Front Cover

Materials and Devices for Bone Disorders

Copyright Page

Contents

List of Contributors

Biography

Preface

1 Introduction to Biomaterials and Devices for Bone Disorders

1.1 Introduction

1.2 Metallic Biomaterials

1.3 Ceramic Biomaterials

1.4 Polymeric Biomaterials

1.5 Composite Biomaterials

1.6 Additive Manufacturing (AM) of Biomaterials

1.7 Biomaterials in Orthopedic Implants Devices

1.7.1 Joint replacements

1.7.2 Implants used in osteosynthesis for stabilization and fracture repair

1.7.3 Spine implants

1.7.4 Nonconventional implants for bone tumor

1.7.5 Multifunctional devices

1.8 Summary and Future Directions

Acknowledgments

References

2 Bone Biology and Effects of Pharmaceutical Intervention on Bone Quality

2.1 Bone Biology

2.1.1 Bone functions

2.1.2 Composition

2.1.3 Architecture

2.1.4 Bone cells

2.1.4.1 Osteoclasts

2.1.4.2 Osteoblast lineage

2.1.4.2.1 The Wnt-signaling system

2.1.4.3 Preosteoblasts

2.1.4.4 Reversal cells

2.1.4.5 Mature osteoblasts

2.1.4.6 Lining cells

2.1.4.7 Osteocytes

2.1.5 Bone remodeling

2.1.5.1 The basic multicellular unit

2.1.5.2 Sequence of bone remodeling

2.1.5.2.1 Origination

2.1.5.2.2 Activation

2.1.5.2.3 Resorption

2.1.5.2.4 Reversal

2.1.5.2.5 Formation

2.1.5.2.6 Mineralization

2.1.5.2.7 Reestablishing osteocyte network

2.1.5.2.8 Quiescence

2.1.6 Fracture repair

2.1.6.1 Stress fractures

2.1.6.2 Complete fractures

2.1.7 Aspects of bone strength

2.1.7.1 Bone shape

2.1.7.2 Bone volume

2.1.7.3 Mineralization density

2.1.7.4 Microarchitecture

2.1.7.5 Collagen structure

2.1.7.6 Ability to repair damage

2.1.7.7 Crystal characteristics

2.1.7.8 Bone marrow

2.1.7.9 Overall bone strength

2.2 Pharmaceutical Intervention

2.2.1 Bone loss with aging or disease

2.2.2 Actions of systemic hormones and local cytokines

2.2.2.1 Estrogen

2.2.2.2 Glucocorticosteroids

2.2.2.3 Thyroid

2.2.2.4 Parathyroid

2.2.2.5 Calcitonin

2.2.2.6 1,25 (OH)2-Cholecalciferol (1,25D)

