The tympanic membrane (TM), more commonly known as the eardrum, consists of a thin layer of tissue in the human ear that receives sound vibrations from outside of the body and transmits them to the auditory ossicles. The TM perforations (TMPs) are a common ontological condition, which in some cases can result in permanent hearing loss. Despite the spontaneous healing capacity of the TM to regenerate in the majority of cases of acute perforation, chronic perforations require surgical interventions. However, the disadvantages of the surgical procedure include infection, anesthetic risks, and high failure of graft patency. The tissue engineering strategy, which includes the applications of a three-dimensional (3D) scaffold, cells, and biomolecules or a combination of them for the closure of chronic perforation, has been considered as an emerging treatment. Using this approach, emerging products are currently under development to regenerate the TM structure and its properties. This research aimed to highlight the problems with the current methods of TMP treatment, and critically evaluate the tissue engineering approaches, which may overcome these drawbacks. The focus of this review is on recent literature to critically discuss the emerging advanced materials used as a 3D scaffold in the development of a TM with cellular engineering, biomolecules, cells, and the fabrications of the TM and its pathway to the clinical application. In this review, we discuss the properties of TM and the advantages and disadvantages of the current clinical products for repair and replacement of the TM. Furthermore, we provide an overview of the in vitro and preclinical studies of emerging products over the past 5 years. The results of recent preclinical studies suggest that the tissue engineering field holds significant promise.
Impact statement
This review highlights the problem with conventional surgical treatment of the tympanic membrane (TM), and critically focuses on the literature on emerging technology of tissue engineering and advanced materials in manufacturing the TM and its application to clinical setting. The advancement of the materials such as graphene as three-dimensional (3D) scaffold, stem cells technology with its growth factor, and fabrication through 3D printing made this biotechnology a possible option for treatment of TM perforations.
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References
1.
KanemaruS.-I., UmedaH., KitaniY., NakamuraT., HiranoS., and ItoJ.Regenerative treatment for tympanic membrane perforation. Otol Neurotol, 32, 1218, 2011.
2.
VolandriG., Di PuccioF., ForteP., and CarmignaniC.Biomechanics of the tympanic membrane. J Biomech, 44, 1219, 2011.
3.
HongP., BanceM., and GratzerP.F.Repair of tympanic membrane perforation using novel adjuvant therapies: a contemporary review of experimental and tissue engineering studies. Int J Pediatr Otorhinolaryngol, 77, 3, 2013.
4.
Villar-FernandezM.A., and Lopez-EscamezJ.A.Outlook for tissue engineering of the tympanic membrane. Audiol Res, 5, 117, 2015.
5.
TimnaC.J., and KumarA.A rare cause of acute tympanic membrane perforation: a case report. Int J Otorhinolaryngol Head Neck Surg, 5, 181, 2019.
6.
LouZ., LouZ., LiuY.-C., and ChangJ.Healing human moderate and large traumatic tympanic membrane perforations using basic fibroblast growth factor, 0.3% ofloxacin eardrops, and Gelfoam patching. Otol Neurotol, 37, 735, 2016.
7.
TehB.M., MaranoR.J., ShenY., FriedlandP.L., DilleyR.J., and AtlasM.D.Tissue engineering of the tympanic membrane. Tissue Eng B Rev, 19, 116, 2013.
8.
SzymanskiA., and GeigerZ. Anatomy, Head and Neck, Ear Tympanic Membrane. StatPearls Publishing, 2019.
9.
ChengJ.T., AarnisaloA.A., HarringtonE., et al.Motion of the surface of the human tympanic membrane measured with stroboscopic holography. Hear Res, 263, 66, 2010.
10.
ZhangX., and GanR.Z.A comprehensive model of human ear for analysis of implantable hearing devices. IEEE Trans Biomed Eng, 58, 3024, 2011.
11.
WuC., ChenY., Al-FurjanM.S.H., NiJ., and YangX.Free vibration model and theoretical solution of the tympanic membrane. Comput Assist Surg, 21, 61, 2016.
12.
KurabiA., BeasleyK.A., ChangL., McCannJ., PakK., and RyanA.F.Peptides actively transported across the tympanic membrane: functional and structural properties. PLoS One, 12, e0172158, 2017.
13.
