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- Herausgeber: John Wiley & Sons
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- Sprache: Englisch
Biopolymers for Biomedical Applications The twenty chapters written by experts in the field of biopolymers and biomedical engineering, provide a complete resource that systematically discusses the most widely used biopolymers and their biomedical applications, and presents all the important research and developments that have occurred in the field. In recent decades, significant progress has been made in polymer science for biomedical applications. The use of biopolymers specifically attracted the focus on the development of therapeutic polymeric systems. The exclusive features of biopolymers, such as biodegradability and biocompatibility make them highly sought after, and major research conducted with them has resulted in various therapeutic systems. However, until now only a few showed a potential to be appropriate for human use. Each chapter covers a single biopolymer, its properties, and biomedical applications. The chapters are arranged systematically, with the most common biopolymers discussed early in the book to give more insight into the field. Further, a specific chapter is dedicated to the application of biopolymers for wound healing. Later, specific chapters are dedicated to the application of bioplastics and biopolymers for the development of medical devices and biosensors, respectively. Additionally, a chapter is dedicated to the application of biopolymers in the field of dentistry, with a special focus on their risk to human health. Keeping in mind recent advanced technologies, a chapter is dedicated solely to the latest progress of biopolymers in 3D and 4D printing for biomedical applications. The final chapter comprehensively explains the future perspectives of biopolymers in the biomedical field. Audience The book is a reference source for scientists, research scholars, chemical and polymer engineers, biologists, biotechnologists, polymer technologists, industrialists, health experts, and policymakers.
