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- Herausgeber: Wiley-VCH
- Kategorie: Fachliteratur
- Sprache: Englisch
Develop natural solutions to biomedical problems with this introduction
A natural polymer is one that forms from biosynthetic or biochemical processes typically found in nature, with corresponding advantages in biocompatibility and biodegradability. These advantages give natural polymers a range of applications, from the use of polysaccharides as structural components to the use of polyphenols as antioxidant active ingredients. In biomedical engineering they are clearly preferable to synthetic polymers in numerous cases, and their applications are more numerous every day.
Natural Polymers for Biomedical Applications offers a comprehensive summary of these polymers and their biomedical applications. It covers the sources, structures, and properties of polysaccharides, polyphenols, and polypeptides, as well as analyzing the latest advances in polymer-based biomedical technologies. The result has ramifications in a vast range of industries and research areas.
In Natural Polymers for Biomedical Applications readers will also find:
- Applications including drug and cell delivery, cell and organoid cultures, tissue regeneration, and more
- Detailed analysis of alginate, cellulose, quercetin, silk fibroin, and many others
- A logical, easy-to-use structure to facilitate rapid access to pertinent information
Natural Polymers for Biomedical Applications is ideal for materials scientists, polymer chemists, biochemists, and any researcher or professional in biomedical or pharmaceutical industries.
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Seitenzahl: 341
Veröffentlichungsjahr: 2024
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Table of Contents
Cover
Table of Contents
Title Page
Copyright
Graphical Abstract
Foreword
Preface
Acknowledgments
Section I: Historical Review of the Development of Natural Polymers
References
Section II: Polysaccharides for Biomedical Application
1 Sources, Structures, and Properties of Alginate
1.1 Alginate‐Based Hydrogel for Biomedical Application
1.2 Alginate‐Based Electrospinning for Biomedical Application
1.3 Alginate‐Based 3D Printing for Biomedical Application
References
2 Sources, Structures, and Properties of Cellulose
2.1 Cellulose‐Based Hydrogel for Biomedical Application
2.2 Cellulose‐Based Electrospinning for Biomedical Application
2.3 Cellulose‐Based 3D Printing for Biomedical Application
References
3 Sources, Structures, and Properties of Hyaluronic Acid
3.1 Hyaluronic‐Acid‐Based Hydrogel for Biomedical Application
3.2 Hyaluronic‐Acid‐Based Electrospinning for Biomedical Application
3.3 Hyaluronic‐Acid‐Based 3D Printing for Biomedical Application
References
4 Sources, Structures, and Properties of Chitosan
4.1 Chitosan‐Based Hydrogel for Biomedical Application
4.2 Chitosan‐Based Electrospinning for Biomedical Application
4.3 Chitosan‐Based 3D Printing for Biomedical Application
References
5 Sources, Structures, and Properties of Other Polysaccharides
5.1 Other Polysaccharides‐Based Hydrogel for Biomedical Application
5.2 Other Polysaccharides‐Based Electrospinning for Biomedical Application
5.3 Other Polysaccharides 3D Printing for Biomedical Application
References
6 Summary
Section III: Polypeptides for Biomedical Application
7 Sources, Structures, and Properties of Collagen
7.1 Collagen‐Based Hydrogel for Biomedical Application
7.2 Collagen‐Based Electrospinning for Biomedical Application
7.3 Collagen‐Based 3D Printing for Biomedical Application
References
8 Sources, Structures, and Properties of Gelatin
8.1 Gelatin‐Based Hydrogel for Biomedical Application
8.2 Gelatin‐Based Electrospinning for Biomedical Application
8.3 Gelatin‐Based 3D Printing for Biomedical Application
References
9 Sources, Structures, and Properties of Silk Fibroin
9.1 Silk‐Fibroin‐Based Hydrogel for Biomedical Application
9.2 Silk‐Fibroin‐Based Electrospinning for Biomedical Application
9.3 Silk‐Fibroin‐Based 3D Printing for Biomedical Application
References
10 Sources, Structures, and Properties of Other Polypeptides
10.1 Other Polypeptides‐Based Hydrogel for Biomedical Application
10.2 Other Polypeptides‐Based Electrospinning for Biomedical Application
10.3 Other Polypeptides‐Based 3D Printing for Biomedical Application
References
11 Summary
Section IV: Other Kinds of Natural Polymers for Biomedical Application
12 Sources, Structures, and Properties of Catechins
12.1 Catechins‐Based Hydrogel for Biomedical Application
12.2 Catechins‐Based Electrospinning for Biomedical Application
12.3 Catechins–Metal Complexes for Biomedical Application
References
13 Sources, Structures, and Properties of Quercetin
13.1 Quercetin‐Based Hydrogel for Biomedical Application
13.2 Quercetin‐Based Electrospinning for Biomedical Application
13.3 Quercetin–Metal Complexes for Biomedical Application
References
14 Sources, Structures, and Properties of Resveratrol
14.1 Resveratrol‐Based Hydrogel for Biomedical Application
14.2 Resveratrol‐Based Electrospinning for Biomedical Application
14.3 Resveratrol–Metal Complexes for Biomedical Application
References
15 Sources, Structures, and Properties of Curcumin
15.1 Curcumin‐Based Hydrogel for Biomedical Application
15.2 Curcumin‐Based Electrospinning for Biomedical Application
15.3 Curcumin–Metal Complexes for Biomedical Application
References
16 Summary
References
17 Conclusion and Outlook
References
Declaration of Competing Interest
Nomenclature
Index
End User License Agreement
List of Illustrations
Chapter 1
Figure 1.1 (a) Fusion membrane nanoparticles (FM‐NPs) were prepared from aut...