LuoH., JiangS., NakmaliD.U., GanR.Z., and LuH.Mechanical properties of a human eardrum at high strain rates after exposure to blast waves. J Dynam Behav Mater, 2, 59, 2016.
14.
ZhouZ., and LuH.On the measurements of viscoelastic functions of a sphere by nanoindentation. Mech Time-Dependent Mater, 14, 1, 2010.
15.
CaminosL., Garcia-ManriqueJ., Lima-RodriguezA., and Gonzalez-HerreraA.Analysis of the mechanical properties of the human tympanic membrane and its influence on the dynamic behaviour of the human hearing system. Appl Bionics Biomech, 2018, 2018.
16.
Van der JeughtS., DirckxJ.J.J., AertsJ.R.M., BraduA., PodoleanuA.G., and BuytaertJ.A.N.Full-field thickness distribution of human tympanic membrane obtained with optical coherence tomography. J Assoc Res Otolaryngol, 14, 483, 2013.
17.
CaiL., StomackinG., PerezN.M., LinX., JungT.T., and DongW.Recovery from tympanic membrane perforation: effects on membrane thickness, auditory thresholds, and middle ear transmission. Hear Res, 384, 107813, 2019.
18.
AhnT.-S., BaekM.-J., and LeeD.Experimental measurement of tympanic membrane response for finite element model validation of a human middle ear. SpringerPlus, 2, 527, 2013.
19.
KimC.-H., and ShinJ.E.Hemorrhage within the tympanic membrane without perforation. J Otolaryngol Head Neck Surg, 47, 1, 2018.
20.
HerkalK., RamasamyK., SaxenaS.K., GanesanS., and AlexanderA.Hearing loss in tympanic membrane perforations: an analytic study. Int J Otorhinolaryngol Head Neck Surg, 4, 1233, 2018.
21.
SogebiO.A., OyewoleE.A., and MabifahT.O.Traumatic tympanic membrane perforations: characteristics and factors affecting outcome. Ghana Med J, 52, 34, 2018.
22.
DündarR., SoyF.K., KuldukE., MulukN.B., and CingiC.A new grafting technique for tympanoplasty: tympanoplasty with a boomerang-shaped chondroperichondrial graft (TwBSCPG). Eur Arch Oto Rhino Laryngol, 271, 2687, 2014.
23.
AyacheS.Cartilaginous myringoplasty: the endoscopic transcanal procedure. Eur Arch Oto Rhino Laryngol, 270, 853, 2013.
24.
MohamadS.H., KhanI., and HussainS.S.M.Is cartilage tympanoplasty more effective than fascia tympanoplasty? A systematic review. Otol Neurotol, 33, 699, 2012.
25.
HardmanJ., MuzaffarJ., NankivellP., and CoulsonC.Tympanoplasty for chronic tympanic membrane perforation in children: systematic review and meta-analysis. Otol Neurotol, 36, 796, 2015.
26.
RibeiroJ.C., RuiC., NaterciaS., JoseR., and AntonioP.Tympanoplasty in children: a review of 91 cases. Auris Nasus Larynx, 38, 21, 2011.
27.
PatilB.C., MisaleP.R., ManeR.S., and MohiteA.A.Outcome of interlay grafting in type 1 tympanoplasty for large central perforation. Indian J Otolaryngol Head Neck Surg, 66, 418, 2014.
28.
MundraR.K., SinhaR., and AgrawalR.Tympanoplasty in subtotal perforation with graft supported by a slice of cartilage: a study with near 100% results. Indian J Otolaryngol Head Neck Surg, 65, 631, 2013.
29.
MandourY.M.H., MohammedS., and MenemM.A.Bacterial cellulose graft versus fat graft in closure of tympanic membrane perforation. Am J Otolaryngol, 40, 168, 2018.
30.
ShehataA., and MohamedS.Chitosan patch scaffold for repair of chronic safe tympanic membrane perforation. Egypt J Otolaryngol, 30, 311, 2014.
31.
KimJ., KimS.W., ParkS., et al.Bacterial cellulose nanofibrillar patch as a wound healing platform of tympanic membrane perforation. Adv Healthcare Mater, 2, 1525, 2013.
32.
