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Decellularized Extracellular Matrix as a Potent Natural Biomaterial for Regenerative Medicine

  • Amin Ebrahimi Sadrabadi
  • Payam Baei
  • Samaneh HosseiniEmail author
  • Mohamadreza Baghaban EslaminejadEmail author
Chapter
  • 15 Downloads
Part of the Advances in Experimental Medicine and Biology book series

Abstract

Decellularization technique is a favorable method used to fabricate natural and tissue-like scaffolds. This technique is important because of its remarkable ability to perfectly mimic the natural extracellular matrix (ECM). ECM-based scaffolds/hydrogels provide structural support for cell differentiation and maturation. Therefore, novel natural-based bioinks, ECM-based hydrogels, and particulate forms of the ECM provide promising strategies for whole organ regeneration. Despite its efficacious characteristics, removal of residual detergent and the presence of various protocols make this technique challenging for scientists and regenerative medicine-related programs. This chapter reviews the most effective physical, chemical, and enzymatic protocols used to remove the cellular components and their challenges. We discuss the applications of decellularized ECM (dECM) in tissue engineering and regenerative medicine with an emphasis on hard tissues.

Keywords

Bioink Decellularization Decellularized ECM ECM mimicry Tissue engineering 

Abbreviations

AF

Annulus fibrosus

ASCs

Adipose stem cells

BdECM

Bladder decellularized ECM

BMSCs

Bone marrow MSCs

cECM

Cardiac muscle ECM

CHAPS

3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate

dDP-ECM

Decellularized dental pulp ECM

dECM

Decellularized ECM

DVN

Decellularized vascular network

ECM

Extracellular matrix

FPSCs

Fat pad-derived stem cells

GAGs

Glycosaminoglycans

hMSCs

Human mesenchymal stem cells

NTIRE

Non-thermal irreversible electroporation

PAA

Peracetic acid

PDCs

Periosteum-derived cells

PLGA

Poly (lactic-co-glycolic acid)