Figure 1.2 (a1) Schematic diagram of hydrogel vesicle formation containing n...
Figure 1.3 (a) Images of hydrogel vesicles generated at different core flow ...
Figure 1.4 (a) Schematic of the chemical structure of sulfated sodium algina...
Figure 1.5 (a) The hydrogel is reversible and can be formed and dissolved re...
Figure 1.6 (a) A hydrogel preparation method formed from polymers and nanopa...
Figure 1.7 (a) Conventional rotary mandrel electrospinning forms a dense pol...
Figure 1.8 (a) Cardiac patch preparation process. (b) Application process: t...
Figure 1.9 (a) Overview of CAM experiments. (b) Quantitative comparison of v...
Chapter 2
Figure 2.1 (a) Preparation of QAS–HAp–CS hydrogel: QAS monomer was first pol...
Figure 2.2 (a) After 12 hours of co‐cultivation, the turbidity of the bacter...
Figure 2.3 (a) Crypts cultured in pure gels showed large areas of dead cells...
Figure 2.4 Schematic illustration for the preparation and chemical structure...
Figure 2.5 (a) Vaginal tissues were covered with electrospun carboxylic acid...
Figure 2.6 Effect of cellulose acetate concentration (wt%) on fiber morpholo...
Figure 2.7 Chemical structure of cellulose and its derivatives.
Figure 2.8 (a) Synthesis of BAPO derivatives and functionalization of cellul...
Figure 2.9 (a) Step‐by‐step 3D printing of a magnetic scaffold including sub...
Chapter 3
Figure 3.1 (a) Schematic diagram depicting the evolution of the mechanical p...
Figure 3.2 (a) The amount of laminin retained in the hyaluronic acid oxidize...
Figure 3.3 Schematic illustrations of the fabrication of self‐assembled HA‐P...
Figure 3.4 Magnetic particles embedded in hydrogels can activate PIEZO2 mech...
Figure 3.5 Diagram illustrating the formation of (Ag‐PGA/HA)‐PVA.
Figure 3.6 (a) Soft and hard methylated hyaluronan were prepared by modifyin...
Figure 3.7 (a) Multi‐step digital photoprocessing bioprinting method to prep...
Figure 3.8 (a) A DLP‐based 3D printing platform is described. (b) A CAD mode...
Chapter 4
Figure 4.1 Fabrication of hybrid CS‐PAM ionic–covalent DN hydrogels.
Figure 4.2 (a) Curing of MeGC‐MMT nanocomposite hydrogels by visible blue li...
Figure 4.3 Schematic representation of the preparation of SCHB2‐thick and SC...
Figure 4.4 Preparation process of CS islanded‐structured scaffolds.
Figure 4.5 (a) Photocross‐linkable methacryloyl chitosan was synthesized. (b...
Figure 4.6 (a) Chemical structures of OHA, GC, and ADH. (b) Photographs of t...
Chapter 5
Figure 5.1 (a) Direct mixing of nanoparticle catalysts into large‐molecular‐...
Figure 5.2 An in situ molded hydrogel material with good biocompatibility, b...
Figure 5.3 Preparation process of starch‐based nanofibers.
Chapter 7
Figure 7.1 (a) Expression and purification of recombinant fusion protein GST...
Figure 7.2 General schematic illustration of the fabrication process and imp...
Figure 7.3 (a) The gross appearance and SEM images of electrospun PCL/collag...
Figure 7.4 (a) Collagen‐modified 3D‐TIPS elastic scaffolds are described. (b...
Chapter 8
Figure 8.1 Schematic of G‐NGO hydrogel synthesized by the Ar‐NT microplasma ...
Figure 8.2 (a) The composition of two bioinks and the method for 3D printing...
Chapter 9
Figure 9.1 Scheme of the BSICT strategy to fabricate pristine SF hydrogels w...
Figure 9.2 (a) Modification of silk protein (SF) molecules with glycerol dim...
Chapter 10
Figure 10.1 (a) Sequences of cysteine‐containing ELPs tested for photocross‐...
Figure 10.2 (a) Bio‐ink formulation. (b) Bio‐ink viscosity profile at differ...
Chapter 13
Figure 13.1 A novel nanomedicine based on natural materials for dual‐targete...
Chapter 15
Figure 15.1 (a) Synthesis route of QCS polymer. (b) Structure of PF127‐CHO p...
