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Über dieses Buch

The book is an excellent reference for scientists, researchers and students working in the field of areas of biopolymeric biomaterials, biomedical engineering, therapeutics, tissue engineering and regenerative medicine. The book is divided into two parts: Part I will focus on the tissue engineering and Part II focuses on therapeutics, functionalization and computer-aided techniques. The book consists of 13 chapters contributed by 20 international contributors who are leading experts in the field of biopolymers and its applications. It will focus on the advancements of chitin and chitosan in regenerative medicine.

Regenerative medicine in tissue engineering is the process of replacing or regenerating human cells, tissues, or organs to restore or establish normal function. It is an incredibly progressive field of medicine that may, in the near future, help with the shortage of life-saving organs available through donation for transplantation vis-a-vis regenerative medicine focuses on therapeutics, functionalization and computer-aided techniques.

It also covers physical and chemical aspects of chitin and chitosan, structural modifications for biomedical applications, chitosan based scaffolds and biomodelling in tissue engineering, nanomedicines and therapeutic applications. With the broad range of applications, the world is waiting for biopolymers to serve as the basis for regenerative medicine and biomedical applications.



Focus on Tissue Engineering


Chitosan Hydrogels for Regenerative Engineering

Research in the field of hydrogels has been actively growing for the past couple of decades. Hydrogels are crosslinked polymers with high water content. They can be prepared from natural, synthetic, and composite polymers using different chemical and physical crosslinking methods. Hydrogels have been widely explored for the delivery of bioactive molecules, drugs, and for other therapeutic applications. Chitosan-based hydrogels have unique advantages owing to their biocompatibility, biodegradability, antimicrobial activity, mucoadhesivity, and low toxicity. This chapter reviews the different methods used for preparing chitosan-based hydrogels and their applications as cell, protein, and drug delivery vehicles to support tissue regeneration.
Aiswaria Padmanabhan, Lakshmi S. Nair

Prospects of Bioactive Chitosan-Based Scaffolds in Tissue Engineering and Regenerative Medicine

Chitosan, a natural-based polymer obtained by alkaline deacetylation of chitin, is non-toxic, biocompatible, and biodegradable. Due to its desired properties, chitosan-based materials are widely considered to fabricate scaffolds for tissue engineering and regenerative medicine. These scaffolds provide characteristic advantages, such as preservation of cellular phenotype, binding and enhancement of bioactive factors, control of gene expression, and synthesis and deposition of tissue-specific extracellular matrix (ECM), to tissue regeneration. Therefore, the scaffolds based on chitosan and its composites have potential to be used in bone, cartilage, liver, nerve, and musculoskeletal tissue engineering.
M. Prabaharan, P. R. Sivashankari

Chitosan-Based Scaffolds for Cartilage Regeneration

Intra-joint trauma often accompanies cartilage damage, as one of the main reasons of osteoarthritis, which often induce severe pain and limited joint function in the final stage. Because of the poor regenerative capacity, cartilage repair has been on the top list of regenerative medicine from decades ago. Recently, the researches of cartilage regeneration are mainly focused on the development of novel scaffolds, which can provide spatial frame and logistic template for stem cells, other progenitor cells, or chondrocytes to proliferate or differentiate into cartilage-like tissues. Among the dazzling scaffolds, chitosan-based systems, including physical hydrogels, chemically cross-linked hydrogels, or porous scaffolds, show great potential in cartilage tissue regeneration. Chitosan possesses superior characteristics, such as biocompatibility, biodegradability, bioabsorbability, low immunogenicity, and intrinsic antibacterial nature, for potential applications in tissue engineering. Specially, the chemical structure of chitosan is similar with various glycosaminoglycans (GAGs), which play important roles in chondrocyte morphology modulation, differentiation, and function. In addition, appropriate mechanical properties and porosity, excellent cell adhesion, and even control release of functional growth factors are achieved in chitosan-based scaffolds. In this chapter, the advancements of different types of chitosan-based scaffolds for cartilage regeneration are systemically summarized, and the future directions are predicted.
Xuezhou Li, Jianxun Ding, Xiuli Zhuang, Fei Chang, Jincheng Wang, Xuesi Chen