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Table of Contents
Cover
Table of Contents
Series Page
Title Page
Copyright Page
Dedication Page
Preface
1 Introduction to Biopolymers
1.1 Introduction
1.2 Classification of Biopolymers
1.3 Commonly Used Biopolymers
1.4 Preparation of Biopolymers
1.5 Commercially Available Biopolymers
1.6 Biomedical Applications of Biopolymers
1.7 Conclusion
References
2 Biomedical Applications of Chitosan and Its Derivatives
2.1 Introduction
2.2 Characteristics of Chitosan
2.3 Application of Chitosan in Biomedicine
2.4 Conclusion
References
3 Biomedical Applications of Alginates
3.1 Introduction
3.2 Structure and Characterization
3.3 General Properties of Alginates
3.4 Alginate and Alginate Composites as a Drug Delivery System
3.5 Biomedical Application of Alginates
3.6 Conclusion and Future Prospective of Alginates
References
4 Biomedical Applications of Cellulose
4.1 Introduction
4.2 Structure and Properties of Cellulose
4.3 Types of Cellulose
4.4 Applications of Cellulose
4.5 Applications in Ocular Systems
4.6 Applications in Skeletal Systems
4.7 Miscellaneous
4.8 Conclusion
References
5 Biomedical Applications of Starch
5.1 Introduction
5.2 Structure and Properties of Starch
5.3 Modified Starches
5.4 Pharmaceutical and Biomedical Applications
5.5 Starch for Novel Drug Delivery
5.6 Encapsulants
5.7 Micro/Nanoparticle Hydrogels
5.8 Scaffolds for Wound Healing
5.9 Conclusions
References
6 Biomedical Applications of Carrageenan
6.1 Introduction
6.2 Structure of Carrageenan
6.3 Biomedical Applications
6.4 Toxicity
6.5 Challenges, Conclusion, and Future Trends
References
7 Biomedical Applications of Gums
7.1 Introduction
7.2 Physicochemical Properties of Gums
7.3 Biomedical Applications of Guar Gum
7.4 Biomedical Applications of Xanthan Gum
7.5 Biomedical Applications of Gum Arabic
7.6 Biomedical Applications of Gum Tragacanth
7.7 Conclusion and Future Perspective
References
8 Biomedical Applications of Cyclodextrin
Abbreviations
8.1 Introduction
8.2 Biomedical Applications of Cyclodextrin
8.3 Future Prospects
8.4 Conclusion
References
9 Biomedical Applications of Dextran
9.1 Introduction
9.2 Biomedical Applications of Dextran
9.3 Conclusion
References
10 Biomedical Applications of Pullulan
10.1 Introduction
10.2 Sources of Pullulan
10.3 Properties of Pullulan
10.4 Biomedical Applications
10.5 Conclusion
References
11 Biomedical Applications of Collagen/Gelatin
11.1 Introduction
11.2 Structure of Collagen
11.3 Modification of Collagen
11.4 Biomedical Applications of Collagen/Gelatin
11.5 Conclusion
References
12 Biomedical Applications of Pectin
12.1 Introduction
12.2 Biomedical Applications of Pectin
References
13 Biomedical Applications of Lignin Derived from Bio-Waste Materials
13.1 Introduction
13.2 Structure of Lignin
13.3 Sources of Lignin
13.4 Extraction of Lignin
13.5 Properties of Lignin for Biomedical Applications
13.6 Biomedical Applications of Lignin
13.7 Therapeutic Applications of Lignin
13.8 Feasibilities, Challenges, and Prospects
13.9 Conclusion
References
14 Biomedical Applications of Polycaprolactone
14.1 Introduction
14.2 Structure of PCL
14.3 Characteristic Properties of PCL
14.4 Synthesis
14.5 Modifications of PCL
14.6 Biomedical Applications of PCL
14.7 Current Challenges
14.8 Conclusion
References
15 Biopolymers for Wound Healing Applications
15.1 Introduction
15.2 Wound Healing Stages
15.3 Biopolymers
15.4 Conclusion and Future Directions
References
16 Bioplastics in Medical Devices
16.1 Introduction
16.2 Plastics and Their Environmental Concern
16.3 Need for Bioplastics
16.4 Bioplastics
16.5 Biomedical Applications of Polylactic Acid
16.6 Biomedical Applications of PLGA
16.7 PLGA in Bone Tissue Engineering
16.8 Biomedical Applications of Poly(ɛ-caprolactone)
16.9 Conclusion
References
17 Biopolymers in Biosensors
17.1 What are Biosensors?
17.2 Biopolymers
17.3 Conclusion
References
18 Biopolymers in Dentistry: A Risk Assessment on Human Health
18.1 Introduction
18.2 Biopolymers in Healthcare
18.3 Classification of Biopolymers
18.4 Biopolymers Used in Dentistry
18.5 Risk Assessment of Biopolymers in Dentistry
18.6 Discussion
18.7 Conclusion
References
19 Progress of Biopolymers in 3D and 4D Printing for Biomedical Applications
19.1 Introduction
19.2 Overview on 3D and 4D Printing Technologies
19.3 4D Printing
19.4 Overview on Biopolymers for 3D and 4D Printing
19.5 Stimuli for 4D Transformation
19.6 Biopolymers Used for 3D and 4D Printing
19.7 Biomedical Applications of Biopolymers Based 3D-and 4D-Printed Bioconstructs
19.8 Other Applications
19.9 Future Perspectives and Conclusion
References
20 Future Perspectives of Biopolymers for Biomedical Applications
20.1 Introduction
20.2 Role of Biopolymers in 3D Printing
20.3 Biopolymers in Recent Intelligent Biomedical Systems
20.4 Critical Aspects of Biopolymers in Biomedical Applications
20.5 Conclusion and Future Perspective
References
Index
End User License Agreement
List of Tables
Chapter 1
Table 1.1 Some commercially available biopolymers.
Table 1.2 Biomedical applications of biopolymers in different aspects.
Chapter 3
Table 3.1 Solubility of alginates in different solvents.
Table 3.2 Biomedical applications of alginates.
Chapter 4
Table 4.1 Types of cellulose with their characteristics.
Table 4.2 Applications of cellulose in a drug delivery system.
Table 4.3 Cellulose-grafted materials with antimicrobial properties.
Table 4.4 Applications of cellulose in tissue engineering.
Table 4.5 Application of cellulose in wound healing.
Table 4.6 Application of cellulose in an ocular drug delivery system.
Table 4.7 Application of cellulose for bone regeneration, cartilage in vertebr...
Chapter 10
Table 10.1 Modified pullulan formulations and their applications in gene deliv...
Table 10.2 Modified pullulan formulations and their applications in tissue eng...
Chapter 11
Table 11.1 Collagen fibers as a skin substitute.
Chapter 12
Table 12.1 Composition of the pectin molecule.
Table 12.2 Commercial sources and biomedical applications of pectin [44].
Chapter 14
Table 14.1 Examples of certain modifications of the PCL polymer that are being...
Table 14.2 Current research in the field of biomedical sciences and the contri...
Chapter 15
Table 15.1 A literature review of the various chitosan-based wound dressings s...
Table 15.2 Commercially available alginate-based dressings.
Chapter 17
Table 17.1 Biosensing applications of biopolymers.
Chapter 18
Table 18.1 Classification of biopolymers.
List of Illustrations
Chapter 1
Figure 1.1 Applications of biopolymers.
Figure 1.2 Classification of biopolymers [6–8].
Figure 1.3 Preparation of alginate biopolymer from microorganisms and molasses...
Figure 1.4 Biomedical applications of biopolymers.
Chapter 2
Figure 2.1 Synthesis and fate of chitin and chitosan.
Figure 2.2 Application of chitosan in different segments.
Figure 2.3 Mechanism of chitosan as an anti-bacterial agent.
Figure 2.4 Role of chitosan in enhancing the anti-cancer potential of drugs.
Chapter 3
Figure 3.1 Structure of alginates [162].
Figure 3.2 (a)
In vitro
blood coagulation test on composite sponges. (b) Cytoc...
Figure 3.3 Improvement in bone formation in mice using alginate-based gel. (a)...
Chapter 4
Figure 4.1 Biomedical applications of cellulose.
Figure 4.2 Progression of tissue regeneration.
Figure 4.3 Bacterial cellulose properties.
Chapter 5
Figure 5.1 Molecular structure of starch: (a) amylose and (b) amylopectin [53]...
Figure 5.2 Schematic representation of a nanocapsule. A bioactive cargo is enc...
Figure 5.3 Schematic representation of the cutaneous wound healing [107].
Chapter 6
Figure 6.1 Multifunctional nanocomposite spray dressing of Kappa-carrageenan-p...
Figure 6.2 An intracellular endo/lysosomal EPI-CAO-AuNPs delivery system with ...
Chapter 7
Figure 7.1 Structure of guar gum [11].
Figure 7.2 Representation of the xanthan repeating unit’s chemical composition...
Figure 7.3 Structure of gum arabic [21].
Figure 7.4 Structure of tragacanth gum polysaccharide [24].
Chapter 8
Figure 8.1 Structure of α, β, and ϓ cyclodextrin.
Figure 8.2 Biomedical applications of cyclodextrins.
Figure 8.3 Structure of the monomeric derivative of cyclodextrins used for mak...
Figure 8.4 Synthesis of cross-linked CD polymer nanogel.
Figure 8.5 A different form of cyclodextrin polymer in drug delivery.
Figure 8.6 Cyclodextrin (CD)–PS inclusion complexes between β-CD and γ-CD with...
Figure 8.7 Structure of P(β-CD)1 and P(β-CD)2.
Figure 8.8 Chemical structure and schematic design of the trimethyl-β-CD (TMe-...
Figure 8.9 Cyclodextrin-based supramolecular inclusion complexes are induced b...
Chapter 9
Figure 9.1 Chemical structure of dextran [22].
Figure 9.2 Dextran-based nanoparticles for delivering insulin [47].
Figure 9.3 (a) Hesperidin. (b) Hesperetin [21].
Figure 9.4 Fabrication of CS/Dex/β-GP hydrogel [19].
Figure 9.5 Encapsulation of UCMSCs in CS/Dex/β-GP hydrogel [19].
Figure 9.6 Detecting mercury with Cu-sensitized Ag–dextran nanocomposite [17].
Chapter 10
Figure 10.1 Structure of pullulan [17].
Figure 10.2 Various pullulan conjugates for imaging applications [122].
Chapter 11
Figure 11.1 Structure of collagen.
Figure 11.2 General structure of collagen: (a) alanine, (b) glycine, (c) hydro...
Figure 11.3 Synthesis and structure of gelatin.
Figure 11.4 Applications of gelatin.
