Biomedical Applications of Polymeric Materials and Composites E-Book
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- Herausgeber: Wiley-VCH Verlag GmbH & Co. KGaA
- Kategorie: Fachliteratur
- Sprache: Englisch
With its content taken from only the very latest results, this is an extensive summary of the various polymeric materials used for biomedical applications.
Following an introduction listing various functional polymers, including conductive, biocompatible and conjugated polymers, the book goes on to discuss different synthetic polymers that can be used, for example, as hydrogels, biochemical sensors, functional surfaces, and natural degradable materials. Throughout, the focus is on applications, with worked examples for training purposes as well as case studies included. The whole is rounded off with a look at future trends.
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Veröffentlichungsjahr: 2016
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Table of Contents
Cover
Title Page
Related Titles
Copyright
List of Contributors
Preface
Chapter 1: Biomaterials for Biomedical Applications
1.1 Introduction
1.2 Polymers as Hydrogels in Cell Encapsulation and Soft Tissue Replacement
1.3 Biomaterials for Drug Delivery Systems
1.4 Biomaterials for Heart Valves and Arteries
1.5 Biomaterials for Bone Repair
1.6 Conclusion
Abbreviations
References
Chapter 2: Conducting Polymers: An Introduction
2.1 Introduction
2.2 Types of Conducting Polymers
2.3 Synthesis of Conducting Polymers
2.4 Surface Functionalization of Conducting Polymers
Abbreviations
References
Chapter 3: Conducting Polymers: Biomedical Applications
3.1 Applications
3.2 Conclusions
Abbreviations
References
Chapter 4: Plasma-Assisted Fabrication and Processing of Biomaterials
4.1 Introduction
4.2 Conclusion
References
Chapter 5: Smart Electroactive Polymers and Composite Materials
5.1 Introduction
5.2 Types of Electroactive Polymers
5.3 Polymer Gels
5.4 Conducting Polymers
5.5 Ionic Polymer–Metal Composites (IPMC)
5.6 Conjugated Polymer
5.7 Piezoelectric and Electrostrictive Polymers
5.8 Dielectric Elastomers
5.9 Summary
References
Chapter 6: Synthetic Polymer Hydrogels
6.1 Introduction
6.2 Polymer Hydrogels
6.3 Synthetic Polymer Hydrogels
6.4 Applications of Synthetic Polymer Hydrogels
6.5 Conclusion
Abbreviations
References
Chapter 7: Hydrophilic Polymers
7.1 Introduction
7.2 Classification
7.3 Applications of Hydrophilic Polymers
7.4 Conclusions
Abbreviations
References
Chapter 8: Properties of Stimuli-Responsive Polymers
8.1 Introduction
8.2 Physically Dependent Stimuli
8.3 Chemically Dependent Stimuli
8.4 Biologically Dependent Stimuli
8.5 Dual Stimuli
8.6 Multistimuli-Responsive Materials
8.7 Conclusion
Abbreviations
References
Chapter 9: Stimuli-Responsive Polymers: Biomedical Applications
9.1 Introduction
9.2 Imaging
9.3 Sensing
9.4 Delivery of Therapeutic Molecules
9.5 Other Applications
9.6 Conclusion
Abbreviations
References
Chapter 10: Functionally Engineered Sol–Gel Derived Inorganic Gels and Hybrid Nanoarchitectures for Biomedical Applications
10.1 Introduction
10.2 Some of the Useful Definitions of Various Gel Forms
10.3 Inorganic Metal-Oxide Gels and Hybrid Nanoarchitectures
10.4 Sol–Gel Synthesis of Inorganic Metal-Oxide Gels
10.5 Physically Cross-Linked Inorganic and Hybrid Gel
10.6 Sol–Gel Derived Hybrid Metal-Oxides Nanostructures
10.7 Biomedical Applications of Sol–Gel Derived Inorganic and Hybrid Nanoarchitectures for Both Therapeutic and Diagnostic (Theranostics) Functions
10.8 Sol–Gel Matrices for Controlled Drug Delivery
10.9 Stimuli-Responsive Drug Delivery Systems
10.10 Sol–Gel Matrix Targeted Cancer Therapy
10.11 Sol–Gel Matrices for Imaging and Radiotherapy (Radiolabeling)
10.12 Concluding Remarks and Future Perspectives
Acknowledgment
Abbreviations
References
Chapter 11: Relevance of Natural Degradable Polymers in the Biomedical Field
11.1 Introduction
11.2 Natural Biopolymers and Its Application
11.3 Conclusion
Abbreviations
References
Chapter 12: Synthetic Biodegradable Polymers for Medical and Clinical Applications
12.1 Introduction
12.2 Polyesters/Poly(α-hydroxy acids)
12.3 Poly(glycolide)
12.4 Polylactide
12.5 Poly(lactic-co-glycolic) Acid
12.6 Poly(-caprolactone)
12.7 Polyurethanes
12.8 Polyanhydrides
12.9 Polyphosphazenes
12.10 Polyhydroxyalkanoates
12.11 Polyorthoesters
12.12 Poly(propylene fumarate)
12.13 Polyacetals
12.14 Polycarbonates
12.15 Polyphosphoesters
12.16 Synthesis and Application of Different Modified Synthetic Biopolymer
12.17 Conclusion
Abbreviations
References
Index
End User License Agreement
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Guide
Cover
Table of Contents
Preface
Begin Reading
List of Illustrations
Chapter 1: Biomaterials for Biomedical Applications
Figure 1.1 Polymer hydrogels used for tissue replacement.
Figure 1.2 Biomaterials utilized for various drug delivery systems.
Figure 1.3 Polymers for artificial vascular grafts.
Figure 1.4 Polymer based matrix for bone repair.
Chapter 2: Conducting Polymers: An Introduction
Figure 2.1 A schematic of the electrochemical synthesis setup [72].
Chapter 3: Conducting Polymers: Biomedical Applications
Figure 3.1 Everything is connected in the world of conductive polymers [28].
Figure 3.2 Schematic representation of functioning of polypyrrole microcontainer electrochemical system.
Figure 3.3 Biosensors classification.
Figure 3.4 TEM and log impedance (
Z
) versus time plot of the PANI-CSA-Ni nanowire (red line) after exposure to cigarette smoke and log impedance response with time of PANI-CSA (black line) in the presence of cigarette smoke.
Figure 3.5 PANI-NF sensors.
Figure 3.6 Scheme of self-assembled monolayers of ATQD-RGD.
Figure 3.7 Conductive wrinkle topographies on PDMS. (a) Schematic diagram of wPPy formation. (b) Images of PPy wrinkle-coated PDMS for cell culture applications: a photograph of the wPPy-on-PDMS (top), its optical microscopic image (middle), and a fluorescent image of NIH3T3 cells grown on the wPPy substrate (bottom).
Figure 3.8 (a) The preparation of NGF-doped porous polypyrrole surfaces and (b) cellular interaction with a porous surface in the presence of electrical stimulation.
Chapter 4: Plasma-Assisted Fabrication and Processing of Biomaterials
Figure 4.1 (a, b) Optical images of myoblast cells cultured on the single-cell patterning substrates. (c) AFM image of a single cell adopting the triangular shape of the pattern feature.
Figure 4.2 Optical images of live neurons cultured on the hexagonal grid pattern, after incubation times of (a, b) 4 days, (c) 7 days, and (d) 21 days.
