Bioactive glasses: special applications outside the skeletal system

Abstract Bioactive glasses were invented 45 years ago and have been in clinical use since the 1980s in otology, orthopaedics and dentistry. Initially born as bioactive materials to fill bone defects, bioactive glasses expanded their biomedical suitability towards a broad spectrum of tissue engineering and therapeutic applications, and research evolution seems to witness that their potential is far from being fully exploited. Classical applications of bioactive glasses involve bone filling materials and dental implants; however, the fascinating question to be answered in the next few years is: how can bioactive glasses be useful in soft tissue regeneration and to treat diseases, such as tumours, that may affect internal organs? This review paper focuses on research that demonstrates the suitability of bioactive glasses in contact with tissues outside the skeletal system, including muscle and nerve tissue regeneration, treatment of diseases affecting sense organs (eye and ear), embolization of neoplastic tissues, cancer radiotherapy via injectable microspheres, and wound dressing. A prospect for future research is also provided, highlighting the potential associated to targeted therapy via local ion release, angiogenesis stimulation and in situ drug release, as well as the promise of biofabrication for the development of bioactive glass-containing composite constructs for organ regeneration.

[1]  A. Boccaccini,et al.  In Vitro Attachment of Staphylococcus Epidermidis to Surgical Sutures with and without Ag-Containing Bioactive Glass Coating , 2004, Journal of biomaterials applications.

[2]  Francesco Baino,et al.  Bioactive glass-derived trabecular coating: a smart solution for enhancing osteointegration of prosthetic elements , 2012, Journal of Materials Science: Materials in Medicine.

[3]  R Shah,et al.  Craniofacial muscle engineering using a 3-dimensional phosphate glass fibre construct. , 2005, Biomaterials.

[4]  J. Ng,et al.  The Porous Polyethylene/Bioglass Spherical Orbital Implant: A Retrospective Study of 170 Cases , 2011, Ophthalmic plastic and reconstructive surgery.

[5]  S. Nazhat,et al.  Bioactive glasses for wound healing , 2011 .

[6]  Francesco Baino,et al.  Bioceramics in ophthalmology. , 2014, Acta biomaterialia.

[7]  Aldo R Boccaccini,et al.  Assessment of polyglycolic acid mesh and bioactive glass for soft-tissue engineering scaffolds. , 2004, Biomaterials.

[8]  F. Baino,et al.  Zirconia-containing radiopaque mesoporous bioactive glasses , 2014 .

[9]  Aldo R. Boccaccini,et al.  Bioactive Glass and Glass-Ceramic Scaffolds for Bone Tissue Engineering , 2010, Materials.

[10]  A. Boccaccini,et al.  Mechanical properties of biodegradable polymer sutures coated with bioactive glass , 2002, Journal of materials science. Materials in medicine.

[11]  M. H. Fernandes,et al.  Degradation studies and biological behavior on an artificial cornea material. , 2011, Investigative ophthalmology & visual science.

[12]  S D Cook,et al.  Implant-bone interface characteristics of bioglass dental implants. , 1980, Journal of biomedical materials research.

[13]  M. Kellomäki,et al.  Bioactive composite for keratoprosthesis skirt. , 2011, Journal of the mechanical behavior of biomedical materials.

[14]  J. Knowles Phosphate based glasses for biomedical applications , 2003 .

[15]  Enrica Verne,et al.  3-D high-strength glass–ceramic scaffolds containing fluoroapatite for load-bearing bone portions replacement , 2009 .

[16]  I. Nolte,et al.  Free Bioverit ® II Implants Coated with a Nanoporous Silica Layer in a Mouse Ear Model — A Histological Study , 2009, Journal of biomaterials applications.

[17]  A. Salgado,et al.  From basics to clinical: A comprehensive review on spinal cord injury , 2014, Progress in Neurobiology.

[18]  J. Knowles,et al.  Bioactive functional materials: a perspective on phosphate-based glasses , 2009 .

[19]  Juan Ye,et al.  Copper-containing mesoporous bioactive glass coatings on orbital implants for improving drug delivery capacity and antibacterial activity , 2014, Biotechnology Letters.

