The standard for long-segment reconstruction of the ureter and urinary diversion is the creation of neotissue using autologous bowel tissue, although associated with multiple complications. Tissue-engineered constructs may provide alternative solutions. In this study, we review ureter reconstruction and urinary diversion using Tissue Engineering approaches. A literature search strategy was applied in PubMed to identify all available preclinical studies published up until September 2018. Subsequently, studies were screened for scaffolds used and relevance (e.g., reconstruction of full circumferential defects in preclinical settings) and further categorized based on whether grafts were directly implanted, seeded with cells before implantation, or preimplanted (with or without cells) before functional implantation. Future prospects are discussed with emphasis on scaffold design and functional tissue maturation of tissue-engineered constructs to foster clinical translation.
Impact Statement
Tissue Engineering (TE) approaches are needed to advance the field of reconstructive urology. We indicate that regeneration of ureteral tissue and the formation of a urinary diversion using TE approaches are possible, although it is currently very time-consuming and complex to achieve well-developed neotissue. Faster regeneration approaches using novel scaffolds are desirable. The findings of this review may help to develop smart hybrid scaffolds and enhance the design of future studies, which may ultimately lead to improved care for patients with ureteral defects as well as to curb complications associated with urinary diversion.
Get full access to this article
View all access options for this article.
References
1.
BurksF.N., and SantucciR.A.Management of iatrogenic ureteral injury. Ther Adv Urol, 6, 115, 2014.
2.
SummertonD.J., KitreyN.D., LumenN., SerafetinidisE., and DjakovicN.European Association of Urology. EAU Guidelines on Iatrogenic Trauma. Eur Urol, 62, 628, 2012.
3.
MartiniA., VillariD., and NicitaG.Long-term complications arising from bowel interposition in the urinary tract. Int J Surg, 44, 278, 2017.
4.
PikeT.W., PandanaboyanaS., Hope-JohnsonT., HostertL., and AhmadN.Ureteric reconstruction for the management of transplant ureteric stricture: a decade of experience from a single centre. Transpl Int England, 28, 529, 2015.
5.
WitjesA.J., LebretT., CompératE.M., et al.Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol, 71, 462, 2017.
6.
FarberN.J., FaienaI., DombrovskiyV., et al.Disparities in the use of continent urinary diversions after radical cystectomy for bladder cancer. Bladder Cancer, 4, 113, 2018.
7.
HautmannR.E., HautmannS.H., and HautmannO.Complications associated with urinary diversion. Nat Rev Urol, 8, 667, 2011.
8.
LangerR., and VacantiJ.P.Tissue engineering. Science, 260, 920, 1993.
9.
HooijmansC.R., TillemaA., LeenaarsM., and Ritskes-HoitingaM.Enhancing search efficiency by means of a search filter for finding all studies on animal experimentation in PubMed. Lab Anim, 44, 170, 2010.
10.
HollisterS.J.Scaffold design and manufacturing: from concept to clinic. Adv Mater, 21, 3330, 2009.
11.
O'BrienF.J.Biomaterials and scaffolds for tissue engineering. Mater Today, 14, 88, 2011.
12.
ShalhavA.L., ElbahnasyA.M., BercowskyE., et al.Laparoscopic replacement of urinary tract segments using biodegradable materials in a large-animal model. J Endourol, 13, 241, 1999.
13.
XieH., ShafferB.S., WadiaY., and GregoryK.W.Use of reconstructed small intestine submucosa for urinary tract replacement. ASAIO J, 46, 268, 2000.
14.
JaffeJ.S., GinsbergP.C., YanoshakS.J., et al.Ureteral segment replacement using a circumferential small-intestinal submucosa xenogenic graft. J Invest Surg, 14, 259, 2001.
15.
SoferM., RoweE., ForderD.M., and DenstedtJ.D.Ureteral segmental replacement using multilayer porcine small-intestinal submucosa. J Endourol, 16, 27, 2002.
16.
DucheneD.A., JacomidesL., OganK., et al.Ureteral replacement using small-intestinal submucosa and a collagen inhibitor in a porcine model. J Endourol, 18, 507, 2004.
EL-AssmyA., HafezA.T., EL-SherbinyM.T., et al.Use of single layer small intestinal submucosa for long segment ureteral replacement: a pilot study. J Urol, 171, 1939, 2004.
19.
DrewaT.The artificial conduit for urinary diversion in rats: a preliminary study. Transplant Proc, 39, 1647, 2007.
20.
SalehipourM., MohammadianR., JahanbiniS., EmadmarvastiV., GeramizadehB., and TanidehN.Is amniotic membrane a suitable biomaterial for reconstruction of long ureteral defects? Saudi J Kidney Dis Transpl, 24, 135, 2013.
