The book on Biomaterials in Regenerative Medicine contains a total of 18 chapters. Selected issues discussed in the previous five sub-chapters were presented in it. The literature review, in this first chapter, deals with technical, biological and medical aspects concerning materials and technologies for medical and dental implantable devices. In the second chapter, the metallic biomaterials and their application in regenerative medicine are presented in detail by the literature review. In addition to these two chapters, all the rest contain the results of their scientific research done by the authors of these chapters. Indeed, the originality of the presented research results constitutes the real value of the book at this moment passed to the readers' hands. The next chapters contain issues about additive technologies and laser manufacturing of materials used in regenerative medicine and mainly in regenerative dentistry. The third chapter is on microporous titanium-based materials located inside the pores by biocompatible thin films to facilitate the implantation and proliferation of living cells in the scaffolds thus produced. In turn, the fourth chapter includes mechanical properties comparison of engineering materials produced by additive and subtractive technologies for dental prosthetic restoration application. It discusses both solid and milled sintered titanium and its alloy, Co-Cr alloy, and sintered ZrO2. In the fifth and sixth chapters, properties of Co-Cr dental alloys fabricated using an additive, technologies were presented. The progress of the application of 3D printing for tissue regeneration in oral and maxillofacial surgery is presented in chapter seven. In the eighth chapter, the issues of the tissue engineering and use of growth factors in bone regeneration are discussed. Laser processing was analysed in chapter nine concerning silicon for its synthesis as better biomaterials. Prospective of characterisation of the skin models and associated with it measurements and simulation of permeation and diffusion in 3D tissues are presented in the tenth chapter. The eleventh chapter also contains the skin regeneration problems explanation and also a description of the biomaterials for tendon and ligament regeneration. The next few chapters deal with natural and artificial gels of polymeric materials. In the twelfth chapter, authors described the hydrogels for regenerative

printing [544], in which the printing of ears, liver and kidneys from living tissues was started in 2013. It is expected that fully functional printed organs can be achieved over the next dozens of years or so [545, 546]. In the meanwhile, there were reports that an Australian team obtained a kidney tissue print with this method for the first time [547]. An American team confirmed in 2014 it is ready to print a heart [548]. A three-dimensional structure is obtained by subsequent formation of layers of living tissues on the gel or sugar matrix substrate [549]. To use the threedimensional printing technique, a polymer-cell mixture can be dosed, leading to the formation of

Table 1. Examples of the application of various bioactive and engineering materials, and their respective material processing and tissue engineering technologies for manufacturing of the hybrid personalised implants and scaffolds [2].

Fabrication stage Investigated materials Technologies applied Areas of application

Selective laser sintering, sintering, the use of organic matrix, lyophilisation of ceramic slip, rapid pressure assisted densification methods, such as rapid hot pressing/spark plasma sintering (SPS), skeletal casting, plastic working, cutting micro-treatment, computer-aided manufacturing, sol-gel methods, 3D printing, electrospinning, atomic layer deposition, and physical vapour deposition

Infiltration, 3D printing, selective laser sintering, electrospinning, atomic layer deposition, physical vapour deposition, pressing, and sol-gel

Cell transplantation, matrix implantation, cell implantation with matrix, breeding of xenogeneic and autologous cells and the stage of clinical activities

methods

Filling the losses of long bones, hip and knee joints, facial-skull bone, losses of joint cartilage cells, oesophagus losses and/or blood vessel losses, dental restorations,

and skin restorations

Ti, Ti alloys with V or Nb, Mg (possibly with additives of Ca, Zn and Mn), ceramic materials Al2O3 and ZrO2, TiO2, resorbable bioglass, e.g., Hench bioglass, from the CaO-SiO2-P2O5 and SiO2- Al2O3 system, hydroxyapatites, polymers, composites

Ti, Ti alloys with V or Nb, Mg (possibly with additives of Ca, Zn and Mn), ceramic materials Al2O3 and ZrO2, TiO2, resorbable bioglass, e.g., Hench bioglass, from the CaO-SiO2-P2O5 I SiO2-Al2O3 system, hydroxyapatites, polymers, composites

A natural protein, synthetic and polysaccharide polymers, including thermosetting, including collagen, fibrin, alginate, silk, hyaluronic acid, chitosan, poly (lactic acid) (PLA), poly(glycolic acid) (PGA), polycaprolactone (PCL) and poly(propylene fumarate) (PPF), polyethylene glycol, Al2O3, resorbable bioglass, hydroxy carbonate apatite (HCA), calcium phosphate (CaPs), hydroxyapatite (HA), B-tricalcium phosphate (B-TCP), biphasic calcium phosphate, composites: collagen + hydroxy - apatite CaPpolymer tricalcium phosphate (TCP)-polycaprolactone (PCL), hydroxyapatite HA/poly(esterurethane)(PU), collagen-bioglass

Adipocytes, chondrocytes, osteoblasts, fibroblasts and skeletal

myocytes

Fabrication of implant bearing structure

14 Biomaterials in Regenerative Medicine

Fabrication of porous implant

Fabrication of coatings inside pores of porous implant part

Fabrication and application of tissue cultures

part

medicine. Natural rubber latex biomaterials in bone regenerative medicine are presented in the thirteenth chapter. A systematic study of ethylene-vinyl acetate (EVA) in the manufacturing of protector devices for the orofacial system was described in the fourteenth chapter. The next few chapters outline other issues regarding regenerative medicine and tissue engineering. The fifteenth chapter includes tailoring bioengineered scaffolds for regenerative medicine. Biomaterials and stem cells as promising tools in tissue engineering and biomedical applications are the content of the sixteenth chapter. Identification of Fe3O4 nanoparticles biomedical purpose by magnetometric methods is the title of the seventeenth chapter. The eighteenth chapter applies to biomaterials for tissue engineering applications in diabetes mellitus.

References

[1] Dobrzański LA. The concept of biologically active microporous engineering materials and composite biological-engineering materials for regenerative medicine and dentistry. Archives of Materials Science and Engineering. 2016;80(2):64-85. DOI: 10.5604/18972764.1229638 [2] Dobrzański LA. Overview and general ideas of the development of constructions, materials, technologies and clinical applications of scaffolds engineering for regenerative

Introductory Chapter: Multi-Aspect Bibliographic Analysis of the Synergy of Technical, Biological and Medical…

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17

[3] Dobrzański LA. Applications of newly developed nanostructural and microporous materials in biomedical, tissue and mechanical engineering. Archives of Materials Sci-

[4] Dobrzański LA. Korszerű mérnöki anyagok kutatásának nanotechnológiai aspektusai.

[5] Dobrzański LA, Dobrzańska-Danikiewicz AD. Metalowe materiały mikroporowate i lite do zastosowań medycznych i stomatologicznych. Open Access Library. 2017;Annal VII

[6] Dobrzański LA, editor. Powder Metallurgy – Fundamentals and Case Studies. Rijeka,

[7] Dobrzański LA, editor. Polymer nanofibers produced by electrospinning applied in regenerative medicine. Open Access Library. 2015;V(3):1-168 (ISBN 978-83-63553-88-3)

[8] Dobrzański LA. Metale i ich stopy. Open Access Library. 2017;VII(2):1-982 (ISBN 978-83-

[9] Nowacki J, Dobrzański LA, Gustavo F. Intramedullary implants for osteosynthesis of long bones. Open Access Library. 2012;11(17):1-150 (in Polish) (ISBN 978-83-63553-07-4)

[10] Dobrzański LA, Dobrzańska-Danikiewicz AD, Achtelik-Franczak A, Szindler M. Structure and properties of the skeleton microporous materials with coatings inside the pores for medical and dental applications. In: Muruganant M et al., editors. Frontiers in Materials Processing, Applications, Research and Technology. Springer Nature Singa-

[11] Dobrzański LA, Dobrzańska-Danikiewicz AD, Achtelik-Franczak A, Dobrzański LB, Szindler M, Gaweł TG. Porous selective laser melted Ti and Ti6Al4V materials for medical applications. In: Dobrzański LA, editor. Powder Metallurgy – Fundamentals and Case Studies. Rijeka, Croatia: InTech; 2017. pp. 161-181 (ISBN 978-953-51-3053-6,

[12] Dobrzański LA, Matula G, Dobrzańska-Danikiewicz AD, Malara P, Kremzer M, Tomiczek B, Kujawa M, Hajduczek E, Achtelik-Franczak A, Dobrzański LB, Krzysteczko J. Composite materials infiltrated by aluminium alloys based on porous skeletons from alumina, Mullite and titanium produced by powder metallurgy techniques. In: Dobrzański LA,

pore Pte Ltd; 2018. pp. 297-320. DOI: 10.1007/978-981-10-4819-7\_26

(1):1-580 (ISBN 978-83-63553- 44-9; International OCSCO World Press, Gliwice)

medicine. Archives of Materials Science and Engineering. 2014;69(2):53-80

Miskolci Egyetem, Multidiszciplináris tudományok. 2016;6(1):21-44

Croatia: InTech; 2017. pp. 1-392 (ISBN 978-953-51- 3053-6)

63553-47-0; International OCSCO World Press, Gliwice)

DOI: 10.5772/65375)

ence and Engineering. 2015;76(2):53-114

The editor, publisher and the whole team of authors, by making this book available to the readers, deeply believe that the detailed information collected in the book, largely deriving from own and original research and R&D works pursued by the authors, will be beneficial for the readers to develop their knowledge and harmonise specific information concerning these topics, and will convince the engineers and medicals about the advantages of using the manufacturing and tissue engineering and advanced biomaterials in regenerative medicine and dentistry. On one hand, it makes possible gaining positive effects in the economic manufacturing of biomaterials and implantable devices; on the other hand, it will ameliorate the fate of many people affected by severe diseases. This awareness justifies the involvement in the execution of research and the effort put in describing their results in this book.