Figure 11.5 Biomedical applications of collagen-based biomaterials.
Figure 11.6 Biomedical applications of collagen fibers.
Chapter 12
Figure 12.1 Chemical structure of pectin [54, 55].
Figure 12.2 SEM images of hydrogels: (a) pure LM pectin, (b) LM pectin hydroge...
Chapter 13
Figure 13.1 Schematic representation of the generalized structure of lignin (i...
Figure 13.2 Schematic representation of the various methods employed for ligni...
Figure 13.3 Schematic representation of the antimicrobial effect of lignin pol...
Chapter 14
Figure 14.1 Structure of polycaprolactone.
Figure 14.2 Characteristics of PCL polymer.
Figure 14.3 Synthesis of PCL through enzymatic action [66].
Figure 14.4 Method of production of 3D porous polymers from PCL [69].
Figure 14.5 Conversion of the original polymer to a blended form to enhance th...
Figure 14.6 A total overview of the biomedical applications of PCL polymers [6...
Figure 14.7 A biodegradable and bioactive PCL 3D porous scaffold [68]. (a) PCL...
Chapter 15
Figure 15.1 Flow chart representing the stages of wound healing.
Chapter 16
Figure 16.1 Representation of the “circular plastic economy” [3].
Figure 16.2 Various plastics and bioplastic-based derivatives [3].
Figure 16.3 The synthesis route of polylactic acid [13].
Figure 16.4 Biomedical applications of polylactic acid.
Figure 16.5 Various biomedical applications of poly lactic-co-glycolic acid (P...
Figure 16.6 Biomedical applications of polycaprolactone.
Chapter 17
Figure 17.1 Schematic representation of the biological applications of chitosa...
Figure 17.2 Applications of gelatin-based pressure sensors to detect physical ...
Figure 17.3 Schematic diagram showing the fabrication of polycaprolactone-silk...
Chapter 18
Figure 18.1 Biopolymers from natural sources [25].
Figure 18.2 Potential adverse reactions to dental materials.
Chapter 19
Figure 19.1 Images of (a) 3D printing set-up, (b, c, d, f, g, and h) scaffolds...
Figure 19.2 3D printer test bed installed on the International Space Station [...
Figure 19.3 (a) Setup of the 3D printer and paste extruder, with an insert dis...
Figure 19.4 Schematics of the temperature-dependent shape recovery of printed ...
Figure 19.5 An illustrated diagram depicting the comprehensive workflow of an
Figure 19.6 Schematics of the 3D-printing-based synthesis of dapagliflozin con...
Figure 19.7 Development of 3D-printed grippers with multiple materials: (a) va...
Figure 19.8 3D printing of raw chicken using a food printer. (a) An up-close v...
Chapter 20
Figure 20.1 Release of medication as a pH-sensitive behavior
Figure 20.2 Release of drug from the PLGA bubble as a function of ultrasound w...
Guide
Cover Page
Table of Contents
Series Page
Title Page
Copyright Page
Dedication Page
Preface
Begin Reading
Index
WILEY END USER LICENSE AGREEMENT
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Scrivener Publishing100 Cummings Center, Suite 541JBeverly, MA 01915-6106
Publishers at ScrivenerMartin Scrivener ([email protected])Phillip Carmical ([email protected])
Biopolymers for Biomedical Applications
Edited by
Annu
School of Mechanical Engineering, Yeungnam University, South Korea
This edition first published 2024 by John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA and Scrivener Publishing LLC, 100 Cummings Center, Suite 541J, Beverly, MA 01915, USA© 2024 Scrivener Publishing LLCFor more information about Scrivener publications please visit www.scrivenerpublishing.com.
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Library of Congress Cataloging-in-Publication Data
ISBN 978-1-119-86502-5
Cover image: Pixabay.ComCover design by Russell Richardson
This book is dedicated to Time, my Mommy and Papa, and my dear Ashish.
Preface
In recent decades, significant progress has been made in polymer science for biomedical applications. The use of biopolymers specifically attracted the focus on the development of therapeutic polymeric systems. The exclusive features of biopolymers, such as biodegradability and biocompatibility make them highly sought after, and major research conducted with them has resulted in various therapeutic systems. However, until now only a few showed potential to be appropriate for human use. Furthermore, the development of artificial biopolymers to make modules for biomedical and pharmacological therapeutic systems is challenging.
This book especially focuses on the naturally available biopolymers with their use and application in the field of biomedical engineering. It elaborates on the specific biomedical applications of the most commonly used natural biopolymers. Natural biopolymers are thoroughly discussed individually, with attention paid to their exquisite biomedical applications.
Herein you will find 20 chapters penned by experts in the field of biopolymers and biomedical engineering. This book is an attempt to provide a complete resource that systematically discusses the most widely used biopolymers and their biomedical applications, and presents all important research and developments that have occurred in the field.
Each chapter covers a single biopolymer, its properties, and biomedical applications. The chapters are arranged systematically, with the most common biopolymers discussed early in the book to give more insight into the field. Further, a specific chapter is dedicated to the application of biopolymers for wound healing. Later, specific chapters are dedicated to the application of bioplastics and biopolymers for the development of medical devices and biosensors, respectively. Additionally, a chapter is dedicated to the application of biopolymers in the field of dentistry, with a special focus on their risk to human health. Keeping in mind recent advanced technologies, a chapter is dedicated solely to the latest progress of biopolymers in 3D and 4D printing for biomedical applications. The final chapter comprehensively explains the future perspectives of biopolymers in the biomedical field.
The book is a reference for scientists, research scholars, academicians, scientists, chemists, biologists, biotechnologists, polymer technologists, industrialists, health experts, and policymakers. To better comprehend the fundamental ideas of biopolymers and their biomedical applications, this book will also benefit undergraduate and graduate students of material science, polymer science, chemical engineering, and biotechnology. The book’s editor and contributors are academic and commercial researchers, and scientists who are leaders in their fields of study.
The contributing authors of this book deserve a huge thank you for their incredibly passionate efforts, as do the Scrivener and Wiley publishing teams for their help.
