Gels Handbook: Fundamentals, Properties, Applications (In 3 Volumes)

Fundamentals, Properties and Applications(In 3 Volumes)Volume 1: Fundamentals of HydrogelsVolume 2: Applications of Hydrogels in Regenerative MedicineVolume 3: Application of Hydrogels in Drug Delivery and Biosensing

Utkan Demirci, Ali Khademhosseini

• Publisher: WSPC
• Year: 2016
• ISBN:
  9789814656122
• Topic: Technology & Engineering
• Subtopic: Chemical & Biochemical Engineering
• Index: Technology & Engineering

Hydrogels are made from a three-dimensional network of cross linked hydrophilic polymers or colloidal particles that contain a large fraction of water. In recent years, hydrogels have attracted significant attention for a variety of applications in biology and medicine. This has resulted in significant advances in the design and engineering of hydrogels to meet the needs of these applications. This handbook explores significant development of hydrogels from characterization and applications. Volume 1 covers state-of-art knowledge and techniques of fundamental aspects of hydrogel physics and chemistry with an eye on bioengineering applications. Volume 2 explores the use of hydrogels in the interdisciplinary field of tissue engineering. Lastly volume 3 focuses on two important aspects of hydrogels, that is, drug delivery and biosensing. Contains 50 colour pages.

Contents:

• Volume 1: Fundamentals of Hydrogels (Qi Wen [Worcester Polytechnic Institute, USA] and Yi Dong [OPKO Diagnostics, LLC, OPKO Health, Inc., USA])
  • Natural Hydrogels (Shangyou-Tee [NTU, Singapore])
  • Types and Chemistry of Synthetic Hydrogels (John Garner [Akina, Inc., USA] and Kinam Park [Purdue University, USA])
  • Computational Nanomechanics of Hydrogels (Hossein Salahshoor and Nima Rahbar [Worcester Polytechnic Institute, USA])
  • Mechanical Properties of Hydrogels (Anne S van Oosten, Peter A Galie and Paul A Janmey [University of Pennsylvania, USA])
  • Hydrogel Architecture (Fariba Dehghani and Ali Fathi [The University of Sydney, Australia])
  • Controlling Hydrogel Biodegradability (Wesley N Sivak, Danielle M Minteer, Bernd Lannau and Kacey G Marra [University of Pittsburgh, Pittsburgh, USA])
  • Tailoring Hydrogel Adhesiveness to Cells, Proteins, and Bacteria (Silviya Petrova Zustiak [Saint Louis University, USA])
  • Photo-Cross-Linking Methods to Design Hydrogels (Brian Amsden [Queen's University, Canada])
  • Self-Assembling Hydrogels (Annada Rajbhandary and Bradley L Nilsson [University of Rochester, USA])
  • Environment Responsive Hydrogels (Yanzhen Yin, Shufei Jiao [Qinzhou University, China], Chao Lang and Junqiu Liu [Jilin University, China])
• Volume 2: Applications of Hydrogels in Regenerative Medicine (Mohammad Reza Abidian [University of Houston, USA], Umut Atakan Gurkan [Case Western Reserve University, USA] and Faramarz Edalat [Emory University, USA])
  • Hydrogels in Regenerative Medicine (Nesrin Hasirc, Cemile Kilic, Aylin Kömez, Gökhan Bahcecioglu and Vasif Hasirci [Middle East Technical University, Turkey])
  • Determining Stem Cell Fate with Hydrogels (Aylin Acun, Andreana Panzo and Pinar Zorlutuna [University of Notre Dame, USA])
  • Applications of Hydrogels in 3D Functional Tissue Models (Tamer Çırak, Tayfun Vural [Hacettepe University, Turkey], Doǧa Kavaz [International Cyprus University, Northern Cyprus] and Emir Baki Denkbaş [Hacettepe University, Turkey])
  • Engineering Regenerative Dextran Hydrogels for Acute Skin Wound Healing (Jie Cheng, Ying Jin, Jeremy J Mao, Guoming Sun [Columbia University Medical Center, USA]) and David M Owens [Columbia University, USA])
  • Application of Hydrogels in Ocular Tissue Engineering (Vipuil Kishore [Florida Institute of Technology, USA], Yunus Alapan [Case Western Reserve University, USA], Ranjani Iyer, Ryan Mclay [Florida Institute of Technology, USA] and Umut A Gurkan [Case Western Reserve University, USA and Louis Stokes Cleveland Veterans Affairs Medical Center, USA])
  • Hydrogels in Bone Tissue Engineering: A Multi-Parametric Approach (Silvia M Mihaila, Rui L Reis, Alexandra P Marques and Manuela E Gomes [University of Minho, Portugal])
  • Hydrogels in Intervertebral Disk (IVD) Repair (Cem Bayram [Aksaray University, Turkey], Murat Demirbilek and Emir Baki Denkbaş [Hacettepe University, Turkey])
  • Hydrogels in Cartilage Tissue Engineering (Antonella Motta, Mariangela Fedel and Claudio Migliaresi [University of Trento, Italy])
  • Application of Hydrogels for Tendon and Ligament Repair and Tissue Engineering (Matteo Stoppato, Friedrich von Flotow [Tufts University] and Catherine K Kuo [Tufts University and Tufts University School of Medicine])
  • Hydrogels in Bone Tissue Engineering (Minh Khanh Nguyen, Julia E Samorezov and Eben Alsberg [Case Western Reserve University, USA])
  • Hydrogels in Cardiac Tissue Engienering (Shauna M Dorsey and Jason A Burdick [University of Pennsylvania, USA])
  • Application of Hydrogels in Heart Valve Tissue Engineering (Jesper Hjortnaes [University Medical Center Utrecht, Netherlands] and Frederick J Schoen [Brigham & Women's Hospital, Harvard Medical School, USA])
  • Hydrogels in Vascular Tissue Engineering (Y J Blinder [Israel Institute of Technology, Israel and Harvard University, USA], D J Mooney [Harvard University, USA] and S Levenberg [Israel Institute of Technology, Israel])
  • Use of Hydrogels in the Engineering of Lung Tissue (Joaquin Cortiella, Jean A Niles, Stephanie P Vega, Lissenya Argueta, Adriene Eastaway and Joan E Nichols [Weill Cornell Medical College, USA])
  • Hydrogels for Hepatic Tissue Engineering (Kerim B Kaylan and Gregory H Underhill [University of Illinois at Urbana-Champaign, USA])
  • Agarose Hydrogel Beads for Treating Diabetes (Nguyen Minh Luan, Yuji Teramura and Hiroo Iwata [Kyoto University, Japan])
  • Hydrogels in Urogenital Applications (James Turner and Jiro Nagatomi [Clemson University, USA])
• Volume 3: Application of Hydrogels in Drug Delivery and Biosensing (Lifeng Kang [NUS, Singapore] and Sheereen Majd [University of Houston, USA]):
  • Modeling Drug Release from Synthetic Hydrogels (Chien-Chi Lin [Indiana University-Purdue University Indianapolis, USA] and Han Shih [Purdue University, USA])
  • Natural Polysaccharide-Based Hydrogels for Controlled Localized Drug Delivery (Roman P Blount, IV and Narayan Bhattarai [North Carolina A&T State University, USA])
  • In Situ Crosslinked Hydrogels for Drug Delivery (Jin Woo Bae and Ki Dong Park [Ajou University, South Korea])
  • Supramolecular Hydrogels for Drug Delivery (Prashant Sawant [RMIT, Australia])
  • BioHybrid Hydrogels as Environment-Sensitive Materials for Systematic Delivery of Therapeutics (Sara Faraji Dana, Jing Pan [NUS, Singapore] and Maziar S Ardejani [King's College London, UK])
  • Application of PEG in Drug Delivery System (Bramasta Nugraha [ETH Zürich, Switzerland and Roche Innovation Center Basel, Switzerland])
  • Hydrogels as Actuators for Biological Applications (Hongrui Jiang and Difeng Zhu [University of Wisconsin Madison, USA])
  • Advances in Smart Hydrogels for Biosensing Applications (Wei Wang, Jimmy Amin, and Zhiqiang Cao [Wayne State University, USA])
  • 3D Cancer Models on Hydrogels (Imran Rizvi, Heather Gudejko, Emma Briars, Shazia Khan, Chun-Te Chiang, [Massachusetts General Hospital and Harvard Medical School, USA], Hamid El-Hamidi, Jonathan P Celli [University of Massachusetts Boston, USA] and Tayyaba Hasan [Massachusetts General Hospital and Harvard Medical School, USA])
  • Hydrogel-Mediated Patterning of Cellular and Biomolecular Microarrays for Screening Assays and Biosensing (You Jung Kang, Soo Hyun Park, and Sheereen Majd [Pennsylvania State University, USA])
  • Protein-Immobilized Hydrogel Microstructures for Optical Biosensing (Won-Gun Koh [Yonsei University, South Korea])
  • Cell-Encapsulating Hydrogels for Biosensing (Pu Chen, Shuqi Wang, Fatih Inci, Sinan Güven, Savas Tasoglu and Utkan Demirci [Stanford University, USA])

