Abstract
Thanks to novel approaches and emerging technologies, tissue engineering and regenerative medicine have made a great effort to regenerate damaged tissue or organ with no donor needed. The approaches involve two fundamental components: bioengineered scaffolds and stem cells. Bioengineered scaffolds which can also be enriched with bioactive molecules such as cytokines, growth factors, and so on have been fabricated using a wide range of synthetically or naturally derived biodegradable and biocompatible polymers. These scaffolds should support cell attachment, migration, proliferation, and/or differentiation by mimicking the duty of native extracellular matrix. Stem cells are the other significant players in formation of the neotissue. Stem cells, bone marrow, or adipose-derived mesenchymal stem cells, in particular, have been widely used for this purpose. Recently, investigators have preferred to use progenitor cells including cardiac and neural cells in tissue engineering and regenerative medicine applications. The synergy of the bioengineered scaffolds and autologous stem cells is crucial for the successful reconstruction of damaged or missing tissues.
This review summarizes a number of excellent studies conducted on current applications of bioengineered scaffolds, novel fabrication methods, stem cells used in tissue engineering and regenerative medicine, and the future of the tissue-engineered products.
Keywords
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- 3D:
-
Three-dimensional
- AMSCs:
-
Adipose-derived mesenchymal stem cells
- CSCs:
-
Cardiac stem cells
- ECM:
-
Extracellular matrix
- ECSs:
-
Embryonic stem cells
- FDA:
-
Food and Drug Administration
- FDM:
-
Fused deposition modeling
- hAMSCs:
-
Human adipose-derived mesenchymal stem cells
- HUVECs:
-
Human umbilical vein endothelial cells
- iPSCs:
-
Induced pluripotent stem cells
- MSCs:
-
Mesenchymal stem cells
- NCSs:
-
Neural stem cells
- NPCs:
-
Neural progenitor cells
- PFP:
-
Powder-fusion printing
- SCI:
-
Spinal cord injury
- SLA:
-
Stereolithographic Apparatus
References
Aguado BA, Bushnell GG, Rao SS et al (2017) Engineering the pre-metastatic niche. Nat Biomed Eng 1:77
Alcayaga-Miranda F, Varas-Godoy M, Khoury M (2016) Harnessing the Angiogenic potential of stem cell-derived exosomes for vascular regeneration. Stem Cells Int 2016:1–11
Arslan YE, Hız MM, Sezgin Arslan T (2015) The use of decellularized animal tissues in regenerative therapies. Kafkas Univ Vet Fak Derg 21:139–145
Arslan YE, Sezgin Arslan T, Derkus B et al (2017) Fabrication of human hair keratin/jellyfish collagen/eggshell-derived hydroxyapatite osteoinductive biocomposite scaffolds for bone tissue engineering: from waste to regenerative medicine products. Colloids Surf B Biointerfaces 154:160–170
Atala A (2004) Tissue engineering and regenerative medicine: concepts for clinical application. Rejuvenation Res 7:15–34
Atala A, Bauer SB, Soker S et al (2006) Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367:1241–1246
Atala A, Kasper FK, Mikos AG (2012) Engineering complex tissues. Sci Transl Med 4:160rv12–160rv12
Badylak SF (2004) Xenogeneic extracellular matrix as a scaffold for tissue reconstruction. Transpl Immunol 12:367–377
Badylak SF, Gilbert TW (2008) Immune response to biologic scaffold materials. Semin Immunol 20:109–116
Badylak SF, Freytes D, Gilbert TW (2009) Extracellular matrix as a biological scaffold material: structure and function. Acta Biomater 5:1–13
Badylak SF, Taylor D, Uygun K (2011) Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng 13:27–53
Bankoti K, Rameshbabu AP, Datta S et al (2017) Accelerated healing of full thickness dermal wounds by macroporous waterborne polyurethane-chitosan hydrogel scaffolds. Mater Sci Eng C 81:133–143
Bellei B, Migliano E, Tedesco M et al (2017) Maximizing non-enzymatic methods for harvesting adipose-derived stem from lipoaspirate: technical considerations and clinical implications for regenerative surgery. Sci Rep 7:1–15
