorescence enhances the in vivo assessment of malignant tissues. Photochem Photobiol. 2005;81(5):1219–26. doi: 10.1562/2005-02-24-RA-449.CrossRefGoogle Scholar
  51. 51.
    Atalla RH. Raman spectral studies of polymorphy in cellulose. Part 1, celluloses I and II. Appleton: The Institute; 1975.Google Scholar
  52. 52.
    Davies JED, Lie Ken Jie MSF, Bakare O. Raman studies of thia fatty acid esters. Chem Phys Lipids. 1990;56(2–3):223–6.CrossRefGoogle Scholar
  53. 53.
    Cagri A, Ustunol Z, Ryser ET. Antimicrobial edible films and coatings. J Food Prot. 2004;67(4):833–48.Google Scholar
  54. 54.
    Połomska M, Kubisz L, Kalawski R, Oszkinis G, Filipiak R, Mazurek A. Fourier transform near infrared Raman spectroscopy in studies on connective tissue. Acta Physica Polonica. 2010;118:136–40.Google Scholar
  55. 55.
    Garvin K, Feschuk C. Polylactide–polyglycolide antibiotic implants. Clin Orthop Relat Res. 2005;437:105–10.CrossRefGoogle Scholar
  56. 56.
    Pariente JL, Kim BS, Atala A. In vitro biocompatibility assessment of naturally derived and synthetic biomaterials using normal human urothelial cells. J Biomed Mater Res. 2001;55(1):33–9.CrossRefGoogle Scholar
  57. 57.
    Su Y, Zeng BF, Zhang CQ, Zhang KG, Xie XT. Study of biocompatibility of small intestinal submucosa (SIS) with Schwann cells in vitro. Brain Res. 2007;1145:41–7. doi: 10.1016/j.brainres.2007.01.138.CrossRefGoogle Scholar
  58. 58.
    Woods AM, Rodenberg EJ, Hiles MC, Pavalko FM. Improved biocompatibility of small intestinal submucosa (SIS) following conditioning by human endothelial cells. Biomaterials. 2004;25(3):515–25.CrossRefGoogle Scholar
  59. 59.
    Dai W, Kloner RA. Mesenchymal stem cell therapy for the injured heart. In: Wollert KC, Filed LJ, editors. Rebuilding the infarcted heart. London: Informa Healthcare; 2007. p. 55–72.CrossRefGoogle Scholar
  60. 60.
    McGuigan AP, Sefton MV. The thrombogenicity of human umbilical vein endothelial cell seeded collagen modules. Biomaterials. 2008;29(16):2453–63. doi: 10.1016/j.biomaterials.2008.02.010.CrossRefGoogle Scholar
  61. 61.
    Yang L, Tsai CM, Hsieh AH, Lin VS, Akeson WH, Sung KL. Adhesion strength differential of human ligament fibroblasts to collagen types I and III. J Orthop Res. 1999;17(5):755–62. doi: 10.1002/jor.1100170521.CrossRefGoogle Scholar
  62. 62.
    Tan WJ, Teo GP, Liao K, Leong KW, Mao HQ, Chan V. Adhesion contact dynamics of primary hepatocytes on poly(ethylene terephthalate) surface. Biomaterials. 2005;26(8):891–8. doi: 10.1016/j.biomaterials.2004.03.041.CrossRefGoogle Scholar
  63. 63.
    Quteish D, Singh G, Dolby AE. Development and testing of a human collagen graft material. J Biomed Mater Res. 1990;24(6):749–60. doi: 10.1002/jbm.820240609.CrossRefGoogle Scholar
  64. 64.
    Lin YC, Tan FJ, Marra KG, Jan SS, Liu DC. Synthesis and characterization of collagen/hyaluronan/chitosan composite sponges for potential biomedical applications. Acta Biomater. 2009;5(7):2591–600. doi: 10.1016/j.actbio.2009.03.038.CrossRefGoogle Scholar
  65. 65.
    Jorge-Herrero E, Fonseca C, Barge AP, Turnay J, Olmo N, Fernandez P, et al. Biocompatibility and calcification of bovine pericardium employed for the construction of cardiac bioprostheses treated with different chemical crosslink methods. Artif Organs. 2010;34(5):E168–76. doi: 10.1111/j.1525-1594.2009.00978.x.CrossRefGoogle Scholar
  66. 66.
    Elbjeirami WM, Yonter EO, Starcher BC, West JL. Enhancing mechanical properties of tissue-engineered constructs via lysyl oxidase crosslinking activity. J Biomed Mater Res A. 2003;66(3):513–21. doi: 10.1002/jbm.a.10021.CrossRefGoogle Scholar
  67. 67.