PRP

Platelet-rich plasma

SDC

Sodium deoxycholate

SDS

Sodium dodecyl sulfate

sECM

skeletal muscle ECM

ToF-SIMS

Time of flight secondary ion mass spectroscopy

TX-100

Triton X-100

UBM

Urinary bladder matrix

WdECM

Wharton’s jelly dECM

References

  1. Ahn G, Min KH, Kim C, Lee JS, Kang D, Won JY, Cho DW, Kim JY, Jin S, Yun WS, Shim JH (2017) Precise stacking of decellularized extracellular matrix based 3D cell-laden constructs by a 3D cell printing system equipped with heating modules. Sci Rep 7:8624Google Scholar
  2. Aiyelabegan HT, Sadroddiny E (2017) Fundamentals of protein and cell interactions in biomaterials. Biomed Pharmacother = Biomedecine & pharmacotherapie 88:956–970Google Scholar
  3. Alqahtani Q, Zaky SH, Patil A, Beniash E, Ray H, Sfeir C (2018) Decellularized swine dental pulp tissue for regenerative root canal therapy. J Dent Res 97:1460–1467Google Scholar
  4. Bagetti Filho HJ, Pereira-Sampaio MA, Favorito LA, Sampaio FJ (2008) Pig kidney: anatomical relationships between the renal venous arrangement and the kidney collecting system. J Urol 179:1627–1630Google Scholar
  5. Bedran-Russo A, Leme-Kraus AA, Vidal CMP, Teixeira EC (2017) An overview of dental adhesive systems and the dynamic tooth-adhesive interface. Dent Clin N Am 61:713–731Google Scholar
  6. Blaudez F, Ivanovski S, Hamlet S, Vaquette C (2019) An overview of decellularisation techniques of native tissues and tissue engineered products for bone, ligament and tendon regeneration. Methods 171:28–40Google Scholar
  7. Bronstein JA, Woon CY, Farnebo S, Behn AW, Schmitt T, Pham H, Castillo AB, Chang J (2013) Physicochemical decellularization of composite flexor tendon-bone interface grafts. Plast Reconstr Surg 132:94–102Google Scholar
  8. Brouki Milan P, Pazouki A, Joghataei MT, Mozafari M, Amini N, Kargozar S, Amoupour M, Latifi N, Samadikuchaksaraei A (2019) Decellularization and preservation of human skin: a platform for tissue engineering and reconstructive surgery. Methods 171:62–67Google Scholar
  9. Brown BN, Badylak SF (2014) Extracellular matrix as an inductive scaffold for functional tissue reconstruction. Transl Res 163:268–285Google Scholar
  10. Burk J, Erbe I, Berner D, Kacza J, Kasper C, Pfeiffer B, Winter K, Brehm W (2013) Freeze-thaw cycles enhance decellularization of large tendons. Tissue Eng Part C Methods 20:276–284Google Scholar
  11. Chameettachal S, Sasikumar S, Sethi S, Sriya Y, Pati F (2019) Tissue/organ-derived bioink formulation for 3D bioprinting. J 3D Print Med 3:39–54Google Scholar
  12. Chen Y-C, Chen R-N, Jhan H-J, Liu D-Z, Ho H-O, Mao Y, Kohn J, Sheu M-T (2015a) Development and characterization of acellular extracellular matrix scaffolds from porcine menisci for use in cartilage tissue engineering. Tissue Eng Part C Methods 21:971–986Google Scholar
  13. Chen K, Lin X, Zhang Q, Ni J, Li J, Xiao J, Wang Y, Ye Y, Chen L, Jin K (2015b) Decellularized periosteum as a potential biologic scaffold for bone tissue engineering. Acta Biomater 19:46–55Google Scholar
  14. Cheng J, Wang C, Gu Y (2019) Combination of freeze-thaw with detergents: a promising approach to the decellularization of porcine carotid arteries. Biomed Mater Eng 30:191–205Google Scholar
  15. Choi JS, Yang HJ, Kim BS, Kim JD, Kim JY, Yoo B, Park K, Lee HY, Cho YW (2009) Human extracellular matrix (ECM) powders for injectable cell delivery and adipose tissue engineering. J Control Release 139:2–7Google Scholar
  16. Choi BH, Choi KH, Lee HS, Song BR, Park SR, Yang JW, Min BH (2014) Inhibition of blood vessel formation by a chondrocyte-derived extracellular matrix. Biomaterials 35:5711–5720Google Scholar
  17. Choi YJ, Kim TG, Jeong J, Yi HG, Park JW, Hwang W, Cho DW (2016) 3D cell printing of functional skeletal muscle constructs using skeletal muscle-derived bioink. Adv Healthc Mater 5:2636–2645Google Scholar