Benning L, Gutzweiler L, Tröndle K et al (2017) Cytocompatibility testing of hydrogels toward bioprinting of mesenchymal stem cells. J Biomed Mater Res Part A 105:3231–3241
Berthiaume F, Maguire TJ, Yarmush ML (2011) Tissue engineering and regenerative medicine: history, progress, and challenges. Annu Rev Chem Biomol Eng 2:403–430
Bhat S, Kumar A (2013) Biomaterials and bioengineering tomorrow’s healthcare. Biomatter 3:37–41
Bianco P, Robey PG, Simmons PJ (2008) Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2:313–319
Börger V, Bremer M, Ferrer-Tur R et al (2017) Mesenchymal stem/stromal cell-derived extracellular vesicles and their potential as novel immunomodulatory therapeutic agents. Int J Mol Sci 18:1450
Bruno S, Camussi G (2013) Role of mesenchymal stem cell-derived microvesicles in tissue repair. Pediatr Nephrol 28:2249–2254
Chan BP, Leong KW (2008) Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur Spine J 17:467–479
Cho S-W, Lim SH, Kim I-K et al (2005) Small-diameter blood vessels engineered with bone marrow-derived cells. Ann Surg 241:506–515
de Paula DRM, Capuano V, Filho DM et al (2017) Biological properties of cardiac mesenchymal stem cells in rats with diabetic cardiomyopathy. Life Sci 188:45–52
Den Hondt M, Vanaudenaerde BM, Maughan EF et al (2017) An optimized non-destructive protocol for testing mechanical properties in decellularized rabbit trachea. Acta Biomater 60:291–301
Derkus B, Emregul KC, Emregul E (2017) A new approach in stem cell research-exosomes: their mechanism of action via cellular pathways. Cell Biol Int 41:466–475
Di Rocco G, Baldari S, Toietta G (2017) Exosomes and other extracellular vesicles-mediated microRNA delivery for cancer therapy. Transl Cancer Res 6:S1321–S1330
Donderwinkel I, van Hest JCM, Cameron NR (2017) Bio-inks for 3D bioprinting: recent advances and future prospects. Polym Chem 8:4451–4471
Erten E, Sezgin Arslan T, Derkus B et al (2016) Detergent-free decellularization of bovine costal cartilage for chondrogenic differentiation of human adipose mesenchymal stem cells in vitro. RSC Adv 6:94236–94246
Fitzpatrick LE, McDevitt TC (2015) Cell-derived matrices for tissue engineering and regenerative medicine applications. Biomater Sci 3:12–24
Flanagan TC, Pandit A (2003) Living artificial heart valve alternatives: a review. Eur Cell Mater 6:28–45
Gao C, Peng S, Feng P et al (2017) Bone biomaterials and interactions with stem cells. Bone Res 5:17059
Gazzarri M, Bartoli C, Mota C et al (2013) Fibrous star poly(ε-caprolactone) melt-electrospun scaffolds for wound healing applications. J Bioact Compat Polym 28:492–507
Geissler SA, Sabin AL, Besser RR et al (2018) Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury. J Neural Eng 15:25004
Gilbert TW, Sellaro TL, Badylak SF (2006) Decellularization of tissues and organs. Biomaterials 27:3675–3683
Godara P, Nordon RE, McFarland CD (2008) Mesenchymal stem cells in tissue engineering. J Chem Technol Biotechnol 83:397–407
Goldman SA, Sim F (2005) Neural progenitor cells of the adult brain (Bock G, Goode J, eds). Novartis Found Symp 265:66–80–97
Gomzikova MO, Rizvanov AA (2017) Current trends in regenerative medicine: from cell to cell-free therapy. Bionanoscience 7:240–245
Gong M, Yu B, Wang J et al (2017) Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis. Oncotarget 8:45200–45212
Goradel NH, Hour FG, Negahdari B et al (2018) Stem cell therapy: a new therapeutic option for cardiovascular diseases. J Cell Biochem 119:95–104
Goyal R, Vega ME, Pastino AK et al (2017) Development of hybrid scaffolds with natural extracellular matrix deposited within synthetic polymeric fibers. J Biomed Mater Res Part A 105:2162–2170
Griffith LG, Naughton G (2002) Tissue engineering–current challenges and expanding opportunities. Science 295:1009–1014
Han C, Sun X, Liu L et al (2016) Exosomes and their therapeutic potentials of stem cells. Stem Cells Int 2016:1–11