Guide
Cover
Table of Contents
Title Page
Copyright
Graphical Abstract
Foreword
Preface
Acknowledgments
Begin Reading
Declaration of Competing Interest
Nomenclature
Index
End User License Agreement
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Natural Polymers for Biomedical Applications
Wenguo Cui and Lei Xiang
Authors
Dr. Wenguo CuiRuijin HospitalShanghai Jiao Tong UniversitySchool of Medicine197 Ruijin 2nd RoadShanghai 200025China
Dr. Lei XiangRuijin HospitalShanghai Jiao Tong UniversitySchool of Medicine197 Ruijin 2nd RoadShanghai 200025China
Cover Image: © Andriy Onufriyenko/Getty Images
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Print ISBN: 978‐3‐527‐35354‐5ePDF ISBN: 978‐3‐527‐84557‐6ePub ISBN: 978‐3‐527‐84559‐0oBook ISBN: 978‐3‐527‐84558‐3
Graphical Abstract
Natural polymer is a type of polymer compound formed based on photosynthesis or biochemical action that is widely found in animals, plants, and bacteria in nature, which has good biocompatibility, biodegradability, and low immunogenicity. This review summarizes the natural polymers basic structure and properties, focusing on the recent progress of natural polymer hydrogels, electrospun fibers, 3D bio‐printing scaffolds, and polyphenol–metal complexes in the field of biomedicine.
Foreword
Source: Yuanjin Zhao (Chapter author).
Professor Yuanjin Zhao
With increasing research on natural polymers and the rapid development of biomanufacturing technology, various natural polymer‐based biomaterials have been widely used to repair and regenerate bone, muscle, tendon, skin, and other tissues and organs. This book focuses on the current state of the manufacturing technologies and applications of natural polymer materials in the biomedical field.
The highlights of the book include a comprehensive analysis of different biomanufacturing methods for biomaterials related to polysaccharides, peptides, and polyphenol natural polymers, mainly covering recent developments in novel biomaterials such as hydrogels, electrospun fibers, metal‐polyphenol nanoparticles, and 3D printing. In addition, the book provides a detailed overview of the advantages and disadvantages of each type of material for application in different scenarios and an entirely rationalized discussion of the future development and research directions of natural polymer‐based biomaterials. Biofabrication technology effectively links clinical research and material development, helping to accelerate the clinical translation of novel natural polymer‐based biomaterials and facilitating the development of targeted therapeutic strategies for different diseases or injuries. This book is a significant contribution to the advancement of translational medicine.
The book is organized in a precise, practical, rigorous, and, most importantly, up‐to‐date manner. It will provide the biomedical field with a reference on the preparation methods of natural polymer‐based biomaterials and enhance the reader's understanding of natural polymers in biomedical applications.
In essence, this book is written in an informative manner, providing beneficial and relevant content for trained physicians and biomaterials researchers in the context of multidisciplinary cross‐fertilization, which will help readers grasp the fundamentals of preparation of various biomaterials and thus deepen their understanding of their application in orthopedics. The authors believe that readers and researchers can gain inspiration and ideas for developing a new generation of natural polymer biomaterials through this book.
Yuanjin Zhao
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital,
School of Pharmacy, Clinical College of Traditional Chinese and Western Medicine,
Nanjing University of Chinese Medicine, Nanjing 210023, China
State Key Laboratory of Bioelectronics, School of Biological Science and
Medical Engineering, Southeast University, Nanjing 210096, China
11 November 2023
Source: Kai Liu (Chapter author).
Professor Kai Liu
Over the past decades, inorganic polymers have been widely used in biomedical applications. However, such biomaterials have always suffered from a lack of bioactivity and poor biocompatibility, so there is an urgent need to innovate from the underlying material design logic. Natural polymer materials have attracted more and more attention from researchers due to their unique bioactivity and good biosafety, and their applications in biomedical fields are springing up.
This book systematically showcases popular and compelling natural polymer‐based biomaterials and biomanufacturing technologies, explains in detail their current development and application potential in many clinical departments such as orthopedics, urology, dermatology, and endocrinology, and further analyzes the natural fit between natural polymer materials and various clinical diseases. One of the book's highlights is the coverage of the most innovative biomaterials manufacturing technologies, which emphasizes the safety of biomanufacturing, which we do not yet fully understand, and the solutions that need to be developed. The book also briefly explains why we should consider using these materials to treat diseases and efficiently repair and regenerate tissues and organs.
The editors and authors of this book hope to enrich the knowledge of frontline clinicians, readers in the biomedical field, and researchers in the field of bioengineering. This book can give many researchers and clinicians a detailed understanding of material science construction and ideas for developing novel biomaterials.
An excellent team consisting of the editors of this book, Prof. Wenguo Cui, Dr. Lei Xiang has made significant contributions to the field of biomedical engineering. The publication of this book will summarize the current applications of natural polymers in the biomedical field promptly and provide necessary references and inspiration to fellow researchers.
Kai Liu
Department of Chemistry, Tsinghua University, Beijing 100084, China
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of
Applied Chemistry, Chinese Academy of Sciences Changchun,
Changchun 130022, China
20 November 2023
Preface
Source: Wenguo Cui (Book author)
Source: Lei Xiang (Book author).