El-FekyA.E.-D.M., AbdelmaksodM.K., MohamedS.A.-M., AldaemR.A., and YousufR.Interlay technique tympanoplasty: surgical difficulties with variable grafts. Zagazig Univ Med J, 25, 539, 2019.
33.
KanemaruS., KanaiR., YoshidaM., KitadaY., OmaeK., and HiranoS.Application of regenerative treatment for tympanic membrane perforation with cholesteatoma, tumor, or severe calcification. Otol Neurotol, 39, 438, 2018.
34.
IndorewalaS., AdedejiT.O., IndorewalaA., and NemadeG.Tympanoplasty outcomes: a review of 789 cases. Iranian J Otorhinolaryngol, 27, 101, 2015.
35.
RubinsteinB.J., RanneyJ.D., KhoshakhlaghP., StrasnickB., and Horn-RanneyE.L.A novel gel patch for minimally invasive repair of tympanic membrane perforations. Int J Pediatr Otorhinolaryngol, 115, 27, 2018.
36.
AkterF. W, hat is TissueEngineering. Tissue Engineering MadeEasy. UK: AcademicPress. 2016.
37.
HarrisonR.H., St-PierreJ.-P., and StevensM.M.Tissue engineering and regenerative medicine: a year in review. Tissue Eng B Rev, 20, 1, 2014.
38.
LuH., HoshibaT., KawazoeN., KodaI., SongM., and ChenG.Cultured cell-derived extracellular matrix scaffolds for tissue engineering. Biomaterials, 32, 9658, 2011.
39.
XuW., LiaoX., ZhangL., and LiuB.Tissue induction, the relationship between biomaterial's microenvironment and mesenchymal stem cell differentiation. J Biomed Sci Eng, 6, 85, 2013.
40.
ShenY., RedmondS.L., TehB.M., et al.Scaffolds for tympanic membrane regeneration in rats. Tissue Eng A, 19, 657, 2012.
41.
KimS.H., LeeH.J., YooJ.-C., et al.Novel transparent collagen film patch derived from duck's feet for tympanic membrane perforation. J Biomater Sci Polym Ed, 29, 997, 2018.
42.
HuangM., LiJ., ChenJ., ZhouM., and HeJ.Preparation of CS/PVA nanofibrous membrane with tunable mechanical properties for tympanic member repair. Macromol Res, 26, 892, 2018.
43.
JinZ., DongY.-H., and LouZ.-H.The effects of fibroblast growth factor-2 delivered via a Gelfoam patch on the regeneration of myringosclerotic traumatic eardrum perforations lying close to the malleus. Am J Otolaryngol, 38, 582, 2017.
44.
HakubaN., TabataY., HatoN., FujiwaraT., and GyoK.Gelatin hydrogel with basic fibroblast growth factor for tympanic membrane regeneration. Otol Neurotol, 35, 540, 2014.
45.
JangC.H., AhnS., LeeJ.W., LeeB.H., LeeH., and KimG.Mesenchymal stem cell-laden hybrid scaffold for regenerating subacute tympanic membrane perforation. Mater Sci Eng C, 72, 456, 2017.
46.
DantiS., MotaC., D'alessandroD., et al.Tissue engineering of the tympanic membrane using electrospun PEOT/PBT copolymer scaffolds: a morphological in vitro study. Hear Balance Commun, 13, 133, 2015.
47.
ParkS.-N., KimH.-M., JinK.-S., MaengJ.-H., YeoS.-W., and ParkS.-Y.Predictors for outcome of paper patch myringoplasty in patients with chronic tympanic membrane perforations. Eur Arch Oto Rhino Laryngol, 272, 297, 2015.
48.
KimJ., KimC.H., ParkC.H., et al.Comparison of methods for the repair of acute tympanic membrane perforations: silk patch vs. paper patch. Wound Repair Regen, 18, 132, 2010.
49.
KimS.H., JeongJ.Y., ParkH.J., et al.Application of a collagen patch derived from duck feet in acute tympanic membrane perforation. Tissue Eng Regen Med, 14, 233, 2017.
50.
LeeJ.H., LeeJ.S., KimD.-K., ParkC.H., and LeeH.R.Clinical outcomes of silk patch in acute tympanic membrane perforation. Clinical and experimental otorhinolaryngology. Korean Soc Otorhinolaryngol Head Neck Surg, 8, 117, 2015.
51.