Harris L, Zalucki O, Clément O et al (2018) Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression. Development 145:dev155689
Hawking SW (1988) A brief history of time: from the big bang to black holes. Bantam, New York
Hixon KR, Melvin AM, Lin AY et al (2017) Cryogel scaffolds from patient-specific 3D-printed molds for personalized tissue-engineered bone regeneration in pediatric cleft-craniofacial defects. J Biomater Appl 32:598–611
Hu J, Seeberger PH, Yin J (2016) Using carbohydrate-based biomaterials as scaffolds to control human stem cell fate. Org Biomol Chem 14:8648–8658
Hussey GS, Keane TJ, Badylak SF (2017) The extracellular matrix of the gastrointestinal tract: a regenerative medicine platform. Nat Rev Gastroenterol Hepatol 14:540–552
Inanç B, Arslan YE, Seker S et al (2009) Periodontal ligament cellular structures engineered with electrospun poly(DL-lactide- co -glycolide) nanofibrous membrane scaffolds. J Biomed Mater Res Part A 90A:186–195
Jokanović V, Čolović B, Antonijević Đ et al (2017) Various methods of 3D and bio-printing. Serbian Dent J 64:136–145
Kamao H, Mandai M, Ohashi W et al (2017) Evaluation of the surgical device and procedure for extracellular matrix–scaffold–supported human iPSC–derived retinal pigment epithelium cell sheet transplantation. Investig Opthalmology Vis Sci 58:211
Kaushik G, Leijten J, Khademhosseini A (2017) Concise review: organ engineering: design, technology, and integration. Stem Cells 35:51–60
Khademhosseini A, Vacanti JP, Langer R (2009) Progress in tissue engineering. Sci Am 300:64–71
Kim HO, Choi S-M, Kim H-S (2013) Mesenchymal stem cell-derived secretome and microvesicles as a cell-free therapeutics for neurodegenerative disorders. Tissue Eng Regen Med 10:93–101
Kolar K, Weber W (2017) Synthetic biological approaches to optogenetically control cell signaling. Curr Opin Biotechnol 47:112–119
Konno M, Hamabe A, Hasegawa S et al (2013) Adipose-derived mesenchymal stem cells and regenerative medicine. Develop Growth Differ 55:309–318
Koudan EV, Bulanova EA, Pereira FDAS et al (2016) Patterning of tissue spheroids biofabricated from human fibroblasts on the surface of electrospun polyurethane matrix using 3D bioprinter. Int J Bioprinting 2:45–52
Langer R, Vacanti J (1993) Tissue Eng Sci (80- ) 260:920–926
Langer RS, Vacanti JP (1999) Tissue engineering: the challenges ahead. Sci Am 280:86–89
Li W, Liu Y, Zhang P et al (2018) Tissue-engineered bone immobilized with human adipose stem cells-derived exosomes promotes bone regeneration. ACS Appl Mater Interfaces 10:5240–5254
Lin H (2002) The stem-cell niche theory: lessons from flies. Nat Rev Genet 3:931–940
Lou G, Chen Z, Zheng M et al (2017) Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases. Exp Mol Med 49:e346
Lui H, Vaquette C, Bindra R (2017) Tissue engineering in hand surgery: a technology update. J Hand Surg Am 42:727–735
Lv H, Wang H, Zhang Z et al (2017) Biomaterial stiffness determines stem cell fate. Life Sci 178:42–48
Mao AS, Mooney DJ (2015) Regenerative medicine: current therapies and future directions. Proc Natl Acad Sci 112:14452–14459
Martinez PR, Goyanes A, Basit AW et al (2017) Fabrication of drug-loaded hydrogels with stereolithographic 3D printing. Int J Pharm 532:313–317
Mason C, Dunnill P (2008) The strong financial case for regenerative medicine and the Regen industry. Regen Med 3:351–363
Mason C, Dunnill P (2010) A brief definition of regenerative medicine [EDITORIAL]. Regen Med 3:1–5
Melhem MR, Park J, Knapp L et al (2017) 3D printed stem-cell-laden, microchanneled hydrogel patch for the enhanced release of cell-secreting factors and treatment of myocardial infarctions. ACS Biomater Sci Eng 3:1980–1987
Murphy KC, Whitehead J, Zhou D et al (2017) Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids. Acta Biomater 64:176–186
NASDAQ Globe News (2017) Global $53 billion Regenerative Medicine Market Analysis & Forecast Report 2017–2021: focus on stem cells, tissue engineering, BioBanking & CAR-T Industries. NASDAQ Globe News Wire