21.
OsmanY., ShokeirA., GabrM., EL-TabeyN., MohsenT., and EL-BazM.Canine ureteral replacement with long acellular matrix tube: is it clinically applicable? J Urol, 172, 1151, 2004.
22.
DahmsS.E., PiechotaH.J., NunesL., DahiyaR., LueT.F., and TanaghoE.A.Free ureteral replacement in rats: regeneration of ureteral wall components in the acellular matrix graft. Urology, 50, 818, 1997.
23.
KloskowskiT., JundzillA., KowalczykT., et al.Ureter regeneration-the proper scaffold has to be defined. PLoS One, 9, e106023, 2014.
24.
ZhaoZ., YuH., XiaoF., WangX., YangS., and LiS.Differentiation of adipose-derived stem cells promotes regeneration of smooth muscle for ureteral tissue engineering. J Surg Res, 178, 55, 2012.
25.
ZhaoZ., YuH., FanC., KongQ., LiuD., and MengL.Differentiate into urothelium and smooth muscle cells from adipose tissue-derived stem cells for ureter reconstruction in a rabbit model. Am J Transl Res, 8, 3757, 2016.
26.
LiaoW., YangS., SongC., LiX., LiY., and XiongY.Construction of ureteral grafts by seeding bone marrow mesenchymal stem cells and smooth muscle cells into bladder acellular matrix. Transplant Proc, 45, 730, 2013.
27.
MengL.C., LiaoW.B., YangS.X., XiongY.H., SongC., and LiuL.Q.Seeding homologous adipose-derived stem cells and bladder smooth muscle cells into bladder submucosa matrix for reconstructing the ureter in a rabbit model. Transplant Proc, 47, 3002, 2015.
28.
LiaoW., YangS., SongC., LiY., MengL., LiX., et al.Tissue-engineered tubular graft for urinary diversion after radical cystectomy in rabbits. J Surg Res, 182, 185, 2013.
29.
MengL., LiaoW., YangS., XiongY., SongC., and LiuL.Tissue-engineered tubular substitutions for urinary diversion in a rabbit model. Exp Biol Med (Maywood), 241, 147, 2016.
30.
GilbertT., SellaroT., and BadylakS.Decellularization of tissues and organs. Biomaterials, 27, 19, 2006.
31.
TaylorD.A., SampaioL.C., FerdousZ., GobinA.S., and TaiteL.J.Decellularized matrices in regenerative medicine. Acta Biomater, 74, 74, 2018.
32.
SyedO., WaltersN.J., DayR.M., KimH.W., and KnowlesJ.C.Evaluation of decellularization protocols for production of tubular small intestine submucosa scaffolds for use in oesophageal tissue engineering. Acta Biomater, 10, 5043, 2014.
33.
YinF.C., and FungY.C.Mechanical properties of isolated mammalian ureteral segments. Am J Physiol, 221, 1484, 1971.
34.
RassoliA., ShafighM., SeddighiA., SeddighiA., DaneshparvarH., and FatouraeeN.Biaxial mechanical properties of human ureter under tension. Urol J, 11, 1678, 2014.
35.
DerhamC., YowH., IngramJ., et al.Tissue engineering small-diameter vascular grafts: preparation of a biocompatible porcine ureteric scaffold. Tissue Eng Part A, 14, 1871, 2008.
36.
TachibanaM., NagamatsuG.R., and AddonizioJ.C.Ureteral replacement using collagen sponge tube grafts. J Urol, 133, 866, 1985.
37.
de JongeP.K.J.D., SimaioforidisV., GeutjesP.J., OosterwijkE., and FeitzW.F.J.Recent advances in ureteral tissue engineering. Curr Urol Rep, 16, 465, 2015.
38.
DongC., and LvY.Application of collagen scaffold in tissue engineering: recent advances and new perspectives. Polymers (Basel). Multidisciplinary Digit Publishing Inst, 8, 42, 2016.
39.
Olde DaminkL.H., DijkstraP.J., van LuynM.J., van WachemP.B., NieuwenhuisP., and FeijenJ.In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide. Biomaterials, 17, 679, 1996.
40.
Olde DaminkL.H., DijkstraP.J., van LuynM.J., van WachemP.B., NieuwenhuisP., and FeijenJ.Cross-linking of dermal sheep collagen using a water-soluble carbodiimide. Biomaterials, 17, 765, 1996.
41.
HaughM.G., MurphyC.M., McKiernanR.C., AltenbuchnerC., and O'BrienF.J.Crosslinking and mechanical properties significantly influence cell attachment, proliferation, and migration within collagen glycosaminoglycan scaffolds. Tissue Eng Part A, 17, 1201, 2011.
42.
