{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:48:45Z","timestamp":1790185725087,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005357","name":"Agent\u00fara na Podporu V\u00fdskumu a V\u00fdvoja","doi-asserted-by":"publisher","award":["APVV-15-0111"],"award-info":[{"award-number":["APVV-15-0111"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Urethral defects originating from congenital malformations, trauma, inflammation or carcinoma still pose a great challenge to modern urology. Recent therapies have failed many times and have not provided the expected results. This negatively affects patients\u2019 quality of life. By combining cells, bioactive molecules, and biomaterials, tissue engineering can provide promising treatment options. This review focused on scaffold systems for urethra reconstruction. We also discussed different technologies, such as electrospinning and 3D bioprinting which provide great possibility for the preparation of a hollow structure with well-defined architecture.<\/jats:p>","DOI":"10.3390\/ma12203449","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T11:46:59Z","timestamp":1571831219000},"page":"3449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Bioengineered Scaffolds as Substitutes for Grafts for Urethra Reconstruction"],"prefix":"10.3390","volume":"12","author":[{"given":"Martina","family":"Culenova","sequence":"first","affiliation":[{"name":"Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusan","family":"Bakos","sequence":"additional","affiliation":[{"name":"International Centre for Applied Research and Sustainable Technology, Jamnickeho 19, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav","family":"Ziaran","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Comenius University, Limbova 5, 833 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Bodnarova","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Measurement, Faculty of Mechanical Engineering, Technical University of Kosice, Letna 9, 042 00 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Varga","sequence":"additional","affiliation":[{"name":"Institute of Histology and Embryology, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5074-9621","authenticated-orcid":false,"given":"Lubos","family":"Danisovic","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia"},{"name":"Regenmed Ltd., Medena 29, 811 01 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.ejmg.2014.03.003","article-title":"Review of genetic and environmental factors leading to hypospadias","volume":"57","author":"Shih","year":"2014","journal-title":"Eur. J. Med. Genet."},{"key":"ref_2","first-page":"209","article-title":"Epidemiology of urethral strictures","volume":"3","author":"Alwaal","year":"2014","journal-title":"Transl. Androl. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S0377-1237(05)80107-8","article-title":"Iatrogenic Disorders","volume":"61","author":"Krishnan","year":"2005","journal-title":"Med. J. Armed. Forces India."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0970-1591.173108","article-title":"Current management of urethral stricture disease","volume":"32","author":"Smith","year":"2016","journal-title":"Indian J. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Davis, N.F., Bhatt, N.R., MacCraith, E., Flood, H.D., Mooney, R., Leonard, G., and Walsh, M.T. (2019). Long-term outcomes of urethral catheterisation injuries: A prospective multi-institutional study. World J. Urol., 1\u20138.","DOI":"10.1016\/S1569-9056(19)31116-9"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ajur.2017.12.005","article-title":"A brief review on anterior urethral strictures","volume":"5","author":"Cheng","year":"2018","journal-title":"Asian J. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1111\/bju.12945","article-title":"Changing trends in the causes and management of male urethral stricture disease in China: an observational descriptive study from 13 centres","volume":"116","author":"Xu","year":"2015","journal-title":"BJU Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.copbio.2009.10.003","article-title":"Engineering organs","volume":"20","author":"Atala","year":"2009","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_9","first-page":"29","article-title":"Tissue engineering in urethral reconstruction","volume":"67","author":"Cui","year":"2014","journal-title":"Arch. espanoles de Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1089\/ten.teb.2012.0737","article-title":"Ureteral Tissue Engineering: Where Are We and How to Proceed?","volume":"19","author":"Simaioforidis","year":"2013","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s00345-008-0316-6","article-title":"Tubularized urethral replacement with unseeded matrices: What is the maximum distance for normal tissue regeneration?","volume":"26","author":"Dorin","year":"2008","journal-title":"World J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.surge.2017.07.002","article-title":"Tissue engineered extracellular matrices (ECMs) in urology: Evolution and future directions","volume":"16","author":"Davis","year":"2018","journal-title":"Surgeon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1369-7021(11)70058-X","article-title":"Biomaterials & scaffolds for tissue engineering","volume":"14","year":"2011","journal-title":"Mater. Today"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"403","DOI":"10.5489\/cuaj.1155","article-title":"Tissue engineering in urology","volume":"3","author":"Matoka","year":"2009","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"204173141880209","DOI":"10.1177\/2041731418802090","article-title":"Bioprinting of tissue engineering scaffolds","volume":"9","author":"Rider","year":"2018","journal-title":"J. Tissue Eng."