#### Notice

The study presented in the chapter was realised in the Medical and Dental Engineering Centre for Research, Design and Production ASKLEPIOS in Gliwice, Poland in the framework of the Project POIR.01.01.01-00-0485/16-00 on 'IMSKA-MAT Innovative dental and maxillofacial implants manufactured using the innovative additive technology supported by computeraided materials design ADDMAT' co-financed by the National Centre for Research and Development in Warsaw, Poland.

### Author details

Leszek A. Dobrzański

Address all correspondence to<EMAIL_ADDRESS>
Science Centre of the Medical and Dental Engineering Centre for Research, Design and Production Asklepios, Gliwice, Poland

## References

medicine. Natural rubber latex biomaterials in bone regenerative medicine are presented in the thirteenth chapter. A systematic study of ethylene-vinyl acetate (EVA) in the manufacturing of protector devices for the orofacial system was described in the fourteenth chapter. The next few chapters outline other issues regarding regenerative medicine and tissue engineering. The fifteenth chapter includes tailoring bioengineered scaffolds for regenerative medicine. Biomaterials and stem cells as promising tools in tissue engineering and biomedical applications are the content of the sixteenth chapter. Identification of Fe3O4 nanoparticles biomedical purpose by magnetometric methods is the title of the seventeenth chapter. The eighteenth chapter

The editor, publisher and the whole team of authors, by making this book available to the readers, deeply believe that the detailed information collected in the book, largely deriving from own and original research and R&D works pursued by the authors, will be beneficial for the readers to develop their knowledge and harmonise specific information concerning these topics, and will convince the engineers and medicals about the advantages of using the manufacturing and tissue engineering and advanced biomaterials in regenerative medicine and dentistry. On one hand, it makes possible gaining positive effects in the economic manufacturing of biomaterials and implantable devices; on the other hand, it will ameliorate the fate of many people affected by severe diseases. This awareness justifies the involvement in

The study presented in the chapter was realised in the Medical and Dental Engineering Centre for Research, Design and Production ASKLEPIOS in Gliwice, Poland in the framework of the Project POIR.01.01.01-00-0485/16-00 on 'IMSKA-MAT Innovative dental and maxillofacial implants manufactured using the innovative additive technology supported by computeraided materials design ADDMAT' co-financed by the National Centre for Research and Devel-

Science Centre of the Medical and Dental Engineering Centre for Research, Design and

applies to biomaterials for tissue engineering applications in diabetes mellitus.

the execution of research and the effort put in describing their results in this book.

Notice

opment in Warsaw, Poland.

16 Biomaterials in Regenerative Medicine

Author details

Leszek A. Dobrzański

Address all correspondence to<EMAIL_ADDRESS>
Production Asklepios, Gliwice, Poland

editor. Powder Metallurgy – Fundamentals and Case Studies. Rijeka, Croatia: InTech; 2017. pp. 95-137 (ISBN 978-953-51-3053-6, DOI: 10.5772/65377)

Dobrzańska-Danikiewicz AD, editors. Metalowe materiały mikroporowate i lite do zastosowań medycznych i stomatologicznych. Gliwice: International OCSCO World

Introductory Chapter: Multi-Aspect Bibliographic Analysis of the Synergy of Technical, Biological and Medical…

http://dx.doi.org/10.5772/intechopen.73094

19

[20] Dobrzański LA, Pakuła D, Staszuk M. Chemical vapor deposition in manufacturing. In: Nee AYC, editor. Handbook of Manufacturing Engineering and Technology. London:

[21] Dobrzański LA, Gołombek K, Lukaszkowicz K. Physical vapor deposition in manufacturing. In: Nee AYC, editor. Handbook of Manufacturing Engineering and Technology.

[22] Dobrzański LA, Dobrzańska-Danikiewicz AD, Tański T, Jonda E, Drygała A, Bonek M. Laser surface treatment in manufacturing. In: Nee AYC, editor. Handbook of Manufacturing Engineering and Technology. London: Springer-Verlag; 2015. pp. 2677-2717 (ISBN 978-

[23] Dobrzański LA, Dobrzańska-Danikiewicz AD. Foresight of the surface Technology in Manufacturing. In: Nee AYC, editor. Handbook of Manufacturing Engineering and Technology. London: Springer-Verlag; 2015. pp. 2587-2637 (ISBN 978-1-4471-4671-1) [24] Dobrzański LA, Trzaska J, Dobrzańska-Danikiewicz AD. Use of neural networks and artificial intelligence tools for Modeling, characterization, and forecasting in material engineering. In: Hashmi S, editor. Comprehensive Materials Processing, G.F. Batalha (Ed.): Vol. 2: Materials Modeling and Characterization. Elsevier Ltd; 2014. pp. 161-198

[25] Dobrzański LA, Dobrzańska-Danikiewicz AD, Gaweł TG, Achtelik-Franczak A. Selective laser sintering and melting of pristine titanium and titanium Ti6Al4V alloy powders and selection of chemical environment for etching of such materials. Archives of Metal-

[26] Dobrzański LA, Dobrzańska-Danikiewicz AD, Malara P, Gaweł T, Dobrzański LB, Achtelik-Franczak A. Fabrication of scaffolds from Ti6Al4V powders using the computer aided laser method. Archives of Metallurgy and Materials. 2015;60(2):1065-1070

[27] Reimann Ł, Żmudzki J, Dobrzański LA. Strength analysis of a three-unit dental bridge framework with the finite element method. Acta of Bioengineering and Biomechanics.

[28] Żmudzki J, Chladek G, Kasperski J, Dobrzański LA. One versus two implant-retained dentures: Comparing biomechanics under oblique mastication forces. Journal of Biome-

[29] Nowak AJ, Dobrzański LA. Geometrical structure investigation of the surface of internal oesophagus prosthesis. Archives of Materials Science and Engineering. 2017;83(2):79-85

[30] Dobrzański LA, Dobrzańska-Danikiewicz AD, Achtelik-Franczak A. The structure and properties of aluminium alloys matrix composite materials with reinforcement made of

Press, Open Access Library, 2017;VII(1):535-580 (ISBN 978-83-63553-44-9)

Springer-Verlag; 2015. pp. 2755-2803 (ISBN 978-1-4471-4669-8)

1- 4471-4669-8)

(ISBN 978-0-08-096532-1)

2015;17(1):51-59

lurgy and Materials. 2015;60(3):2039-2045

chanical Engineering. 2013;135(5):054503-1-054503-4

London: Springer-Verlag; 2015. pp. 2719-2754 (ISBN 978-1-4471-4669-8)

Dobrzańska-Danikiewicz AD, editors. Metalowe materiały mikroporowate i lite do zastosowań medycznych i stomatologicznych. Gliwice: International OCSCO World Press, Open Access Library, 2017;VII(1):535-580 (ISBN 978-83-63553-44-9)

[20] Dobrzański LA, Pakuła D, Staszuk M. Chemical vapor deposition in manufacturing. In: Nee AYC, editor. Handbook of Manufacturing Engineering and Technology. London: Springer-Verlag; 2015. pp. 2755-2803 (ISBN 978-1-4471-4669-8)

editor. Powder Metallurgy – Fundamentals and Case Studies. Rijeka, Croatia: InTech;

[13] Dobrzański LA, Dobrzańska-Danikiewicz AD, Achtelik-Franczak A, Dobrzański LB, Hajduczek E, Matula G. Fabrication Technologies of the Sintered Materials Including Materials for medical and dental application. In: Dobrzański LA, editor. Powder Metallurgy – Fundamentals and Case Studies. Rijeka, Croatia: InTech; 2017. pp. 17-52 (ISBN

[14] Dobrzański LA. Stan wiedzy o materialach stosowanych w implantologii oraz medycynie regeneracyjnej. In: Dobrzański LA, Dobrzańska-Danikiewicz AD, editors. Metalowe materiały mikroporowate i lite do zastosowań medycznych i stomatologicznych. Gliwice: International OCSCO World Press. Open Access Library, 2017;VII(1):117-120 (ISBN 978-