The purpose of this book is to systematically review and comment on the latest research progress of various natural polymers in biomedical fields, covering the sources, structures, and preparation methods of different types of natural polymers, as well as their applications in drug delivery, cell culture, tissue engineering, etc., and providing detailed and informative valuable reference materials for the design and application of natural polymer materials. The research provides detailed, informative, and valuable references for the design and application of natural polymer materials. With the rapid development of the biomedical field in the past decades, natural polymers have attracted more and more attention from researchers because of their excellent biocompatibility, biodegradability, and low immunogenicity. Compared with synthetic polymers, natural polymers have unique molecular structures, abundant reactive groups, and biosignals, which can better mimic the microenvironment of cell growth in vivo and become ideal material platforms for tissue engineering and drug delivery systems. This book systematically describes the sources, structures, and properties of various natural polymers, including alginate, cellulose, hyaluronic acid, chitosan, gelatin, silk protein, starch, and dextran, and focuses on the recent advances in biomedical applications of these natural polymers in the past ten years, including the preparation, modification strategies, and drug delivery systems for natural polymer hydrogels, electrostatically spun fibers, 3D printed scaffolds, polyphenol–metal complexes. These include the preparation of natural polymer hydrogels, electrostatically spun fibers, 3D printed scaffolds, polyphenol–metal complexes, and their modification strategies and effects on drug delivery, cell culture, and tissue engineering.
Polysaccharide‐based natural polymers have the ability to mimic extracellular matrix and provide support for cell adhesion and proliferation. Peptide such as collagen and gelatin contain special amino acid sequences, which can provide signals for cell adhesion. Polyphenolic compounds such as catechins and isoflavones have antioxidant pharmacological activities. By modulating the structure of these natural macromolecules and adding bioactive groups, researchers have prepared various biomaterials suitable for drug delivery, cell culture, and tissue regeneration, including injectable hydrogels, electrostatically spun fibrous membranes, and 3D‐printed scaffolds. These biomaterial platforms have demonstrated excellent results in promoting cellular differentiation, controlled drug release, and repairing tissue damage in ex vivo and in vivo experiments.
We believe that the major contribution of this book lies in the comprehensive and systematic introduction of the structural features, preparation methods, and properties of various types of natural polymers, with a focus on summarizing the latest progress of their current biomedical frontiers, including hydrogels, electrostatic spinning, 3D bioprinting, and polyphenol–metal complexes, which can provide detailed and informative references for the design and application of natural polymers. We believe that with the accelerated cross‐fertilization of biomedicine and materials science, natural polymers have great potential and development prospects in the biomedical field. The publication of this book will certainly promote the basic research and translational application of natural polymers and help to explore the potential of natural polymers in the era of smart medicine and precision medicine.
Wenguo Cui, Lei Xiang
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and
Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and
Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine,
197 Ruijin 2nd Road, Shanghai 200025, China
01 December 2023
Acknowledgments
This work was supported by grants from the National Key Research and Development Program of China (2020YFA0908200), National Natural Science Foundation of China (81930051), Shanghai Jiao Tong University “Medical and Research” Program (ZH2018ZDA04), and “The Project Supported by the Foundation of National Facility for Translational Medicine (Shanghai) (TMSK‐2020‐117).”
Section IHistorical Review of the Development of Natural Polymers
Natural polymer is a type of polymer compound formed based on photosynthesis or biochemical action that is widely found in animals, plants, and bacteria in nature. Compared with synthetic polymers, it has good biocompatibility, biodegradability, and low immunogenicity. Polysaccharides and polypeptides are often used as structural components because they can mimic the extracellular matrix environment and are rich in a variety of biologically active model sites, giving biological materials more biological activity and improving the biocompatibility of the materials. Polyphenols are often used as active ingredients in biomaterials due to their anti‐oxidant, anti‐free radical, and anti‐cancer effects. There are various forms of biomaterials based on natural polymers. This book summarizes the basic structure and properties of natural polymers, focusing on the recent progress of natural polymer hydrogels, electrospun fibers, 3D bio‐printing scaffolds, and polyphenol–metal complexes in the field of biomedicine.
Biomedicine covers many aspects such as drug and gene delivery, cell culture, and tissue engineering. With the continuous cross‐fusion of biomedicine and materials science, many researchers are devoted to finding potential high‐quality materials that can be used in the field of biomedicine, and more and more researchers have begun to use nature as a teacher to design and develop various types of bionic materials. In fact, bionics is not only limited to the simulation of the structure of some biological organs, but also includes the further development and utilization of natural materials that exist in nature [1, 2]. In the field of biomedicine, with the further development of various purification processes and continuous breakthroughs in the field of biochemistry, great changes have taken place in people's understanding of all kinds of natural active substances. Nature is just like a huge treasure, which contains many “pearls” with unique structure and activity that need to be discovered. Here, we mainly summarize the application of natural polymers in biomedical field in recent years.
Natural polymers have attracted more and more attention in biomedicine field in the past decades because of their advantages such as biodegradability, low toxicity, and low immunogenicity [3]. Natural polymer is a very broad concept, and we mainly introduce three types of natural polymers in this book: polysaccharides, peptides, and polyphenols. In this book, we will focus on the hot materials and technological forms in the biomedical field, including the cutting‐edge applications of natural polymers in the fields of hydrogels, electrospinning, polyphenol–metal complexes, and 3D bio‐printing.