Composite Chitosan-Calcium Phosphate Scaffolds for Cartilage Tissue Engineering

Cartilage covering the articulating surfaces of bones in diarthrodial joints provides for almost frictionless motion. If this tissue is damaged either due to traumatic injury or disease, it lacks the ability of self-repair. The goal of cartilage tissue engineering is to regenerate healthy hyaline cartilage by combining chondrocytes or stem cells with a variety of natural and synthetic scaffold materials. Chitin is one of the most abundant naturally occurring polysaccharides. Its deacetylated derivative chitosan is biocompatible, biodegradable, and may retain functional characteristics that promote site-appropriate tissue reconstruction. This chapter includes methods for fabrication of chitosan-calcium phosphate (CHI–CaP) composite scaffolds, scaffold physical characteristics, as well as techniques for creation of cartilage/CHI–CaP biphasic constructs. Coating CHI–CaP scaffolds with type I collagen facilitates formation of a continuous layer of neocartilage with approximately uniform thickness over the cell-seeded area. Aspects of the scaffold’s degradation are also discussed.
Anuhya Gottipati, Steven H. Elder

Chitosan-Gelatin Composite Scaffolds in Bone Tissue Engineering

Regenerative medicine focuses on repair/replacement of the damaged tissue or organ in our body. This is done by growing cells on scaffold materials which help in its attachment, migration and proliferation. Chitosan being natural polymer has many unique properties such as being biocompatible, biodegradable and also has antibacterial and wound-healing abilities. Gelatin a derivative of collagen, which is widely present in our body, has been used as a composite with chitosan for promoting cell attachment, proliferation, and differentiation. Composite scaffolds have also shown better mechanical and functional properties because these composites are made of polymer and inorganic/organic blenders. Overall this review focuses on the role of chitosan-gelatin-based composite scaffolds in bone tissue engineering.
M. Nivedhitha Sundaram, S. Deepthi, R. Jayakumar

Chitin and Chitosan Nanocomposites for Tissue Engineering

Chitin and chitosan are the most widely used biodegradable and biocompatible materials subsequent to cellulose. Nowadays a wide range of materials, including those classified as organic, inorganic, and biological are used in the synthesis, fabrication, and processing of nanostructures with unique physical properties. The properties of the polymer significantly improve by dispersing a few percentage of nanoparticle in the polymer matrix. In this context, we are focusing on the preparation, characterization, and bioactivity of chitin and chitosan nanocomposite in detail. The morphological changes occur in presence of nanoparticle. The improvement of thermal and mechanical properties including dynamic mechanical behavior of chitin and chitosan in presence of different nanofillers has been discussed in detail with suitable example as potential material for bone and wound tissue engineering applications. We summarize the physicochemical and drug delivery properties of chitin and chitosan composites. The cytocompatibility of the nanocomposites is assessed with improved cell attachment and proliferation using different human cells. This chapter enhances the understanding of biological uses of chitin and chitosan with their improved properties in presence of nanoparticles. A new approach at the intersection of biology and nanotechnology is focused to develop the next promising eco-friendly biopolymer nanocomposites.
Arun Kumar Mahanta, Pralay Maiti

Chitin, Chitosan, and Silk Fibroin Electrospun Nanofibrous Scaffolds: A Prospective Approach for Regenerative Medicine