  18. Choudhury D, Tun HW, Wang T, Naing MW (2018) Organ-derived decellularized extracellular matrix: a game changer for bioink manufacturing? Trends Biotechnol 36:787–805Google Scholar
  19. Datta P, Ayan B, Ozbolat IT (2017) Bioprinting for vascular and vascularized tissue biofabrication. Acta Biomater 51:1–20Google Scholar
  20. Daugs A, Hutzler B, Meinke M, Schmitz C, Lehmann N, Markhoff A, Bloch O (2017) Detergent-based decellularization of bovine carotid arteries for vascular tissue engineering. Ann Biomed Eng 45:2683–2692Google Scholar
  21. Dequach JA, Mezzano V, Miglani A, Lange S, Keller GM, Sheikh F, Christman KL (2010) Simple and high yielding method for preparing tissue specific extracellular matrix coatings for cell culture. PLoS One 5:e13039Google Scholar
  22. Dong X, Wei X, Yi W, Gu C, Kang X, Liu Y, Li Q, Yi D (2009) RGD-modified acellular bovine pericardium as a bioprosthetic scaffold for tissue engineering. J Mater Sci Mater Med 20:2327–2336Google Scholar
  23. Dzamba BJ, Desimone DW (2018) Extracellular matrix (ECM) and the sculpting of embryonic tissues. Curr Top Dev Biol 130:245–274Google Scholar
  24. Dzobo K, Motaung K, Adesida A (2019) Recent trends in decellularized extracellular matrix bioinks for 3D printing: an updated review. Int J Mol Sci 20:pii: E4628Google Scholar
  25. Edgar L, Altamimi A, Garcia Sanchez M, Tamburrinia R, Asthana A, Gazia C, Orlando G (2018) Utility of extracellular matrix powders in tissue engineering. Organogenesis 14:172–186Google Scholar
  26. Elder BD, Kim DH, Athanasiou KA (2010) Developing an articular cartilage decellularization process toward facet joint cartilage replacement. Neurosurgery 66:722–727Google Scholar
  27. Esser TU, Roshanbinfar K, Engel FB (2019) Promoting vascularization for tissue engineering constructs: current strategies focusing on HIF-regulating scaffolds. Expert Opin Biol Ther 19:105–118Google Scholar
  28. Farag A, Hashimi SM, Vaquette C, Volpato FZ, Hutmacher DW, Ivanovski S (2018) Assessment of static and perfusion methods for decellularization of PCL membrane-supported periodontal ligament cell sheet constructs. Arch Oral Biol 88:67–76Google Scholar
  29. Farrokhi A, Pakyari M, Nabai L, Pourghadiri A, Hartwell R, Jalili R, Ghahary A (2018) Evaluation of detergent-free and detergent-based methods for decellularization of murine skin. Tissue Eng Part A 24:955–967Google Scholar
  30. Faulk DM, Carruthers CA, Warner HJ, Kramer CR, Reing JE, Zhang L, D’amore A, Badylak SF (2014) The effect of detergents on the basement membrane complex of a biologic scaffold material. Acta Biomater 10:183–193Google Scholar
  31. Fernandez-Perez J, Ahearne M (2019) The impact of decellularization methods on extracellular matrix derived hydrogels. Sci Rep 9:14933Google Scholar
  32. Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simoes MJ, Cerri PS (2015) Biology of bone tissue: structure, function, and factors that influence bone cells. Biomed Res Int 2015:421746Google Scholar
  33. Frantz C, Stewart KM, Weaver VM (2010) The extracellular matrix at a glance. J Cell Sci 123:4195–4200Google Scholar
  34. Gao LP, Du MJ, Lv JJ, Schmull S, Huang RT, Li J (2017) Use of human aortic extracellular matrix as a scaffold for construction of a patient-specific tissue engineered vascular patch. Biomed Mater 12:065006Google Scholar
  35. Giobbe GG, Crowley C, Luni C, Campinoti S, Khedr M, Kretzschmar K, De Santis MM, Zambaiti E, Michielin F, Meran L, Hu Q, Van Son G, Urbani L, Manfredi A, Giomo M, Eaton S, Cacchiarelli D, Li VSW, Clevers H, Bonfanti P, Elvassore N, De Coppi P (2019) Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture. Nat Commun 10:5658Google Scholar
  36. Hickey D, Hukins D (1980) Relation between the structure of the annulus fibrosus and the function and failure of the intervertebral disc. Spine 5:106–116Google Scholar