AnnuDecember 2023
1Introduction to Biopolymers
Gurleen Kaur, Rajinder Kaur and Sukhminderjit Kaur*
Department of Biotechnology, Chandigarh University, Mohali, Punjab, India
Abstract
Biopolymers have engrossed imperative position substantially in every recognizable field of research, manufacturing, and production sector such as pharmaceutical or therapeutic sector, edible industry, textile department, agronomics, cosmetics, and automotive industries due to their biodegradable, biocompatible, and superior resilience demeanor. Chitosan, cellulose, collagen, keratin, pectin, carrageenan, alginate, dextran, curdlan, and starch are the commonly utilized biopolymers by researchers in various fields of interest. Biopolymers can originate from natural sources and can be chemically obtained from biological elements or absolutely synthesized from microorganisms. On the basis of type of origin, polymer backbone, and repeating monomer units, biopolymers can be categorized into three different categories. Biopolymers have been irrefutably acknowledged and accepted in the biomedical region owing to its phenomenal usefulness in wound healing, tissue engineering, drug delivery, medical implants, and gene therapy. Chitosan, cellulose, dextran, alginate, pectin, curdlan, and starch are few commonly used biopolymers. This chapter discusses an introduction to biopolymers, its classification, commonly used biopolymers in different sectors, commercially available biopolymers, and biomedical applications of distinct biopolymers.
Keywords: Biopolymers, biomedical applications, wound healing, tissue engineering, medical implants, gene therapy, drug delivery
1.1 Introduction
Any material made up of long repeating monomer units is termed a polymer. Polymers have been extensively used in human being’s routine life for their use in vast applications. Among the polymers, biopolymers or the natural polymers have acquired unique consideration due to inexhaustibility, adaptability, biodegradability, and reasonability. Biopolymers are the larger structures organized from monomeric units synthesized typically from living beings such as microorganisms, herbs, shrubs, and animals with a covalent bond formation in their units [1]. The synthesis of biopolymers has achieved heavier interest in comparison to synthetic polymers like polyethylene, teflon, nylon, polyester, and many more due to distressing surrounding ecological troubles such as non-degradability, global heating, more expenses, burning of nonrenewable synthetic polymers, and unsustainability. Biopolymers are a magnificent substitute for synthetic and chemically synthesized polymers that are invariably being scrutinized to alleviate issues generated by the use of synthetic polymers [2]. One of the most valuable aspects owned by biopolymers is their easy degradation, which can be achieved with the extensive sort of disposal mechanisms such as decomposition in soil, landfill disposition, thermo-mechanical recycling, chemical recycling, microbial degradation, anaerobic digestion, and carbon dioxide neutral incineration [3]. A wide range of applications are associated with the use of biopolymers in the field of medical and pharmaceutical industry, agriculture sector, edible industry, automotive department, cosmetics, and textile industry [47, 51–54] (Figure 1.1).
Over the past few years, biopolymeric substances have enlivened the researchers for its utilization in the biomedical sector including drug delivery, tissue engineering, wound healing, gene therapy, and medical implantation due to their indispensable characteristic features. Biopolymers are being used as film, powders, and hydrogels in cardiac and liver tissue engineering, wound healing, and wound dressing because of its biodegradability and non-destructive behavior. Natural biopolymers such as alginate, chitosan, agar, collagen, casein, carrageenan, and starch have been extensively utilized in injectable and inhalation structures, drug delivery, and scaffold development [4, 5]. Biopolymers demonstrate multifaceted performance in different functionalities within the individual’s body like balance the resilience and hydration of skin, development of tissues through cell embracing, further governing the demeanor of cells by sending chemical signals to them, and providing flexibility to the gastrointestinal tract and joints through lubrication [1]. The chapter elucidates about the basic knowledge of biopolymers, classification of biopolymers, preparation of biopolymers, characterization of biopolymers, commercial availability of biopolymers, and their applications in various fields.
Figure 1.1 Applications of biopolymers.
1.2 Classification of Biopolymers
On the basis of type of origin, polymer backbone, and repeating monomer units, biopolymers can be categorized into three different categories as given in Figure 1.2.
1.3 Commonly Used Biopolymers
1.3.1 Chitosan
Chitosan is a derivative of chitin and one of the extensively considered polysaccharides obtained naturally. It is frequently derived from the cell wall of fungi and the firm outer covering of insects and crustaceans. Structurally, chitosan is formed by connecting glucosamine and N-acetyl-glucosamine via β-1,4 glycosidic linkages. Chitosan is widely employed in tissue engineering scaffold formation and wound dressing [9, 46, 49, 50].
1.3.2 Alginate
Alginate is a significant anionic unbranched linear polysaccharide also referred to as alginic acid. It is predominantly procured from the cell wall of brown algae or seaweeds, especially Laminaria and Ascophyllum species. Alginate can also be extracted in extracellular form from certain bacteria. Alginate is biosynthesized through copolymerization of β-d-mannuronic acid and α-l-guluronic acid possessing diverse quantities of 1,4 linkages of both monomer acid residues and is able to bind to different molecules having compliant absorptivity, biodegradability, and a biologically functional state [9]. Alginate is principally efficacious for tissue engineering by supporting the repair of liver, cartilage, pancreas, periphery nerve, and blood vessels [10].
Figure 1.2 Classification of biopolymers [6–8].
1.3.3 Cellulose
Cellulose is one of the extensively used existing biopolymers of glucose, allocated in plants as well as fibers like linen and cotton. Acetobacter xylinum is the bacterial species known to synthesize cellulose. Cellulose is made up of numerous hundreds to thousands of D-glucose monomer units linked by β(1→4) linear chains. Cellulose is an important biopolymer used in controlled drug delivery. Cellulose ether is utilized in solid tablets that permit the swelling-induced delivery of drug when anatomical fluid forms a communication with the tablet solely [11].
1.3.4 Starch
Starch is the fundamental energy reservoir plant polysaccharide which occurs in the granule form of amylopectin and amylose. Amylopectin is branched glucose polymer with high molecular weight, while amylose is a linear polymer made up of glucose monomers linked through α-D-(1-4) glycosidic bonds. The hydrogel of starch demonstrates resistance against gastric juices; therefore, it has applications in oral drug delivery and site-specific delivery systems. Starch is recognized for tissue engineering also because it assists in cartilage scaffold generation owing to its bone communicating characteristics [12].