2.2.2.7 Insulin and insulin-like growth factor

2.2.2.8 Serotonin

2.2.2.9 Local cytokines

2.2.3 Calcium supplementation

2.2.4 Bone formation with osteoporosis medications

2.2.5 Raloxifene

2.2.6 Bisphosphonates

2.2.6.1 Short-term effects

2.2.6.2 Long-term effects

2.2.6.3 Fracture healing

2.2.7 Denosumab

2.2.8 Teriparatide

2.2.9 Strontium

2.2.10 Emerging therapies

2.2.10.1 Cathepsin K inhibitors

2.2.10.2 Romosozumab

2.2.11 Other medications or substances that affect bone strength

2.2.11.1 Anticonvulsants

2.2.11.2 Selective serotonin reuptake inhibitors

2.2.11.3 Carbonic anhydrase inhibitors

2.2.11.4 Thiazide diuretics

2.2.11.5 Rosiglitazone

2.2.11.6 Bortezomib

2.2.11.7 Lithium

2.2.11.8 Elements toxic to the bone

2.2.11.9 Fluoride

2.3 Summary

References

3 Bone Disorders

3.1 Introduction

3.2 Metabolic Diseases

3.2.1 Osteoporosis

3.2.2 Paget’s disease

3.3 Degenerative Disc Disease

3.4 Osteoarthritis

3.5 Fracture

3.6 Bone Cancers

3.6.1 Osteosarcoma

3.6.2 Ewing’s sarcoma

3.6.3 Chondrosarcoma

3.7 Summary and Future Directions

References

4 Implants for Joint Replacement of the Hip and Knee

4.1 Historical Perspective

4.2 Design and Material Issues, Clinical Outcome

4.2.1 Current bearing materials in hip and knee replacement

4.2.1.1 New polyethylenes

4.2.1.2 Ceramic-on-ceramic bearings

4.2.1.3 Metal-on-metal bearings

4.2.2 Cemented hip arthroplasty

4.2.2.1 Acrylic bone cement: Polymethylmethacrylate

4.2.2.2 Firmness and durability of implant–cement composite

4.2.2.3 Material and design of cemented implants

4.2.2.4 Cementing technique during THA

4.2.2.5 Clinical evidence for cemented THA

4.2.2.6 Clinical evidence for partially cemented THA (cementless cup-cemented stem)

4.2.2.7 Current indications for cemented or partially cemented THA

4.2.2.8 Conclusion

4.2.3 Cementless hip arthroplasty

4.2.4 Cemented total knee replacement

4.3 Current Critical Issues

4.3.1 Introduction of new technologies to orthopedics

4.3.2 Younger more active patient population

4.3.2.1 Indications

4.3.2.2 Surgical technique

4.3.2.3 Design and material options

4.3.3 Prosthetic joint infection

4.3.3.1 Prevention of PJI

4.3.3.2 Diagnostics

4.3.3.3 Treatment

4.3.4 Wear and osteolysis

4.3.4.1 Wear of prosthetic surfaces

4.3.4.2 Periprosthetic osteolysis

4.3.4.3 Strategies aimed at diminishing the risk for osteolysis and aseptic loosening

4.3.5 Hip: Other concerns (dislocation, big heads, alternative bearing surfaces, head–neck taper interface)

4.3.5.1 Dislocation

4.3.5.2 Prevention

4.3.5.3 Treatment of dislocated THA

4.3.5.4 Modular component exchange

4.3.5.5 Reorientation of THA

4.3.5.6 Improvement of abductor moment

4.3.5.7 Dual-mobility cups

4.3.5.8 Constrained liners

4.3.5.9 Large femoral heads

4.3.5.10 Concerns related to large femoral heads

4.3.5.11 Alternative bearing surfaces

4.3.5.12 Ceramic-on-ceramic

4.3.5.13 Metal-on-metal

4.3.5.14 Ceramic-on-metal

4.3.5.15 New materials

4.3.5.16 Carbon-fiber-reinforced polyaryletheretherketone

4.3.5.17 Head–Neck taper interface damage

4.3.5.18 What is clear?

4.3.6 Other issues with TKA (malalignment, stiffness, allergy, patient satisfaction)

4.3.7 Patients with severe bone-related comorbidities (elderly patients with osteoporosis, patients with rheumatic diseases...