    Kamenskiy AV, Dzenis YA, Mactaggart JN, Lynch TG, Jaffar Kazmi SA, Pipinos II. Nonlinear mechanical behavior of the human common, external, and internal carotid arteries in vivo. J Surg Res. 2012;176(1):329–36. doi: 10.1016/j.jss.2011.09.058.CrossRefGoogle Scholar
  68. 68.
    Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407(6801):249–57. doi: 10.1038/35025220.CrossRefGoogle Scholar
  69. 69.
    Kaab MJ, Gwynn IA, Notzli HP. Collagen fibre arrangement in the tibial plateau articular cartilage of man and other mammalian species. J Anat. 1998;193(Pt 1):23–34.CrossRefGoogle Scholar
  70. 70.
    Penkova R, Goshev I, Gorinstein S, Nedkov P. Stabilizing effect of glycerol on collagen type I isolated from different species. Food Chem. 1999;66(4):483–7.CrossRefGoogle Scholar
  71. 71.
    Muller-Ehmsen J, Krausgrill B, Burst V, Schenk K, Neisen UC, Fries JW, et al. Effective engraftment but poor mid-term persistence of mononuclear and mesenchymal bone marrow cells in acute and chronic rat myocardial infarction. J Mol Cell Cardiol. 2006;41(5):876–84. doi: 10.1016/j.yjmcc.2006.07.023.CrossRefGoogle Scholar
  72. 72.
    Zhang H, Song P, Tang Y, Zhang XL, Zhao SH, Wei YJ, et al. Injection of bone marrow mesenchymal stem cells in the borderline area of infarcted myocardium: heart status and cell distribution. J Thorac Cardiovasc Surg. 2007;134(5):1234–40. doi: 10.1016/j.jtcvs.2007.07.019.CrossRefGoogle Scholar
  73. 73.
    Dai W, Hale SL, Kay GL, Jyrala AJ, Kloner RA. Delivering stem cells to the heart in a collagen matrix reduces relocation of cells to other organs as assessed by nanoparticle technology. Regen Med. 2009;4(3):387–95. doi: 10.2217/rme.09.2.CrossRefGoogle Scholar
  74. 74.
    Godbey WT, Hindy SB, Sherman ME, Atala A. A novel use of centrifugal force for cell seeding into porous scaffolds. Biomaterials. 2004;25(14):2799–805. doi: 10.1016/j.biomaterials.2003.09.056S0142961203007981.CrossRefGoogle Scholar
  75. 75.
    Anamelechi CC, Clermont EC, Novak MT, Reichert WM. Dynamic seeding of perfusing human umbilical vein endothelial cells (HUVECs) onto dual-function cell adhesion ligands: Arg–Gly–Asp (RGD)-streptavidin and biotinylated fibronectin. Langmuir. 2009;25(10):5725–30. doi: 10.1021/la803963r.CrossRefGoogle Scholar
  76. 76.
    Feil G, Christ-Adler M, Maurer S, Corvin S, Rennekampff HO, Krug J, et al. Investigations of urothelial cells seeded on commercially available small intestine submucosa. Eur Urol. 2006;50(6):1330–7. doi: 10.1016/j.eururo.2006.05.041.CrossRefGoogle Scholar
  77. 77.
    Zhang Y, Kropp BP, Lin HK, Cowan R, Cheng EY. Bladder regeneration with cell-seeded small intestinal submucosa. Tissue Eng. 2004;10(1–2):181–7. doi: 10.1089/107632704322791835.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Terry W. J. Steele
    • 1
  • Charlotte L. Huang
    • 1
  • Evelyne Nguyen
    • 1
  • Udi Sarig
    • 1
    • 2
  • Saranya Kumar
    • 1
  • Effendi Widjaja
    • 3
  • Joachim S. C. Loo
    • 1
  • Marcelle Machluf
    • 2
  • Freddy Boey
    • 1
  • Zlata Vukadinovic
    • 4
  • Andreas Hilfiker
    • 4
  • Subbu S. Venkatraman
    • 1
  1. 1.Division of Materials Technology, Materials and Science EngineeringNanyang Technological UniversitySingaporeSingapore
  2. 2.Faculty of Biotechnology and Food EngineeringTechnion—Israel Institute of TechnologyHaifaIsrael
  3. 3.Process Science and ModelingInstitute of Chemical and Engineering Sciences, Agency for Science, Technology and Research (A*STAR)SingaporeSingapore
  4. 4.Leibniz Research Labs for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery Hannover Medical School (MHH)Hans-Borst-Zentrum (HBZ)HannoverGermany

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