At present, there are two main considerations when designing materials applied in tissue engineering field: one is whether the prepared material can meet the mechanical properties under normal physiological activities; the other is that on the basis of satisfying mechanical properties, whether it is conducive to cell proliferation and the microenvironment of tissue repair [4, 5]. The emergence of natural polymers development is how to design natural material which can well meet these two requirements. Natural polymers with different molecular weights and modification methods can be selected to achieve flexible control of their mechanical properties. Polysaccharide materials have signal regulation capabilities in cell membranes and cells [6, 7]. The special structure and protein sequence of peptides can mimic the extracellular matrix very well, creating external conditions for tissue regeneration [8, 9].
The design of materials in the field of drug and gene delivery generally considers the following points: First, protect the activity of the drug and deliver it to the target site. For example, oral drugs should avoid the destruction of drug activity by gastric acid and protect the intestines. The second is to achieve long‐acting and sustained release of the drug and prolong the effective time of the drug [10]. The third is the low toxicity and functionalization of the drug carrier. The drug carrier needs to have low immunogenicity and synergistic or strengthening effect on the drug. The use of electrostatic forces between natural polymers and drugs to encapsulate or achieve sustained drug release by regulating the degradation rate has been widely used in the field of biomedicine [11]. In addition, there are many materials with environmental strain ability in natural polymers, such as temperature responsiveness, pH responsiveness, and enzyme responsiveness, and based on these properties, environmentally intelligent responsive drug carrier can achieve on‐demand release of drugs. In addition, polyphenols have a certain pharmacological activity. Polyphenols, when combined with anticancer drugs such as doxorubicin, can have excellent synergistic effect, which can improve tumor cell killing rate, and the disadvantage of low bioavailability of polyphenols can be overcome by forming polyphenol–metal complex.
The purpose of this book is to summarize the recent application of natural polymer materials in cell culture, drug delivery, and tissue engineering, on the basis of introducing the source, structure, and basic properties of various natural polymers and hoping to provide a useful reference for researchers to design biomedical materials derived from natural polymers.
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Giraldo, J.P., Landry, M.P., Faltermeier, S.M. et al. (2014). Plant nanobionics approach to augment photosynthesis and biochemical sensing (vol 13, pg 400, 2014).
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Kadumudi, F.B., Hasany, M., Pierchala, M.K. et al. (2021). The manufacture of unbreakable bionics via multifunctional and self‐healing silk‐graphene hydrogels.
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33: 2100047.
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Matsuda, T., Kawakami, R., Namba, R. et al. (2019). Mechanoresponsive self‐growing hydrogels inspired by muscle training.
Science
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Lin, W.F., Kluzek, M., Iuster, N. et al. (2020). Cartilage‐inspired, lipid‐based boundary‐lubricated hydrogels.
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Haas, K.T., Wightman, R., Meyerowitz, E.M., and Peaucelle, A. (2020). Pectin homogalacturonan nanofilament expansion drives morphogenesis in plant epidermal cells.
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Tokatlian, T., Read, B.J., Jones, C.A. et al. (2019). Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers.
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Matsumoto, A., Pasut, A., Matsumoto, M. et al. (2017). mTORC1 and muscle regeneration are regulated by the LINC00961‐encoded SPAR polypeptide.
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Buszczak, M., Signer, R.A.J., and Morrison, S.J. (2014). Cellular differences in protein synthesis regulate tissue homeostasis.
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Miao, Y.B., Lin, Y.J., Chen, K.H. et al. (2021). Engineering nano‐ and microparticles as oral delivery vehicles to promote intestinal lymphatic drug transport.
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11
Lin, F., Wang, Z., Xiang, L. et al. (2021). Charge‐guided micro/nano‐hydrogel microsphere for penetrating cartilage matrix.
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31: 2107678.
Section IIPolysaccharides for Biomedical Application
1Sources, Structures, and Properties of Alginate
Alginate, also known as alginic acid, is a kind of natural linear anionic polysaccharide widely used in the field of biomedicine. Alginate is mainly distributed in the cell wall of brown algae and extracted in the form of acidification and sodium salt. In recent years, some researchers have extracted alginate through microbial fermentation of Pseudomonas aeruginosa[1].
Alginate is a straight‐chain polymer composed of 1‐4‐linked β‐D‐mannuronic acid (M) or α‐L‐guluronic acid (G), which is interspersed with regions containing alternating M–G sequence [2]. The chemical structure of alginate from different sources is also quite different. Alginate from algae has high content of Poly G and excellent antibacterial activity, while alginate from microorganism has high content of Poly M, which can induce monocytes to produce inflammatory mediators such as interleukin‐1, interleukin‐6, and tumor necrosis factor. Na+ in alginate guluronic acid (Poly G) can be exchanged with divalent cations to form physically cross‐linked hydrogels, in which the cross‐linking model with Ca2+ is called “eggs‐box model” (side‐by‐side Poly G can form a pore conducive to Ca2+ cross‐linking, and each Poly G binds to the corresponding two Poly G in an orderly manner) [3]. During the cross‐linking process, the alginate droplets containing the required protein will be extruded from the gel frame to form alginate microspheres. Due to the mild cross‐linking conditions and excellent mechanical properties, alginate hydrogel has become a research hotspot in the field of cell encapsulation and tissue engineering. Owing to the free hydroxyl and carboxyl groups, alginate also has excellent bio‐adhesion. In addition, the pH sensitivity of alginate (which shrinks under low pH conditions) also has a great prospect in targeted drug delivery.