Figure 4.3 VSMC adhered (first day) and grown (fifth day) on pristine and plasma treated PE (a), and 3T3 adhered (first day) and grown (third day) on pristine and plasma treated PE (b).
Figure 4.4 Surface dependent focal adhesion formation (denoted by arrows). Cells were seeded on (a) PLLA, (b) PLLA-gAA-chitosan, and (c) PLLA-gAA-gelatin at a seeding density of 10
4
cell cm
−2
and cultured for 12 h. Scale = 20 µm.
Figure 4.5 Cell morphology observed on (a) PLLA, (b) PLLA-gAA-gelatin, and (c) PLLA-gAA-chitosan by SEM at day 7. Complete endothelialization was observed on both modified PLLA substrates, but not on PLLA substrate. Scale = 100 µm.
Figure 4.6 (A) Optical microscopic images of DI water droplets showing the difference of oxygen and nitrogen plasma treatment on maintaining the hydrophilic nature of Si-DLC surface. The oxygen treated surfaces exhibit prolonged wettability by showing consistent wetting angle measured for a period of 20 days, whereas nitrogen treated surface lost its hydrophilic nature. (Orlanda 2010 [143]. American Chemical Society.) (B) Variation of sp
3
/sp
2
ratio with respect to silicon doping concentration in DLC film. (Ahmed 2013 [144]. Reproduced with permission of Elsevier.) (C) SEM images showing platelet adhesion on substrates coated with TIN, A-Si and F-DLC coatings. The adhered platelets are significantly reduced in F-DLC films (g and h) compared to others.
Figure 4.7 (A) The SEM images showing the antibacterial activity of DLC film against bacterium
E. coli
and
P. aeruginosa
. The bacterium tends to lose its shape with cytoplasmic projections indicating the rupturing of cell wall when bacteria come in contact with DLC films. (Marciano 2011 [153]. Reproduced with permission of Elsevier.) (B) The TEM images describing the antibacterial activity of Cu embedded nanostructured DLC film against bacterium
S. aureus
and
E. coli
. The cytoplasm leakage is clearly visible (arrow marked region) due to destruction of cell walls by Cu diffusion. The inset picture represents the adhered bacterium
S. aureus
(round morphology) and
E. coli
(tubular morphology) on glass substrate for the same incubation time.
Figure 4.8 (A) The SEM micrographs showing the stability of DLC films over TIN coatings for 10
4
cycles of impact fatigue test. The DLC film does not show cohesive or adhesive failure during the course of the experiment. (Wang 2010 [164]. Reproduced with permission of Elsevier.) (B) Wear volume produced by metal-on-metal and DLC-on-DLC pairs with respect to number of test runtime. The smooth DLC pairs exhibit significantly reduced wear volume compared to MoM pairs.
Chapter 5: Smart Electroactive Polymers and Composite Materials
Figure 5.1 Conventional self-oscillating gel.
Figure 5.2 Poly(hydroxyethyl methacrylate).
Figure 5.3 Structures of common conducting polymers.
Figure 5.4 Mechanism of ionic polymer–metal composites.
Figure 5.5 Schematic of direct piezoelectric effect; (a) piezoelectric material, (b) energy generation under tension, (c) energy generation under compression.
Figure 5.6 Principle of dielectric elastomer actuators.
Chapter 6: Synthetic Polymer Hydrogels
Figure 6.1 Classification of hydrogels.
Figure 6.2 Structure of PNIPAM.
Figure 6.3 PNIPAM solution (a) below and (b) above sol–gel transition temperature [23].
Figure 6.4 Structure of poly acrylic acid.
Figure 6.5 Structure of poly(HEMA).
Figure 6.6 Structure of PEG.
Figure 6.7 Structure of (a) poly(ethylene glycol methacrylate) (PEGMA) and (b) poly(ethylene glycol dimethacrylate) (PEGDMA).
Figure 6.8 Structure of PEGMA.
Figure 6.9 Chemical structure of (a) poly(glycolic acid), (b) poly(lactic acid).
Figure 6.10 Structure of Polyvinyl pyrrolidone.
Chapter 7: Hydrophilic Polymers
Figure 7.1 Classification of hydrophilic polymers based on source.
Figure 7.2 Structure of Agarose.
Figure 7.3 Structure of inulin.
Figure 7.4 Structure of chitosan.
Figure 7.5 Schematic illustration of chitosan's versatility. At low pH (less than about 6), chitosan's amine groups are protonated conferring polycationic behavior to chitosan. At higher pH (above about 6.5), chitosan's amines are deprotonated and reactive.
Figure 7.6 Structure of cellulose.
Figure 7.7 Structure of HPMC.
Figure 7.8 Structure of HEC.
Figure 7.9 Structure of Na-CMC [62].
Figure 7.10 Structure of HPCTS.
Figure 7.11
N
-Carboxybutyl chitosan and 5-methylpyrrolidinone chitosan.
Figure 7.12 Structure of PAAM.
Figure 7.13 Structure of PAA.
Figure 7.14 Structure of PEO.
Figure 7.15 Generic structure of poly[(organo)phosphazenes].
Figure 7.16 Structure of PHPMA.
Figure 7.17 Structure of DIVEMA and sodium salt of DIVEMA.
Figure 7.18 Chemical structures of three types of POZ [117].
Figure 7.19 Structure of PVP.
Figure 7.20 Structure of PNIPAM.
Figure 7.21 Structure of PVA.
Chapter 8: Properties of Stimuli-Responsive Polymers
Figure 8.1 Classification of stimuli-responsive polymers.
Figure 8.2 Thermoresponsive gelation mechanisms of PNIPAM-HA and PNIPAM-gelatin [7].
Figure 8.3 Formation of nanocages from polymers of PEG (blue), PPG (red), and methacrylate groups (green).
Figure 8.4 Molecular structures of oligo(ethylene glycol) methacrylates frequently used for synthesizing thermoresponsive biocompatible polymers [85].
Figure 8.5
l
-Asparagines and aspartic acid [89].
Figure 8.6 (a, b) AFM topographical images and (c, d) schematics of PDMS–PEO brushes ((a, c) 33% PDMS, (b, d) 56% PDMS) in air
z
scale – 10 nm.
Figure 8.7 (a, b) AFM topographical images and (c, d) schematics of PDMS–PEO brushes ((a, c) PDMS 33%, (b, d) PDMS 56%) in water
z
scale – 25 nm.
Figure 8.8 Schematic illustration for fabricating a stretchable dry adhesive with micropillars.
Figure 8.9 PDMAEMA polymer end functionalized with azobenzene, which can be stimulated by light, temperature, and change of the pH value [187].
Figure 8.10 Stimuli-responsive polymer system with causal interaction [190].
Chapter 9: Stimuli-Responsive Polymers: Biomedical Applications
Figure 9.1 Classification of biomedical application of smart polymer.
Figure 9.2 Demonstrations of the pNIPAM actuators stimulated by human skin temperature and sunlight. (a) Wearable sheet actuated by skin temperature wraps around a finger. (b) Schematic of the smart curtain design. Photos of (c) before sunlight exposure (closed), (d) after exposure for 15 min (open), and (e) after terminating sunlight exposure (closed).