[20]  T. Gilchrist,et al.  In vitro nerve repair--in vivo. The reconstruction of peripheral nerves by entubulation with biodegradeable glass tubes--a preliminary report. , 1998, British journal of plastic surgery.

[21]  Aldo R Boccaccini,et al.  Effect of bioactive glasses on angiogenesis: a review of in vitro and in vivo evidences. , 2010, Tissue engineering. Part B, Reviews.

[22]  Jung Keun Hyun,et al.  Phosphate glass fibres promote neurite outgrowth and early regeneration in a peripheral nerve injury model , 2015, Journal of tissue engineering and regenerative medicine.

[23]  Michael T. Wilson,et al.  Antimicrobial effect of silver-doped phosphate-based glasses. , 2006, Journal of biomedical materials research. Part A.

[24]  R. Gillette,et al.  Effects of a bioactive glass on healing of closed skin wounds in dogs. , 2001, American journal of veterinary research.

[25]  D. Boyd,et al.  Mixture designs to assess composition–structure–property relationships in SiO2–CaO–ZnO–La2O3–TiO2–MgO–SrO–Na2O glasses: Potential materials for embolization , 2013, Journal of biomaterials applications.

[26]  Larry L. Hench,et al.  Genetic design of bioactive glass , 2009 .

[27]  M. Himelfarb,et al.  Auditory brain-stem responses in guinea pigs following middle ear implantation of Ceravital , 2004, European Archives of Oto-Rhino-Laryngology.

[28]  I. Hochmair-Desoyer,et al.  A Bone-Anchored Percutaneous Connector System for Neural Prosthetic Applications , 1997, Ear, nose, & throat journal.

[29]  B. Blencke,et al.  Untersuchungen über die Reaktion von Weichgeweben auf glaskeramische Implantate , 2004, Archiv für orthopädische und Unfall-Chirurgie, mit besonderer Berücksichtigung der Frakturenlehre und der orthopädisch-chirurgischen Technik.

[30]  Francesco Baino,et al.  Three-dimensional glass-derived scaffolds for bone tissue engineering: current trends and forecasts for the future. , 2011, Journal of biomedical materials research. Part A.

[31]  J. Knowles,et al.  Sequential identification of a degradable phosphate glass scaffold for skeletal muscle regeneration , 2014, Journal of tissue engineering and regenerative medicine.

[32]  H. Brömer,et al.  [Studies on soft tissue reactions to implantation of glass ceramics (author's transl)]. , 1975, Archiv fur orthopadische und Unfall-Chirurgie.

[33]  L. da Cruz,et al.  The bionic eye: a review , 2012, Clinical & experimental ophthalmology.

[34]  J. Reekers,et al.  Uterine artery embolization versus hysterectomy in the treatment of symptomatic uterine fibroids: 2 years' outcome from the randomized EMMY trial. , 2007, American journal of obstetrics and gynecology.

[35]  O. Peitl,et al.  Biosilicate® Ototoxicity and Vestibulotoxicity evaluation in guinea-pigs , 2009, Brazilian journal of otorhinolaryngology.

[36]  Dosimetric characterization of 142Pr glass seeds for brachytherapy. , 2008, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[37]  T. Lenarz,et al.  Histological evaluation of novel ossicular chain replacement prostheses: an animal study in rabbits , 2007, Acta oto-laryngologica.

[38]  Larry L. Hench,et al.  Broad-Spectrum Bactericidal Activity of Ag2O-Doped Bioactive Glass , 2002, Antimicrobial Agents and Chemotherapy.

[39]  P. Antonelli,et al.  Bioglass middle ear prosthesis: long-term results. , 1996, The American journal of otology.

[40]  D. Boyd,et al.  Composition–property relationships for an experimental composite nerve guidance conduit: evaluating cytotoxicity and initial tensile strength , 2011, Journal of materials science. Materials in medicine.

[41]  H. Kim,et al.  Effects of phosphate glass fiber-collagen scaffolds on functional recovery of completely transected rat spinal cords. , 2012, Acta biomaterialia.

[42]  Xiaofeng Chen,et al.  Healing effect of bioactive glass ointment on full-thickness skin wounds , 2012, Biomedical materials.