1.3.5 Keratin
The protein keratin belongs to the class of polypeptide comprising different amino acids possessing disulphidecysteine intermolecular linkage. Keratin is highly useful in neural tissue regeneration. Keratin is classified on the basis of the presence of sulfur like soft and hard keratin [13]. Soft keratin contains lesser sulfur concentration, organized by cytoplasm filamentous clusters which are packed in unconstrained form, and offers flexibility to the epidermis, while hard keratin contains more sulfur concentration which supports epidermis stiffness comprising intermediate filaments organized in a systematic cluster entrenched in a cross-linked matrix. Two forms of keratin are known, including α-keratin and β-keratin. α-Keratin is present in hair, wool, and nails, whereas β-keratin is present in beaks and avian claws [13].
1.3.6 Carrageenan
Carrageenan is a general term assigned to the class of gelatinous and mucilaginous polysaccharide obtained from the class of Rhodophyceaea and red seaweed. Carrageenan is sulfated galactan having a repeated linear chain of d-galactose and 3,6-anhydro-d-galactose. Such polysaccharide possesses an antiviral aspect, by working as an interrupter of numerous enveloped viruses, antithrombotic potential through heparin co-factor II, and anticoagulant property. Kappa-carrageenan is scrutinized as a diabetic wound matrix and in regenerative medicines [9, 11].
1.3.7 Dextran
One of the complex glucans is dextran that is composed of a predominant chain of D-glucose associated through a α-(1,6) link with likely branches of D-glucose of α-(1,2), α-(1,3), and α-(1,4) links. The application of dextran includes gene transfection and nano-scale drug carrier. The generation of dextran takes place by employing a fermentation process using lactic acid bacteria in a sucrose medium. Dextran is also produced through an enzymatic pathway as it permits the generation of dextran with particular features [14].
1.3.8 Curdlan
This exopolysaccharide is constituted from monomers of glucose joined through β-(1,3) glycosidic linkages, synthesized by yeast origin like Saccharomyces cerevisiae, fungal species like Poria cocos, Aureobasidium pullulan, and different bacteria sources such as Paenibacillus, Alcaligenes, and Agrobacterium. Since many years ago, curdlan has been employed as dietary fibers for the growth of beneficial microorganisms in the gut and in pharmaceutical industries. It has also been reported that curdlan has the potential to inhibit the propagation of malaria parasite (merozoites) and therefore regarded as beneficial for the termination of malaria [15, 48].
1.3.9 Collagen
Collagen is the basic structural component of vertebrates and is an exceedingly copious mammalian protein. Fibroblasts assist in the formation of collagen and normally emerge from reticulum cells. Collagen has more affinity, no cytotoxicity, less antigenicity, and more extensile strength, biocompatibility, and degradability. Collagen exists in amino acids with a ternary helical structure including glycine, proline, and hydroxyproline [9]. Collagen is well acknowledged for tissue-based material such as vascular prosthesis and prosthetic heart valves due to elevated life expectation with a reduced risk of infection in several patients [11].
1.3.10 Pectin
This structural heteropolysaccharide is accommodated within the cell wall of terrestrial plants. Economic pectin is entirely obtained from apple pomace and citrus peel. Pectin exclusively comprises D-galactouronic acid monomers joined together through α-1,4-glycosidic bond. Pectin is greatly employed in food industry, target drug delivery, wound restoration, and tissue engineering. Pectin is endowed with biocompatibility, anti-inflammation characteristics, and biodegradability and restricts COX-2 and iNOS enzymes owing to the existence of esters in combination with galactouronic acid [16].
1.4 Preparation of Biopolymers
Biopolymers can be developed by using various techniques and methods. Majority of biopolymers formerly prevail in an environment or are synthesized by microorganisms. When biopolymers are formed with the assistance of microorganisms, particular source of nourishment and optimum environmental conditions are obligatory. Biopolymers are created either by a monomer’s chemical polymerization or through fermentation. Nearly all biopolymers are compatible and consistent, with negative antagonistic influence on the biological system. The technique for the production of biopolymers from a bacterial source is understood as a consequence of their deterrence system or as a repository compound [4].
In a literature study, researchers worked on the preparation of alginate biopolymer from four Azotobacter strains (Azotobacter MB1, MB2, MB3, and MB4) [17]. Alginate is an extracellular biopolymer which exists typically in specific brown seaweeds (Turbinaria, Ascophyllum, Laminaria, Lessonia, and Sargassum) commonly referred to as alginophyter or is secreted from natural derivatives. Azotobacter and Pseudomonas are the bacterial species known to produce alginate. Even though the vital origin for the secretion of alginate is seaweeds, bacterial sources are investigated and accepted as superior candidates for alginate production in comparison to algal alginates [18]. As Azotobacter is a nitrogen-fixing bacteria, alginate synthesis increases with the inclusion of a nitrogen source. Bhoir et al. [17] used the centrifugation method for the extraction of alginate from rhizospheric Azotobacter strains. Azotobacter was grown on Ashby’s mannitol broth for 48 h. After 48 h, the culture was suspended in saline and then centrifuged to remove the supernatant. Formalin and ethanol were added to the supernatant for 30 min. The supernatant was again centrifuged. The supernatant so obtained was discarded, thus obtaining the alginate pellet (Figure 1.3). Bhoir et al. (2020) also carried out a preparation of alginate using molasses. Initially, distilled water and ammonium sulfate were added to sugarcane bagasse and then heated. The solution was cooled and filtered using muslin cloth and further inoculated with Azotobacter strain and incubated. Aliquots were removed subsequently on each alternate day; saline was used for growth suspension, and centrifugation was performed. Finally, alginate pellets were obtained [17].
Figure 1.3 Preparation of alginate biopolymer from microorganisms and molasses.
1.5 Commercially Available Biopolymers
Biopolymers find various industrial applications such as cosmetics, food packaging, pharmaceuticals, and medicine. Given below in Table 1.1 is the list of companies that provide quality-grade biopolymers to be used in various industries.
Table 1.1 Some commercially available biopolymers.