Nemeno-Guanzon JG, Lee S, Berg JR et al (2012) Trends in tissue engineering for blood vessels. J Biomed Biotechnol 2012:1–14
Nerem RM (2010) Regenerative medicine: the emergence of an industry. J R Soc Interface 7:S771–S775
Ning L-J, Jiang Y-L, Zhang C-H et al (2017) Fabrication and characterization of a decellularized bovine tendon sheet for tendon reconstruction. J Biomed Mater Res Part A 105:2299–2311
Ozler SB, Bakirci E, Kucukgul C et al (2017) Three-dimensional direct cell bioprinting for tissue engineering. J Biomed Mater Res Part B Appl Biomater 105:2530–2544
Pereira RF, Bártolo PJ (2015) 3D photo-fabrication for tissue engineering and drug delivery. Engineering 1:090–112
Plagnol AC, Rowley E, Martin P et al (2009) Industry perceptions of barriers to commercialization of regenerative medicine products in the UK. Regen Med 4:549–559
Porter JR, Ruckh TT, Popat KC (2009) Bone tissue engineering: a review in bone biomimetics and drug delivery strategies. Biotechnol Prog 25:1539–1560
Pournaqi F, Ghiaee A, Vakilian S et al (2017) Improved proliferation and osteogenic differentiation of mesenchymal stem cells on polyaniline composited by polyethersulfone nanofibers. Biologicals 45:78–84
Prajumwongs P, Weeranantanapan O, Jaroonwitchawan T et al (2016) Human embryonic stem cells: a model for the study of neural development and neurological diseases 2016
Quan Q, Chang B, Meng HY et al (2016) Use of electrospinning to construct biomaterials for peripheral nerve regeneration. Rev Neurosci 27:761–768
Repina NA, Rosenbloom A, Mukherjee A et al (2017) At light speed: advances in optogenetic systems for regulating cell signaling and behavior. Annu Rev Chem Biomol Eng 8:13–39
Riazifar M, Pone EJ, Lötvall J et al (2017) Stem cell extracellular vesicles: extended messages of regeneration. Annu Rev Pharmacol Toxicol 57:125–154
Rim NG, Shin CS, Shin H (2013) Current approaches to electrospun nanofibers for tissue engineering. Biomed Mater 8:14102
Rosenzweig ES, Brock JH, Lu P et al (2018) Restorative effects of human neural stem cell grafts on the primate spinal cord. Nat Med 24:484–490
Sadtler K, Singh A, Wolf MT et al (2016) Design, clinical translation and immunological response of biomaterials in regenerative medicine. Nat Rev Mater 1:16040
Safari S, Malekvandfard F, Babashah S et al (2016) Mesenchymal stem cell-derived exosomes: a novel potential therapeutic avenue for cardiac regeneration. Cell Mol Biol 62:66–73
Saito S, Hiemori K, Kiyoi K et al (2018) Glycome analysis of extracellular vesicles derived from human induced pluripotent stem cells using lectin microarray. Sci Rep 8:3997
Santoso MR, Yang PC (2017) Molecular imaging of stem cells and exosomes for myocardial regeneration. Curr Cardiovasc Imaging Rep 10:37
Seker S, Arslan YE, Elcin YM (2010) Electrospun Nanofibrous PLGA/fullerene-C60 coated quartz crystal microbalance for real-time Gluconic acid monitoring. IEEE Sensors J 10:1342–1348
Seyler TM, Bracey DN, Plate JF et al (2017) The development of a xenograft-derived scaffold for tendon and ligament reconstruction using a Decellularization and oxidation protocol. Arthrosc J Arthrosc Relat Surg 33:374–386
Shenghui H, Nakada D, Morrison SJ (2009) Mechanisms of stem cell self-renewal. Annu Rev Cell Dev Biol 25:377–406
Soletti L, Hong Y, Guan J et al (2010) A bilayered elastomeric scaffold for tissue engineering of small diameter vascular grafts. Acta Biomater 6:110–122
Subia B, Kundu J, Kundu CS (2010) Biomaterial scaffold fabrication techniques for potential tissue engineering applications. In: Eberli D (ed) Tissue Eng. InTech, p 524
Sutherland AJ, Beck EC, Dennis SC et al (2015) Decellularized cartilage may be a chondroinductive material for osteochondral tissue engineering (Almarza A, ed). PLoS One 10:e0121966
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676
Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science (80- ) 282:1145–1147