[15] Dobrzański LA, Achtelik-Franczak A. Struktura i wlasnosci tytanowych szkieletowych materialów mikroporowatych wytworzonych metoda selektywnego spiekania laserowego do zastosowan w implantologii oraz medycynie regeneracyjnej. In: Dobrzański LA, Dobrzańska-Danikiewicz AD, editors. Metalowe materiały mikroporowate i lite do zastosowań medycznych i stomatologicznych. Gliwice: International OCSCO World Press,

[16] Dobrzanska-Danikiewicz AD, Gawel TG, Kroll L, Dobrzanski LA. Nowe porowate materialy kompozytowe metalowo-polimerowe wytwarzane z udzialem selektywnego stapiania laserowego. In: Dobrzański LA, Dobrzańska-Danikiewicz AD, editors. Metalowe materiały mikroporowate i lite do zastosowań medycznych i stomatologicznych. Gliwice: International OCSCO World Press, Open Access Library. 2017;VII(1):245-288 (ISBN 978-83-

[17] Dobrzanska-Danikiewicz AD, Dobrzanski LA, Szindler M, Achtelik-Franczak A, Dobrzanski LB. Obróbka powierzchni materialów mikroporowatych wytworzonych metoda selektywnego spiekania laserowego w celu uefektywnienia proliferacji zywych komórek. In: Dobrzański LA, Dobrzańska-Danikiewicz AD, editors. Metalowe materiały mikroporowate i lite do zastosowań medycznych i stomatologicznych. Gliwice: International OCSCO World Press, Open Access Library. 2017;VII(1):289-375 (ISBN 978-83-

[18] Dobrzański LA, Achtelik-Franczak A. Struktura i wlasnosci materialów kompozytowych do zastosowan medycznych o osnowie odlewniczych stopów aluminium wzmacnianych tytanowymi szkieletami wytworzonymi metoda selektywnego spiekania laserowego. In: Dobrzański LA, Dobrzańska-Danikiewicz AD, editors. Metalowe materiały mikroporowate i lite do zastosowań medycznych i stomatologicznych. Gliwice: International OCSCO World Press, Open Access Library, 2017;VII(1):376-433 (ISBN 978-83-

[19] Dobrzański LA. Autorska koncepcja rozwoju implanto-skafoldów oraz materialów biologiczno-inzynierskich do aplikacji w medycynie i stomatologii. In: Dobrzański LA,

Open Access Library, 2017;VII(1):186-244 (ISBN 978-83-63553-44-9)

2017. pp. 95-137 (ISBN 978-953-51-3053-6, DOI: 10.5772/65377)

978-953-51-3053-6, DOI: 10.5772/65376)

83-63553-44-9)

18 Biomaterials in Regenerative Medicine

63553-44-9)

63553-44-9)

63553-44-9)

titanium skeletons. Archives of Materials Science and Engineering. 2016;80(1):16-30. DOI: 10.5604/18972764.1229614

[43] Dobrzański LA, Reimann Ł, Krawczyk C. Effect of age hardening on corrosion resistance and hardness of CoCrMo alloys used in dental engineering. Archives of Materials

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[44] Szindler M, Dobrzański LA, Szindler MM, Pawlyta M, Jung T. Comparison of surface morphology and structure of Al2O3 thin films deposited by sol-gel and ALD methods. Journal of Achievements in Materials and Manufacturing Engineering. 2017;2(82):49-57.

[45] Dobrzański LA, Dobrzańska-Danikiewicz AD, Gaweł TG. Individual implants of a loss of palate fragments fabricated using SLM equipment. Journal of Achievements in Materials and Manufacturing Engineering. 2016;77(1):24-30. DOI: 10.5604/17348412.1229665

[46] Dobrzański LA, Dobrzańska-Danikiewicz AD, Gaweł TG. Ti6Al4V porous elements coated by polymeric surface layer for biomedical applications. Journal of Achievements

[47] Nowak AJ, Dobrzański LA. Wear abrasive resistance of intracorporeal prosthesis of oesophagus. Journal of Achievements in Materials and Manufacturing Engineering. 2015;

[48] Dobrzański LA, Adamiak M, Karoń M, Nieradka B. Influence of inorganic additives on morphology of electrospun fibres. Journal of Achievements in Materials and Manufactur-

[49] Hudecki A, Pawlyta M, Dobrzański LA, Chladek G. Micro and ceramic nanoparticles surface properties examination with gas adsorption method and microscopic transmission. Journal of Achievements in Materials and Manufacturing Engineering.

[50] Dobrzański LA, Achtelik-Franczak A, Król M. Computer aided design in selective laser sintering (SLS) – Application in medicine. Journal of Achievements in Materials and

[51] Reimann Ł, Dobrzański LA, Nieradka B, Kusy M, Riedlmajer R. Influence the heat treatment of two base metal alloys used on dental prosthesis on corrosion resistance. Journal of Achievements in Materials and Manufacturing Engineering. 2013;57(2):83-90

[52] Dobrzański LA, Reimann Ł. Digitization procedure of creating 3D model of dental bridgework reconstruction. Journal of Achievements in Materials and Manufacturing

[53] Dobrzański LA, Dobrzańska-Danikiewicz AD, Gaweł TG. Computer-aided design and selective laser melting of porous biomimetic materials. Advances in Materials and

[54] Nowak AJ, Dobrzański LA. Badania struktury geometrycznej powierzchni wewnątrzustrojowej protezy przełyku. Przetwórstwo Tworzyw. 2015;21(4(166)):337-342

Processing Technologies. 2017;3(1):70-82. DOI: 10.1080/2374068X.2016. 1247339

in Materials and Manufacturing Engineering. 2015;71(2):53-59

Science and Engineering. 2012;57(1):5-12

DOI: 10.5604/01.3001.0010.2354

ing Engineering. 2015;68(2):64-71

Engineering. 2012;55(2):469-476

Manufacturing Engineering. 2013;60(2):66-75

69(1):26-32

2013;61(2):257-262

[43] Dobrzański LA, Reimann Ł, Krawczyk C. Effect of age hardening on corrosion resistance and hardness of CoCrMo alloys used in dental engineering. Archives of Materials Science and Engineering. 2012;57(1):5-12

titanium skeletons. Archives of Materials Science and Engineering. 2016;80(1):16-30.

[31] Dobrzański LA, Hudecki A, Chladek G, Król W, Mertas A. Biodegradable and antimicrobial polycaprolactone nanofibers with and without silver precipitates. Archives of

[32] Kremzer M, Dobrzański LA, Dziekońska M, Macek M. Atomic layer deposition of TiO2 onto porous biomaterials. Archives of Materials Science and Engineering. 2015;75(2):63-69

[33] Dobrzański LA, Dobrzańska-Danikiewicz AD, Szindler M, Achtelik-Franczak A, Pakieła W. Atomic layer deposition of TiO2 onto porous biomaterials. Archives of Materials

[34] Dobrzański LA, Dobrzańska-Danikiewicz AD, Achtelik-Franczak A, Dobrzański LB. Comparative analysis of mechanical properties of scaffolds sintered from Ti and Ti6Al4V powders. Archives of Materials Science and Engineering. 2015;73(2):69-81 [35] Dobrzański LA, Hudecki A, Chladek G, Król W, Mertas W. Surface properties and antimicrobial activity of composite nanofibers of polycaprolactone with silver precipita-

[36] Dobrzański LA, Hudecki A. Structure, geometrical characteristics and properties of biodegradable micro- and polycaprolactone nanofibers. Archives of Materials Science

[37] Nowak AJ, Dobrzański LA, Rybczyński R, Mech R. Finite element method application for modelling of internal oesophageal prosthesis. Archives of Materials Science and

[38] Stefański T, Malara P, Kloc-Ptaszna A, Janoszka B, Postek-Stefańska L, Tyrpień-Golder K, Dobrzański LA. Erosive potential of calcium-supplemented citric acid on bovine

[39] Żmudzki J, Chladek G, Malara P, Dobrzański LA, Zorychta M, Basa K. The simulation of mastication efficiency of the mucous- borne complete dentures. Archives of Materials

[40] Malara P, Kloc-Ptaszna A, Dobrzański LA, Górniak M, Stefański T. Water dilution and alcohol mixing on erosive potential of orange juice on bovine enamel. Archives of

[41] Chladek G, Żmudzki J, Malara P, Dobrzański LA, Krawczyk C. Effect of influence of introducing silver nanoparticles on tribological characteristics of soft liner. Archives of