Figure 9.3 Fluorescence reflectance imaging of a nude mouse (a, b, c) before and (d, e, f) 3 h after the injection of GadoSiPEG2C (K, kidneys; B, bladder). Fluorescence reflectance imaging of some organs after dissection (g) of a control mouse (no particles injection) and (h) of the nude mouse visualized on pictures (a–f). (i) Fluorescence reflectance imaging of a nude mouse after the injection of GadoSi2C (particles without PEG). Each image is acquired with an exposure time of 200 ms.
Figure 9.4 Fluorescence images of solutions containing
7
at (a) pH 7.6 and (b) pH 6.8 when the solutions are irradiated at 330 nm.
Figure 9.5 Dispersion–flocculation behavior of magnetite-PNIPAM nanoparticles, as a function of temperature and magnetic field (concentration = 20 mg ml
−1
).
Figure 9.6 (a) Light-controlled formation of DNA duplex based on azobenzene isomerization in the hydrogel. (b) Reversible volume transition of the DNA-cross-linked hydrogel regulated by UV and visible light.
Figure 9.7 Cumulative drug releases from micelles at different temperatures.
Figure 9.8 Biological testing of membranes: (b–g) tissue response to implanted nanogelloaded membrane (25% nanogel, 27% ferrofluid) after 4 and 45 days of implantation: (b) top view, 4 days postimplantation; (c) histological section of membrane–tissue interface, 400× magnification; (d) histological section of capsule inflammatory response, 100× magnification; (e) top view, 45 days postimplantation; (f) histological section of membrane–tissue interface, 40× magnification; (g) histological section of capsule inflammatory response, 400× magnification.
Figure 9.9 Targeting mechanism of gene delivery in nanoparticle systems.
Figure 9.10 Various drug delivery systems for drug and gene delivery.
Figure 9.11 Cells (in red, with blue nuclei) interact with the tissue-engineered scaffold through chemical (green ovals) and mechanical stimuli and with each other (yellow circles). These interactions define the cell microenvironment and guide cellular function and differentiation.
Figure 9.12 L929 cell culture on NIPAM–MMA copolymer. (a) Phase-contrast micrograph after 72 h and (b) neutral red-stained cells indicating their viability on copolymer.
Chapter 10: Functionally Engineered Sol–Gel Derived Inorganic Gels and Hybrid Nanoarchitectures for Biomedical Applications
Figure 10.1 Classification of various types of gels.
Figure 10.2 Classification of gels based on nature of solvent.
Figure 10.3 Classification of gels based on physical interactions.
Figure 10.4 Classification of gels based on drying techniques.
Figure 10.5 (a) Flow curve representing various types of rheological behavior. (b) Viscosity curve of a pseudoplastic and dilatant gel. (c) Viscosity–time curve of thixotropic gels.
Figure 10.6 The two main types inorganic gels derived from sol–gel technique are colloidal and polymeric gel.
Figure 10.7 Basic synthesis scheme for the metal-oxide aerogels.
Figure 10.8 Various materials obtained by sol–gel technology and its processing route.
Figure 10.9 An overview of various external stimuli-triggered formation of soft gel for designing functional soft biomaterial.
Figure 10.10 (a) Photograph of thixotropically reversible alumino-siloxane gel. (b) Step-strain time dependent rheological analysis of the alumino-siloxane gel. (c) Schematic representation of possible structural changes in aquagel subjected to shear flow.
Figure 10.11 General synthetic pathway for (A) mesoporous silica (B) mesoporous inorganic–organic hybrid silica.
Figure 10.12 Different methods adopted for drug loading in aerogel matrix. (a) Addition of drug before gelation in sol–gel synthesis. (b) Addition of drug during aging process in sol–gel process. (c) Addition of drugs in pure (dried) aerogels obtained after sol–gel synthesis.
Figure 10.13 (a) Step-strain time-dependent rheological analysis demonstrating the mechano-responsive (thixotropic) behavior of alumino-siloxane gels. (b)
In vitro
release profile of fluconazole from various alumino-siloxane gels formulations and marketed Flucos gel, with 0.5% (w/w) fluconazole loading, at physiological pH 7.4 and temperature 37 ± 1 °C.
Figure 10.14 (a) Ordered mesoporous materials new perspective for controlled drug delivery systems and (b) bone regeneration for tissue engineering.
Figure 10.15 Various external and internal stimuli suitable for a smart drug delivery system from sol–gel mesoporous silica.
Figure 10.16 Schematic of the stimuli-responsive delivery system (magnet-MSN) based on mesoporous silica nanorods capped with superparamagnetic iron oxide nanoparticles. The controlled release mechanism of the system is based on reduction of the disulfide linkage between the Fe
3
O
4
nanoparticle caps and the linker-MSN hosts by reducing agents such as DHLA.
Figure 10.17 Schematic representation of the CdS nanoparticle-capped mesoporous silica-based drug/neurotransmitter delivery system. The controlled release mechanism of the system is based on chemical reduction of the disulfide linkage between the CdS caps and the mesoporous silica-hosts.
Figure 10.18 Schematic representations of administrative route followed by mesoporous nanostructured material developed for cancer targeted therapy.
Figure 10.19 Schematic illustration of a multi-responsive nanogated ensemble based on supramolecular polymeric network-capped mesoporous silica.
Figure 10.20 Schemes of the immobilizations of (i) APTES and (ii) FA-NHS molecules on the luminescent Eu:NPS surfaces and (iii) targeting and (iv) imaging of the proliferated HeLa cells by visible-light excitation and luminescence.
Figure 10.21 (A) A schematic illustration of the synthesis of 64Cu-NOTA-mSiO
2
-PEG-TRC105. Uniform mSiO
2
nanoparticles (1) were first modified with –SH groups to form mSiO
2
-SH (2). mSiO
2
-SH was PEGylated with Mal-PEG5k-NH
2
to form mSiO
2
-PEG-NH
2
(3), which was subjected to NOTA conjugation and subsequent PEGylation to yield NOTA-mSiO
2
-PEG-Mal (4). NOTA-mSiO
2
-PEGTRC105 (5) could be obtained by reacting TRC105-SH with (4)
64
Cu-labelingwasperformed in the last step to generate
64
Cu-NOTAmSiO
2
-PEG-TRC105. (B) Serial coronal PET images of 4T1 tumor-bearing mice at different time points post injection of (a)
64
Cu-NOTA-mSiO
2
-PEG-TRC105, (b)
64
Cu-NOTA-mSiO
2
-PEG, or (c)
64
Cu-NOTA-mSiO
2
-PEG-TRC105 with a blocking dose of TRC105. Tumors were indicated by yellow arrowheads.
Figure 10.22 (a) PET image co-registered with the corresponding CT image of mice taken 1 h after injection
89
Zr-DFO-MSNs (b)
89
ZrCl4 solution into the tail vein. (c) Biodistribution curve of
89
Zr-DFO-MSNs as compared to
89
ZrCl4 in salt form.
Figure 10.23
In vivo
SPECT/CT imaging of a nude mouse injected with DT10 141Ce-rCONPs, at (a) 2 h, (b) 24 h, (c) 72 h, and (d) 144 h post injection. Images shown here were obtained from volume renderings that were adjusted to a uniform scale.
Chapter 11: Relevance of Natural Degradable Polymers in the Biomedical Field
Figure 11.1 Chemical structures of chitosan modified with different sulfate groups. 2-
N
-Sulfated chitosan, 2SCS;6-
O
-Sulfated chitosan, 6SCS; 2-
N
, 6-
O
-Sulfated chitosan, 26SCS [14].