  37. Hinderer S, Layland SL, Schenke-Layland K (2016) ECM and ECM-like materials – biomaterials for applications in regenerative medicine and cancer therapy. Adv Drug Deliv Rev 97:260–269Google Scholar
  38. Hong X, Yuan Y, Sun X, Zhou M, Guo G, Zhang Q, Hescheler J, Xi J (2018) Skeletal extracellular matrix supports cardiac differentiation of embryonic stem cells: a potential scaffold for engineered cardiac tissue. Cell Physiol Biochem 45:319–331Google Scholar
  39. Hoshiba T, Chen G, Endo C, Maruyama H, Wakui M, Nemoto E, Kawazoe N, Tanaka M (2016) Decellularized extracellular matrix as an in vitro model to study the comprehensive roles of the ECM in stem cell differentiation. Stem Cells Int 2016:6397820Google Scholar
  40. Hu L, Gao Z, Xu J, Zhu Z, Fan Z, Zhang C, Wang J, Wang S (2017) Decellularized swine dental pulp as a bioscaffold for pulp regeneration. Biomed Res Int 2017:9342714Google Scholar
  41. Huling J, Ko IK, Atala A, Yoo JJ (2016) Fabrication of biomimetic vascular scaffolds for 3D tissue constructs using vascular corrosion casts. Acta Biomater 32:190–197Google Scholar
  42. Hung S-H, Su C-H, Lee F-P, Tseng H (2013) Larynx decellularization: combining freeze-drying and sonication as an effective method. J Voice 27:289–294Google Scholar
  43. Iulian, Antoniac LD, Csaki I, Mates IM, Vranceanu D (2017) Potential of the magnesium powder as filler for biomedical composites. Biomater Tissue Technol 1:1–5Google Scholar
  44. Jang J, Kim TG, Kim BS, Kim SW, Kwon SM, Cho DW (2016) Tailoring mechanical properties of decellularized extracellular matrix bioink by vitamin B2-induced photo-crosslinking. Acta Biomater 33:88–95Google Scholar
  45. Jansen KA, Atherton P, Ballestrem C (2017) Mechanotransduction at the cell-matrix interface. Semin Cell Dev Biol 71:75–83Google Scholar
  46. Jiang L, Zhang W, Wei L, Zhou Q, Yang G, Qian N, Tang Y, Gao Y, Jiang X (2018) Early effects of parathyroid hormone on vascularized bone regeneration and implant osseointegration in aged rats. Biomaterials 179:15–28Google Scholar
  47. Kajbafzadeh AM, Khorramirouz R, Nabavizadeh B, Ladi Seyedian SS, Akbarzadeh A, Heidari R, Masoumi A, Azizi B, Seyed Hossein Beigi R (2019) Whole organ sheep kidney tissue engineering and in vivo transplantation: effects of perfusion-based decellularization on vascular integrity. Mater Sci Eng C Mater Biol Appl 98:392–400Google Scholar
  48. Kant RJ, Coulombe KLK (2018) Integrated approaches to spatiotemporally directing angiogenesis in host and engineered tissues. Acta Biomater 69:42–62Google Scholar
  49. Kheir E, Stapleton T, Shaw D, Jin Z, Fisher J, Ingham E (2011) Development and characterization of an acellular porcine cartilage bone matrix for use in tissue engineering. J Biomed Mater Res A 99:283–294Google Scholar
  50. Kim JK, Koh YD, Kim JO, Seo DH (2016) Development of a decellularization method to produce nerve allografts using less invasive detergents and hyper/hypotonic solutions. J Plast Reconstr Aesthet Surg 69:1690–1696Google Scholar
  51. Li S, Harrison D, Carbonetto S, Fassler R, Smyth N, Edgar D, Yurchenco PD (2002) Matrix assembly, regulation, and survival functions of laminin and its receptors in embryonic stem cell differentiation. J Cell Biol 157:1279–1290Google Scholar
  52. Li M, Zhang T, Jiang J, Mao Y, Zhang A, Zhao J (2019) ECM coating modification generated by optimized decellularization process improves functional behavior of BMSCs. Mater Sci Eng C 105:110039Google Scholar
  53. Lin CH, Kao YC, Ma H, Tsay RY (2018) An investigation on the correlation between the mechanical property change and the alterations in composition and microstructure of a porcine vascular tissue underwent trypsin-based decellularization treatment. J Mech Behav Biomed Mater 86:199–207Google Scholar
  54. Lu H, Hoshiba T, Kawazoe N, Chen G (2012) Comparison of decellularization techniques for preparation of extracellular matrix scaffolds derived from three-dimensional cell culture. J Biomed Mater Res A 100:2507–2516Google Scholar