[42] Reimann Ł, Dobrzański LA. Influence of the casting temperature on dental co-base alloys properties. Archives of Materials Science and Engineering. 2013;60(1):5-12

enamel. Archives of Materials Science and Engineering. 2013;64(2):175-181

tions. Archives of Materials Science and Engineering. 2014;70(2):53-60

DOI: 10.5604/18972764.1229614

20 Biomaterials in Regenerative Medicine

Materials Science and Engineering. 2015;76(1):5-26

Science and Engineering. 2015;75(1):5-11

and Engineering. 2014;70(1):5-13

Engineering. 2013;64(2):198-204

Science and Engineering. 2013;63(2):75-86

Materials Science and Engineering. 2013;62(1):15-21

Materials Science and Engineering. 2013;62(1):5-14

[55] Dobrzański LA, Wolany W. Biomaterials manufacturing using SLS method, 20th Jubilee international seminar of Ph.D. students, SEMDOK 2015, Terchova, Slovakia; 2015. pp. 109–112

[67] Postek-Stefańska L, Stefański T, Malara P, Kloc-Ptaszna A, Dobrzański LA. Ocena biopolimerów polisacharydowych jako inhibitorów procesu roztwarzania szkliwa w kwasie cytrynowym, Biomateriały i mechanika w stomatologii, XV Konferencja, Pro-

Introductory Chapter: Multi-Aspect Bibliographic Analysis of the Synergy of Technical, Biological and Medical…

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[68] Reimann Ł, Dobrzański LA, Żmudzki J. Struktura i własności utwardzanego wydzieleniowo stopu CoCrMoW, Biomateriały i mechanika w stomatologii, XIII Konferencja, Program i

[69] Reimann Ł, Dobrzański LA, Żmudzki J. Wpływ własności materiału metalowego na ugięcie trzypunktowego mostu protetycznego, Biomateriały i mechanika w stomatologii,

[70] Malara P, Kloc-Ptaszna A, Dobrzański LA, Stefański T, Górniak M, Chladek G. Wpływ wybranych dodatków na potencjał erozyjny soku pomarańczowego w stosunku do szkliwa zębów, Biomateriały i mechanika w stomatologii, XIII Konfrencja, Program i

[71] Hudecki A, Dobrzański LA, Chladek. Własności nanowłókien polimerowych PLA i PCL z dodatkiem wypełniacza o własnościach przeciwdrobnoustrojowych otrzymywanych w polu elektrostatycznym, Biomateriały i mechanika w stomatologii, XIII Konfrencja,

[72] Hudecki A, Dobrzański LA, Chladek G. Własności mikro i nanowypełniaczy ceramicznych przewidywanych do poprawy własności materiałów polimerowych przeznaczonych dla stomatologii, Biomateriały i mechanika w stomatologii, XIII

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**Chapter 2**

**Provisional chapter**

**Up-to-Date Knowledge and Outlooks for the Use of**

In all cases, when a material has to be used in medical applications, the knowledge of its physical, chemical and biological properties is of fundamental significance, since the direct contact between the biological system and the considered device could generate reactions whose long-term effects must be clearly quantified. The class of materials that exhibits characteristics that allow their use for the considered applications are commonly called *biomaterials*. Patients suffering from different diseases generate a great demand for real therapies, where the use of biomaterials are mandatory. Commonly, metallic biomaterials are used because their structural functions; the high strength and resistance to fracture they can offer, provide reliable performance primarily in the fields of orthopedics and dentistry. In metals, because of their particular structure, plastic deformation takes place easier, inducing good formability in manufacturing. The present paper is not encyclopaedic, but reports in the first part some current literature data and perspectives about the possibility of use different class of metallic materials for medical applications, while the second part recalls some results of the current research in this field carried out by the authors.

**Keywords:** biomaterials, metallic biomaterials, morphology, biocompatibility, implanted

**Up-to-Date Knowledge and Outlooks for the Use of**

DOI: 10.5772/intechopen.69970

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

© 2018 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

Generally, materials are playing an important role in our society. Apart other materials, biomaterials became key elements for the human well-being. The beginning of biomaterials goes back to thousands of years (the use of metals in dental implants dates back to 200 A.D.), while

after World War II, a real expansion of biomaterials can be considered [1].

**Metallic Biomaterials: Review Paper**

**Metallic Biomaterials: Review Paper**

Ildiko Peter, Ladislau Matekovits and Mario Rosso

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.69970

Ildiko Peter, Ladislau Matekovits

and Mario Rosso

**Abstract**

antenna

**1. Introduction**

**1.1. Outline**

**Provisional chapter**

## **Up-to-Date Knowledge and Outlooks for the Use of Metallic Biomaterials: Review Paper Metallic Biomaterials: Review Paper**

**Up-to-Date Knowledge and Outlooks for the Use of**

DOI: 10.5772/intechopen.69970

Ildiko Peter, Ladislau Matekovits and Mario Rosso and Mario Rosso

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.69970

Ildiko Peter, Ladislau Matekovits

#### **Abstract**

In all cases, when a material has to be used in medical applications, the knowledge of its physical, chemical and biological properties is of fundamental significance, since the direct contact between the biological system and the considered device could generate reactions whose long-term effects must be clearly quantified. The class of materials that exhibits characteristics that allow their use for the considered applications are commonly called *biomaterials*. Patients suffering from different diseases generate a great demand for real therapies, where the use of biomaterials are mandatory. Commonly, metallic biomaterials are used because their structural functions; the high strength and resistance to fracture they can offer, provide reliable performance primarily in the fields of orthopedics and dentistry. In metals, because of their particular structure, plastic deformation takes place easier, inducing good formability in manufacturing. The present paper is not encyclopaedic, but reports in the first part some current literature data and perspectives about the possibility of use different class of metallic materials for medical applications, while the second part recalls some results of the current research in this field carried out by the authors.

**Keywords:** biomaterials, metallic biomaterials, morphology, biocompatibility, implanted antenna

## **1. Introduction**

#### **1.1. Outline**

Generally, materials are playing an important role in our society. Apart other materials, biomaterials became key elements for the human well-being. The beginning of biomaterials goes back to thousands of years (the use of metals in dental implants dates back to 200 A.D.), while after World War II, a real expansion of biomaterials can be considered [1].

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

Actually, biomaterials can be employed for both short-term or permanently, amplifying or partially or completely replacing some organs, tissues, or other elements of the body with the aim to save or to improve the people's well-being. The numbers of the aged people are quickly increasing that in turn requires a greater call to substitute failed body parts with artificial devices made of biomaterials. Additionally, the ongoing tendency to move in the direction of using short-term implants and/or degradable ones constitutes one of the key progresses in biomaterials research. Further important issues are correlated to the possibility to reduce as much as possible implant related infections by means of infection-resistant biomaterials, which usually involves the application of suitable coatings. The use of any biomaterial is influenced by different features, i.e., composition, mechanical strength, rate of degradation (in case of temporary application), growth rate of the human cells, osteoinduction, osteoconduction, etc. [2].

However, according to some research, e.g., [6], stainless steels can suffer pitting, crevice, corrosion fatigue, stress corrosion cracking, and galvanic corrosion within the human body accelerated by their reduced wear resistance. Additionally, appearance of allergic reaction limits their use as orthopedic joint prosthesis [7, 8]. Release of metallic ions, as corrosion product, in the human body can reduce the lifetime of the implant leading to an additional surgical procedure [9–12]. If high amount of Ni ions is released in the tissues, development of the most

**C Mn P S Si Cr Ni Mo N Cu**

Up-to-Date Knowledge and Outlooks for the Use of Metallic Biomaterials: Review Paper

http://dx.doi.org/10.5772/intechopen.69970

47

F138 0.03 2.0 0.025 0.01 0.75 17.0–19.0 13.0–15.0 2.25–3.0 0.10 0.50 F1314 0.03 4.0–6.0 0.025 0.01 0.75 20.5–23.5 11.5–13.5 2.0–3.0 0.20–0.40 0.50 F1586 0.08 2.0–4.25 0.025 0.01 0.75 19.5–22.0 9.0–11.0 2.0–3.0 0.25–0.50 0.25 F2229 0.08 21–24 0.03 0.01 0.75 19.0–23.0 0.10 0.50–1.50 0.90 0.25

The corrosion resistance of stainless steels can be modified by the (i) different oxygen concentration (generally, low oxygen content contributes to a higher corrosion rate, because the growth of the protective oxide layer is delayed on the surfaces of the metallic implant), (ii) pH value which can be altered from a neutral condition to lower values due to the inflammatory cell secretions, and (iii) presence of aqueous ions level in the surrounding body fluid. If possible, the concentration of the released metal ions has to be as reduced as possible, and it has to be innocuous for the human body during a long service period [17]. The high elastic modulus of stainless steel is considered as one of the highest difficulties leading to the damage of the bone by stress shielding which is directly connected to the failure of the implant. During the time, *Cobalt-Chromium alloys* have been developed, which reveal some superior properties and some drawbacks relating to their production costs than stainless steels [18, 19]. The alloys belonging to this family show high corrosion resistance attributable to the natural growth of the passive oxide film on the top of the metallic device which is resistant also in the

**Table 2** reports the composition of the most important alloys belonging to these classes used

CoCrMo has been used for many years in dental applications and for the manufacturing of artificial joints, while for prosthetic stem productions, for hip and knee joints the alloy containing Ni has been employed [21]. CoCrMo alloy, because of its high corrosion and wear resistance, is used for joint prostheses for the femoral head in combination with an ultra-high

common contact allergy [13, 14] and cancer [15, 16] can be favored.