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1002\/polb.22259","article-title":"Biomedical Applications of Biodegradable Polymers","volume":"49","author":"Ulery","year":"2011","journal-title":"J. Polym. Sci. Part B Polym. Phys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/S0140-6736(10)62354-9","article-title":"Tissue-engineered autologous urethras for patients who need reconstruction: an observational study","volume":"377","author":"Esquiliano","year":"2011","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1111\/j.1464-410X.2005.05741.x","article-title":"Growth of bone marrow stromal cells on small intestinal submucosa: An alternative cell source for tissue engineered bladder","volume":"96","author":"Zhang","year":"2005","journal-title":"BJU Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8889","DOI":"10.1016\/j.biomaterials.2010.07.108","article-title":"Tissue-engineered conduit using urine-derived stem cells seeded bacterial cellulose polymer in urinary reconstruction and diversion","volume":"31","author":"Bodin","year":"2010","journal-title":"Biomaterials"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1159\/000277661","article-title":"Tissue-Engineered Transplants for the Treatment of Severe Hypospadias","volume":"73","author":"Fossum","year":"2010","journal-title":"Horm. Res. Paediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.eururo.2008.01.061","article-title":"Tissue-Engineered Buccal Mucosa Urethroplasty\u2014Clinical Outcomes","volume":"53","author":"Bhargava","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Abbas, T.O., Yalcin, H.C., and Pennisi, C.P. (2019). From Acellular Matrices to Smart Polymers: Degradable Scaffolds that are Transforming the Shape of Urethral Tissue Engineering. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071763"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1177\/0963689717725528","article-title":"Human Amniotic Membrane and Amniotic Membrane\u2013Derived Cells: How Far Are We from Their Use in Regenerative and Reconstructive Urology?","volume":"27","author":"Ramuta","year":"2018","journal-title":"Cell Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/term.1647","article-title":"Penile urethra replacement with autologous cell-seeded tubularized collagen matrices: Collagen matrices for urethral replacement","volume":"9","author":"Kornitzer","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.eururo.2012.07.041","article-title":"Cell-Seeded Tubularized Scaffolds for Reconstruction of Long Urethral Defects: A Preclinical Study","volume":"63","author":"Orabi","year":"2013","journal-title":"Eur. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.biomaterials.2015.08.009","article-title":"Urethral tissue regeneration using collagen scaffold modified with collagen binding VEGF in a beagle model","volume":"69","author":"Jia","year":"2015","journal-title":"Biomaterials"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.actbio.2016.07.033","article-title":"Engineered acellular collagen scaffold for endogenous cell guidance, a novel approach in urethral regeneration","volume":"43","author":"Pinnagoda","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10057","DOI":"10.1038\/s41598-018-27621-9","article-title":"Fiber density of collagen grafts impacts rabbit urethral regeneration","volume":"8","author":"Larsson","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.aju.2012.01.008","article-title":"Cell-seeded tubular acellular matrix for replacing a long circumferential urethral defect in a canine model: Is it clinically applicable?","volume":"10","author":"Shokeir","year":"2012","journal-title":"Arab. J. Urol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7447","DOI":"10.1016\/j.biomaterials.2012.06.087","article-title":"In-vivo performance of high-density collagen gel tubes for urethral regeneration in a rabbit model","volume":"33","author":"Micol","year":"2012","journal-title":"Biomaterials"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.colsurfb.2015.06.049","article-title":"A tubular gelatin scaffold capable of the time-dependent controlled release of epidermal growth factor and mitomycin C","volume":"135","author":"Zhu","year":"2015","journal-title":"Colloids Surfaces B Biointerfaces"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1111\/j.1464-410X.2006.06691.x","article-title":"Urethral replacement using epidermal cell-seeded tubular acellular bladder collagen matrix","volume":"99","author":"Fu","year":"2007","journal-title":"BJU Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2017.02.005","article-title":"Tubular collagen scaffolds with radial elasticity for hollow organ regeneration","volume":"52","author":"Versteegden","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1002\/term.2685","article-title":"Self-expandable tubular collagen implants","volume":"12","author":"Versteegden","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11934-015-0567-x","article-title":"Silk Fibroin Scaffolds for Urologic Tissue Engineering","volume":"17","author":"Sack","year":"2016","journal-title":"Curr. Urol. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.biomaterials.2016.01.032","article-title":"Structural and functional evaluation of oxygenating keratin\/silk fibroin scaffold and initial assessment of their potential for urethral tissue engineering","volume":"84","author":"Lv","year":"2016","journal-title":"Biomaterials"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.msec.2013.08.037","article-title":"Design of 3D scaffolds for tissue engineering testing a tough polylactide-based graft copolymer","volume":"34","author":"Dorati","year":"2014","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"102","DOI":"10.4161\/biom.1.1.17447","article-title":"Knitted polylactide 96\/4 L\/D structures and scaffolds for tissue engineering: shelf life, in vitro and in vivo studies","volume":"1","author":"Annala","year":"2011","journal-title":"Biomatter"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/j.1464-410X.2010.09310.x","article-title":"Developing biodegradable scaffolds for tissue engineering of the urethra: Biodegradable