[43]  Larry L. Hench,et al.  Bonding mechanisms at the interface of ceramic prosthetic materials , 1971 .

[44]  R. Happonen,et al.  Compositional dependence of bioactivity of glasses in the system Na2O-K2O-MgO-CaO-B2O3-P2O5-SiO2. , 1997, Journal of biomedical materials research.

[45]  F. Baino,et al.  Bioactive glass and glass-ceramic foam scaffolds for bone tissue restoration , 2014 .

[46]  Z. Chen,et al.  [Tissue interaction with bioglass ceramic implanted in the rabbit cornea]. , 2001, Yan ke xue bao = Eye science.

[47]  Delbert E Day,et al.  Bioactive glass in tissue engineering. , 2011, Acta biomaterialia.

[48]  K. Lobel Ossicular Replacement Prostheses , 1996 .

[49]  J. Ng,et al.  A Novel Approach to Re-pegging Hydroxyapatite Implants Using Bioactive Glass , 2006, Ophthalmic plastic and reconstructive surgery.

[50]  G. E. Merwin Bioglass Middle Ear Prosthesis: Preliminary Report , 1986, The Annals of otology, rhinology, and laryngology.

[51]  B. Oum,et al.  Effect of Synthetic Bone Glass Particulate on the Fibrovascularization of Porous Polyethylene Orbital Implants , 2006, Ophthalmic plastic and reconstructive surgery.

[52]  Zenner Hp,et al.  Tympanoplasty type II with ionomeric cement and titanium-gold-angle prostheses. , 1998 .

[53]  Aldo R Boccaccini,et al.  A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics. , 2011, Biomaterials.

[54]  R P Happonen,et al.  Titanium and bioactive glass-ceramic coated titanium as materials for keratoprosthesis. , 1996, Experimental eye research.

[55]  A. Seifalian,et al.  Modern surgical management of peripheral nerve gap. , 2010, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[56]  A. Boccaccini,et al.  Composite surgical sutures with bioactive glass coating. , 2003, Journal of biomedical materials research. Part B, Applied biomaterials.

[57]  Nigel P Hunt,et al.  Development of a novel smart scaffold for human skeletal muscle regeneration , 2016, Journal of tissue engineering and regenerative medicine.

[58]  A. Lansdown,et al.  Silver absorption and antibacterial efficacy of silver dressings. , 2005, Journal of Wound Care.

[59]  I Olsen,et al.  Processing, characterisation and biocompatibility of iron-phosphate glass fibres for tissue engineering. , 2004, Biomaterials.

[60]  Larry L. Hench,et al.  Clinical performance of skeletal prostheses , 1995 .

[61]  Jessy D. Dorn,et al.  Interim results from the international trial of Second Sight's visual prosthesis. , 2012, Ophthalmology.

[62]  Aldo R Boccaccini,et al.  Bioactive glasses beyond bone and teeth: emerging applications in contact with soft tissues. , 2015, Acta biomaterialia.

[63]  S. Dorozhkin,et al.  A detailed history of calcium orthophosphates from 1770s till 1950. , 2013, Materials science & engineering. C, Materials for biological applications.

[64]  Julian R Jones,et al.  Melt-derived bioactive glass scaffolds produced by a gel-cast foaming technique. , 2011, Acta biomaterialia.

[65]  Lei Chen,et al.  Copper-containing mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity. , 2013, Biomaterials.

[66]  A. Boccaccini,et al.  Evaluation of antibacterial and cytotoxic effects of nano‐sized bioactive glass/collagen composites releasing tetracycline hydrochloride , 2014, Journal of applied microbiology.

[67]  H P Zenner,et al.  Tympanoplasty type II with ionomeric cement and titanium-gold-angle prostheses. , 1998, The American journal of otology.

[68]  Michael T. Wilson,et al.  Effect of Silver Content on the Structure and Antibacterial Activity of Silver-Doped Phosphate-Based Glasses , 2007, Antimicrobial Agents and Chemotherapy.

[69]  B. Sampson,et al.  Silver aids healing in the sterile skin wound: experimental studies in the laboratory rat , 1997, The British journal of dermatology.