**Table 1.** Composition (wt%) of some austenitic stainless steels [5].

Generally, two basic types of such alloys are commonly employed:

• Cobalt-Chromium-Molybdenum (CoCrMo) alloy and

• Cobalt-Nickel-Chromium-Molybdenum (CoNiCrMo) alloy.

chloride-rich background [20–23].

**Steels (ASTM)**

for the production of orthopedic implants.

molecular weight polyethylene cup.

The present review is not encyclopedic and does not completely cover any features about biomaterials, regenerative medicine (RM), and tissue engineering (TE) aspects, but it shows some essential features belonging to such a wide-ranging subject. Some experimental results here presented deal with the outcome of some of the investigations performed by the authors on the development of metallic biomaterials and their possible use for medical implant development. It also includes the description of a multidisciplinary application where a data transmission system is referred to that has been possible to be developed because of the existence of large dimension implanted device. Nowadays, other similar applications are under focus: controlled drug delivery from swallowed capsules by means of external (to the body) control through a communication system that requires the use of an antenna, explicitly a metallic device, is just one of the many applications that could be nominated.

#### **1.2. Metallic biomaterials**

Metallic biomaterials show excellent structural functions, superior than ceramic and polymeric biomaterials and for a long time they have been usually employed to substitute unhealthy natural parts or to repair different organs of the human body. Extension of metal made implants was firstly determined by the request to repair bone and later on their application for orthopedic purpose has been increased together with the short-term applications of pins and screws, followed by the use of permanent implants for total joint substitution. Further evolution involves the use of metals and their alloys for dental applications and recently there is a higher tendency for their use in non-conventional reconstructive surgery of organs and hard tissue. There are only some areas where the use of metallic biomaterials is exploited such as joint prostheses, bone fixation plates, pins and screws, dental implants and materials, ocular, contact and intra-ocular lenses, vascular grafts, urinary and intra-vascular catheters, surgical meshes, and voice prostheses.

Within the different class of biomaterials, firstly, *stainless steel* has been used for medical purpose. This is principally due to their low cost, good corrosion resistance conferred by the presence of Cr, allowing the development of the passive and protective oxide layer. **Table 1** reports the composition of the most important/recommended stainless steels used for the manufacturing of orthopedic implants. ASTM F138 and F139 reveal higher biomedical interest because of a better fatigue strength, higher ductility, and better machinability [3], but the high Ni content determines possible toxicity and allergy [4].

**Table 1.** Composition (wt%) of some austenitic stainless steels [5].

Actually, biomaterials can be employed for both short-term or permanently, amplifying or partially or completely replacing some organs, tissues, or other elements of the body with the aim to save or to improve the people's well-being. The numbers of the aged people are quickly increasing that in turn requires a greater call to substitute failed body parts with artificial devices made of biomaterials. Additionally, the ongoing tendency to move in the direction of using short-term implants and/or degradable ones constitutes one of the key progresses in biomaterials research. Further important issues are correlated to the possibility to reduce as much as possible implant related infections by means of infection-resistant biomaterials, which usually involves the application of suitable coatings. The use of any biomaterial is influenced by different features, i.e., composition, mechanical strength, rate of degradation (in case of temporary application), growth rate of the human cells, osteoinduction, osteoconduction, etc. [2]. The present review is not encyclopedic and does not completely cover any features about biomaterials, regenerative medicine (RM), and tissue engineering (TE) aspects, but it shows some essential features belonging to such a wide-ranging subject. Some experimental results here presented deal with the outcome of some of the investigations performed by the authors on the development of metallic biomaterials and their possible use for medical implant development. It also includes the description of a multidisciplinary application where a data transmission system is referred to that has been possible to be developed because of the existence of large dimension implanted device. Nowadays, other similar applications are under focus: controlled drug delivery from swallowed capsules by means of external (to the body) control through a communication system that requires the use of an antenna, explicitly a metallic device, is just

Metallic biomaterials show excellent structural functions, superior than ceramic and polymeric biomaterials and for a long time they have been usually employed to substitute unhealthy natural parts or to repair different organs of the human body. Extension of metal made implants was firstly determined by the request to repair bone and later on their application for orthopedic purpose has been increased together with the short-term applications of pins and screws, followed by the use of permanent implants for total joint substitution. Further evolution involves the use of metals and their alloys for dental applications and recently there is a higher tendency for their use in non-conventional reconstructive surgery of organs and hard tissue. There are only some areas where the use of metallic biomaterials is exploited such as joint prostheses, bone fixation plates, pins and screws, dental implants and materials, ocular, contact and intra-ocular lenses, vascular grafts, urinary and intra-vascular

Within the different class of biomaterials, firstly, *stainless steel* has been used for medical purpose. This is principally due to their low cost, good corrosion resistance conferred by the presence of Cr, allowing the development of the passive and protective oxide layer. **Table 1** reports the composition of the most important/recommended stainless steels used for the manufacturing of orthopedic implants. ASTM F138 and F139 reveal higher biomedical interest because of a better fatigue strength, higher ductility, and better machinability [3], but the

one of the many applications that could be nominated.

catheters, surgical meshes, and voice prostheses.

high Ni content determines possible toxicity and allergy [4].

**1.2. Metallic biomaterials**

46 Biomaterials in Regenerative Medicine

However, according to some research, e.g., [6], stainless steels can suffer pitting, crevice, corrosion fatigue, stress corrosion cracking, and galvanic corrosion within the human body accelerated by their reduced wear resistance. Additionally, appearance of allergic reaction limits their use as orthopedic joint prosthesis [7, 8]. Release of metallic ions, as corrosion product, in the human body can reduce the lifetime of the implant leading to an additional surgical procedure [9–12]. If high amount of Ni ions is released in the tissues, development of the most common contact allergy [13, 14] and cancer [15, 16] can be favored.

The corrosion resistance of stainless steels can be modified by the (i) different oxygen concentration (generally, low oxygen content contributes to a higher corrosion rate, because the growth of the protective oxide layer is delayed on the surfaces of the metallic implant), (ii) pH value which can be altered from a neutral condition to lower values due to the inflammatory cell secretions, and (iii) presence of aqueous ions level in the surrounding body fluid. If possible, the concentration of the released metal ions has to be as reduced as possible, and it has to be innocuous for the human body during a long service period [17]. The high elastic modulus of stainless steel is considered as one of the highest difficulties leading to the damage of the bone by stress shielding which is directly connected to the failure of the implant.

During the time, *Cobalt-Chromium alloys* have been developed, which reveal some superior properties and some drawbacks relating to their production costs than stainless steels [18, 19].

The alloys belonging to this family show high corrosion resistance attributable to the natural growth of the passive oxide film on the top of the metallic device which is resistant also in the chloride-rich background [20–23].

Generally, two basic types of such alloys are commonly employed:

**Table 2** reports the composition of the most important alloys belonging to these classes used for the production of orthopedic implants.

CoCrMo has been used for many years in dental applications and for the manufacturing of artificial joints, while for prosthetic stem productions, for hip and knee joints the alloy containing Ni has been employed [21]. CoCrMo alloy, because of its high corrosion and wear resistance, is used for joint prostheses for the femoral head in combination with an ultra-high molecular weight polyethylene cup.

by interstitial solid solution strengthening. Cp-Ti is available in four grades, where (i) grade I corresponds to the lowest O content and yield strength and at the same time to the highest ductility and (ii) grade IV reveals the highest O content and the highest strength combined with the lowest ductility. **Table 3** reports the grades of different cp-Ti with the maximum limits of the interstitial elements and some mechanical properties. Due to the capacity for stimulating

and due to the reaction of the hydroxylated surface area with the inorganic phase constituents

Ti6Al4V alloy reveals outstanding mechanical strength, high biocompatibility and consents good implant-bone integration. However, over the years, some weaknesses during the use of such alloy have been noticed: (i) it has higher elastic modulus than bone, producing stressshielding effect, (ii) it shows lower wear resistance too, and (iii) the release of Al and/or V can

The research community has dedicated high attention to these problems, and the trend is to develop new Ti alloys, by alloying the basic alloy and reducing as much as possible or even totally removing the release of any toxic elements. In this scenario, alternatives alloy with (*α* + *β*) structure, without V have been obtained, i.e., Ti6Al7Nb, Ti5Al2.5Fe, Ti6Al6Nb1Ta, and Ti5Al3Mo4Zr, which at the beginning have been developed for airspace application. These alloys reveal higher corrosion resistance, fatigue properties than other biomaterials, principally governed by the size and the distribution of the *α* and *β* phases [28]. Such structure can be obtained during mechanically working till to obtain the preferred form followed by fast cooling at room temperature and annealing for recrystallization within the (*α* + *β*) two-phase field