At present, the modification of alginate is mainly based on the following two aspects: Firstly, the alginate materials with different properties were obtained by adjusting the content of Poly M and Poly G in alginate. Secondly, the active sites of alginate (carboxyl group, hydroxyl group, 1‐4 glycosidic, internal glycolic bonds) were modified to improve the properties of the derived materials.
1.1 Alginate‐Based Hydrogel for Biomedical Application
1.1.1 Drug and Cell Delivery
Systematic administration of antibiotics is the main cause of widespread drug resistance throughout the body, and the development of a local targeted administration system is an effective way to solve this clinical problem. In order to solve many side effects of intravenous application of antibiotics, Czuban et al. [4] prepared tetrazine‐modified alginate hydrogel. Based on the principle of the inverse electron‐demand Diels–Alder chemistry, vancomycin and daptomycin loaded with hydrogel can be released at the site of infection, and this hydrogel can repeatedly achieve drug loading and local release, significantly reducing adverse reactions caused by the use of antibiotics.
Autologous tumor cell vaccine is an individualized therapeutic strategy to activate tumor‐specific immune response. However, it has limited efficacy in “cold” solid tumors that lack tumor‐infiltrating T cells and are insensitive to immunotherapy. Ke et al. constructed a dendritic cell (DC)‐activated hydrogel system using bifunctional fusion membrane nanoparticles (FM‐NPs) composed of autologous tumor cell membranes and Mycobacterium leprae membrane extract to provide tumor antigenic signals and to interact with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Nanoparticles (NPs) composed of autologous tumor cell membranes and Mycobacterium leucocephala membrane extracts were used to provide tumor antigen signaling and were co‐loaded with GM‐CSF in an alginate hydrogel. Rapid release of GM‐CSF recruited DCs; FM‐NPs continuously activated the maturation of DCs and provided tumor antigens. The hydrogel system could increase the infiltration of effector memory T cells and activate “cold” tumors to exert significant anti‐tumor effects. This study provides a feasible strategy to overcome the bottleneck of the efficacy of autologous tumor vaccines in “cold” tumors and points out a new direction to improve the clinical efficacy [5] (Figure 1.1).
The adenosinergic axis limits the effectiveness of current tumor immunotherapy by inhibiting the activity of effector T cells. How to effectively remodel the adenosinergic axis has become a key target to improve the effect of anti‐tumor immunotherapy. Zhao et al. constructed an injectable hydrogel system based on alginic acid, and used the synergistic effects of adenosine deaminase, docetaxel, and benzotricarboxylic acid to realize the conversion from immunosuppressive adenosine to immuno‐strengthening inosine to remodel the adenosinergic axis and exert anti‐tumor effects. Docetaxel and benzotricarboxylic acid synergistically induced a large release of ATP, which triggered a strong immune response; adenosine deaminase catalyzed the conversion of adenosine to inosine, which further enhanced the immune effect; and ultimately achieved the reversal of the negative feedback from adenosine to positive feedback from inosine. The hydrogel strategy reshaped the adenosinergic axis through cascade amplification of ATP‐mediated anti‐tumor immune response, which provided a new idea and means to enhance the effect of tumor immunotherapy [6].
Figure 1.1 (a) Fusion membrane nanoparticles (FM‐NPs) were prepared from autologous tumor cell membranes and Bacillus membrane extracts. (b) Sodium alginate solution was cross‐linked with cationic solution to form hydrogels at room temperature. (c) FM‐NPs and sodium alginate solution were used to form a hydrogel in vivo, which attracted dendritic cells and were activated by FM‐NPs. Mature dendritic cells carrying tumor antigens stimulated the increase of effector memory T‐cells, which exerted anti‐tumor effects.
Source: Ref. [5]/John Wiley & Sons.
In the postoperative treatment of breast cancer, high local recurrence rates and potential wound infections pose significant risks to patient survival. To overcome these challenges, Wu et al. conducted a study on a nanocomposite dual‐network (NDN) hydrogel. The hydrogel was constructed using polyethylene glycol acrylate (PEGDA) and alginate, embedded with 125i‐labeled RGDY peptide‐modified gold nanorods (125I‐GNR‐RGDY). This study formed hydrogels with a dual‐network structure by near infrared (NIR) light‐induced polymerization of PEGDA and endogenous Ca2+ cross‐linking of alginate to construct a second network. This design enabled the hydrogel to exhibit stable photothermal effects and radiolabeling under NIR light irradiation. Photothermal therapy synergizes with brachytherapy by inhibiting DNA self‐repair, promoting blood circulation, and improving the hypoxic microenvironment to enhance the therapeutic effect. This study provides a novel therapeutic approach by in situ injection of a precursor solution into the lumen of excised mouse cancerous breasts to form a rapidly gelatinizing hydrogel. By combining photothermal therapy and radiation therapy, this approach is expected to reduce the risk of local recurrence and decrease the likelihood of wound infection in postoperative breast cancer patients. This targeted therapeutic strategy offers new prospects for improving the outcome and survival of breast cancer patients [7].