[70]  J C Knowles,et al.  Controlled delivery of antimicrobial gallium ions from phosphate-based glasses. , 2009, Acta biomaterialia.

[71]  R. Reck Tissue reactions to glass ceramics in the middle ear. , 1981, Clinical otolaryngology and allied sciences.

[72]  H. Zeiger,et al.  Complications Following Enucleation and Implantation of Multiple Glass Spheres in the Orbit , 1987, Ophthalmic plastic and reconstructive surgery.

[73]  J. Bébéar,et al.  Ceravital in ossiculoplasty: experimental studies and early clinical results , 1986, The Journal of Laryngology & Otology.

[74]  David F. Williams On the mechanisms of biocompatibility. , 2008, Biomaterials.

[75]  A. Clare,et al.  Bio-glasses : an introduction , 2012 .

[76]  T Gilchrist,et al.  Peripheral nerve repair by means of a flexible biodegradable glass fibre wrap: a comparison with microsurgical epineurial repair. , 2007, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[77]  Julian R Jones,et al.  Review of bioactive glass: from Hench to hybrids. , 2013, Acta biomaterialia.

[78]  Tajalli Keshavarz,et al.  Fabrication of a novel poly(3‐hydroxyoctanoate) / nanoscale bioactive glass composite film with potential as a multifunctional wound dressing , 2010 .

[79]  David B Dunson,et al.  High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. , 2003, American journal of obstetrics and gynecology.

[80]  A. Boccaccini,et al.  Simple fabrication technique for multilayered stratified composite scaffolds suitable for interface tissue engineering , 2012 .

[81]  U. Gross,et al.  Keratoprothese aus Glaskeramik , 1978 .

[82]  María Vallet-Regí,et al.  Bioceramics for drug delivery , 2013 .

[83]  A. Boccaccini,et al.  Development and characterisation of silver-doped bioactive glass-coated sutures for tissue engineering and wound healing applications. , 2004, Biomaterials.

[84]  Nicola E Starritt,et al.  Sutureless repair of the facial nerve using biodegradable glass fabric , 2011, The Laryngoscope.

[85]  Mules Ph Evisceration of the globe with artificial vitreous. 1884-1895. , 1990 .

[86]  L. Hench Glass and Glass‐Ceramic Technologies to Transform the World , 2011 .

[87]  R. Grenman,et al.  Interactions between the bioactive glass S53P4 and the atrophic rhinitis-associated microorganism klebsiella ozaenae. , 1999, Journal of biomedical materials research.

[88]  J. Knowles,et al.  Characterisation of antibacterial copper releasing degradable phosphate glass fibres. , 2005, Biomaterials.

[89]  N. Pugno,et al.  Bonding strength of glass-ceramic trabecular-like coatings to ceramic substrates for prosthetic applications. , 2013, Materials science & engineering. C, Materials for biological applications.

[90]  G. Geyer Implantate in der Mittelohrchirurgie , 1992 .

[91]  Afsaneh Amiri,et al.  Preparation and evaluation of novel nano-bioglass/gelatin conduit for peripheral nerve regeneration , 2014, Journal of Materials Science: Materials in Medicine.

[92]  Edgar Dutra Zanotto,et al.  In vitro osteogenesis on a highly bioactive glass-ceramic (Biosilicate). , 2007, Journal of biomedical materials research. Part A.

[93]  S. Störkel,et al.  Bioactive Glass‐Ceramics in Middle Ear Surgery An 8‐Year Review a , 1988, Annals of the New York Academy of Sciences.

[94]  Changyou Gao,et al.  Bioactive glasses-incorporated, core-shell-structured polypeptide/polysaccharide nanofibrous hydrogels. , 2013, Carbohydrate polymers.

[95]  L. Yao,et al.  A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery , 2012, Journal of The Royal Society Interface.

[96]  Jörg-Uwe Meyer,et al.  Retina implant: a bioMEMS challenge , 2002 .

[97]  R. Birngruber,et al.  Gentle Retinal Photocoagulation by Automatic Temperature Control , 2010 .

[98]  M. Lewis,et al.  Soluble phosphate glass fibres for repair of bone-ligament interface , 2005, Journal of materials science. Materials in medicine.