*β*-Ti and near *β*-Ti alloys, i.e., Ti12Mo6Zr-2Fe, 35.5Nb7.3Zr5.7Ta, and Ti13Nb13Zr, introduced in the 1990s and their continuous improvement have been one of the leading topics of orthopedic materials research, because they contain superior amount of *β*-stabilizing elements and they are characterized by a considerably lower elastic modulus than other biometals (44– 51 GPa for water-quenched and cold-worked Ti-13Nb-13Zr alloy compared to 110 GPa for Ti6Al4V). Additionally, good formability, high hardenability, excellent corrosion resistance, and better notch sensitivity (measure of how sensitive a material to notches or geometric discontinuities is) than the (*α* + *β*) Ti alloys characterize such alloys. In order to amplify the wear resistance, surface hardening can be carried out by aging in an oxygen-rich environment

**Ti grade O N H σyield (MPa) σultimate (MPa) %E** 0.18 0.03 0.015 170 240 24 0.25 0.03 0.015 275 345 20 0.35 0.05 0.015 380 450 18 0.40 0.05 0.015 483 550 15

**Table 3.** Maximum limits of the interstitial elements and mechanical properties of different cp-Ti grades.

determine permanent diseases, i.e., osteomalacia and Alzheimer's disease [27].

3−) present in the bone, cp-Ti is principally used for endosseous dental

Up-to-Date Knowledge and Outlooks for the Use of Metallic Biomaterials: Review Paper

ions inside the passive TiO<sup>2</sup>

http://dx.doi.org/10.5772/intechopen.69970

layer

49

fast osseointegration, coming from the incorporation of OH−

)

and determine a fatigue strength more than 650 MPa.

(prevalently Ca2+and (PO<sup>4</sup>

implants manufacturing.

**Table 2.** Composition (wt%) of some CoCrMo and Co-Ni alloys [5].

However, Ni and Co ions, when released, are susceptible to induce allergic responses: Ni is carcinogenic and causes a toxicity problem, which can be avoided using an as much as possible low level of Ni.

Actually, *Ti and its alloys* have been received much more attention, even if they have been used since the late 1960s. Due to the fact that Ti is completely inert and resistant to corrosion in any fluids in the human body and tissues, these alloys exhibit the best biocompatibility among metallic biomaterials combined to good fatigue resistance, excellent in vivo corrosion resistance which is acquired by the growth on their surface of the stable passive oxide layer. In addition, showing some properties which are close to the human bones, i.e., strength, density, and relatively low elastic modulus, these alloys began to be extensively employed for joint replacements. Lower elastic moduli than other metallic biomaterial allow obtaining less stress-shielding phenomenon. Generally, Ti and its alloys are used for bone fixation, joint substitution, pacemakers, implants for dental, artificial heart valves, components and stents in rapid blood centrifuges due to their chemical stability and particular high strength [24]. Central position has been made for a commercially *pure Ti* (cp-Ti, ASTM F67), *Ti6Al4V alloy* (ASTM F136) strengthened by alloys obtained by the modification of them and *Ti-based shape memory alloys* (SMA) [25, 26]. Cp-Ti is typically used in dental and spinal surgery, Ti6Al4V for the manufacturing of artificial knee, hip and shoulder joints and for bone fixators, while SMAs are employed as orthodontic equipment and temporary spine and long bones fixations.

According to ISO 5832-2, four grades of cp-Ti are recognized for medical applications. Cp-Ti can contain a minor level of interstitial elements (O, N, and H) affecting the mechanical properties by interstitial solid solution strengthening. Cp-Ti is available in four grades, where (i) grade I corresponds to the lowest O content and yield strength and at the same time to the highest ductility and (ii) grade IV reveals the highest O content and the highest strength combined with the lowest ductility. **Table 3** reports the grades of different cp-Ti with the maximum limits of the interstitial elements and some mechanical properties. Due to the capacity for stimulating fast osseointegration, coming from the incorporation of OH− ions inside the passive TiO<sup>2</sup> layer and due to the reaction of the hydroxylated surface area with the inorganic phase constituents (prevalently Ca2+and (PO<sup>4</sup> ) 3−) present in the bone, cp-Ti is principally used for endosseous dental implants manufacturing.

Ti6Al4V alloy reveals outstanding mechanical strength, high biocompatibility and consents good implant-bone integration. However, over the years, some weaknesses during the use of such alloy have been noticed: (i) it has higher elastic modulus than bone, producing stressshielding effect, (ii) it shows lower wear resistance too, and (iii) the release of Al and/or V can determine permanent diseases, i.e., osteomalacia and Alzheimer's disease [27].

The research community has dedicated high attention to these problems, and the trend is to develop new Ti alloys, by alloying the basic alloy and reducing as much as possible or even totally removing the release of any toxic elements. In this scenario, alternatives alloy with (*α* + *β*) structure, without V have been obtained, i.e., Ti6Al7Nb, Ti5Al2.5Fe, Ti6Al6Nb1Ta, and Ti5Al3Mo4Zr, which at the beginning have been developed for airspace application. These alloys reveal higher corrosion resistance, fatigue properties than other biomaterials, principally governed by the size and the distribution of the *α* and *β* phases [28]. Such structure can be obtained during mechanically working till to obtain the preferred form followed by fast cooling at room temperature and annealing for recrystallization within the (*α* + *β*) two-phase field and determine a fatigue strength more than 650 MPa.

However, Ni and Co ions, when released, are susceptible to induce allergic responses: Ni is carcinogenic and causes a toxicity problem, which can be avoided using an as much as pos-

**Cr Mo Ni Fe C Si Mn W P S Other**

26–30 5–7 1.0 0.01 0.05 1.0 1.0 - - - 0.25N

26–30 5–7 1.0 0.01 0.25 1.0 1.0 - - - 0.25N

F563 18–22 3–4 15–25 0.01 0.05 0.5 1.0 3.0–4.0 - 0.01 0.50–3.5

F1058 19–21 6-8 14–16 0.01 0.15 1.2 1.0–2.0 - 0.015 0.015 0.10 Be

1.0 1.0 0.2 0.02 0.01 0.25N

0.15 0.15 - 0.015 0.01 1.0 Ti

0.40 1.0–2.0 14–16 0. 04 0.03 -

0.3Al 0.01B

Ti

39.0- 41.0 Co

max

max

0.15

Actually, *Ti and its alloys* have been received much more attention, even if they have been used since the late 1960s. Due to the fact that Ti is completely inert and resistant to corrosion in any fluids in the human body and tissues, these alloys exhibit the best biocompatibility among metallic biomaterials combined to good fatigue resistance, excellent in vivo corrosion resistance which is acquired by the growth on their surface of the stable passive oxide layer. In addition, showing some properties which are close to the human bones, i.e., strength, density, and relatively low elastic modulus, these alloys began to be extensively employed for joint replacements. Lower elastic moduli than other metallic biomaterial allow obtaining less stress-shielding phenomenon. Generally, Ti and its alloys are used for bone fixation, joint substitution, pacemakers, implants for dental, artificial heart valves, components and stents in rapid blood centrifuges due to their chemical stability and particular high strength [24]. Central position has been made for a commercially *pure Ti* (cp-Ti, ASTM F67), *Ti6Al4V alloy* (ASTM F136) strengthened by alloys obtained by the modification of them and *Ti-based shape memory alloys* (SMA) [25, 26]. Cp-Ti is typically used in dental and spinal surgery, Ti6Al4V for the manufacturing of artificial knee, hip and shoulder joints and for bone fixators, while SMAs

are employed as orthodontic equipment and temporary spine and long bones fixations.

According to ISO 5832-2, four grades of cp-Ti are recognized for medical applications. Cp-Ti can contain a minor level of interstitial elements (O, N, and H) affecting the mechanical properties

sible low level of Ni.

**Alloys (ASTM)**

F799 (low C)

F799 (high C)

F15 27–30 5–7 1.0 0.01 0.35

48 Biomaterials in Regenerative Medicine

F562 19–21 9–10.5 33–37 0.01 0.25

F90 19–21 - 9–11 0.01 0.05–

**Table 2.** Composition (wt%) of some CoCrMo and Co-Ni alloys [5].

*β*-Ti and near *β*-Ti alloys, i.e., Ti12Mo6Zr-2Fe, 35.5Nb7.3Zr5.7Ta, and Ti13Nb13Zr, introduced in the 1990s and their continuous improvement have been one of the leading topics of orthopedic materials research, because they contain superior amount of *β*-stabilizing elements and they are characterized by a considerably lower elastic modulus than other biometals (44– 51 GPa for water-quenched and cold-worked Ti-13Nb-13Zr alloy compared to 110 GPa for Ti6Al4V). Additionally, good formability, high hardenability, excellent corrosion resistance, and better notch sensitivity (measure of how sensitive a material to notches or geometric discontinuities is) than the (*α* + *β*) Ti alloys characterize such alloys. In order to amplify the wear resistance, surface hardening can be carried out by aging in an oxygen-rich environment

**Table 3.** Maximum limits of the interstitial elements and mechanical properties of different cp-Ti grades.

determining the growth of a hard oxide film on the surface with an interstitial solid solution strengthening of the subsurface section atmosphere [29].