Figure 11.2 Biological activities modulated by the interaction of proteins with heparan sulfate [60].
Figure 11.3 Morphologies of keratin nanoparticles in a TEM image.
Figure 11.4 Chemical structure of dextran [79].
Figure 11.5 Antifungal properties of dextran-based hydrogels with or without AmB. (a) Schematic representation of the preparation of amphogels, (c) SEM images of dextran-based gels without (c1) and with (c2) AmB incubated with
Candida albicans
for 48 h.
Figure 11.6 Schematic illustration of the formation of the zein/chitosan complex for encapsulation of α-tocopherol [202].
Figure 11.7 Possible cross-linking mechanism for the reaction of casein with genipin in an aqueous system [261].
Chapter 12: Synthetic Biodegradable Polymers for Medical and Clinical Applications
Figure 12.1 Classification of biodegradable polymer.
Figure 12.2 Cycling performance of LiFePO
4
electrodes prepared using different binders, at 0.1 °C between 2.7 and 4.3 V at room temperature.
Figure 12.3 Concept of a hemostatic foam to treat noncompressible hemorrhage. (a) Hemorrhage occurring from a wound in the torso region cannot be treated by applying compression of a bandage. (b) Hemostatic foam can be sprayed into the wound cavity. (c) The foam expands into the cavity and forms a solid barrier that counteracts the expulsion of blood. Active ingredients in the foam can also interact with the blood, promoting blood clotting or gelation. (d) The net result is that hemostasis is rapidly achieved, and the bleeding is thereby contained.
Figure 12.4 Endocytic uptake and intracellular trafficking of hyperbranched copolymer-based micelles in cells.
Figure 12.5 PEI in red fluorescent protein (RFP). (a) Cyclic PEI RFP expression and (b) linear PEI RFP expression.
List of Tables
Chapter 1: Biomaterials for Biomedical Applications
Table 1.1 Natural and synthetic polymers commonly used in the synthesis of hydrogels [10]
Table 1.2 Types of biomaterials used for preparation of scaffolds for bone tissue Engineering
Table 1.3 Types of biomaterials (polymers, ceramics, and composite) used for preparation of scaffolds for bone tissue Engineering
Chapter 2: Conducting Polymers: An Introduction
Table 2.1 Various conducting polymers
Table 2.2 Types of conducting polymers and their properties and applications
Table 2.3 Comparison of chemical and electrochemical polymerization methods used to prepare CPs
Chapter 5: Smart Electroactive Polymers and Composite Materials
Table 5.1 Conductivity of common CPs.
a
Chapter 6: Synthetic Polymer Hydrogels
Table 6.1 Applications of synthetic polymer hydrogels
Chapter 7: Hydrophilic Polymers
Table 7.1 Use of cellulose and chitosan derivatives [125]
Chapter 8: Properties of Stimuli-Responsive Polymers
Table 8.1 Various applications of pH-sensitive polymers for drug delivery systems
Chapter 9: Stimuli-Responsive Polymers: Biomedical Applications
Table 9.1 Advantages and limitations of various stimuli-responsive polymers
Chapter 11: Relevance of Natural Degradable Polymers in the Biomedical Field
Table 11.1 Pectin-containing hydrocolloid wound dressings [110]
Edited by Raju Francis and D. Sakthi Kumar
Biomedical Applications of Polymeric Materials and Composites
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Editors
Prof. Raju Francis
Mahatma Gandhi University
School of Chemical Sciences
Priyadarsini Hills
686560 Kottayam
Kerala
India
Prof. D. Sakthi Kumar
Toyo University
Bio Nano Electronics Research Center
350-858 Kawagoe
Japan
Cover:
Getty Images, Medical Art Inc.
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Preface
Natural and synthetic polymer materials and composites are extensively used as biomaterials for various biomedical applications such as tissue engineering, implantable devices, drug delivery, gene delivery, bioimaging, and so on. Advances in polymer chemistry have allowed the creation of a wide range of biomaterials based on polymers and composites for different biomedical applications according to the nature of their use. The versatility and ease of modification of the chemical, physical, surface, and biomimetic properties of polymers have made them very much dear to the researchers working in the biomedical field. Applications of biomaterials have led to the development of polymers that are biocompatible, biodegradable, and/or resorbable.
A variety of research results are published almost daily on polymers and composites by enhancing their properties as biomaterials to meet the ongoing and evolving challenges in the biomedical field. This book, Biomedical Applications of Polymeric Materials and Composites, is intended to update and provide detailed information to students, technicians, researchers, scientists, and teachers working in the biomedical field by taking the contents only from the very latest results and presenting an extensive summary of the various polymeric materials used in biomedical applications.
This book consists of 12 Chapters.
Chapter 1, “Biomaterials for biomedical applications,” provides an introduction to the various biomaterials currently used in biomedical applications. Selection of the appropriate biomaterials plays a key role in the design and development of the biomedical product. Nowadays, the strategy for biomaterials to be used as biomedical devices is that they should be biocompatible and must elicit a desirable cellular response to harness control over cellular interactions during its usage. This chapter provides detailed information on the current approach for developing biomaterials that can create cellular response by including protein growth factors, anti-inflammatory drugs, gene delivery vectors, and other bioactive vectors. Polymers are generally known to be insulating materials; however, it has been discovered that some polymers can be conductors and semiconductors. Chapter 2, “Conducting polymers – An introduction,” provides information on conducting polymers, as these polymers can be used for different applications in biomedical devices. Chapter 3, “Conducting Polymers: Biomedical Applications,” details the importance of using conducting biopolymers in the biomedical field and provides information of various biopolymers that are used in this field.
Chapter 4, “Plasma-assisted fabrication and processing of biomaterials,” provides information on low-temperature plasma-assisted methods to fabricate and modify the surface of biomaterials. Plasma is also used for sterilization and disease management. Chapter 5, “Smart electroactive polymers and composite materials,” describes such materials. Upon application of an electric voltage, the shape of some polymeric materials can be modified, which can be used as actuators and sensors. Because of their similarities with some biological tissues based on the achievable stress and force, these polymers can be used as artificial muscles. Chapter 6, “Synthetic polymer hydrogels,” provides information of some of the rapidly developing groups of materials that find applications in many fields such as pharmacy, medicine, and agriculture. Chapter 7, “Hydrophilic polymers,” describes various natural, synthetic, and semisynthetic hydrophilic polymers. These types of polymers have the lion's share of applications in the field of biomaterials.
Chapter 8 describes the “Properties of stimuli-responsive polymers.” These types of polymers are the most exciting and emerging class of materials, and have the ability to respond to external stimuli such as temperature, pH, ionic strength, light, and electric and magnetic fields. Since these materials can respond to external stimuli, they find many applications in the biomedical field. Chapter 9, “Stimuli-responsive polymers: Biomedical applications,” provides details about various polymers that find applications in the biomedical field based on their stimuli-responsive properties. This interesting property has enabled the development of smart systems that are useful in bioimaging, sensing (diagnosis), controlled drug delivery, regenerative medicine (therapy), bioseparation, gating valves for transport, and microfluidics. Chapter 10, “Functionally engineered sol–gel inorganic gels and hybrid nanostructures for biomedical applications,” describes nanostructured inorganic gels, mostly metal oxide gels and hybrid nanoarchitectures developed through sol–gel synthesis, and their various biomedical applications.