[99]  T. Gilchrist,et al.  An evaluation using techniques to assess muscle and nerve regeneration of a flexible glass wrap in the repair of peripheral nerves. , 2007, Acta neurochirurgica. Supplement.

[100]  P. H. Mules Evisceration of the globe with artificial vitreous. 1884-1895. , 1990, Advances in ophthalmic plastic and reconstructive surgery.

[101]  J. Lousteau,et al.  Phosphate glass fibres and their role in neuronal polarization and axonal growth direction. , 2012, Acta biomaterialia.

[102]  S. Deb,et al.  Bioresorbable Glass Fibres Facilitate Peripheral Nerve Regeneration , 2005, Journal of hand surgery.

[103]  Wei Fan,et al.  Hypoxia-mimicking mesoporous bioactive glass scaffolds with controllable cobalt ion release for bone tissue engineering. , 2012, Biomaterials.

[104]  P. Hantson,et al.  Encephalopathy with seizures after use of aluminium-containing bone cement , 1994, The Lancet.

[105]  Sara Ferraris,et al.  Biomaterials for orbital implants and ocular prostheses: overview and future prospects. , 2014, Acta biomaterialia.

[106]  R. Witmer,et al.  [Biocompatibility of bioactive glass-ceramic in cornea and conjunctiva]. , 1978, Bericht uber die Zusammenkunft. Deutsche Ophthalmologische Gesellschaft.

[107]  V Mironov,et al.  Biofabrication: a 21st century manufacturing paradigm , 2009, Biofabrication.

[108]  María Vallet-Regí,et al.  Bioceramics: From Bone Regeneration to Cancer Nanomedicine , 2011, Advanced materials.

[109]  M. Towler,et al.  Silver coated bioactive glass particles for wound healing applications , 2012, Journal of Materials Science: Materials in Medicine.

[110]  Michael T. Wilson,et al.  Antimicrobial Gallium‐Doped Phosphate‐Based Glasses , 2008 .

[111]  H. Schubert,et al.  Rasterelektronenmikroskopische Untersuchung des Zellwachstums auf maschinell bearbeitbarer Biovitrokeramik und Glaskohlenstoff in vitro und in vivo , 1985 .

[112]  Robert Liska,et al.  Processing of 45S5 Bioglass® by lithography-based additive manufacturing , 2012 .

[113]  S. Koscielny,et al.  Untersuchungen zum Einfluss von Biokeramiken auf biologische Leistungen von Mikroorganismen , 2001, HNO.

[114]  D. Boyd,et al.  FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. , 2012, Injury.

[115]  C. Wang,et al.  [An experimental study of bioactive glass ceramics as orbital implants]. , 1997, Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University.

[116]  D. Boyd,et al.  Temporal analysis of dissolution by-products and genotoxic potential of spherical zinc–silicate bioglass: “Imageable beads” for transarterial embolization , 2014, Journal of biomaterials applications.

[117]  E. Söderling,et al.  Antibacterial effects of a bioactive glass paste on oral microorganisms. , 1998, Acta odontologica Scandinavica.

[118]  S. Moane,et al.  Composition–structure–property (Zn2+ and Ca2+ ion release) evaluation of Si–Na–Ca–Zn–Ce glasses: Potential components for nerve guidance conduits , 2011 .

[119]  Dai Fukumura,et al.  Engineering vascularized tissue , 2005, Nature Biotechnology.

[120]  C. Wang,et al.  [Clinical study of bioactive glass ceramics as orbital implants]. , 1997, Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University.

[121]  J. Reekers,et al.  Uterine artery embolization versus hysterectomy in the treatment of symptomatic uterine fibroids: 2 years' outcome from the randomized EMMY trial. , 2007, American journal of obstetrics and gynecology.

[122]  Elizabeth G Loboa,et al.  Naturally derived and synthetic scaffolds for skeletal muscle reconstruction. , 2015, Advanced drug delivery reviews.

[123]  Andrew A. Wong,et al.  Cobalt toxicity — an emerging clinical problem in patients with metal‐on‐metal hip prostheses? , 2011, The Medical journal of Australia.