LeeJ.H., KimD., ParkH.S., et al.A prospective cohort study of the silk fibroin patch in chronic tympanic membrane perforation. Laryngoscope, 126, 2798, 2016.
52.
ShenY., RedmondS.L., TehB.M., et al.Tympanic membrane repair using silk fibroin and acellular collagen scaffolds. Laryngoscope, 123, 1976, 2013.
53.
KimJ.H., BaeJ., LimK.T., et al.Development of water-insoluble chitosan patch scaffold to repair traumatic tympanic membrane perforations. J Biomed Mater Res A, 90, 446, 2009.
54.
SeonwooH., KimS.W., ShinB., et al.Latent stem cell-stimulating therapy for regeneration of chronic tympanic membrane perforations using IGFBP2-releasing chitosan patch scaffolds. J Biomater Appl, 34, 198, 2019.
55.
GeãoC., Costa-PintoA.R., Cunha-ReisC., et al.Thermal annealed silk fibroin membranes for periodontal guided tissue regeneration. J Mater Sci Mater Med, 30, 27, 2019.
56.
FarokhiM., MottaghitalabF., ReisR.L., RamakrishnaS., and KunduS.C.Functionalized silk fibroin nanofiber as drug carriers: advantages and challenges. J Controll Release, 321, 324, 2020.
57.
YangG., LiX., HeY., MaJ., NiG., and ZhouS.From nano to micro to macro: electrospun hierarchically structured polymeric fibers for biomedical applications. Prog Polym Sci, 81, 80, 2018.
58.
Gouma, P.-I., and Han, D. Electrospun bioscaffolds that mimic the topology of extracellular matrix. In: BaloghL.P., ed. Nanomedicine in Cancer. New York, USA: Pan Stanford, 2017, pp. 185–96.
59.
BraghirolliD.I., SteffensD., and PrankeP.Electrospinning for regenerative medicine: a review of the main topics. Drug Discov Today, 19, 743, 2014.
60.
SainoE., FocareteM.L., GualandiC., et al.Effect of electrospun fiber diameter and alignment on macrophage activation and secretion of proinflammatory cytokines and chemokines. Biomacromolecules, 12, 1900, 2011.
61.
ImmichA.P.S., PennacchiP.C., NavesA.F., et al.Improved tympanic membrane regeneration after myringoplastic surgery using an artificial biograft. Mater Sci Eng C, 73, 48, 2017.
62.
LiL., ZhangW., HuangM., et al.Preparation of gelatin/genipin nanofibrous membrane for tympanic member repair. J Biomater Sci Polym Ed, 29, 2154, 2018.
63.
KimJ., KimS.W., ChoiS.J., LimK.T., et al.A healing method of tympanic membrane perforations using three-dimensional porous chitosan scaffolds. Tissue Eng A, 17, 2763, 2011.
64.
LouZ., and HeJ.A randomised controlled trial comparing spontaneous healing, gelfoam patching and edge-approximation plus gelfoam patching in traumatic tympanic membrane perforation with inverted or everted edges. Clin Otolaryngol, 36, 221, 2011.
65.
LouZ.C., TangY.M., ChenH.Y., and XiaoJ.The perforation margin phenotypes and clinical outcome of traumatic tympanic membrane perforation with a Gelfoam patch: our experience from a retrospective study of seventy-four patients. Clin Otolaryngol, 40, 389, 2015.
66.
LouZ., XuL., YangJ., and WuX.Outcome of children with edge-everted traumatic tympanic membrane perforations following spontaneous healing versus fibroblast growth factor-containing gelfoam patching with or without edge repair. Int J Pediatr Otorhinolaryngol, 75, 1285, 2011.
67.
OmaeK., KanemaruS., NakataniE., et al.Regenerative treatment for tympanic membrane perforation using gelatin sponge with basic fibroblast growth factor. Auris Nasus Larynx, 44, 664, 2017.
68.
XueK., WangX., YongP.W., et al.Hydrogels as emerging materials for translational biomedicine. Adv Ther, 2, 1800088, 2019.
69.
FarokhiM., Jonidi ShariatzadehF., SoloukA., and MirzadehH.Alginate based scaffolds for cartilage tissue engineering: a review. Int J Polym Mater Polym Biomater, 69, 230, 2020.