Chapter 11, “Relevance of Natural Degradable Polymers in the Biomedical field,” highlights the importance of natural degradable polymers for biomedical applications. In modern medicine, natural degradable polymers have their own indisputable place, particularly in drug delivery applications, because they degrade after serving their specific roles. Natural degradable polymers alone cannot meet the demand for applications in the biomedical field. Therefore, with the help of modern chemistry, many biodegradable synthetic polymers have been developed with a wide range of applications such as sutures, implants, drug delivery vehicles, and so on. A variety of synthetic methods have allowed the development of many polymers that meet the functional demands and materials with the desired physical, chemical, biological, biochemical, and degradation properties. Chapter 12, “Synthetic biodegradable polymers for Medical and Clinical Applications,” is included to describe the various synthetic degradable polymers that find interesting applications in the biomedical field.
We believe that this book provides in-depth discussions and details on the polymers and their composites that have applications in the biomedical field based on recent research results in this magnificent field. Throughout the book, we have focused on recent applications, with worked examples and case studies for training purposes, which will serve the purpose of this book, that is, to update students, technicians, researchers, scientists, and teachers who work in the biomedical field.
We express our sincere thanks and appreciation to the 20 scientists for contributing chapters to this book and their constant cooperation from submission of the first drafts to revision and final fine-tuning of their chapters commensurate with the reviews. We extend our appreciation to our respective host institutions, namely Mahatma Gandhi University, Kottayam, India, and Toyo University, Japan, for their encouragement and support.
Finally, we wish to extend our thanks to Wiley-VCH and all their staff involved in the publication and promotion of this book, which will hopefully be useful to those working in the biomedical field.
Raju FrancisD. Sakthi Kumar
India
Japan
18 July 2016
List of Contributors
Surjith Alancherry
James Cook University
College of Science
Technology and Engineering
James Cook Drive
Townsville, QLD 4811
Australia
Solaiappan Ananthakumar
Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST) Functional Materials Section Materials Science and Technology Division (MSTD)
Thiruvananthapuram 695019
Kerala
India
Deepa K. Baby
Rajagiri School of Engineering and Technology
Department of Basic science and Humanities
Rajagiri Valley
Kakkanad, Kochi 682039
Kerala
India
Kateryna Bazaka
James Cook University
College of Science
Technology and Engineering
James Cook Drive
Townsville, QLD 4811
Australia
and
Queensland University of Technology
Institute of Health and Biomedical Innovation
Brisbane, QLD 4000
Australia
Brahatheeswaran Dhandayuthapani
Toyo University
BioNano Electronics Research Centre
Kawagoe
Saitama 3508585
Japan
and
Collaborative Research and Education Program
Nanoscale Research Facility
Indian Institute of Technology-Delhi
Hauz Khaz 110016
Delhi
India
Joby Eldho
R&D Deposition Materials
EMD Performance Materials
1429 Hilldale Avenue
Haverhill, MA 01832
USA
Harikrishna Erothu
Aston University
Chemical Engineering and Applied Chemistry
Aston Triangle
Birmingham
West Midlands B4 7ET
UK
Raju Francis
Mahatma Gandhi University
School of Chemical Sciences
Priyadarshini Hills
Kottayam 686560
Kerala
India
J. Mary Gladis
Indian Institute of Space Science and Technology
Department of Chemistry Valiamala
Thiruvananthapuram 695547
India
Geethy P. Gopalan
Mahatma Gandhi University
School of Chemical Sciences
Priyadarshini Hills
Kottayam 686560
Kerala
India
Daniel S. Grant
James Cook University
College of Science, Technology and Engineering
James Cook Drive
Townsville, QLD 4811
Australia
Mohan V. Jacob
James Cook University
College of Science, Technology and Engineering
James Cook Drive
Townsville, QLD 4811
Australia
Nidhin Joy
Mahatma Gandhi University
School of Chemical Sciences
Priyadarshini Hills
Kottayam 686560
Kerala
India
Anitha C. Kumar
Acharya Nagarjuna University
Department of Chemistry
Nagarjuna Nagar
Guntur 522510
Andhra Pradesh
India
and
Aston University
Chemical Engineering and Applied Chemistry
Aston Triangle
Birmingham
West Midlands B4 7ET
UK
Dasappan Sakthi kumar
Toyo University
BioNano Electronics Research Centre
Kawagoe
Saitama 3508585
Japan
and
Collaborative Research and Education Program
Nanoscale Research Facility, Indian Institute of Technology-Delhi
Hauz Khaz 110016
Delhi
India
Vazhayal Linsha
Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Functional Materials Section
Materials Science and Technology Division (MSTD)
Thiruvananthapuram 695019
Kerala
India
Kallyadan Veettil Mahesh
Council of Scientific and Industrial Research
National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Functional Materials Section, Materials Science and Technology Division (MSTD)
Thiruvananthapuram 695019
Kerala
India
T.P.D. Rajan
Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Materials Science and Technology Division
Industrial Estate PO
Pappanamcode
Thiruvananthapuram 695018
India
Anjaly Sivadas
Mahatma Gandhi University
School of Chemical Sciences
Priyadarshini Hills
Kottayam 686560
Kerala
India
Chapter 1Biomaterials for Biomedical Applications
Brahatheeswaran Dhandayuthapani and Dasappan Sakthi kumar
1.1 Introduction
Biomaterials play numerous critical roles in biomedical applications. Historically, biomaterials were obtained from natural sources, such as purified collagen, gelatin, silk, or cotton. Advances in polymer chemistry supplemented these natural polymers with first-generation medical polymers. Currently, polymers are used in a wide range of biomedical applications, including applications in which the polymer remains in intimate contact with cells and tissues for prolonged periods. Although many of these polymer materials have been tested for various applications, it is widely recognized that the current range of biomaterials available will not be adequate for the vast range of applications in drug delivery, artificial organs, and tissue engineering technologies. To select appropriate materials for biomedical applications, it will help to understand the influence of these materials on viability, growth, and function of attached or adjacent cells. The selection of biomaterials plays a key role in the design and development of biomedical products. While the classical selection criterion for a safe, stable implant dictated choosing a passive, inert material, it is now deduced that any such device is capable of eliciting a cellular response [1, 2]. Therefore, it is now widely accepted that a biomaterial must interact with tissue to repair, rather than simply be a static replacement. Furthermore, biomaterials used directly in tissue repair or replacement applications (e.g., artificial skin) must be more than biocompatible; they must elicit a desirable cellular response. Consequently, a major focus of biomaterials for tissue engineering applications centers on harnessing control over cellular interactions with biomaterials, often including components to manipulate cellular response within the supporting biomaterial as a key design component. Specific examples of such components include protein growth factors, anti-inflammatory drugs, gene delivery vectors, and other bioactive factors to elicit the desired cellular response [3, 4].
It is important for the developer of biomedical products to have several biomaterial options available, because each application calls for a unique environment for cell–cell interactions. Examples of some such applications are as follows:
Support for new tissue growth (wherein cell–cell communication and cell availability to nutrients, growth factors, and pharmaceutically active agents must be maximized);
Prevention of cellular activity (where tissue growth, such as in surgically induced adhesions, is undesirable);
Guided tissue response (enhancing a particular cellular response while inhibiting others);
Enhancement of cell attachment and subsequent cellular activation (e.g., fibroblast attachment, proliferation, and production of extracellular matrix (ECM) for dermis repair);
Inhibition of cellular attachment and/or activation (e.g., platelet attachment to a vascular graft); and
Prevention of a biological response (e.g., blocking antibodies against homograft or xenograft cells used in organ replacement therapies).