The presence of immunosuppressive cells in the tumor microenvironment, especially tumor‐associated macrophages (TAMs), poses a limitation on T‐cell infiltration and activation, which in turn constrains the anticancer effect of immune checkpoint blockade. Li et al. developed a biocompatible alginate‐based hydrogel that carries encapsulated nanoparticles loaded with pessitinib (PLX). The hydrogel gradually released PLX at the tumor site by blocking the colony‐stimulating factor 1 receptor (CSF1R) in order to reduce the presence of TAMs. This strategy not only creates an environment conducive to promoting local and systemic delivery of anti‐PD‐1 antibodies (aPD‐1), thereby inhibiting postoperative tumor recurrence, but also further contributes to T‐cell infiltration of tumor tissue by reprogramming the tumor immunosuppressive microenvironment. In addition, the postoperative inflammatory environment triggers platelet activation, which promotes the release of aPD‐1 and reactivates T cells by binding to the PD‐1 receptor. It was noted that hydrogels can act as local reservoirs for sustained release of PLX‐NP and P‐aPD‐1 to enhance the efficacy of tumor immunotherapy. The immunotherapeutic effect of systemic injection of P‐aPD‐1 could also be further enhanced by the hydrogel strategy of local depletion of TAMs, broadening the route of administration of immune checkpoint inhibitors. This study provides new ideas for regulating the tumor immune environment and improving the therapeutic effect [8].
Refractory keratitis and diabetic foot ulcers pose a great threat to human health due to drug‐resistant bacterial infections and prolonged tissue hypoxia, and novel and effective therapeutic strategies are urgently needed. A self‐oxygenated bilayer hydrogel was developed and prepared for the treatment of these diseases by Zhu et al. The inner hydrogel was composed of oxidized sodium alginate and carboxymethyl chitosan‐containing photosensitizer PCN‐224 and pH indicator bromothymol blue, while the outer hydrogel contained photosynthetic cyanobacteria. The inner hydrogel could sense the change of pH value to monitor the bacterial infection in real time and release PCN‐224 in response to the infection for photodynamic bactericidal treatment; the cyanobacteria in the outer hydrogel continued to photosynthesize to produce oxygen to alleviate the hypoxic state of the tissues, enhance the effect of photodynamic therapy, and provide the necessary oxygen for the wound‐healing process. In diabetic rat skin ulcer model and refractory keratitis animal model, the hydrogel could effectively sterilize, reduce inflammation, promote blood vessel regeneration and fibrous tissue formation, and significantly improve the therapeutic effect. The self‐oxygenated bilayer hydrogel provides a novel strategy for the treatment of refractory ocular and skin diseases, and shows great application prospects and value [9].
Gan et al. used microfluidic electrospray technology to encapsulate mesenchymal stem‐cell‐derived exosomes in multilayered sodium alginate‐gelatin (Gel) microcapsules for the targeted release of exosomes for protective delivery in the gastrointestinal tract and treatment of inflammatory bowel disease. In this study, inspired by the acid–base stability of Gel capsules, a novel multilayer microcapsule was prepared to encapsulate MSC‐derived exosomes. The exosomes were first encapsulated in a core of sodium alginate gel microspheres using microfluidic electrospray technology and then coated with a Gel interlayer to protect them from degradation. The resistance of the microcapsules to gastric juices was enhanced by the use of a synthesized enteric polymer outer coating. The results showed that the prepared microcapsules could effectively protect the stability and bioactivity of exosomes against gastrointestinal digestion, and enable the release of exosomes at the site of intestinal injury to perform the biological functions of immunomodulation and damage repair. Therefore, the exosome‐encapsulated microcapsules provide a new strategy of effective protection and targeted release for various oral cell therapies [10].
Zhang et al. designed an injectable hydrogel to simultaneously modulate T‐cell exhaustion and MHC I expression for enhanced T‐cell‐based cancer immunotherapy. The hydrogel utilized sodium‐oxidized alginate‐modified tumor cell membrane vesicles (O‐TMV) as the gelling agent and contained axitinib, 4‐1BB antibody, and PF‐06446846 nanoparticles. After the immune response was triggered by the O‐TMV antigen, the hydrogel demonstrated superior immunotherapeutic effects through multiple mechanisms. 4‐1BB antibody promoted T‐cell mitochondrial biogenesis, axitinib reversed T‐cell exhaustion, and PF‐06446846 amplified MHC I expression to improve T‐cell recognition of tumor cells. O‐TMV@ABP hydrogel effectively inhibited tumor growth through strong immune responses and long‐term memory immune response effectively inhibits tumor growth, metastasis, and recurrence. This innovative strategy provides a new concept for T‐cell‐based cancer immunotherapy and demonstrates the strong potential of the hydrogel platform [11].