  55. Luo L, Eswaramoorthy R, Mulhall KJ, Kelly DJ (2016) Decellularization of porcine articular cartilage explants and their subsequent repopulation with human chondroprogenitor cells. J Mech Behav Biomed Mater 55:21–31Google Scholar
  56. Maddox E, Zhan M, Mundy GR, Drohan WN, AWHB (2000) Optimizing human demineralized bone matrix for clinical application. Tissue Eng 6:441–448Google Scholar
  57. Masaeli E, Karamali F, Loghmani S, Eslaminejad MB, Nasr-Esfahani MH (2017) Bio-engineered electrospun nanofibrous membranes using cartilage extracellular matrix particles. J Mater Chem B 5:765–776Google Scholar
  58. Monibi FA, Bozynski CC, Kuroki K, Stoker AM, Pfeiffer FM, Sherman SL, Cook JL (2016) Development of a micronized meniscus extracellular matrix scaffold for potential augmentation of meniscal repair and regeneration. Tissue Eng Part C Methods 22:1059–1070Google Scholar
  59. Morissette Martin P, Shridhar A, Yu C, Brown C, Flynn LE (2018) Decellularized adipose tissue scaffolds for soft tissue regeneration and adipose-derived stem/stromal cell delivery. Methods Mol Biol 1773:53–71Google Scholar
  60. Naik A, Griffin M, Szarko M, Butler PE (2019) Optimizing the decellularization process of an upper limb skeletal muscle; implications for muscle tissue engineering. Artif Organs 44:178–183Google Scholar
  61. Naso F, Gandaglia A (2018) Different approaches to heart valve decellularization: a comprehensive overview of the past 30 years. Xenotransplantation 25:e12354Google Scholar
  62. Osidak EO, Karalkin PA, Osidak MS, Parfenov VA, Sivogrivov DE, Pereira F, Gryadunova AA, Koudan EV, Khesuani YD, Capital Ka CVA, Belousov SI, Krasheninnikov SV, Grigoriev TE, Chvalun SN, Bulanova EA, Mironov VA, Domogatsky SP (2019) Viscoll collagen solution as a novel bioink for direct 3D bioprinting. J Mater Sci Mater Med 30:31Google Scholar
  63. Pati F, Jang J, Ha DH, Won Kim S, Rhie JW, Shim JH, Kim DH, Cho DW (2014) Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat Commun 5:3935Google Scholar
  64. Pellegata AF, Tedeschi AM, De Coppi P (2018) Whole organ tissue vascularization: engineering the tree to develop the fruits. Front Bioeng Biotechnol 6:56Google Scholar
  65. Penolazzi L, Mazzitelli S, Vecchiatini R, Torreggiani E, Lambertini E, Johnson S, Badylak SF, Piva R, Nastruzzi C (2012) Human mesenchymal stem cells seeded on extracellular matrix-scaffold: viability and osteogenic potential. J Cell Physiol 227:857–866Google Scholar
  66. Rana D, Zreiqat H, Benkirane-Jessel N, Ramakrishna S, Ramalingam M (2017) Development of decellularized scaffolds for stem cell-driven tissue engineering. J Tissue Eng Regen Med 11:942–965Google Scholar
  67. Rancy SK, Schmidle G, Wolfe SW (2019) Does anyone need a vascularized graft? Hand Clin 35:323–344Google Scholar
  68. Sawkins MJ, Bowen W, Dhadda P, Markides H, Sidney LE, Taylor AJ, Rose FR, Badylak SF, Shakesheff KM, White LJ (2013) Hydrogels derived from demineralized and decellularized bone extracellular matrix. Acta Biomater 9:7865–7873Google Scholar
  69. Schwarzbauer JE (1991) Fibronectin: from gene to protein. Curr Opin Cell Biol 3:786–791Google Scholar
  70. Sesli M, Akbay E, Onur MA (2018) Decellularization of rat adipose tissue, diaphragm, and heart: a comparison of two decellularization methods. Turk J Biol = Turk biyoloji dergisi 42:537–547Google Scholar
  71. Sheikh Z, Najeeb S, Khurshid Z, Verma V, Rashid H, Glogauer M (2015) Biodegradable materials for bone repair and tissue engineering applications. Materials 8:5744–5794Google Scholar
  72. Somuncu OS (2019) Decellularization concept in regenerative medicine. Adv Exp Med Biol 1212:71–85Google Scholar