4.3.7.1 Osteoporosis

4.3.7.1.1 Indication for THA/TKA

4.3.7.1.2 Design and material options

4.3.7.2 Systemic inflammatory diseases

4.3.7.2.1 Design and material options

4.3.7.2.2 Evidence for THA/TKA

4.3.7.3 Osteonecrosis of the hip

4.3.7.3.1 Indication for THA

4.3.7.3.2 Design and material option

4.3.7.3.3 Evidence for THA

4.3.7.4 Renal osteopathy

4.3.7.4.1 Design and material option

4.3.7.4.2 Evidence for THA/TKA

4.3.7.5 Paget disease

4.3.7.5.1 Design and material option

4.3.7.5.2 Evidence for THA/TKA

4.4 Future Trends and Next-Generation Devices

4.4.1 Improved patient selection

4.4.2 Improved surgical technique and instrumentation

4.4.3 Improved implant design

4.4.4 Improved bearing surfaces

4.4.5 Improving implant integration and avoiding infection

4.5 Conclusion

References

5 Material and Mechanobiological Considerations for Bone Regeneration

5.1 Introduction

5.2 Physiology of Bone Regeneration

5.2.1 Inflammation and hematoma

5.2.2 Soft callus and neovascularization

5.2.3 Immature bone

5.2.4 Bone remodeling

5.3 Mechanical Properties of Materials for Bone Regeneration

5.3.1 Native bone and grafts

5.3.2 Metals

5.3.3 Ceramics

5.3.4 Polymers

5.3.5 Composites

5.3.6 FDA regulatory pathways and testing considerations

5.4 Cell-Level Mechanobiology of Bone Regeneration

5.4.1 Cell-level mechanosensors

5.4.2 Intrinsic physical factors

5.4.3 Extrinsic physical factors

5.5 Tissue-Level Mechanobiology of Bone Regeneration

5.5.1 In vivo mechanobiology of bone regeneration

5.5.2 Computational modeling of bone regeneration

5.6 Conclusions and Future Directions

References

6 Ceramics in Bone Grafts and Coated Implants

6.1 Introduction

6.2 Bioinert Ceramics

6.2.1 Aluminum oxide

6.2.2 Zirconia

6.3 Calcium Phosphates

6.3.1 Bioceramics and bone remodeling

6.3.2 Role of trace elements on bioactivity of bioceramics

6.4 Ceramic Scaffolds

6.4.1 Ceramic scaffold fabrication techniques

6.4.2 In vitro and in vivo properties of bone scaffolds

6.4.3 In vivo and in vitro performance of CaP–polymer composite scaffold

6.5 Ceramics in Drug Delivery

6.6 Bioceramic Coatings

6.6.1 Challenges of HA coatings

6.6.2 Significance of HA coating in revision surgeries

6.6.3 Coating properties and characterization standards

6.6.3.1 Crystallographic Information

6.6.3.2 Environmental stability

6.6.3.3 Tensile bond strength

6.6.4 Coating preparation techniques

6.6.4.1 Plasma-sprayed HA coating

6.6.4.2 Laser-assisted coating

6.6.4.3 Electrophoretic deposition

6.6.4.4 Sol-gel deposition

6.6.4.5 Biomimetic deposition

6.6.4.6 Compositionally graded coating

6.7 Bone Cement

6.8 Bioglass for Bone Regeneration

6.9 Summary and Future Directions

References

7 Ceramic Coatings in Load-Bearing Articulating Joint Implants

7.1 Introduction

7.2 Knee Simulator Study Involving NSD-Coated Titanium Articulating Against Polyethylene

7.3 Knee Simulator Study Involving Articulation of NSD on NSD

7.4 Role of Ceramic-Boriding on CoCr for Subsequent CVD Diamond Deposition

7.5 Biocompatibility and Osteo-Integration of Nanodiamond Coated Implant

7.6 Nanodiamond (ND) Wear-Debris and Influence of Size and Concentration of Wear-Debris on Inflammation

7.7 Summary and Future Perspectives

Acknowledgments

References

8 Polymers and Composites for Orthopedic Applications

8.1 Introduction

8.2 Nondegradable Polymers and Composites for Orthopedic Applications

8.2.1 Poly(methyl methacrylate)

8.2.2 Polyaryletherketones

8.2.3 Ultrahigh-molecular-weight polyethylene

8.2.4 Polypropylene

8.2.5 Polysulfone

8.2.6 Polydimethylsiloxane

8.3 Biodegradable Polymers and Composites for Orthopedic Applications

8.3.1 Synthetic polymers

8.3.1.1 Poly(α-esters)

8.3.1.2 Polyfumarates

8.3.1.3 Polyurethanes

8.3.1.4 Polyanhydrides

8.3.1.5 Poly(amino acids) and pseudo poly(amino acids)

8.3.1.6 Polyphosphazenes

8.3.2 Natural polymers

8.3.2.1 Protein-based polymers

8.3.2.2 Polysaccharide-based polymers

8.3.2.3 Natural polyesters (polyhydroxyalkanoates)

8.4 Major Applications of Polymers and Their Composites for Orthopedic Applications

8.4.1 Bone-related applications

8.4.1.1 Bone cements

8.4.1.2 Bone replacements

8.4.1.3 Bone repair and regeneration

8.4.1.4 Plates, pins, nails, and screws

8.4.2 Spinal applications

8.4.2.1 Intervertebral disc replacement and regeneration

8.4.2.2 Spacer in intervertebral artificial disc replacement

8.5 Conclusions

References

9 Surface Modifications and Surface Characterization of Biomaterials Used in Bone Healing

9.1 Introduction