Company
Product
Biopolymer used
Application
References
Badische Anilin –und SodaFabrik (BASF)
Ecovio
Poly lactic acid
Biodegradable superior quality flexible bioplastic
[19]
Badische Anilin –und SodaFabrik (BASF)
Ecoflex
Cellulose, lignin, starch, polyhydroxyalkanoates
Durable and completely biodegradable bioplastic
[20]
Integra
NeuraGen
Collagen
Resorbable implant used for the restoration of peripheral nerve discontinuities
[21]
Integra
DuraGen
Collagen
One of the safest and highly efficacious dural grafts to repair and restore dura mater (outer membrane of brain and spinal cord)
[22]
Integra
SurgiMend
Collagen matrix
Acellular matrix developed principally for reconstructive and plastic surgery
[23]
Integra
Integra Bilayer Matrix wound dressing
Collagen, glycosaminoglycan and polysiloxane
Effective wound dresser, offer scaffold for capillary growth and cellular invasion
[24]
Integra
Integra Bovine Pericardium dural graft
Collagen
For the reconstruction of dura mater
[25]
Total Carbion
Luminy
Polylactic acid
Rigid food packaging
[26]
Anika
Orthovisc
Hyaluronic acid
Employed for the treatment of joint pain produced by osteoarthritis
[27]
Braskem
Braskem FL900PP-CF filament
Polypropylene
Used in automotive, nautical, aerospace and sports materials, provides low shrinkage, reduced dryness and resistant to chemicals and water
[28]
1.6 Biomedical Applications of Biopolymers
1.6.1 Drug Delivery
Naturally existing biopolymers, specifically the polysaccharide form, have been employed in the medicament field for the effective and target delivery of an extensive sort of analeptic agents. After cellulose, chitosan is the second most consistently existing substantial polysaccharide and is well endowed with biodegradable and biocompatible mucoadhesive property, which is why it is being considered for the formation of nanoparticles and microparticles. Such developed particles have been utilized as a promising carrier in the field of pharmaceutics for numerous therapeutic agents such as in medication, vaccines, and stimulants for parental and non-parental applications [29]. As in drug delivery, chitosan biopolymer has been examined as the most stable biologically active and pervious polymer.
The administration and formulation of a therapeutically functional compound for the objective of supporting an adept drug plasma proportion and to deliver the drug to the target site of action is referred to as drug delivery. Nanotechnology has been employed as one of the eminent and proficient techniques in the establishment of unique drug delivery mechanisms via encapsulating the particular drug in a nano- or micro-particle arrangement [29]. The inclusion of a pharmacological agent within the polysaccharide polymeric matrix may strengthen the stability of a bioactive component from deterioration, enhance absorption, target drug delivery, and improve the pharmacological response. Alginate, chitosan, and carrageenan are the predominantly consumed polysaccharides in numerous medicinal applications [30].
In a literature study, researchers worked on the formation and interpretation of biopolymer-based nanoparticles to enhance the disintegration of curcumin within a gastrointestinal environment. Curcumin is a polyphenol having pharmaceutical applications such as anti-tumor, antiviral, anti-inflammatory, and antioxidant characteristics. Ionotrophic gelation was used for the development of numerous hydrogel matrices based on sodium carrageenan as well as alginate comprising curcumin-loaded chitosan particles. The entrapment of such polyphenol in chitosan indicated a substantial increment of disintegration of curcumin in aqueous media. After incubation, approximately 95% of curcumin release was observed in vitro[31]. Carrageenan principally assisted in increased curcumin delivery from hydrogel matrices. Hence, chitosan, alginate, and carrageenan act as promising biopolymers for curcumin’s improved aqueous-phase solubility.
In a recent study, Dutta et al. [32] reviewed the transdermal drug delivery aspect of xyloglycan to overcome acne remedy failure [32]. Xyloglycan is a biodegradable, mucoadhesive, and safe polysaccharide which is obtained from vascular plants’ cell wall and is generously found in tamarind seeds. Xyloglycan is usually utilized as a stabilizer, thickener, and gelling agent. Xyloglycan was used as a gelling agent for the formation of clindamycin-loaded transdermal patch. The administration of the drug was in the form of patches via the transdermal system to prevent it from intestinal degradation. Xyloglycan demonstrated more bioavailability and greater drug release [32]. Biopolymers demonstrate excellent potential and effectiveness to be used in the field of drug delivery for the proficient and maximum release of a drug to the target site.
1.6.2 Tissue Engineering
Since the midst of the 19th century, scientists are working for the formation of biopolymeric materials to be used in field of pharmaceutics, especially as a restorative device in tissue engineering for the provisional insert of scaffolds. Tissue engineering requires different scaffolds such as in skeletal muscle, bone, neural tissues, cartilage, and vascular tissues. Currently, numerous leading technologies and approaches are being selected to make a porous scaffold for rejuvenating tissues or organs for a convenient and acceptable application in tissue engineering [10]. The progress of tissue engineering is based upon the correct choice of biocompatible polymeric nanomaterials or micro-materials for the matrices’ build-up that would further demonstrate histocompatibility, superlative anatomical structure, cogent operational aspect, and mechanical features.
Biopolymers, due to their compatible features, are recognized as a substitute material to synthetic materials in the formation of scaffold. Biswal (2020) reviewed that collagen-based NeuraGen is greatly powerful for the restoration of peripheral nerve in approximately 43% of patients [10]. In a literature study, Perez-Guzman et al. [33] reviewed about zein as a promising biopolymer for tissue engineering by providing resistance to microbes, antibacterial properties, biodegradability, and compatibility [33]. Zein also worked as an eminent polymer in cardiac tissue engineering application with the presence of poly-glycerol sebacate [33]. Through electrospinning procedure, zein was used in research to form porous scaffold to repair serious skin damage. In a research, the combination of zein, gum arabic, and polycaprolactone was used to imitate a scaffold similar to the skin’s naturally occurring cells and tissues [34]. For the development of a skin scaffold, gum arabic and zein acted as the polysaccharide and protein component, respectively, while polycaprolactone provided firmness and resilience to the scaffold. The results demonstrated the profitable fabrication of a biopolymeric nanofibrous scaffold with interrelated fibrous organization and showed antibacterial aspect against Escherichia coli. The hydrophobicity of the scaffold was improved with the presence of gum arabic. Successful proliferation and adherence to the formulated scaffold was illustrated by fibroblast cells. Greater hydrophobicity, suitable porosity, surface for attachment, growth, and proliferation of cells on the fabricated scaffold supported that biopolymers are the potential candidates to be used in tissue engineering application [34].