scaffolds for tissue engineering of the urethra","volume":"107","author":"Selim","year":"2011","journal-title":"BJU Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1089\/teb.2007.0133","article-title":"Biodegradable Polyurethanes: Synthesis and Applications in Regenerative Medicine","volume":"14","author":"Guelcher","year":"2008","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.biomaterials.2010.09.050","article-title":"Differential affinity of vitronectin versus collagen for synthetic biodegradable scaffolds for urethroplastic applications","volume":"32","author":"Hicks","year":"2011","journal-title":"Biomaterials"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1002\/jbm.b.33144","article-title":"Nano\/microfibrous polymeric constructs loaded with bioactive agents and designed for tissue engineering applications: A review: Nano\/Microfibrous Polymeric Constructs","volume":"102","author":"Puppi","year":"2014","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/S0142-9612(00)00047-8","article-title":"In vitro and in vivo degradation of porous poly(dl-lactic-co-glycolic acid) foams","volume":"21","author":"Lu","year":"2000","journal-title":"Biomaterials"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/jbm.b.30982","article-title":"An innovative method to obtain porous PLLA scaffolds with highly spherical and interconnected pores","volume":"86","author":"Vaquette","year":"2008","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1089\/ten.1995.1.15","article-title":"Fabrication of Controlled Release Biodegradable Foams by Phase Separation","volume":"1","author":"Lo","year":"1995","journal-title":"Tissue Eng."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s10544-007-9097-8","article-title":"Fabrication of multi-layered biodegradable drug delivery device based on micro-structuring of PLGA polymers","volume":"9","author":"Ryu","year":"2007","journal-title":"Biomed. Microdevices"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1080\/09205063.2015.1116885","article-title":"Electrospinning as a powerful technique for biomedical applications: A critically selected survey","volume":"27","author":"Grande","year":"2016","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.msec.2006.05.019","article-title":"Electrospinning for tissue engineering scaffolds","volume":"27","author":"Lannutti","year":"2007","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"27659","DOI":"10.3390\/ijms161126050","article-title":"Application of Wnt Pathway Inhibitor Delivering Scaffold for Inhibiting Fibrosis in Urethra Strictures: In Vitro and in Vivo Study","volume":"16","author":"Zhang","year":"2015","journal-title":"IJMS"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lv, X., Guo, Q., Han, F., Chen, C., Ling, C., Chen, W., and Li, B. (2016). Electrospun Poly(l-lactide)\/Poly(ethylene glycol) Scaffolds Seeded with Human Amniotic Mesenchymal Stem Cells for Urethral Epithelium Repair. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17081262"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.jss.2013.04.016","article-title":"Evaluation of stretched electrospun silk fibroin matrices seeded with urothelial cells for urethra reconstruction","volume":"184","author":"Xie","year":"2013","journal-title":"J. Surg. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s11255-014-0854-3","article-title":"Preparation of PCL\/silk fibroin\/collagen electrospun fiber for urethral reconstruction","volume":"47","author":"Wei","year":"2015","journal-title":"Int. Urol. Nephrol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.7150\/thno.18833","article-title":"Fabrication of Tissue-Engineered Bionic Urethra Using Cell Sheet Technology and Labeling By Ultrasmall Superparamagnetic Iron Oxide for Full-Thickness Urethral Reconstruction","volume":"7","author":"Zhou","year":"2017","journal-title":"Theranostics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.eururo.2011.05.051","article-title":"Mechanical Stimuli-induced Urothelial Differentiation in a Human Tissue-engineered Tubular Genitourinary Graft","volume":"60","author":"Cattan","year":"2011","journal-title":"Eur. Urol."},{"key":"ref_55","first-page":"15","article-title":"3D Bioprinting Technologies for Tissue Engineering Applications","volume":"Volume 1078","author":"Gu","year":"2018","journal-title":"Genome Editing"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/nbt.3413","article-title":"A 3D bioprinting system to produce human-scale tissue constructs with structural integrity","volume":"34","author":"Kang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"032002","DOI":"10.1088\/1758-5090\/8\/3\/032002","article-title":"Bioink properties before, during and after 3D bioprinting","volume":"8","author":"Lin","year":"2016","journal-title":"Biofabrication"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.3390\/ma11112199","article-title":"An Introduction to 3D Bioprinting: Possibilities, Challenges and Future Aspects","volume":"11","author":"Rider","year":"2018","journal-title":"Materials"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jbiotec.2018.08.019","article-title":"Determination of geometrical and viscoelastic properties of PLA\/PHB samples made by additive manufacturing for urethral substitution","volume":"284","author":"Schnitzer","year":"2018","journal-title":"J. Biotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.actbio.2016.12.008","article-title":"3D bioprinting of urethra with PCL\/PLCL blend and dual autologous cells in fibrin hydrogel: An in vitro evaluation of biomimetic mechanical property and cell growth environment","volume":"50","author":"Zhang","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1706913","DOI":"10.1002\/adma.201706913","article-title":"Digitally Tunable Microfluidic Bioprinting of Multilayered Cannular Tissues","volume":"30","author":"Pi","year":"2018","journal-title":"Adv. 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