70.
HoffmanA.S.Hydrogels for biomedical applications. Adv Drug Deliv Rev, 64, 18, 2012.
71.
TehB.M., ShenY., FriedlandP.L., AtlasM.D., and MaranoR.J.A review on the use of hyaluronic acid in tympanic membrane wound healing. Expert Opin Biol Ther, 12, 23, 2012.
72.
MurphyS.V, and Atala, A. 3D bioprinting of tissues and organs. Nat Biotechnol, 32, 773, 2014.
73.
RadenkovicD., SoloukA., and SeifalianA.Personalized development of human organs using 3D printing technology. Med Hypotheses, 87, 30, 2016.
74.
KongL., YangG., YuJ., et al.Surgical treatment of intra-articular distal radius fractures with the assistance of three-dimensional printing technique. Medicine, 99, e19259, 2020.
75.
KuoC.-Y., WilsonE., FusonA., et al.Repair of tympanic membrane perforations with customized bioprinted ear grafts using chinchilla models. Tissue Eng A, 24, 527, 2018.
76.
KuoC.-Y., ErankiA., PlaconeJ.K., et al.Development of a 3D printed, bioengineered placenta model to evaluate the role of trophoblast migration in preeclampsia. ACS Biomater Sci Eng, 2, 1817, 2016.
77.
BružauskaitėI., BironaitėD., BagdonasE., and BernotienėE.Scaffolds and cells for tissue regeneration: different scaffold pore sizes—different cell effects. Cytotechnology, 68, 355, 2016.
78.
UpadhyayR.K.Role of biological scaffolds, hydro gels and stem cells in tissue regeneration therapy. Adv Tissue Eng Regen Med Open Access, 2, 20, 2017.
79.
SeetharamanR., MahmoodA., KshatriyaP., PatelD., and SrivastavaA.An overview on stem cells in tissue regeneration. Curr Pharm Design, 25, 2086, 2019.
80.
DuscherD., BarreraJ., WongV.W., et al.Stem cells in wound healing: the future of regenerative medicine? A mini-review. Gerontology, 62, 216, 2016.
81.
El BabaB., BarakeC., MoukarbelR., JurjusR., SertelS., and JurjusA.Stem cells in the management of tympanic membrane perforation: an update. In: PhamP., ed. Neurological Regeneration. Stem Cells in Clinical Applications. Cham: Springer, 2017, p. 181.
82.
KimS.W., KimJ., SeonwooH., et al.Latent progenitor cells as potential regulators for tympanic membrane regeneration. Sci Rep, 5, 11542, 2015.
83.
von UngeM., DirckxJ.J.J., and OliviusN.P.Embryonic stem cells enhance the healing of tympanic membrane perforations. Int J Pediatr Otorhinolaryngol, 67, 215, 2003.
84.
MaharajanN., ChoG.W., and JangC.H.Application of mesenchymal stem cell for tympanic membrane regeneration by tissue engineering approach. Int J Pediatr Otorhinolaryngol, 133, 109969, 2020.
85.
GoncalvesS., BasE., GoldsteinB.J., and AngeliS.Effects of cell-based therapy for treating tympanic membrane perforations in mice. Otolaryngol Head Neck Surg, 154, 1106, 2016.
86.
GoncalvesS., BasE., LangstonM., GrobmanA., GoldsteinB.J., and AngeliS.Histologic changes of mesenchymal stem cell repair of tympanic membrane perforation. Acta Oto-Laryngol, 137, 411, 2017.
87.
LiewL.J., ChenL.Q., WangA.Y., Von UngeM., AtlasM.D., and DilleyR.J.Tympanic membrane derived stem cell-like cultures for tissue regeneration. Stem Cells Dev, 27, 649, 2018.
88.
KurabiA., SchaererD., NoackV., et al.Active transport of peptides across the intact human tympanic membrane. Sci Rep, 8, 1, 2018.
89.
MoreS., NandgudeT., and PoddarS.Vesicles as a tool for enhanced topical drug delivery. Asian J Pharm, 10, S196, 2016.
90.
LouZ., TangY., and YangJ.A prospective study evaluating spontaneous healing of aetiology, size and type-different groups of traumatic tympanic membrane perforation. Clin Otolaryngol, 36, 450, 2011.
91.