Stem cell injection therapy has significant efficacy in the treatment of many diseases such as diabetes, but simple stem cell injection has the problems of immune rejection and graft removal. In order to solve these problems, Delcassian et al. [12] loaded COOH‐modified iron oxide nanoparticles and living islet cells into alginate hydrogel. On the one hand, the immune rejection of alginate hydrogel is significantly reduced; on the other hand, iron oxide nanoparticles can make the inhibitor move directionally in the magnetic field, which solves the problem of recovery after failed transplantation (Figure 1.2).
An adhesive and adjustable methacrylic‐acid‐modified alginate saline gel has been developed by Hasani‐Sadrabadi et al. [13], which was coated with gingival mesenchymal stem cells and hydroxyapatite particles were introduced to induce bone regeneration, which effectively repaired mouse craniofacial bone defects. Whitehead Jacklyn et al. [14] reported that hydroxyapatite nanoparticles adsorbed BMP‐2 were added to mesenchymal stromal cell spheres and then embedded in Arginine–Glycine–Aspartic acid (RGD)‐modified alginate hydrogels. They found that the viscoelastic dynamic mechanical properties of alginate hydrogels obtained by ionic cross‐linking significantly enhanced the therapeutic potential of MSCs spheres in bone formation and repair. Hung et al. [15] have prepared a peptide‐modified viscous hydrogel which can double stimulate MSCs. On the one hand, QK peptides are used to functionalize alginate to promote the secretion of angiogenic factors; on the other hand, RGD modification promotes cell adhesion and proliferation.
Figure 1.2 (a1) Schematic diagram of hydrogel vesicle formation containing nanoparticles; (a2) MRI and magnetic retrieval for diabetic transplantation. (b) TEM images of different nanoparticles and microscopic images of hydrogel capsules containing 0.25–5 mg/ml nanoparticles. (c,d) Conductivity and zeta potential of nanoparticles in saline or saline‐sodium alginate. The conductivity and zeta potential of the nanoparticles were reduced compared to that of sodium alginate. (e–h) Magnetic recovery experiments were performed on hydrogels containing nanoparticles. As the concentration of nanoparticles increased, the traveling distance of the hydrogel increased; decreasing the capsule size decreased the traveling distance.
Source: Ref. [12]/John Wiley & Sons.
Hasturk et al. prepared enzyme‐cross‐linked alginate and alginate/gelatin composite microspheres by a simple and economical centrifugation method for microencapsulation protection of mammalian cells. The composite microspheres were more structurally stable under ionic conditions and had better mechanical properties than the ionically cross‐linked alginate microspheres only. It was shown that the human mesenchymal stem cells and neural progenitor cells encapsulated in the composite microspheres were effectively protected against various environmental factors, including extracellular toxins, acidosis, apoptotic factors, ultraviolet radiation, hypoxic conditions, and mechanical stresses. The microencapsulated cells maintained high viability, proliferation, and directed differentiation after extrusion through a 27‐gauge needle. This demonstrated that the novel microencapsulation strategy has promising applications in cell injection delivery and three‐dimensional bioprinting. Overall, the double‐cross‐linked composite microspheres provide a new, simple, and effective method for microenvironmental regulation and protection of mammalian cells [16].
Myocardial infarction (MI) is a major cause of sudden cardiac death, and platelet‐rich fibrin is beneficial for restoring vascular regeneration in the infarcted area due to its richness in growth factors. Based on its biocompatibility and cost‐effectiveness, alginate hydrogel is an advantageous way to achieve targeted delivery of platelet‐rich fibrin. Qian et al. achieved infiltration of M2 macrophages in the infarcted area through the construction of alginate hydrogel, which is beneficial for improving the degree of myocardial fibrosis, and this hydrogel can also provide strong mechanical support for the ventricular wall and improve cardiac function [17].
Localized stem cell delivery to the human locomotor system and major weight‐bearing tissues requires high structural strength of the delivery platform. Panebianco et al. used degradable alginate microspheres to microencapsulate mesenchymal cells to protect the cells and maintain cell viability and phenotype upon release. The composite of cell‐carrying microspheres with high‐modulus cross‐linked fibrin gels balanced biomechanical properties and cell biological activity. The composites showed better cell survival and matrix synthesis than fibrin gels alone. The biomechanical stability of the composites and their ability to promote extracellular matrix synthesis were verified in large animal in vitro experiments. The composites significantly improved biomechanical function and biological repair compared with discectomy alone [18].
Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, and the local hypertonicity makes the wound prolonged, Theocharidis et al. thoroughly investigated the potential application of alginate dressings for the local delivery of macrophages and their secretory products for the treatment of DFU. By preparing alginate dressings with a microporous structure, they were able to achieve a uniform loading of primary macrophages and realized the loading of macrophages with different polarization states (M0, M1, M2a, M2c) onto the dressing and their migration into the wound. The experimental results demonstrated that the treatment of each macrophage subtype promoted DFU healing in db/db mice [19].
1.1.2 Cell and Organoid Culture
Different hydrogel micropatterns can be formed by adjusting the cross‐linking density of various parts of the hydrogel. Jeon et al. [20]