VaradyS., FriedmanE., YapW.T., LageA., and RichieJ.P.Ureteral replacement with a new synthetic material: Gore-Tex. J Urol, 128, 171, 1982.
43.
SabaneghE.S., DowneyJ.R., and SagoA.L.Long-segment ureteral replacement with expanded polytetrafluoroethylene grafts. Urology, 48, 312, 1996.
44.
PetersJ.J., ShingletonW.B., MorganD., AllenB., and FowlerJ.E.J.Neointimized Gore-Tex graft for ureteral prosthesis in the dog. Urology, 48, 379, 1996.
45.
BaltaciS., OzerG., OzerE., SoygürT., BeşaltiO., and AnafartaK.Failure of ureteral replacement with Gore-Tex tube grafts. Urology, 51, 400, 1998.
46.
SinghC., WongC., and WangX.Medical textiles as vascular implants and their success to mimic natural arteries. J Funct Biomater, 6, 500, 2015.
47.
Muerza-CascanteM.L., HaylockD., HutmacherD.W., and DaltonP.D.Melt electrospinning and its technologization in tissue engineering. Tissue Eng Part B Rev, 21, 187, 2015.
48.
WangX., ZhangL., ChenQ., et al.A nanostructured degradable ureteral stent fabricated by electrospinning for upper urinary tract reconstruction. J Nanosci Nanotechnol, 15, 9899, 2015.
49.
BasuJ., JayoM.J., IlaganR.M., et al.Regeneration of native-like neo-urinary tissue from nonbladder cell sources. Tissue Eng Part A, 18, 1025, 2012.
50.
de JongeP., SimaioforidisV., GeutjesP., OosterwijkE., and FeitzW.Ureteral reconstruction with reinforced collagen scaffolds in a porcine model. J Tissue Eng Regen Med, 12, 80, 2018.
51.
de JongeP.K.J.D., SloffM., JankeH.P., et al.Ureteral reconstruction in goats using tissue-engineered templates and subcutaneous preimplantation. Tissue Eng Part A, 24, 863, 2018.
52.
GeutjesP., RoelofsL., HoogenkampH., et al.Tissue engineered tubular construct for urinary diversion in a preclinical porcine model. J Urol, 188, 653, 2012.
53.
SloffM., SimaioforidisV., GeutjesP.J., et al.Novel tubular constructs for urinary diversion: a biocompatibility study in pigs. J Tissue Eng Regen Med, 11, 2241, 2017.
54.
SloffM., SimaioforidisV., TiemessenD.M., et al.Tubular constructs as artificial urinary conduits. J Urol, 196, 1279, 2016.
55.
KoensM.J.W., GeutjesP.J., FarajK.A., HilbornJ., DaamenW.F., and van KuppeveltT.H.Organ-specific tubular and collagen-based composite scaffolds. Tissue Eng Part C Methods, 17, 327, 2011.
Committee for Advanced Therapies (CAT), CAT ScientificSecretariat, SchneiderC.K., et al.Challenges with advanced therapy medicinal products and how to meet them. Nat Rev Drug Discov, 9, 195, 2010.
59.
LuL., ArbitH.M., HerrickJ.L., SegovisS.G., MaranA., and YaszemskiM.J.Tissue engineered constructs: perspectives on clinical translation. Ann Biomed Eng, 43, 796, 2015.
60.
SchleifenbaumS., PrietzelT., AustG., et al.Acellularization-induced changes in tensile properties are organ specific—an in-vitro mechanical and structural analysis of porcine soft tissues. PLoS One, 11, e0151223, 2016.
61.
SinghA., LeeD., JeongH., et al.Tissue-engineered neo-urinary conduit from decellularized trachea. Tissue Eng Part A, 24, 1456, 2018.
62.
GongW., LeiD., LiS., et al.Hybrid small-diameter vascular grafts: anti-expansion effect of electrospun poly ɛ-caprolactone on heparin-coated decellularized matrices. Biomaterial, 76, 359, 2016.
63.
JohnsonC., SheshadriP., KetchumJ.M., NarayananL.K., WeinbergerP.M., and ShirwaikerR.A.In vitro characterization of design and compressive properties of 3D-biofabricated/decellularized hybrid grafts for tracheal tissue engineering. J Mech Behav Biomed Mater, 59, 572, 2016.
64.
RapoportH.S., FishJ., BasuJ., et al.Construction of a tubular scaffold that mimics J-shaped stress/strain mechanics using an innovative electrospinning technique. Tissue Eng Part C Methods, 18, 567, 2012.
65.
JankeH.P., BohlinJ., LommeR.M.L.M., et al. Bioinspired coupled helical coils for soft tissue engineering of tubular structures–Improved mechanical behavior of tubular collagen type I templates. Acta Biomater, 59, 234, 2017.