Intensive studies have been done to a wide range of natural and synthetic polymeric scaffolds which have been done for the use of implantable and temporal devices in tissue engineering. Biodegradable and biocompatible scaffolds having a highly open porous structure with compatible mechanical strength are needed to provide an optimal microenvironment for cell proliferation, migration, differentiation, and guidance for cellular in growth at host tissue. One of the most abundantly available biopolymer chitins and its deacetylated derivatives is chitosan which is non-toxic and biodegradable. It has potential biomedical applications such as tissue engineering scaffolds, wound dressings, separation membranes, antibacterial coatings, stent coatings, and biosensors. Recent literature shows the use of chitin and chitosan in electrospinning to produce scaffolds with improved cytocompatibility, which could mimic the native extra-cellular matrix (ECM). Similarly, silk from the Bombyx mori silkworm, a protein-based natural fiber, having superior machinability, biocompatibility, biodegradation, and bioresorbability, has evolved as an important candidate for biomedical porous material. This chapter focuses on recent advancements made in chitin, chitosan, and silk fibroin-based electrospun nanofibrous scaffolds, emphasizing on tissue engineering for regenerative medicine.
Brijesh K. Singh, Pradip Kumar Dutta

Focus on Therapeutics, Functionalization and Computer Aided Techniques


Chitosan: A Potential Therapeutic Dressing Material for Wound Healing

A wide variety of polymers have been used over decades for the preparation of dressing materials for wound healing applications. But the dressing materials based on polysaccharides such as chitosan (CS) have received tremendous attention of the worldwide researchers as a consequence of its important properties like anti-infectional activity, biocompatibility, biodegradability, nontoxicity to mention a few. CS helps in every phase of wound healing such as acting as barrier against microbes, absorbing exudates, accelerates the infiltration of inflammatory cells like neutrophils and helps in healing without scar formation. A reason behind the popularity of CS is that not only it can easily be processed as gels, films, fibers, and scaffolds but also can be blended with natural as well as synthetic polymers to reduce price and improve properties like mechanical, wettability, gas permeability, and handling. Apart from natural and synthetic polymers, CS is also blended with nanoparticles and growth factors to which it shows better antibacterial activity and reduce time span for wound healing. The present chapter aims to focus on feasibility of combining natural polymers, synthetic polymers, nanoparticles, and growth factors with CS for the preparation of wound dressings as basic healthcare materials for regenerative medicine.
D. Archana, Pradip Kumar Dutta, Joydeep Dutta

Recent Advances in Chitosan-Based Nanomedicines for Cancer Chemotherapy

Chitosan, a cationic polysaccharide, has prompted the continuous impetus for the development of tumor targeted drug delivery systems, thanks to the polymer’s biocompatibility, low toxicity, and biodegradability. The presence of primary hydroxyl and amine groups on its backbone allows it for chemical modifications to control its physical properties. The nanomedicines prepared from chitosan and its derivatives can be delivered through different routes, such as oral, intravenous, and intraperitoneal. Chitosan-based nanomedicines including nanoparticles, microspheres, drug conjugates, micelles, hydrogels, etc. are in various stages of development. This polymer is being currently investigated for simultaneous delivery of two chemotherapeutic agents or chemotherapeutic agent with a gene carrier to produce synergistic effects. This chapter summarizes the recent advances in application of chitosan and its derivatives as a carrier for chemotherapeutic agents as well as gene carriers for cancer chemotherapeutics.
Ankit Saneja, Chetan Nehate, Noor Alam, Prem N. Gupta

Chitosan: A Promising Substrate for Regenerative Medicine in Drug Formulation

Chitosan plays a most important role in the regenerative medication for wound healing. The adhesive nature of chitosan, with their antifungal and bactericidal character, and their permeability to oxygen, is a very important property associated with the treatment of wounds. Different derivatives and combination of chitosan have been reported for this purpose in the form of hydrogels, fibers, membranes, scaffolds and sponges. The purpose of the chapter is to have a closer look in the work done directly by different researchers on the chitosan formulation with potential medicinal applications to provide a better understanding of its usability in regenerative medicine.
Madhu Kashyap, D. Archana, Alok Semwal, Joydeep Dutta, Pradip Kumar Dutta