[124]  Michael T. Wilson,et al.  The effect of increasing copper content in phosphate-based glasses on biofilms of Streptococcus sanguis. , 2003, Biomaterials.

[125]  R. Baskar,et al.  Cancer and Radiation Therapy: Current Advances and Future Directions , 2012, International journal of medical sciences.

[126]  Larry L. Hench,et al.  The story of Bioglass® , 2006, Journal of materials science. Materials in medicine.

[127]  D. Boyd,et al.  Experimental composite guidance conduits for peripheral nerve repair: an evaluation of ion release. , 2012, Materials science & engineering. C, Materials for biological applications.

[128]  T. Chirila,et al.  The origins of the artificial cornea: Pellier de Quengsy and his contribution to the modern concept of keratoprosthesis. , 1999, Gesnerus.

[129]  D. Day,et al.  Effects of borate-based bioactive glass on neuron viability and neurite extension. , 2014, Journal of biomedical materials research. Part A.

[130]  L. Hupa,et al.  Examining porous bio-active glass as a potential osteo-odonto-keratoprosthetic skirt material , 2013, Journal of Materials Science: Materials in Medicine.

[131]  S. Merchant,et al.  Histopathology of Ossicular Grafts and Implants in Chronic Otitis Media , 2007, The Annals of otology, rhinology, and laryngology.

[132]  Xiabin Jing,et al.  Fabrication and Drug Delivery of Ultrathin Mesoporous Bioactive Glass Hollow Fibers , 2010 .

[133]  Aldo R. Boccaccini,et al.  Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview of their biological applications and strategies for new developments , 2011, Journal of The Royal Society Interface.

[134]  H. Brömer,et al.  [Study on the use of glass ceramics in osteo-odonto-keratoplasty]. , 1978, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde.

[135]  R. Grenman,et al.  Bioactive glass S53P4 in repair of septal perforations and its interactions with the respiratory infection-associated microorganisms Haemophilus influenzae and Streptococcus pneumoniae. , 2001, Journal of biomedical materials research.

[136]  Ronald Deumens,et al.  Repairing injured peripheral nerves: Bridging the gap , 2010, Progress in Neurobiology.

[137]  L L Hench,et al.  Toxicology and biocompatibility of bioglasses. , 1981, Journal of biomedical materials research.

[138]  L. Hench,et al.  Bacteriostatic action of a novel four-component bioactive glass. , 2000, Journal of biomedical materials research.

[139]  A. Krause A propos de la tolérance intracornéenne de la céramique de verre bioactive , 1992 .

[140]  Julian R Jones,et al.  Optimising bioactive glass scaffolds for bone tissue engineering. , 2006, Biomaterials.

[141]  E. Saino,et al.  Mesoporous Bioactive Glass as a Multifunctional System for Bone Regeneration and Controlled Drug Release , 2012, Journal of applied biomaterials & functional materials.

[142]  J. Lousteau,et al.  Resorbable hollow phosphate glass fibres as controlled release systems for biomedical applications , 2013 .

[143]  Michael T. Wilson,et al.  Effect of Silver-Doped Phosphate-Based Glasses on Bacterial Biofilm Growth , 2008, Applied and Environmental Microbiology.

[144]  Jonathan C. Knowles,et al.  Structural Characteristics of Antibacterial Bioresorbable Phosphate Glass , 2008 .

[145]  C. Tonda-Turo,et al.  Novel systems for tailored neurotrophic factor release based on hydrogel and resorbable glass hollow fibers. , 2014, Materials science & engineering. C, Materials for biological applications.

[146]  D. Day Glasses for Radiotherapy , 2012 .

[147]  J. O'Brien,et al.  Intraorbital implants after enucleation and their complications: a 10-year review. , 1998, Archives of ophthalmology.

[148]  D. Boyd,et al.  Time-dependent evaluation of mechanical properties and in vitro cytocompatibility of experimental composite-based nerve guidance conduits. , 2011, Journal of the mechanical behavior of biomedical materials.

[149]  G P Clarke,et al.  A New Approach to the Cochlear Implant , 1977, Proceedings of the Royal Society of Medicine.

[150]  Vladimir Mironov,et al.  Nanotechnological Strategies for Biofabrication of Human Organs , 2012 .