Fe, Mg, and Zn are all vital nutritional elements for a healthy body and generally reveal excellent biocompatibility in the human body, with no any sign of local or systemic toxicity biodegradable materials than polymers for load-bearing applications. Both pure Fe and pure Mg have been reported to possess excellent biocompatibility in the human body and show no

Up-to-Date Knowledge and Outlooks for the Use of Metallic Biomaterials: Review Paper

http://dx.doi.org/10.5772/intechopen.69970

51

Mg and its alloys (i.e., (AZ91, WE43, AM50, and LAE442) can be considered as favorable alloys for medical applications, and they have already been positively verified *in vivo* and in clinical studies and it has been reported that development of new bone is facilitated [50–52], when they are implanted as bone fixtures. The elastic modulus of Mg (41–45 GPa) is closer to that of natural bone (3–20 GPa). However, the mechanical properties of such alloys, i.e., strength and the elongation to fracture are not always acceptable which combined to the development of significant quantities of hydrogen limits their widespread use. Some studies [53–55] have reported as alternative solution the use of Fe-based alloys. However, the implants realized using such alloys reveal some reactions like those developed in longterm uses which is predominantly due to the low-degradation rate of pure Fe in biological

In Refs. [53, 54] the authors have developed Fe35Mn alloy with a higher degradation rate compared to the pure Fe; however, compared to Mg-based alloys, the interested value is still

Even with the significant evolution carried out over the time on the implants made of by bio-

Current evolutions of biomaterials and the constantly increasing demand for new technologies have transformed the field of TE and RM too. In such areas, biomaterials have received more and more attention and can be placed in pole position for repairing tissue functions by joining materials design and engineering with cell therapy. RM is considered new frontline of medical research; however, the idea of generating synthetic tissues is not so recent, since it goes back to 1938 [57]. Biomaterials can offer physical sustain for engineered tissues and can control and guide the cells. RM involves the replacement or restoration of human cells, tissue

Biomaterials engineering involves production, processing, characterization, and knowledge of innovative materials, including metallic ones. The most important limitations of RM is related to the generally health-care programs: the inclination to substitute conservative methodologies with new therapies is not so immediate. A large use of RM would be possible when a deep knowledge related to all connecting aspects (positive and negative outcomes) will be absolutely solved [60]. For the use on large scale RM, the ideas developed at laboratory level have to be inserted and totally transformed into widespread commercial products. In the past century, achievements in medicine have included different approaches and fundamentally, three different lines can be really able to follow the objective of RM: (i) cell-based therapy (meaning of introducing new and healthy cells in pathologic tissues), (ii) use of both biological

signs of local or systemic toxicity [45, 48, 49].

at least one order of magnitude inferior.

degradable alloys, many tasks are still unexplained.

or organs, to repair or create typical function [58, 59].

**1.3. Biomaterials in tissue engineering and regenerative medicine**

atmosphere [56].

A class of special Ti alloys, developed in Japan, with exclusive physical-mechanical properties and large range of possibilities in medical applications are Gum alloys, belonging to the *β*-type of Ti alloys, fundamentally expressed as Ti (Ta, Nb, and V) + (Zr, Hf, and O). These alloys have excellent mechanical behavior at room temperature: an ultra-low Young's modulus (60–70 GPa) and a non-linear elastic behavior, an extended elastic limit, ultra-high strength (>1 GPa), superplastic-like deformability, Invar-like thermal expansion, and Elinvar-like thermal dependence of the elastic modulus making available several prospects for their application [30]. Such alloy, with no hazardous elements, combines extremely low elastic modulus with extremely high strength and can be considered a perfect candidate for many medical implants.

The capacity to return to the initial memorized shape varying the temperature is the most important features of *shape memory alloys*. Such a particular characteristic can be exploited in critical medical application, when recovering the original shape after large deformations induced by mechanical load and for conserving the deformed shape up to the heat-induced recovery of the original shape has primary importance [31]. Generally, in orthopedic, dental, and cardiovascular uses NiTi alloy (Nitinol) is employed because its good corrosion resistance and pseudoelastic property (reversible elastic response to an applied stress). However, the study [32] reports that at temperatures equal to the human body the formation of a passive layer on NiTi is not as much protective than the passive layer on Ti6Al4V. Additionally, there are some limitations too in the widespread use of such alloy because even if some studies have revealed that NiTi alloy is biocompatible [31, 33, 34], the possible release of Ni ions represents a serious apprehension [13, 15] because Ni is highly allergenic element, and it can induce intense inflammatory reactions.

*Zr, Ta, and Nb* have been employed as constituent elements of Ti alloys for medical applications because of their good biocompatibility and high corrosion resistance. Zr belongs to the same group as Ti and exhibits similar properties [35]. Recently, Zr-Nb [36, 37] and Zr-Mo [38] have been developed. Ta and Nb are non-toxic elements, and they exhibit very similar physical and chemical properties. Ta exhibits excellent chemical stability and good biocompatibility similar to that of Ti:Ta has been employed in dental and orthopedic applications such as radiographic bone markers, vascular clips, and as a material for cranial defect repair and nerve repair since the 1940s [39, 40]. In particular, porous Ta has been developed for bone in-growth applications, i.e., hip and knee arthroplasty, spinal surgery, and bone graft substitutes [41, 42]. Introduction of Ta in TiNi shape memory alloy determines a low incidence of artefacts, according to [43, 44], the blood compatibility of Ta is higher than that of other metals.

Recently, among other research, *biodegradable metals and their alloys* have attracted high interest, because of their possibility of degradation in biological surroundings. The main benefit of this class of materials is related to the fact that after the tissue has appropriately restored and they are no longer useful, the removal of follow-up surgery is avoided allowing higher protection since physical irritation and chronic inflammatory local reactions are totally excluded [45–47].

Fe, Mg, and Zn are all vital nutritional elements for a healthy body and generally reveal excellent biocompatibility in the human body, with no any sign of local or systemic toxicity biodegradable materials than polymers for load-bearing applications. Both pure Fe and pure Mg have been reported to possess excellent biocompatibility in the human body and show no signs of local or systemic toxicity [45, 48, 49].

determining the growth of a hard oxide film on the surface with an interstitial solid solution

A class of special Ti alloys, developed in Japan, with exclusive physical-mechanical properties and large range of possibilities in medical applications are Gum alloys, belonging to the *β*-type of Ti alloys, fundamentally expressed as Ti (Ta, Nb, and V) + (Zr, Hf, and O). These alloys have excellent mechanical behavior at room temperature: an ultra-low Young's modulus (60–70 GPa) and a non-linear elastic behavior, an extended elastic limit, ultra-high strength (>1 GPa), superplastic-like deformability, Invar-like thermal expansion, and Elinvar-like thermal dependence of the elastic modulus making available several prospects for their application [30]. Such alloy, with no hazardous elements, combines extremely low elastic modulus with extremely high strength and can be considered a perfect candidate for many medical

The capacity to return to the initial memorized shape varying the temperature is the most important features of *shape memory alloys*. Such a particular characteristic can be exploited in critical medical application, when recovering the original shape after large deformations induced by mechanical load and for conserving the deformed shape up to the heat-induced recovery of the original shape has primary importance [31]. Generally, in orthopedic, dental, and cardiovascular uses NiTi alloy (Nitinol) is employed because its good corrosion resistance and pseudoelastic property (reversible elastic response to an applied stress). However, the study [32] reports that at temperatures equal to the human body the formation of a passive layer on NiTi is not as much protective than the passive layer on Ti6Al4V. Additionally, there are some limitations too in the widespread use of such alloy because even if some studies have revealed that NiTi alloy is biocompatible [31, 33, 34], the possible release of Ni ions represents a serious apprehension [13, 15] because Ni is highly allergenic element, and it can

*Zr, Ta, and Nb* have been employed as constituent elements of Ti alloys for medical applications because of their good biocompatibility and high corrosion resistance. Zr belongs to the same group as Ti and exhibits similar properties [35]. Recently, Zr-Nb [36, 37] and Zr-Mo [38] have been developed. Ta and Nb are non-toxic elements, and they exhibit very similar physical and chemical properties. Ta exhibits excellent chemical stability and good biocompatibility similar to that of Ti:Ta has been employed in dental and orthopedic applications such as radiographic bone markers, vascular clips, and as a material for cranial defect repair and nerve repair since the 1940s [39, 40]. In particular, porous Ta has been developed for bone in-growth applications, i.e., hip and knee arthroplasty, spinal surgery, and bone graft substitutes [41, 42]. Introduction of Ta in TiNi shape memory alloy determines a low incidence of artefacts, according to [43, 44], the blood compatibility of Ta is higher than that of

Recently, among other research, *biodegradable metals and their alloys* have attracted high interest, because of their possibility of degradation in biological surroundings. The main benefit of this class of materials is related to the fact that after the tissue has appropriately restored and they are no longer useful, the removal of follow-up surgery is avoided allowing higher protection since physical irritation and chronic inflammatory local reactions are totally excluded [45–47].

strengthening of the subsurface section atmosphere [29].

implants.