1.6.3 Wound Healing
The disorganization or disrupt of biological and cellular continuance of tissues is inflicted by wounds causing abnormal physiological functioning. The healing of wound is thereupon a convoluted and eminent anatomical response which aids in the refurbishment of tissue integrity for accurate body functioning. The wound healing mechanism comprises a profoundly incorporated cascade of uninterrupted and coinciding biological occurrence. The presence of inchoate cells and cellular disruption likewise exposes susceptible zones for microbiological infection. Synchronized accomplishment of an array of biological episodes and prevention against infecting microbes are therefore essential for hemostasis, tissue restoration, and maturation. The fundamental target in wound administration is to cure and repair the wound in a minimum possible time period and lessen pain with no uneasiness to the patient, whereas microbial infection and nutritive inefficiency will be the aftereffects of a slow healing procedure [35].
Presently, wound healing requires materials with inherent compatible and antimicrobial aspects such as polysaccharides. In a recent study, researchers worked on the cynoflan biopolymer as a useful wound healer which is produced by Crocosphaera chwakensis CCY0110, a unicellular marine cyanobacterium [36]. The researchers concluded that such naturally synthesized extracellular cynoflan biopolymer elucidated the ability to be employed for skin dressing because it manifests a compatible behavior and permits the proliferation and migration of fibroblast and endothelial cells. Furthermore, maximum (100%) viability of the cells was observed, without causing tissue death and apoptosis, thus promoting optimum conditions for cell adherence and proliferation that are important for wound healing. Moreover, in vivo studies illustrated that, for skin wound restoration, cynoflan absolutely adjust to the wound platform without causing a local or intrinsic inflammatory or oxidative reaction [36].
Another polysaccharide—chitosan—has the potential to communicate with epithelial cells in conjugation with mucus, ultimately assisting in the rigid intracellular junction’s opening and therefore improving the permissibility of the epithelium. Considering diabetic wounds, chitosan is regarded to heal the wounds by reconstructing destructed tissue, eminent to lessen the chances of limb amputation. Alginate is the anionic polysaccharide which is known to be useful in wound healing [9]. Dressing with alginate improves the formation of collagen in skin, therefore administering the major extensible component and aiding in the regulation of skin growth. Alginate has the potential to absorb water and body fluids to accordingly develop a hydrophilic gel, therefore creating a moist condition for the restoration of wound. It has been reported that alginate dressing triggers monocytes to synthesize inflated TNF- and IL-6 cytokine levels [9]. Such biopolymers have proficiency and prove to be beneficial for the wound healing process (Figure 1.4).
Figure 1.4 Biomedical applications of biopolymers.
1.6.4 Medical Implants
The principal purpose of an implantable device is to change the impaired structure or organ to maintain normal functioning of the body as it imitates the specific body part. The usually employed therapeutic implants comprises cardiovascular, knee, breast, cartilage, ear, and eye implants. Implants own adeptness to support an injured organ, inspect, restore, rejuvenate, and administer drugs and treatment to the target site. Ceramics, synthetic polymers, and metals were among the classic or conventional components employed as implants, but they exhibited immunological denial by the body as a serious disadvantage of traditional implants. Synthetic polymers demonstrate a serious issue of non-degradability within the body, and they follow hydrolysis for their breakdown in releasing carbon dioxide that further reduces the pH, thus causing tissue and cell mortality [37]. Therefore, biopolymers have gained much attention owing to their lesser density, biodegradability, inexpensive characteristic, and good mechanical, chemical, and thermal stability. Some of the biopolymers used in the development of implants are cellulose, silk, collagen, and poly(3-hydroxyalkanoates). Due to the biopolymer’s similarity with the extracellular matrix, biocompatibility is demonstrated with no evidence of activation of a negative immune response [38]. Poly(3-hydroxyalkanoates) (PHAs) are employed for the formation of adherence obstructer, nerve and bone grafts, cardiac patches, and sutures. Actively maturing cardiovascular valve grafts are recreated with heart valve implantation as poly-lactic acid, decellularized extracellular matrix, poly-glycolic acid, and polycaprolactone support the differentiation, development, and cell growth. Poly(3-hydroxyoctanoate), a type of PHA, was used for the synthesis of trileaflet cardiac valve implant embedded with autologous cells. The valves illustrated appropriate functioning and minimum regurgitation [38]. Massive research has been conducted for the use of biopolymers to resolve the concerns associated with the field of ophthalmology, including the diverse parts of the eye such as corneal stroma retinal pigment epithelium, corneal endothelium, and limbal and corneal epithelium. Gelatin biopolymer is well known to restore ocular segments. Damage of the limbal epithelial stem cell causes suffering with pain, impaired vision, redness, and swelling, which are the major problems connected with limbal and corneal epithelium [38]. Limbal epithelial stem cell transplantation is the one and only method to regain normal vision. Chitosan and gelatin were employed for the construction of limbal epithelial stem cell substrata carrier. The activity was assessed by culturing corneal epithelial cells over distinct chitosan–gelatin membranes. As a result, biopolymers were reported with non-toxicity and greater cell proliferation features [39].