The processability of biomaterials is a key step for developing biomedical applications. Nine potential biomedical applications areas have been identified [5]:
Membranes in extracorporeal applications such as oxygenators;
Bioactive membranes, for example, controlled release delivery systems and artificial cells;
Disposable equipment, for example, blood bags and disposable syringes;
Sutures and adhesives including biodegradable and nonbiodegradable materials;
Cardiovascular devices such as vascular grafts;
Reconstructive and orthopedic implants;
Ophthalmic devices such as corneas and contact lenses;
Dental restorative materials including dentures;
Degradable plastic commodity products.
This chapter surveys the various biomaterials that have been used or are under consideration for use in biomedical applications.
1.2 Polymers as Hydrogels in Cell Encapsulation and Soft Tissue Replacement
Hydrogels are one of the most promising classes of biomaterials for biomedical applications because they have good biocompatibility and a large amount of equilibrium water content [6]. Wichterle [7] achieved the following four crucial criteria with the design.
Preventing component release.
Creating a stable chemical and biochemical structure.
Having a high permeability for nutrients and waste.
Assuming physical characteristics similar to those of natural living tissue.
Hydrogels have water content and mechanical properties that are similar to those of human tissue and find use in many biomedical applications. The first biomedical use for synthetic hydrogels, which was established in 1954, was as an orbital implant. Wichterle designed soft contact lenses from hydrogels in 1961. Since then, hydrogel use for biomedical applications has included wound dressings, drug delivery systems, hemodialysis systems, artificial skin, and tissue engineering [8–10]. The structural similarity of hydrogels to that of the human ECM creates promising applications as a scaffold material for cell-based tissue engineering [10]. Hern and Hubbell [11] first modified PEGA with the adhesive peptide arginyl–glycyl–aspartic acid (RGD) to enhance cell adhesion and promote tissue spreading. In separate experiments, PEG methacrylate has been modified with phosphoester and RGD to enhance bone engineering [12, 13]. In addition, hyaluronic acid has been copolymerized with PEGDA+RGD to support cell attachment and proliferation as well as to improve cartilage repair [14, 15]. Poly(γ-benzyl l-glutamate) (PBLG) is one of the synthetic polypeptides that has attracted attention for use in drug delivery matrices [16]. Hydrogels developed by combining polyisobutylene (PIB) and hydrophilic polymer segments were used for coating Gore-Tex vascular grafts and showed good biocompatibility [17]. These hydrogels were also used as membrane carriers for insulin-producing porcine platelet implants [18]. Shu et al. [19] synthesized thiolated HA and then conjugated it to PEG for the benefit of in situ injection and cell encapsulation and proliferation. PEG and HA may be further modified by physical cross-linking of bioactive factors, which is one of the methods used to create biomimetic hydrogels. Growth factors remain active after encapsulation to enhance the proliferation and differentiation of encapsulated cells or to improve local tissue regeneration [20, 21]. Growth factors that have been entrapped in hydrogels include bone morphogenetic protein-2 (BMP-2), fibroblast growth factor, vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), and transforming growth factor β (TGF-β), among others [21–25].
The examples in the following paragraph illustrate the effect of biomimetic hydrogels on three different tissues. Several groups have demonstrated in vivo secretion of cartilaginous matrix using chondrocytes encapsulated in hydrogels. The use of hydrogels to support chondrocyte growth and matrix production is well established. Current efforts focus on bringing hydrogels closer to clinical applications. Lee et al. [20] incorporated TGF-β1 into a chitosan scaffold in which chondrocytes were cultured. The chondrocytes cultured in scaffolds containing TGF-β1 exhibited significantly greater proliferation and GAG and type II collagen production than did chondrocytes cultured in control scaffolds lacking TGF-β1. Recently, thermoplastic biodegradable hydrogels have been designed for biomedical applications including drug delivery systems: polyisobutylene (PIB)-based materials as potential materials for soft tissue replacement, specifically for vascular grafts and breast implants [26] (Figure 1.1). Polyesters (PET), fluoropolymers (PTFE), polypropylene (PP), polyurethanes (PU), and silicones have played a crucial role in the development of polymeric materials for soft tissue replacement [27]. This biomaterial represents a conceptually new soft biomaterial for potential biomedical application (Table 1.1).
Figure 1.1 Polymer hydrogels used for tissue replacement.
Table 1.1 Natural and synthetic polymers commonly used in the synthesis of hydrogels [10]
Natural hydrogels
Synthetic polymers
Hyaluronic acid (HA)
Hydroxyethyl methacrylate (HEMA)
Chondroitin sulfate
Methoxyethyl methacrylate (MEMA)
Matrigel
N
-Vinyl-2-pyrrolidone (NVP)
Alginate
N
-Isopropyl Aam (NIPAAm)
Collagen
Acrylic Acid (AA)
Fibrin
Poly(ethylene glycol) acrylate (PEGA)
Chitosan
Poly(ethylene oxide) diacrylate (poly(ethylene glycol) diacrylate (PEGDA))
Silk
Poly(vinyl alcohol) (PVA)
Gelatin, Agarose, and Dextran
Poly(fumarates)
1.3 Biomaterials for Drug Delivery Systems
A defining therapeutic feature of a biodegradable polymer used in modern drug delivery is facile degradation into oligomers or monomers with concomitant kinetically controlled drug release profiles. Polymeric delivery systems are mainly used to achieve either temporal or spatial control of drug delivery [28]. Essentially, polymeric vehicles enable drugs to be delivered over an extended period of time and to the local site of action. They are designed to enhance drug safety and efficacy, and to improve patient compliance. The use of polymers is designed to maintain therapeutic levels of the drug, reduce ide-effects, decrease the amount of drug molecule and the dosage frequency, and facilitate the delivery of drugs with short in vivo half-lives [29]. In polymer-based drug delivery, polyalkylcyanoacrylates (PACAs) have evolved diverse versatility as drug nanoparticle carriers for indomethacin [30], gangliosides [31], oligonucleotides [32], anti-epileptic medications including Ethosuximide [33], insulin [34], saquinavir [35], hemoglobin [36], and nucleoside analogs against human immunodeficiency virus (HIV) [37]. Translational research into poly(ethylene glycol) (PEG)–PACAs and actively targeted PACA systems [38, 39] have shown great promise for use in vivo such as the recently completed phase I and phase II studies of Doxorubicin Transdrug® for primary liver cancer.