D-Glucosamine and N-Acetyl D-Glucosamine: Their Potential Use as Regenerative Medicine

Glucosamine (GlcN), an amino sugar, is a compound derived from substitution of a hydroxyl group of a glucose molecule with an amino group. GlcN and its acetylated derivative, N-acetylglucosamine (GlcNAc), have been widely used in food, cosmetics, and pharmaceutical industries and are currently produced by acid hydrolysis of chitin (a linear polymer of GlcNAc) extracted from crab and shrimp shells. In this review, distribution and production of GlcN and GlcNAc, their chemistry and determination in the complex samples will be treated first. This review will describe the procedure to identify a high-quality glucosamine product for Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) and to clarify confusing product information and nomenclature. GlcN is a precursor of the glycosaminoglycans and proteoglycans that make up articular cartilage. Glucosamine sulfate and glucosamine hydrochloride have used for the treatment of osteoarthritis for more than 30 years, with no major known side effects. The notion that augmenting the intake of the precursor molecule, glucosamine, may directly stimulate articular proteoglycan synthesis to modulate osteoarthritis has provided the rationale for its widespread use. Theoretically, exogenous glucosamine may augment glycosaminoglycan synthesis in cartilage. There is a simultaneous theoretical concern that it might also induce insulin resistance in insulin-sensitive tissues. While the efficacy of glucosamine was published in the definitive medical journals, there were views against it. This concern will be also discussed. While glucosamine was not effective without combination with chondroitin sulfate in the some trial, glucosamine alone was effective in the other trial. Some concerns about these trials will be discussed together with the mechanism of action of glucosamine and chondroitin for antiarthritic potential. Finally, the review will focus on the biomedical and other application of the glucosamine and chitosan oligosaccharide. Such biomedical applications include wound healing, bone regeneration, antibacterial effect, and oral hygiene. It also discusses the role of chitosan oligosaccharide as a drug carrier for molecular therapies, such as the drug and the gene delivery systems and the role in imaging for tumor and cancer detection.
Tanvi Jain, Hridyesh Kumar, Pradip Kumar Dutta

Functionalized Chitosan: A Quantum Dot-Based Approach for Regenerative Medicine

Quantum dots (QDs) are the semiconducting inorganic substances that form luminescent nanocrystals with unique optical properties. The formation of shell and or functionalization of it may be utilized as probes or carriers for target-specific cells or tissues for proper utilization in the field of regenerative medicine. Thus, the association of chitosan makes the entire body as biocompatible and suitable for optical stability in physiological environment. QDs-bound hybridization probe design reported for detection of intracellular pre-miRNA using chitosan poly(γ-glutamic acid) complex as a gene vector toward the progress and prognosis of cancer. It is also demonstrated that chitosan-based QD hybrid nanospheres can be internalized by tumor cells and hence act as labeling agent in cell imaging by optical microscopy. The challenge of such cell imaging in the field of molecular imaging is also being discussed. Overall, the interest in using chitosan–QDs in regenerative medicine and the current barriers to moving the technique into the clinic as great challenges will also be discussed.
Hridyesh Kumar, Pradip Kumar Dutta

Development and Selection of Porous Scaffolds Using Computer-Aided Tissue Engineering

Tissue engineering is considered a multidisciplinary field where the involvement of many course of studies as well as utilization of knowledge of various researchers/scientists and medical practitioners provided good health care and esthetics concepts. Porous scaffolds play very important role in tissue engineering and many of the relevant disciplines. Henceforth, the development and selection of proper scaffolds, particularly in the form of porous due to multifaceted microstructure-like veins and capillaries is essential. Computer-Aided Tissue Engineering (CATE) is an important tool to categorize the porous scaffolds in terms of design, modeling as well as experimental validation. The present article describes the selection of materials, facilitated properties, experimental methods, knowledge of computer to fabricate scaffolds.
Nitin Sahai, Tanvi Jain, Sushil Kumar, Pradip Kumar Dutta


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