Toh WS, Lai RC, Hui JHP et al (2016) MSC exosome as a cell-free MSC therapy for cartilage regeneration: implications for osteoarthritis treatment. Semin Cell Dev Biol
Torella D, Ellison GM, Karakikes I et al (2007) Cardiovascular development: towards biomedical applicability. Cell Mol Life Sci 64:661–673
Tuan RS, Boland G, Tuli R (2003) Adult mesenchymal stem cells and cell-based tissue engineering. Arthritis Res Ther 5:32–45
Ullah I, Subbarao RB, Rho GJ (2015) Human mesenchymal stem cells – current trends and future prospective. Biosci Rep 35:1–18
Vacanti CA (2006) The history of tissue engineering. J Cell Mol Med 10:569–576
van de Kamp J, Paefgen V, Wöltje M et al (2017) Mesenchymal stem cells can be recruited to wounded tissue via hepatocyte growth factor-loaded biomaterials. J Tissue Eng Regen Med 11:2988–2998
Vargas-Alfredo N, Dorronsoro A, Cortajarena AL et al (2017) Antimicrobial 3D porous scaffolds prepared by additive manufacturing and breath figures. ACS Appl Mater Interfaces 9:37454–37462
Vasudevan S, Huang J, Botterman B et al (2014) Detergent-free decellularized nerve grafts for long-gap peripheral nerve reconstruction. Plast Reconstr Surg Glob Open 2:e201
Vizoso F, Eiro N, Cid S et al (2017) Mesenchymal stem cell Secretome: toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci 18:1852
Wang X, Fang Q, You C et al (2014) Construction of skin substitutes using minced split-thickness autografts and biodegradable synthetic scaffolds. Burns 40:1232–1233
Wang Y, Bao J, Wu X et al (2016) Genipin crosslinking reduced the immunogenicity of xenogeneic decellularized porcine whole-liver matrices through regulation of immune cell proliferation and polarization. Sci Rep 6:24779
Wang L, Kang J, Sun C et al (2017) Mapping porous microstructures to yield desired mechanical properties for application in 3D printed bone scaffolds and orthopaedic implants. Mater Des 133:62–68
Wei C-C, Lin AB, Hung S-C (2014) Mesenchymal stem cells in regenerative medicine for musculoskeletal diseases: bench, bedside, and industry. Cell Transplant 23:505–512
White IA, Sanina C, Balkan W et al (2016) Mesenchymal stem cells in cardiology. In: Gnecchi M (ed) Mesenchymal stem cells, methods in molecular biology. Springer, New York, pp 55–87
Wiles K, Fishman JM, De Coppi P et al (2016) The host immune response to tissue-engineered organs: current problems and future directions. Tissue Eng Part B Rev 22:208–219
Wolf MT, Dearth CL, Sonnenberg SB et al (2015) Naturally derived and synthetic scaffolds for skeletal muscle reconstruction. Adv Drug Deliv Rev 84:208–221
Xing Q, Qian Z, Jia W et al (2017) Natural extracellular matrix for cellular and tissue biomanufacturing. ACS Biomater Sci Eng 3:1462–1476
Xu S, Lu F, Cheng L et al (2017) Preparation and characterization of small-diameter decellularized scaffolds for vascular tissue engineering in an animal model. Biomed Eng Online 16:55
Yu B, Zhang X, Li X (2014) Exosomes derived from mesenchymal stem cells. Int J Mol Sci 15:4142–4157
Zhang L, Hu J, Athanasiou KA (2009) The role of tissue engineering in articular cartilage repair and regeneration. Crit Rev Biomed Eng 37:1–57
Zhang J, Liu X, Li H et al (2016) Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway. Stem Cell Res Ther 7:1–14
Zhang Y-Z, Liu F, Song C-G et al (2018) Exosomes derived from human umbilical vein endothelial cells promote neural stem cell expansion while maintain their stemness in culture. Biochem Biophys Res Commun 495:892–898
Acknowledgments
The authors would like to thank Prof. Kaan C. Emregul for his comments and language proofreading.
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Erten, E., Arslan, Y.E. (2018). The Great Harmony in Translational Medicine: Biomaterials and Stem Cells. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 4. Advances in Experimental Medicine and Biology(), vol 1119. Springer, Cham. https://doi.org/10.1007/5584_2018_231
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