1.6.5 Gene Therapy
Cystic fibrosis is remarkably an existing and often fatal genetic disease in North American and European regions. Aberrant ion transit in the epithelium of numerous tissues occurs due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. As a consequence, unnaturally adhesive and dense mucus is generated, which obstructs and clogs the organs—predominantly the lung—subjecting it to cystic fibrosis pathology [40]. The dominant root of lethality in cystic fibrosis is pulmonary disorder as repetitive bacterial infection and constant inflammation happens; those further result in a dynamic damage to the lung tissues. For such a specific gene disease, the defect of the cystic fibrosis transmembrane conductance regulator gene requires an immediate and effective correction solution. Efficacious gene transfer structures require two segments consisting of a therapeutic nucleic acid and a transporter molecule which carries or bind to the nucleic acid. As of elevated immune response to vectors, the clinical techniques for cystic fibrosis genetic treatment have generally remained unsuccessful. However, due to a reported greater transfection proficiency, gene therapy aimed attention at viral vectors in cystic fibrosis therapy, although the application of viral vectors accelerates several issues with respect to biosafety, probable immune responses, and serious inflammation [41]. Hence, non-viral vectors stand out as an apparently secured alternative. The application of biocompatible and biologically degradable biopolymers like polylactic-co-glycolic acid and chitosan is evolving into more acceptable polymers for utilization in nanotechnology-based therapeutics for different diseases. In the literature studies, researchers worked on chitosan and polylactic-co-glycolic acid-based nanoparticles for cystic fibrosis lung gene therapy. The researchers generated the biopolymer-based CFTR-specific locked nucleic acid delivery system. The fabricated delivery method was developed in water, which was further nebulized such that it expedited a greater-performance aerosol dose transfer to the lungs, therefore maintaining biophysical characteristics with respect to particle size and indicating that such formulated biopolymer-based locked nucleic acid nanoparticles are advisable for cellular uptake and doubtlessly beneficial for clinical applications [40]. In another study, researchers evaluated and created an alendronate-formulated gelatin-based osteotropic nanocarrier for gene therapy studies. Bone-related disorders differ in their cause and behavior; however, a bone disorder’s general aspect of characterization includes hydroxyapatite exposure and inflammation. Four component systems were developed, which consisted of DNA, gemini surfactant, gelatin biopolymer, and alendronate sodium trihydrate [42]. Alendronate sodium trihydrate-formulated gelatin assisted in the formation of the core of nanoparticles and targeted the bone cells (Table 1.2). The formulated gelatin was examined for its efficiency to target osteoblastic gene cells. The formulated gelatin biopolymer was optimized with various ratios of gemini surfactant and DNA so as to develop a perfect system for in vitro transfection of kidney embryonic cells (HEK-293) and osteoblastic cells (MG-63). The results reported that the alendronate-formulated gelatin biopolymer is regarded as an efficient and favorable bone-targeting biopolymer. The alendronate sodium trihydrate-formulated gelatin acted as a potential vector for the development of cationic nanocomplexes for increased gene delivery to bone tissues [42].
Table 1.2 Biomedical applications of biopolymers in different aspects.
Application
Biopolymer used
Mode of action
References
Drug delivery
Sodium carrageenan, alginate, and chitosan
Improved curcumin disintegration in gastrointestinal system
[31]
Xyloglycan
Increment in bioavailability and more drug release to overcome acne treatment failure
[32]
Ethylcellulose
Assisted in development of vaginal mucoadhesive bilayer film by working as precursor for antiviral drug controlled release
[43]
Tissue engineering
Collagen
Peripheral nerve restoration
[10]
Zein
Important biopolymer for cardiovascular tissue engineering, provides resistance against microbes
[33]
Zein, gum arabic, and polycaprolactone
Mimics skin scaffold, imparts resilience and firmness to scaffold, successful adherence, and proliferation to scaffold
[34]
Dextran
Possess water solubility, biodegradability, and biocompatible properties; does not induce immune response indicating its appropriateness for tissue scaffold formation
[44]
Hyaluronic acid
Demonstrates antiinflammation and nonimmunogenicity features
[44]
Chitosan
Imparts mechanical structure that imitates extra cellular matrix
[44]
Wound healing
Cynoflan
Assists in skin dressing owing to its characteristics of migration and proliferation of endothelial cell and fibroblast
[36]
Chitosan
Useful for diabetic wound healing, reduces the limb amputation chances
[9]
Alginate
Enhance collagen formation in skin, assist in skin growth regulation, and triggers monocytes
[9]
Keratin and fibrin
Reconstruction of tissues for skin wound dressing consequently indicated cell adhesion, proliferation, and cell viable properties
[45]
Medical implants
Poly(3-hydroxyoctanoate)
Development of cardiovascular valve implant
[38]
Gelatin
Replacement of stroma
[38]
Chitosan, heparin, and collagen
Development of bioartificial liver, showed adequate hepatocyte and blood compatibility
[38]
Gelatin and chitosan
Aids in limbal epithelial stem cell implant, more cell proliferation
[39]
Hyaluronic acid
Useful in ear and throat implant, formation of specialized tissues like synovial fluid and vocal folds
[38]
Gene therapy
Chitosan and polylactic-co-glycolic acid
Cystic fibrosis lung gene therapy
[40]
Gelatin
Alendronate formulated gelatin-based osteotropic nanocarrier to cure bone disorder
[42]
1.7 Conclusion
The quest to work with biopolymers in different areas has expanded in order to diminish the utilization of non-biodegradable and non-compatible materials so as to decrease the ecological pollution and imbalance caused by the employment of synthetic materials. Biopolymers support multifarious benefits in the therapeutic and biomedical fields. The resources that can be utilized in wound repair, engineering of tissues, medical implants, target site delivery of drugs, and gene therapy ought to have a non-cytotoxic behavior, biodegradability, biocompatibility, should not induce immune response, more functional attribute, potent to assist cell proliferation and adhesion, adequate mechanical aspects, and sustain mechanical strength. Biopolymers are endowed with such characteristics and have the potential to successfully accomplish the requirements. Biopolymers have acquired abundant attention as a sustainable candidate in research studies as they have the efficiency of addressing ecological necessity and are suitable than synthetic materials. Naturally obtained biopolymers are copiously available, like alginate, chitosan, xanthan, collagen, and pectin, while certain biopolymers are synthesized using chemical processes. The preference for biopolymer relies upon their source, characteristics, and formation mechanisms to evenly exist without any complications in a specific field of application. However, the higher expense for the formation of biopolymers is obstruction if they are designed to take over traditional polymers. Therefore, in the future, additional studies and research must be conducted to generate inexpensive biopolymers that would accommodate the rigorous requirement of human well-being and ecological adverse effect studies. Future studies can also be planned to explore extraction approaches and development mechanisms that will balance the drawback of expensive production and assist in the commercialization of biopolymers with improved characteristics.
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