LouZ.C., LouZ.H., and XiaoJ.Regeneration of the tympanic membrane using fibroblast growth factor-2. J Laryngol Otol, 132, 470, 2018.
92.
LouZ.C., YangJ., TangY., and FuY.H.Topical application of epidermal growth factor with no scaffold material on the healing of human traumatic tympanic membrane perforations. Clin Otolaryngol, 41, 744, 2016.
93.
Zhengcai-LouM., Zihan-LouM., and Yongmei-TangM.Comparative study on the effects of EGF and bFGF on the healing of human large traumatic perforations of the tympanic membrane. Laryngoscope, 126, E23, 2016.
94.
LouZ.-C., DongY., and LouZ.-H.Comparative study of epidermal growth factor and observation only on human subacute tympanic membrane perforation. Am J Otolaryngol, 40, 209, 2019.
95.
Santa MariaP.L., KimS., VarsakY.K., and YangY.P.Heparin binding–epidermal growth factor-like growth factor for the regeneration of chronic tympanic membrane perforations in mice. Tissue Eng A, 21, 1483, 2015.
96.
Santa MariaP.L., Santa MariaC., KimS., and YangY.P.Single administration of a sustained-release formulation of KB-R7785 inhibits tympanic membrane regeneration in an animal model. J Int Adv Otol, 12, 237, 2016.
97.
LouZ., and LouZ.A comparative study to evaluate the efficacy of EGF, FGF-2, and 0.3%(w/v) ofloxacin drops on eardrum regeneration. Medicine, 96, e7654, 2017.
98.
LouZ., TangY., and WuX.Analysis of the effectiveness of basic fibroblast growth factor treatment on traumatic perforation of the tympanic membrane at different time points. Am J Otolaryngol, 33, 244, 2012.
99.
LouZ., LouZ., TangY., and XiaoJ.Utility of basic fibroblast growth factor in the repair of blast-induced total or near-total tympanic membrane perforations: a pilot study. Am J Otolaryngol, 36, 794, 2015.
100.
LouZ., HuangP., YangJ., XiaoJ., and ChangJ.Direct application of bFGF without edge trimming on human subacute tympanic membrane perforation. Am J Otolaryngol, 37, 156, 2016.
101.
ZhangQ., and LouZ.Impact of basic fibroblast growth factor on healing of tympanic membrane perforations due to direct penetrating trauma: a prospective non-blinded/controlled study. Clin Otolaryngol, 37, 446, 2012.
102.
LouZ., WangY., and YuG.Effects of basic fibroblast growth factor dose on traumatic tympanic membrane perforation. Growth Factors, 32, 150, 2014.
103.
LouZ., and WangY.Evaluation of the optimum time for direct application of fibroblast growth factor to human traumatic tympanic membrane perforations. Growth Factors, 33, 65, 2015.
104.
Yamamoto-FukudaT., AkiyamaN., and KojimaH.Keratinocyte growth factor (KGF) induces stem/progenitor cell growth in middle ear mucosa. Int J Pediatr Otorhinolaryngol, 128, 109699, 2020.
105.
AtlasM., DilleyR., AllardyceB., and RajkhowaR. Improved silk fibroin glycerol membranes. Google Patents.
106.
TehB.M., RedmondS.L., ShenY., AtlasM.D., MaranoR.J., and DilleyR.J.TGF-α/HA complex promotes tympanic membrane keratinocyte migration and proliferation via ErbB1 receptor. Exp Cell Res, 319, 790, 2013.
107.
RöösliC., von BürenT., GassmannN.B., and HuberA.M.The impact of platelet-derived growth factor on closure of chronic tympanic membrane perforations: a randomized, double-blind, placebo-controlled study. Otol Neurotol, 32, 1224, 2011.
108.
SaeediM., AjalloueianM., ZareE., et al.The Effect of PRP-enriched gelfoam on chronictympanic membrane perforation: a double-blind randomized clinical trial. Int Tinnitus J, 21, 108, 2017.
109.
MandourM.F., ElsheikhM.N., and KhalilM.F.Platelet-rich plasma fat graft versus cartilage perichondrium for repair of medium-size tympanic membrane perforations. Otolaryngol Head Neck Surg, 160, 116, 2019.
110.