Polyphosphazenes have been used for controlled release of naproxen [40–42], calcitonin [43], colchicines [44], (diamine) platinum [45], (dach) platinum (II) [46], insulin [47], other model proteins [48, 49], methylprednisolone [50, 51], methotrexate [52], tacrolimus [53], tempamine [54], and plasmid deoxyribonucleic acid [55]. Studies of blood biocompatibility in vitro with polyorganophosphazenes have shown no morphological changes or aggregation with platelets [56] and good biocompatibility after transplantation [57]. The first long-term biocompatibility in vivo study with polyphosphazene was reported in 2003 by Huang et al. [58] with a porcine coronary stent model, which showed no signs of either hyperplasia or proliferative response after 6 months. In the same family as polyphosphazenes, polyphosphoesters (PPEs) are inorganic polymers. To date, biocompatibility studies have been quite favorable, showing limited toxicity [59]. Numerous studies by Leong's group have used PPEs for block copolymer design including poly(2-aminoethyl propylene phosphate) (PPE-EA) for gene delivery [60–63] and PPE microspheres for nerve growth factor delivery. In vivo studies with the Paclimer delivery system, 10% w/w paclitaxel encapsulated in biodegradable polyphosphoester microspheres, with a single intratumoral or intraperitonel injection showed 80% release of the drug after 90 days in a human lung cancer xenograft model. This sustained release showed significant inhibition of nonsmall cell lung cancer nodules with three- to sixfold longer tumor doubling times compared with free paclitaxel and vehicle controls [64–66]. A recent translational canine study to evaluate dose escalation and neurotoxicity showed excellent results throughout the 120-day study with no evidence of systemic toxicity or gross morphological or physiological changes in the animals [67]. Polyesters represent perhaps the largest family of biodegradable polymers including aliphatic polyesters such as poly(glycolic acid) (PGA), poly(lactic acid) (PLA), poly(lactide-co-glycolide) (PLGA), polydioxanone, polyglyconate, polycaprolactone, and polyesteramide [68]. Several biodegradable polyesters, many of which are PGA derivatives, have also been used in nonviral gene delivery primarily to alleviate cytotoxicity such as poly[α-(4-aminobutyl)-l-glycolic acid] (PAGA) [69, 70], poly(d,l-lactic acid-co-glycolic acid) (PLGA) [71–73], PEG–PLGA–PEG [74] and poly(4-hydroxyl-1-proline esters) [75, 76]. PCL block copolymers have been used to deliver doxorubicin [77], cyclosporine A [78, 79], geldanamycin [80], rapamycin [81], 97 amphotericin B [82, 83], dihydrotestosterone [84], indomethacin [85, 86], and paclitaxel [87]. Polyorthoesters (POEs) were developed and reported by Heller et al., nearly 40 years ago for use as implanted biomaterials and as drug delivery vehicles [88] (Figure 1.2).
Figure 1.2 Biomaterials utilized for various drug delivery systems.
Biodegradable polymers have truly revolutionized controlled drug delivery design and biomaterial applications for implants and tissue engineering. A biodegradable derivative of poly(ethylene glycol)-co-poly(l-lysine) (PEG–PLL) with grafted histidine residues has been synthesized for local gene therapy with transgene expression levels fourfold higher than PLL alone [89, 90]. With the help of biodegradable stents, clinicians can site-specifically control drug release to treat coronary artery disease through delivery of traditional small molecules and, now, gene therapy [91, 92]. Biodegradable block copolymers and block copolypeptides have significantly endowed novel drug delivery systems with beneficial pharmacokinetic and biocompatible properties.
1.4 Biomaterials for Heart Valves and Arteries
Devices or natural tissues can be used to replace heart valves or arteries. These replacement materials are used when the natural heart valves or arteries fail to function properly, which can result in death or severe disability if left uncorrected. Such replacement materials help to restore the flow of blood that the body needs in order to function properly. Natural tissues are commonly used as replacement materials; alternatively, pyrolytic carbon mechanical valves are used to replace heart valves, while metal stents can be used to hold arteries open. However, there is interest in the development of polymers as replacement materials for heart valves and for use with stents. Heart valves are composed of connective tissue (collagen, elastin, and glycosaminoglycans [93], and open or close in response to pressure gradients and hemodynamics [94]. Flexible leaflet aortic replacement valves were developed in the 1960s [95]. There has been recent interest in developing polymeric valves from polyurethanes. Polyurethanes have good blood compatibility [96] and can be made into physiological shapes, forming valves that are flexible [97]. Synthetic poly(carbonate urethane) valves have been recently developed for both the aortic and the mitral positions [98]. In vivo results are promising, with tests being performed without anticoagulants in some cases, and show greater signs of durability than bioprostheses when tested in calves [99], or sheep [100].
Materials such as braided polyester, polybutester (a butylene terephthalate and poly(tetramethylene ether glycol) copolymer), polypropylene, PTFE, or e-PTFE can be used for replacement of mitral valves related repairs. However, during chordal replacement, the synthetic suture acts as a neochord. PTFE has been found to have material properties that are closer in nature to natural chordae than other materials such as braided polyester [101]. An alternative to synthetic chordae is the use of natural tissues, such as glutaraldehyde-tanned pericardial strips [102]. However, PTFE has been found to produce better clinical results than glutaraldehyde-tanned pericardial strips for chordal replacement [103]. Developments of new chordal replacement materials may further improve mitral valve repair in the long term. Tissue engineered synthetic chordae made from cultured fibroblast and smooth muscle cells have been reported, with added type I collagen [104, 105]. However, replacement synthetic chordae with properties closer in nature to real chordae may well provide benefits for mitral valve replacement (Figure 1.3).
Figure 1.3 Polymers for artificial vascular grafts.
Stents are usually composed of metal wires forming the outer boundaries of an open cylinder. The most widely used stents are made from stainless steel [106] and are relatively inert when in place. Stents have been very successful clinically and may well be used in over 50% of angioplasty procedures [107]. The placement of stents may damage the arterial endothelial layer [108], which may cause some of the problems associated with stents. Initially, stents were designed to be bioinert (by using materials such as stainless steel). However, coatings may be necessary to avoid restenosis. Polymer coatings, including natural polymers such as heparin (a polysaccharide), have been used on stents. Stents coated with resorbable polymers such as polycaprolactone and polyorthoester, and copolymers such as polyglycolic–polylactic acid, poly(hydroxybutyrate valerate), and poly(ethylene oxide)–poly(butylene terephthalate) have been compared in vivo as resorbable stent coatings [109]. Phosphorylcholine applied to the stents has the potential to prevent the stent from inducing the formation of a thrombus on its surface [110]. Currently, polymers within stents hold most promise as coatings used to control drug delivery or release from or near stents to reduce restenosis and thrombus formation.
Polymer fibers composed of polydioxanones (PDS) were first tested for use as monofilament biodegradable surgical sutures and the degradation profile was later found to be affected by gamma irradiation [111]. Katz et al. [112] reported biodegradable, poly(trimethylene carbonates) for monofilament surgical sutures currently marketed as Maxon. PLGA composed of LA–GA 10–90 has long-found utility as Vicryl (polyglactin 910), a biodegradable surgical suture licensed by Ethicon (Somerville, New Jersey) and, in 2002, Vicryl Plus became the first marketed suture designed to contain an antibacterial agent, Triclosan or 5-chloro-2-(2,4-dichlorophenoxy)phenol [113]. Lendlein and Langer reported a new thermoplastic elastomer based on PCL and poly(dioxanone), with both homopolymers having been used as suture materials [114]. Currently, much effort is being focused on using polyurethane (PU) in biomedical applications such as cardiac-assist pumps and blood bags, to chronic implants such as heart valves and vascular graft, hemodialysis bloodline sets, center venous catheters (CVCs), and intravenous (IV) bags [115, 116]. Lin et al., demonstrated that water-soluble chitosan/heparin immobilized PU membranes effectively improved in vitro hemocompatibility and superior biocompatibility [117].