50 Biomaterials in Regenerative Medicine

other metals.

induce intense inflammatory reactions.

Mg and its alloys (i.e., (AZ91, WE43, AM50, and LAE442) can be considered as favorable alloys for medical applications, and they have already been positively verified *in vivo* and in clinical studies and it has been reported that development of new bone is facilitated [50–52], when they are implanted as bone fixtures. The elastic modulus of Mg (41–45 GPa) is closer to that of natural bone (3–20 GPa). However, the mechanical properties of such alloys, i.e., strength and the elongation to fracture are not always acceptable which combined to the development of significant quantities of hydrogen limits their widespread use. Some studies [53–55] have reported as alternative solution the use of Fe-based alloys. However, the implants realized using such alloys reveal some reactions like those developed in longterm uses which is predominantly due to the low-degradation rate of pure Fe in biological atmosphere [56].

In Refs. [53, 54] the authors have developed Fe35Mn alloy with a higher degradation rate compared to the pure Fe; however, compared to Mg-based alloys, the interested value is still at least one order of magnitude inferior.

Even with the significant evolution carried out over the time on the implants made of by biodegradable alloys, many tasks are still unexplained.

#### **1.3. Biomaterials in tissue engineering and regenerative medicine**

Current evolutions of biomaterials and the constantly increasing demand for new technologies have transformed the field of TE and RM too. In such areas, biomaterials have received more and more attention and can be placed in pole position for repairing tissue functions by joining materials design and engineering with cell therapy. RM is considered new frontline of medical research; however, the idea of generating synthetic tissues is not so recent, since it goes back to 1938 [57]. Biomaterials can offer physical sustain for engineered tissues and can control and guide the cells. RM involves the replacement or restoration of human cells, tissue or organs, to repair or create typical function [58, 59].

Biomaterials engineering involves production, processing, characterization, and knowledge of innovative materials, including metallic ones. The most important limitations of RM is related to the generally health-care programs: the inclination to substitute conservative methodologies with new therapies is not so immediate. A large use of RM would be possible when a deep knowledge related to all connecting aspects (positive and negative outcomes) will be absolutely solved [60]. For the use on large scale RM, the ideas developed at laboratory level have to be inserted and totally transformed into widespread commercial products. In the past century, achievements in medicine have included different approaches and fundamentally, three different lines can be really able to follow the objective of RM: (i) cell-based therapy (meaning of introducing new and healthy cells in pathologic tissues), (ii) use of both biological or synthetic materials (use of cells and extra cellular matrix providing structural and functional support), and (iii) implantation of scaffolds seeded with cells (mixture of the earlier mentioned two possibilities) [61].

Generally, metallic ions have a significant role for some day-to-day living biological processes, being essential for many biochemical reactions: i.e. K, Na, Ca, Mg. Ca2+ ions level governs the intra- and inter-cellular communications, blood coagulation and muscle contraction, Mg2+ ions support photosynthesis, the electron transfer routes are generally based on Fe proteins, transport of oxygen requires Fe and Cu containing proteins, Zn has the main role in regulation of DNA transcription are only some cases which highlight the importance of them [62–66].

In addition, metallic ions have interesting capacity and can be exploited as therapeutic agents in tissue engineering. There are a large number of metallic ions which are vital cofactors of enzymes (Co, Cu, Fe, Mn, Zn, Ag, Sr, V, and Ga), and their specific properties can be correlated to their use for therapeutic purpose. The geometry and valence of metal ions, their hydrolytic and redox activity, Lewis acidity, radiochemical properties directly involve fast kinetics, higher affinity to interact with other ions with high flexibility to be inserted in engineered biomaterials allowing the modification/revision of cellular functions and their metabolism. Actually, there is a continuous growth in medical field of the use of metal ions in RM and tissue engineering, with a special attention concerned to their therapeutic properties. However, the possible toxicity of metal ions in case of their eventually local release has to be carefully considered, when exploiting them [67–70].

Wirobond®280 (Co60.9, Cr25, Mo4.8, W6.2, Ga2.9) and Ti6Al4V have been considered as reference material. The microstructures of the alloys investigated are reported in **Figure 1**, where a relatively homogeneous structure has been observed. Major details are reported in Refs. [71–73]. Following some structural and microstructural characterization (**Figure 1** reports the general morphology of the investigated alloys) combined with some mechanical properties evaluation, which can be found in [71–73], some words are spent about the corrosion behavior, verified by static immersion test, of the metallic alloys prepared, because such line is directly associated to the biocompatibility behavior of the metal alloys. The test has been carried out according to the route specified in the Standard ISO 10271/2011 at 37°C (±1°C). According to the standard, immersion of the samples has been realized in acid solution (7.5 ml lactic acid, 5.85 g NaCl,

**Cr Mo Si Ti Other Co**

Up-to-Date Knowledge and Outlooks for the Use of Metallic Biomaterials: Review Paper

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53

CoCrMoTi4 26.5 6.0 1.0 4.0 1.5 bal. CoCrMoTi6 28.0 4.5 1.0 6.0 0.5 bal.

**Alloy Ti Nb Ta Zr O** TiNb 71.4 24 1 3 0.6

value has been corrected to arrive to the neutral situation. The samples have been monitored after the permanence in the acid solution for 28 days. As a reference solution, an acid solution maintained in the same condition without any metallic alloy inside has been used. The sample surfaces, following corrosion test, have been investigated by scanning electron microscopy

O) simulating the biological environment. The pH

300 ml H<sup>2</sup>

O di grade 2 purity, and 700 ml H<sup>2</sup>

**Alloys Chemical composition (wt%)**

**Table 4.** Chemical composition of the experimentally developed alloys.

**Table 5.** Chemical composition (at %) of the Ti-Nb alloy.

**Figure 1.** Optical micrographs of the investigated alloys.

## **2. Real case study**

Some fundamental aspects related to metallic biomaterials and their use in RM and TE are integrated with some experimental results obtained by the authors [71–75] during the years spent studying the development and characterization of metallic materials for medical purpose. In particular, some results, (1) prevalently related to the corrosion resistance, which can be directly associated with their biocompatibility of some (i) Ti-enriched Co-based traditional alloys to be submitted for dental application and (ii) TiNb alloys for load-bearing implant production will be reminded here; (2) the third line (iii) involves the possibility of using an implanted two-element antenna array placed on a metallic cylinder (metal made implant) embedded in a polymer dielectric that acts as the substrate between the ground plane and radiators with the purpose to use it for in-body communications.

#### **2.1. Some details and the corrosion resistance of the experimentally prepared biometals**

Cold crucible levitation melting technique with induction heating system has been used for the metallic alloys manufacturing, which guarantee high purity melts, important features for materials used for surgical implants. Enhancement with Ti has been performed in the case of the Co-based basic alloy. **Table 4** reports the chemical compositions of the alloys for dentistry, while **Table 5** reports the composition of the alloy used for load-bearing implant production.

**Table 4.** Chemical composition of the experimentally developed alloys.

**Table 5.** Chemical composition (at %) of the Ti-Nb alloy.

or synthetic materials (use of cells and extra cellular matrix providing structural and functional support), and (iii) implantation of scaffolds seeded with cells (mixture of the earlier

Generally, metallic ions have a significant role for some day-to-day living biological processes, being essential for many biochemical reactions: i.e. K, Na, Ca, Mg. Ca2+ ions level governs the intra- and inter-cellular communications, blood coagulation and muscle contraction, Mg2+ ions support photosynthesis, the electron transfer routes are generally based on Fe proteins, transport of oxygen requires Fe and Cu containing proteins, Zn has the main role in regulation of

In addition, metallic ions have interesting capacity and can be exploited as therapeutic agents in tissue engineering. There are a large number of metallic ions which are vital cofactors of enzymes (Co, Cu, Fe, Mn, Zn, Ag, Sr, V, and Ga), and their specific properties can be correlated to their use for therapeutic purpose. The geometry and valence of metal ions, their hydrolytic and redox activity, Lewis acidity, radiochemical properties directly involve fast kinetics, higher affinity to interact with other ions with high flexibility to be inserted in engineered biomaterials allowing the modification/revision of cellular functions and their metabolism. Actually, there is a continuous growth in medical field of the use of metal ions in RM and tissue engineering, with a special attention concerned to their therapeutic properties. However, the possible toxicity of metal ions in case of their eventually local release has to be