66.
HoogenkampH.R., PotM.W., HafmansT.G., et al.Scaffolds for whole organ tissue engineering: construction and in vitro evaluation of a seamless, spherical and hollow collagen bladder construct with appendices. Acta Biomater, 43, 112, 2016.
67.
SinghA., LeeD., SopkoN., et al.Biomanufacturing seamless tubular and hollow collagen scaffolds with unique design features and biomechanical properties. Adv Healthc Mater, 6, 1601136, 2017.
68.
ShiJ.G., FuW.J., WangX.X., et al.Tissue engineering of ureteral grafts by seeding urothelial differentiated hADSCs onto biodegradable ureteral scaffolds. J Biomed Mater Res Part A, 100A, 2612, 2012.
69.
FuW.J., XuY.D., WangZ.X., et al.New ureteral scaffold constructed with composite poly(L-lactic acid)-collagen and urothelial cells by new centrifugal seeding system. J Biomed Mater Res Part A, 100A, 1725, 2012.
70.
SloffM., JankeH.P., de JongeP.K.J.D., et al. The impact of γ-irradiation and EtO degassing on tissue remodeling of collagen-based hybrid tubular templates. ACS Biomater Sci Eng, 4, 3282, 2018.
71.
VardarE., EngelhardtE.M., LarssonH.M., et al.Tubular compressed collagen scaffolds for ureteral tissue engineering in a flow bioreactor system. Tissue Eng Part A, 21, 2334, 2015.
72.
MagnanM., LévesqueP., GauvinR., et al.Tissue engineering of a genitourinary tubular tissue graft resistant to suturing and high internal pressures. Tissue Eng Part A, 15, 197, 2009.
73.
CattanV., BernardG., RousseauA., et al.Mechanical stimuli-induced urothelial differentiation in a human tissue-engineered tubular genitourinary graft. Eur Urol, 60, 1291, 2011.
74.
SeifarthV., GrosseJ.O., GossmannM., et al.Mechanical induction of bi-directional orientation of primary porcine bladder smooth muscle cells in tubular fibrin-poly(vinylidene fluoride) scaffolds for ureteral and urethral repair using cyclic and focal balloon catheter stimulation. J Biomater Appl, 32, 321, 2017.
75.
WangY., FuQ., ZhaoR.Y., and DengmC.L.Muscular tubes of urethra engineered from adipose-derived stem cells and polyglycolic acid mesh in a bioreactor. Biotechnol Lett, 36, 1909, 2014.
76.
FuQ., DengC.L., ZhaoR.Y., WangY., and CaoY.The effect of mechanical extension stimulation combined with epithelial cell sorting on outcomes of implanted tissue-engineered muscular urethras. Biomaterials, 35, 105, 2014.
77.
BodinA., BharadwajS., WuS., GatenholmP., AtalaA., and ZhangY.Tissue-engineered conduit using urine-derived stem cells seeded bacterial cellulose polymer in urinary reconstruction and diversion. Biomaterials, 31, 8889, 2010.
78.
ZhaoL.C., WeinbergA.C., LeeZ., et al.Robotic ureteral reconstruction using buccal mucosa grafts: a multi-institutional experience. Eur Urol, 73, 419, 2018.
79.
MarkiewiczM.R., DeSantisJ.L., MargaroneJ.E., PogrelM.A., and ChuangS.-K.Morbidity associated with oral mucosa harvest for urological reconstruction: an overview. J Oral Maxillofac Surg, 66, 739, 2008.
80.
Ram-LiebigG., BarbagliG., HeidenreichA., et al.Results of use of tissue-engineered autologous oral mucosa graft for urethral reconstruction: a multicenter, prospective, observational trial. EBioMedicine, 23, 185, 2017.
81.
OggC.S., SaxtonH.M., and CameronJ.S.Percutaneous needle nephrostomy. Br Med J, 4, 657, 1969.
82.
XuT., BinderK.W., AlbannaM.Z., et al.Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications. Biofabrication, 5, 015001, 2012.
83.
KangH-.W., LeeS.J., KoI.K., KenglaC., YooJ.J., and AtalaA.A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol, 34, 312, 2016.
84.
ZhangK., FuQ., YooJ., et al.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. Acta Biomater, 50, 154, 2017.
85.
SloffM., de VriesR., GeutjesP., et al.Tissue engineering in animal models for urinary diversion: a systematic review. PLoS One, 9, e98734, 2014.
86.
LeonhäuserD., VogtM., TolbaR.H., and GrosseJ.O.Potential in two types of collagen scaffolds for urological tissue engineering applications—are there differences in growth behaviour of juvenile and adult vesical cells? J Biomater Appl, 30, 961, 2016.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