9.1.1 Objective of this chapter

9.2 Current Biomaterials for Bone Healing

9.2.1 Load-bearing

9.2.2 Metal implants

9.2.3 Bioactive ceramics

9.2.4 Bioactive glasses

9.2.5 Bone substitute used in oral and maxillofacial bone disorders

9.3 Use of Precision Manufacturing to Improve Biomaterials Fabrication and Biological Response

9.3.1 Nano-phase methods of biomaterials fabrication

9.3.2 Surface adhesion molecules on cell membranes

9.3.3 Examples of surface modification

9.3.4 Photolithography processing

9.3.5 Deep reactive ion etching

9.3.6 Surface modification by overlays or coatings

9.3.6.1 Plasma-enhanced chemical vapor deposition coating

9.3.7 Surface modification of solid-state micropores for selective cell surface binding

9.3.8 Surface biomolecular functionalization

9.3.9 Surface functionalization example: preparation of anti-EGFR aptamers

9.3.10 Immobilization of aptamers on SiO2 substrate

9.3.11 Protein binding and electrical detection

9.4 Surface Characterization of Biomineral and Biomaterial Surfaces

9.4.1 Microcomputed tomography measurements

9.4.2 Raman spectroscopy analysis

9.4.3 Electron microscopy

9.4.4 X-ray diffraction

9.4.5 Surface compositional analysis

9.4.6 Optical property characterization

9.4.7 Fourier transform infrared (FTIR) spectroscopy analysis

9.4.7.1 Biological surface characterization

9.4.7.1.1 In vitro bioactivity testing of SiONx and SiONPx coatings

9.4.8 SBF dissolution test

9.4.9 Inductively coupled plasma-optical emission spectra (ICP-OES) analyses

9.4.10 Thermodynamics of surfaces: surface energy and surface tension

9.4.10.1 Goniometric analysis

9.4.11 Cell proliferation analysis

9.4.12 Cell differentiation analysis

9.4.13 X-ray absorption near-edge structure analyses

9.4.14 Histological staining for collagen elongation

9.5 Current Challenges and Future Trends

9.5.1 Nanogap break junctions for molecular detection of cancer

9.5.2 Biomechanical discrimination of cancer cells using solid-state micropores

9.6 Summary

References

10 Predictive Methodologies for Design of Bone Tissue Engineering Scaffolds

10.1 Introduction

10.1.1 Bio and synthetic polymers and nanoscale additives

10.1.2 Polymer scaffold manufacturing methods in laboratory and manufacturing technologies

10.1.2.1 Particulate leaching

10.1.2.2 Freeze-drying

10.1.2.3 Electrospinning

10.1.2.4 Textiles techniques

10.1.2.5 Solid free-form (SFF) fabrication

10.1.2.6 Three-dimensional printing

10.1.2.7 Fused deposition modeling

10.2 In vitro Mechanical Properties: Methods and Challenges

10.2.1 Ab initio

10.2.2 Molecular modeling

10.2.3 FE methods

10.2.4 Degradation of polymers and nanocomposites

10.3 Molecular Modeling for Design of Scaffolds

10.3.1 Successful material design in polymer clay nanocomposite

10.3.2 MD for tissue engineering scaffolds

10.4 Use of FE Methods for Predictive Capabilities of Scaffold Properties

10.5 Degradation of Scaffolds in Cell Culture Media and Modeling Degradation

10.6 Development of Multiscale Modeling Strategies for Scaffold Mechanics

10.7 Summary

10.8 Perspectives and Future Directions on the in silico Approach to Scaffold Design

References

11 Ethical Issues in Biomaterials Research

11.1 Introduction

11.2 Ethical Issues With Emerging Technologies

11.2.1 Nanobiotechnology and ethics

11.2.2 Stem cell research and ethics

11.2.3 Tissue engineering

11.3 Cost versus Benefit Analysis

11.4 Resource Allocation for Biomedical Research

11.5 Ethical Issues With Authorship

11.6 Discussion

11.7 Current Challenges and Future Directions

11.8 Guidelines for Ethical Practice in Biomaterials Research

References

12 Research on Bone Disorders—From Ideas to Clinical Use Product—The Path to Commercialization

12.1 Introduction

12.2 What is the Path to Commercialization?

12.3 The Research Topic—The Big Idea. Is it really that Big?

12.4 The Big Idea—Short-term and Near-term Research

12.5 Long-term Research

12.6 The Patent—A Step to Monetization of Research and the Big Idea

12.7 Claims—Are They Broad Enough to Keep the Competition out of This Space?

12.8 Freedom to Practice/Operate—Can Some Other Patent Stop This Technology?

12.9 What Are the Regulations Around This Big Idea Product?

12.10 What Is the Cost of Making This Product?

12.11 Conclusion

13 Current Challenges and Future Needs in Biomaterials and Devices for Bone Disorders

13.1 Introduction

13.2 Current Challenges and Future Needs

13.3 Summary

Acknowledgments

Index

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