1.5 Biomaterials for Bone Repair
Bone is a metabolically active, highly vascularized tissue with a unique ability to regenerate without creating a scar [118]. Bone repair was proposed to be one of the first, major applications of tissue engineering [119]. The general concept of bone tissue engineering is based on the formation of a tissue engineering construct to encourage the regeneration of the damaged tissue [120]. The main physiological functions of the ECM include storage of the nutrients, growth factors, and cytokines as well as mechanical stabilization for anchorage-dependent cells [121]. In the context of bone tissue engineering, the scaffold should possess the following properties [122]:
biocompatibility,
bioresorbability/biodegradability,
open/interconnected porosity,
suitable topography and surface chemistry, and
appropriate mechanical properties.
To fulfill the above requirements, several different types of the materials have been proposed [123, 124]. Based on the origin, the scaffold materials may be divided into two main groups: (i) naturally derived materials such as collagen, glycosaminoglycans (GAGs), starch, chitosan, and alginates; and (ii) synthetic ones, including metals, ceramics, bioactive glasses, and polymers (listed in Table 1.2) [125–127]. In addition, the surface properties of the scaffold will influence cell adhesion and activity.
Table 1.2 Types of biomaterials used for preparation of scaffolds for bone tissue Engineering
Polymer
3D architecture
Naturally derived materials
Collagen
Fibrous, sponge, hydrogel
Starch
Porous
Chitosan
Sponge, fibers
Alginates
Hydrogel, sponge
Hyaluronic acid (HA)
Hydrogel
Polyhydroxyalkanotes (PHA)
Porous, hydrogel
Synthetic polymers
Polyurethanes (PU)
Porous
Poly(-hydroxy acids) (i.e., PLLA, PGLA)
Porous
Poly(-caprolactone) (PCL)
Sponge, fibers
Poly(propylene fumarates) (PPF)
Hydrogel
Titanium
Mesh
Calcium phosphate
Porous
The current generation of synthetic bone substitutes is helping to overcome the problems associated with availability and donor-site morbidity. Alternatives to autografts and allograft preparations have included calcium-phosphates, bioactive glass, polymers, and many other composite materials [128–130]. Over the years, many materials have been described for application in bone repair (Table 1.3).
Table 1.3 Types of biomaterials (polymers, ceramics, and composite) used for preparation of scaffolds for bone tissue Engineering
Polymers
Ceramics
Composite/natural
Polylactic acid
Bioglass
Poly(
d
,
l
-lactide-co-glycolide) - bioactive glass
Polyglycolic acid
Sintered hydroxyapatite
Extracellular matrix (ECM)
Polycaprolactone
Glass-ceramic A–W
Hyaluronan-linear glycosaminoglycan (GAG)
Polyanhydrides
Hydroxyapatite (HA)-calcium phosphate-based ceramic
Demineralized bone matrix (DBM)
Polyphosphazenes
Collagraft – commercial graft. HA tricalcium phosphate ceramic fibrillar collagen
Polymethylmethacrylate (PMMA)
Bioactive glass
Polytetrafluoroethylene (PTFE)
Sol–gel-derived bioactive glass
Organic and inorganic synthetic polymers have been used in a wide variety of biomedical applications. Other biodegradable polymers currently being studied for potential tissue engineering applications include polycaprolactone, polyanhydrides, and polyphosphazenes [131–133]. PMMA has also been widely used in dentistry. Other polymers such as polytetrafluoroethylene (PTFE) have also been used for augmentation and guided bone regeneration [134, 135]. Ceramics have also been widely used in orthopedic and dental applications [136] (Figure 1.4).
Figure 1.4 Polymer based matrix for bone repair.
HA is biocompatible, and stimulates osseo-conduction [137, 138]. By recruiting osteoprogenitor cells and causing them to differentiate into osteoblast-like bone-forming cells, it is resorbed and replaced by bone at a slow rate [139]. Bioactive glasses are another class of interesting material as they elicit a specific biological response at the interface of the material, which results in the formation of a bond between tissues and the material [140]. Calcium phosphate (CaP)-based biomaterials have found many applications for bone substitution and repair. These materials show excellent in vivo biocompatibility, cell proliferation, and resorption [141].
1.6 Conclusion
In this chapter, a range of biomaterials from various polymers used for biomedical applications have been described. Biomaterials need to possess a number of key features to meet the stringent requirements of biomedical applications. The chosen biomaterial must provide a biocompatible and biodegradable matrix with interconnected pores to ensure that the body tolerates the conduit and also promotes nutrient and cellular diffusion. Furthermore, the material initially needs to provide mechanical stability and act as a template to guide three-dimensional tissue growth. There is great potential to produce replacement blood vessels and heart valves, which can be met with further advancements in tissue engineering. Developments in the area of cellular replacement tissues have led to replacement arteries and heart valves that can potentially allow host cell infiltration. Tissue engineering of an artery with an ECM made by cells in culture also led to a replacement artery with suitable properties for implantation. It is likely that there will be further advances with these technologies. Developments in polymeric material for use with stents in drug delivery systems, and to produce heart valves may allow further developments in replacement devices. While, at present, polymer stents have not proved to be successful, improvements in technology may allow their use in the future. The ultimate test for all new devices that are used to repair or replace arteries or heart valves is how well they perform clinically, and how they compare with existing devices. The development of these valves into successful clinical implants will ultimately depend on their long-term function, which can only be determined clinically. Furthermore, their long-term durability will also determine their clinical value and lead to complete optimization of their production; very useful techniques will be available that may help produce prominent cardiovascular replacement materials. Furthermore, just as it is true that no one material will satisfy all the design parameters required in all applications within the tissue engineering field, it is also true that a wide range of materials can be tailored for discrete applications, through the use of the most appropriate processing methodologies and processing parameters selected.
Abbreviations
AA
acrylic acid
BMP-2
bone morphogenetic protein-2
CVCs
center venous catheters
DBM
demineralized bone matrix
GAG
glycosaminoglycan
HA
hyaluronic acid
HEMA
hydroxyethyl methacrylate
IGF-1
insulin-like growth factor 1
IV
intravenous
MEMA
methoxyethyl methacrylate
NIPAAm
N
-isopropyl Aam
NVP
N
-vinyl-2-pyrrolidone
PACAs
polyalkylcyanoacrylates
PAGA
poly[
α
-(4-aminobutyl)-
l
-glycolic acid]
PCL
Polycaprolactone
PDS
polydioxanones
PEG
poly(ethylene glycol)
PEGA
poly(ethylene glycol) acrylate
PEGDA
poly(ethylene oxide) diacrylate (poly(ethylene glycol) diacrylate
PEG–PLL
poly(ethylene glycol)-co-poly(
l
-lysine)
PET
polyesters
PIB
polyisobutylene
PIB
polyisobutylene
PLA
poly(lactic acid)
PLGA
poly(
d
,
l
-lactic acid-co-glycolic acid)
PLGA
poly(lactide-co-glycolide)
PMMA
polymethylmethacrylate
POEs
polyorthoesters
PP
Polypropylene
PPE-EA
Poly(2-aminoethyl propylene
phosphate)
PPF
poly(propylene fumarates)
PTFE
polytetrafluoroethylene
PTFE
fluoropolymers
PU
polyurethane
PVA
poly(vinyl alcohol)
TGF-β
transforming growth factor β
VEGF
vascular endothelial growth factor
CaP
calcium phosphate
ECM
extracellular matrix
PBLG
poly(
γ
-benzyl
l
-glutamate)
RGD
arginyl–glycyl–aspartic acid
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