  73. Soucy KG, Smith EF, Monreal G, Rokosh G, Keller BB, Yuan F, Matheny RG, Fallon AM, Lewis BC, Sherwood LC, Sobieski MA, Giridharan GA, Koenig SC, Slaughter MS (2015) Feasibility study of particulate extracellular matrix (P-ECM) and left ventricular assist device (HVAD) therapy in chronic ischemic heart failure bovine model. ASAIO J 61:161–169Google Scholar
  74. Stapleton TW, Ingram J, Katta J, Knight R, Korossis S, Fisher J, Ingham E (2008) Development and characterization of an acellular porcine medial meniscus for use in tissue engineering. Tissue Eng A 14:505–518Google Scholar
  75. Tsai CH, Chou MY, Jonas M, Tien YT, Chi EY (2002) A composite graft material containing bone particles and collagen in osteoinduction in mouse. J Biomed Mater Res 63:65–70Google Scholar
  76. Wang X, Ao Q, Tian X, Fan J, Tong H, Hou W, Bai S (2017) Gelatin-based hydrogels for organ 3D bioprinting. Polymers 9:401Google Scholar
  77. White LJ, Taylor AJ, Faulk DM, Keane TJ, Saldin LT, Reing JE, Swinehart IT, Turner NJ, Ratner BD, Badylak SF (2017) The impact of detergents on the tissue decellularization process: a ToF-SIMS study. Acta Biomater 50:207–219Google Scholar
  78. Whitlock PW, Seyler TM, Parks GD, Ornelles DA, Smith TL, Van Dyke ME, Poehling GG (2012) A novel process for optimizing musculoskeletal allograft tissue to improve safety, ultrastructural properties, and cell infiltration. JBJS 94:1458–1467Google Scholar
  79. Willemse J, Verstegen MMA, Vermeulen A, Schurink IJ, Roest HP, Van Der Laan LJW, De Jonge J (2020) Fast, robust and effective decellularization of whole human livers using mild detergents and pressure controlled perfusion. Mater Sci Eng C Mater Biol Appl 108:110200Google Scholar
  80. Woods T, Gratzer PF (2005) Effectiveness of three extraction techniques in the development of a decellularized bone–anterior cruciate ligament–bone graft. Biomaterials 26:7339–7349Google Scholar
  81. Xiao T, Guo W, Chen M, Hao C, Gao S, Huang J, Yuan Z, Zhang Y, Wang M, Li P, Peng J, Wang A, Wang Y, Sui X, Zhang L, Xu W, Lu S, Yin H, Yang J, Liu S, Guo Q (2017) Fabrication and in vitro study of tissue-engineered cartilage scaffold derived from Wharton’s jelly extracellular matrix. Biomed Res Int 2017:5839071Google Scholar
  82. Xing Q, Yates K, Tahtinen M, Shearier E, Qian Z, Zhao F (2015) Decellularization of fibroblast cell sheets for natural extracellular matrix scaffold preparation. Tissue Eng Part C Methods 21:77–87Google Scholar
  83. Xu H, Xu B, Yang Q, Li X, Ma X, Xia Q, Zhang Y, Zhang C, Wu Y, Zhang Y (2014) Comparison of decellularization protocols for preparing a decellularized porcine annulus fibrosus scaffold. PLoS One 9:e86723Google Scholar
  84. Xu K, Kuntz LA, Foehr P, Kuempel K, Wagner A, Tuebel J, Deimling CV, Burgkart RH (2017) Efficient decellularization for tissue engineering of the tendon-bone interface with preservation of biomechanics. PLoS One 12:e0171577Google Scholar
  85. Youngstrom DW, Barrett JG, Jose RR, Kaplan DL (2013) Functional characterization of detergent-decellularized equine tendon extracellular matrix for tissue engineering applications. PLoS One 8:e64151Google Scholar
  86. Zahiri S, Masaeli E, Poorazizi E, Nasr-Esfahani MH (2018) Chondrogenic response in presence of cartilage extracellular matrix nanoparticles. J Biomed Mater Res Part A 106:2463–2471Google Scholar
  87. Zambon JP, Ko IK, Abolbashari M, Huling J, Clouse C, Kim TH, Smith C, Atala A, Yoo JJ (2018) Comparative analysis of two porcine kidney decellularization methods for maintenance of functional vascular architectures. Acta Biomater 75:226–234Google Scholar

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Authors and Affiliations

  1. 1.Department of Stem Cells and Developmental Biology, Cell Science Research CenterRoyan Institute for Stem Cell Biology and Technology, ACECRTehranIran
  2. 2.Department of Cell Engineering, Cell Science Research CenterRoyan Institute for Stem Cell Biology and Technology, ACECRTehranIran

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