KakehataS., HiroseY., KitaniR., et al.Autologous serum eardrops therapy with a chitin membrane for closing tympanic membrane perforations. Otol Neurotol, 29, 791, 2008.
111.
MohantyS., ManimaranV., UmamaheswaranP., JeyabalakrishnanS., and ChelladuraiS.Endoscopic cartilage versus temporalis fascia grafting for anterior quadrant tympanic perforations—A prospective study in a tertiary care hospital. Auris Nasus Larynx, 45, 936, 2018.
112.
YawnR.J., DedmonM.M., O'ConnellB.P., VirginF.W., and RivasA.Tympanic membrane perforation repair using porcine small intestinal submucosal grafting. Otol Neurotol, 39, e332, 2018.
113.
NemadeS.V., ShindeK.J., and SampateP.B.Comparison between clinical and audiological results of tympanoplasty with double layer graft (modified sandwich fascia) technique and single layer graft (underlay fascia and underlay cartilage) technique. Auris Nasus Larynx, 45, 440, 2018.
114.
CiğerE., BalcıM.K., İşlekA., and ÖnalK.The wheel-shaped composite cartilage graft (WsCCG) and temporalis fascia for type 1 tympanoplasty: a prospective, randomized study. Eur Arch Oto Rhino Laryngol, 275, 2975, 2018.
115.
IslahS.A.M., and PalliyalippadiT.B.T.Evaluation of graft uptake in type 1 tympanoplasty with dry and wet temporalis fascia graft. J Evol Med Dent Sci, 5, 7684, 2016.
116.
BiskinS., DamarM., OktemS.N., SakalliE., ErdemD., and PakirO.A new graft material for myringoplasty: bacterial cellulose. Eur Arch Oto Rhino Laryngol, 273, 3561, 2016.
117.
GünT., BoztepeO.F., AtanD., İkincioğullarıA., and DereH.Comparison of hyaluronic acid fat graft myringoplasty, fat graft myringoplasty and temporal fascia techniques for the closure of different sizes and sites of tympanic membrane perforations. J Int Adv Otol, 12, 137, 2016.
118.
D'EreditàR.Porcine small intestinal submucosa (SIS) myringoplasty in children: a randomized controlled study. Int J Pediatr Otorhinolaryngol, 79, 1085, 2015.
119.
De DorlodotC., De BieG., DeggoujN., DecatM., and GérardJ.-M.Are bovine pericardium underlay xenograft and butterfly inlay autograft efficient for transcanal tympanoplasty? Eur Arch Oto Rhino Laryngol, 272, 327, 2015.
120.
AlzahraniM., and SalibaI.Hyaluronic acid fat graft myringoplasty vs fat patch fat graft myringoplasty. Eur Arch Oto Rhino Laryngol, 272, 1873, 2015.
121.
MukherjeeM., and PaulR.Minimyringoplasty: repair of small central perforation of tympanic membrane by fat graft: a prospective study. Indian J Otolaryngol Head Neck Surg, 65, 302, 2013.
122.
KocS., AkyuzS., GurbuzlerL., and AksakalC.Fat graft myringoplasty with the newly developed surgical technique for chronic tympanic membrane perforation. Eur Arch Oto Rhino Laryngol, 270, 1629, 2013.
123.
SalibaI., and WoodsO.Hyaluronic acid fat graft myringoplasty: a minimally invasive technique. Laryngoscope, 121, 375, 2011.
124.
PinhoA.M.de M.R., Kencis, C.C.S., Miranda, D.R.P., and de Sousa Neto, O.M. Traumatic perforations of the tympanic membrane: immediate clinical recovery with the use of bacterial cellulose film. Braz J Otorhinolaryngol, S1808-8694, 30595, 2019.
125.
JungJ.Y., YunH.-C., KimT.-M., et al.Analysis of effect of eggshell membrane patching for moderate-to-large traumatic tympanic membrane perforation. J Audiol Otol, 21, 39, 2017.
126.
JunH.J., OhK.-H., YooJ., et al.A new patch material for tympanic membrane perforation by trauma: the membrane of a hen egg shell. Acta Oto Laryngol, 134, 250, 2014.
127.
SimsekG., and AkinI.Early paper patching versus observation in patients with traumatic eardrum perforations: comparisons of anatomical and functional outcomes. J Craniofac Surg, 25, 2030, 2014.
128.
FarhadiM., MirzadehH., SoloukA., et al.Collagen-immobilized patch for repairing small tympanic membrane perforations: in vitro and in vivo assays. J Biomed Mater Res A, 100, 549, 2012.
129.
AcharyaA.N., CoatesH., Tavora-VieiraD., and RajanG.P.A pilot study investigating basic fibroblast growth factor for the repair of chronic tympanic membrane perforations in pediatric patients. Int J Pediatr Otorhinolaryngol, 79, 332, 2015.
130.
SeonwooH., KimS.W., KimJ., et al.Regeneration of chronic tympanic membrane perforation using an EGF-releasing chitosan patch. Tissue Eng A, 19, 2097, 2013.
131.
ShenY., RedmondS.L., PapadimitriouJ.M., et al.The biocompatibility of silk fibroin and acellular collagen scaffolds for tissue engineering in the ear. Biomed Mater, 9, 15015, 2014.
132.
LeeO.J., LeeJ.M., KimJ.H., et al.Biodegradation behavior of silk fibroin membranes in repairing tympanic membrane perforations. J Biomed Mater Res A, 100, 2018, 2012.
133.
WielandA.M., SundbackC.A., HartA., KuligK., MasiakosP.T., and HartnickC.J.Poly (glycerol sebacate)-engineered plugs to repair chronic tympanic membrane perforations in a chinchilla model. Otolaryngol Head Neck Surg, 143, 127, 2010.
134.
LeeH., JangC.H., and KimG.H.A polycaprolactone/silk-fibroin nanofibrous composite combined with human umbilical cord serum for subacute tympanic membrane perforation; an in vitro and in vivo study. J Mater Chem B, 2, 2703, 2014.
135.
JangC.H., ChoY.B., YeoM., et al.Regeneration of chronic tympanic membrane perforation using 3D collagen with topical umbilical cord serum. Int J Biol Macromol, 62, 232, 2013.
136.
WeberD.E., SemaanM.T., WasmanJ.K., BeaneR., BonassarL.J., and MegerianC.A.Tissue-engineered calcium alginate patches in the repair of chronic chinchilla tympanic membrane perforations. Laryngoscope, 116, 700, 2006.
137.
AllardyceB.J., RajkhowaR., DilleyR.J., RedmondS.L., AtlasM.D., and WangX.Glycerol-plasticised silk membranes made using formic acid are ductile, transparent and degradation-resistant. Mater Sci Eng C, 80, 165, 2017.
138.
LevinB., RedmondS.L., RajkhowaR., EikelboomR.H., AtlasM.D., and MaranoR.J.Utilising silk fibroin membranes as scaffolds for the growth of tympanic membrane keratinocytes, and application to myringoplasty surgery. J Laryngol Otol, 127, S13, 2013.
139.
LeeM.C., SeonwooH., GargP., et al.Chitosan/PEI patch releasing EGF and the EGFR gene for the regeneration of the tympanic membrane after perforation. Biomater Sci, 6, 364, 2018.
140.
AltuntaşE.E., and SümerZ.Biocompatibility evaluation of cigarette and carbon papers used in repair of traumatic tympanic membrane perforations: experimental study. Eur Arch Oto Rhino Laryngol, 270, 81, 2013.
141.
KozinE.D., BlackN.L., ChengJ.T., et al.Design, fabrication, and in vitro testing of novel three-dimensionally printed tympanic membrane grafts. Hear Res, 340, 191, 2016.
142.
HottM.E., MegerianC.A., BeaneR., and BonassarL.J.Fabrication of tissue engineered tympanic membrane patches using computer-aided design and injection molding. Laryngoscope, 114, 1290, 2004.
143.
SeifalianA.M., HancockS. Composite material and its method of production. Patent GB (GB1811090, 2017), WO, EP and US (2020).
144.
NezakatiT. Development of a graphene-POSS-nanocomposite conductive material for biomedical application [PhD thesis]. London UniversityCollege, London. 2016. Supervisor Professor Alexander Seifalian
145.
Nezakati,T., SeifalianA., TanA., and SeifalianA.M.Conductive Polymers: opportunities and Challenges in Biomedical Applications. Chem Rev, 118, 6766, 2018.
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