Readership: Pharmaceutical researchers and bioengineers, material scientists, biologists, physicians and students with an interest in the field of tissue engineering and regenerative medicine.

Chapter 1

Natural Hydrogels

Shangyou-Tee

Department of Physics, Nanyang Technological University, Singapore

1.Introduction

Gels are ubiquitous materials that can be found all around our everyday lives. In fact most of our tissues and organs are gels. Most gels are made up of a network of polymers or colloids that is filled by a fluid.¹ At steady state when the gel is neither stressed nor strained, it will not flow.² That is, a gel’s elastic modulus, G’, is greater than its loss modulus, G”; a gel is thus a solid albeit a soft and squishy one. Even though the network of polymers or colloids that form a continuous 3D network in a gel can be very dilute (less than 1% by weight), this dilute network is enough to support shear stresses and thus gives the gel its solid-like material properties.³

1.1.Types and chemistry of natural hydrogels

A hydrogel is simply a gel where the fluid discontinuous phase is water whereas the solid continuous phase is still a network of polymers or colloids.⁴ Hydrogels can be characterized by how their networks are held together. “Physical” hydrogels have their polymer network linked together by entanglements, ionic, hydrogen bonds or other forces. “Chemical” hydrogels, on the other hand, have their networks linked by permanent chemical bonds. In general, the links or connections of physical hydrogels are transient in nature and are therefore weaker than those of chemical hydrogels. These transient connections are also sometimes reversible compared to the covalent chemical connections.⁵

Natural hydrogels that are formed from protein such as collagen or fibrin or from polysaccharides such as agarose or alginate are all around us and have been known for a long time. Synthetic hydrogels have to be polymerized in the laboratory and are first reported in 1954.⁶ Such artificial hydrogels are highly customizable and can be tailored to specific applications by fine-tuning their mesh size,^7–9 polymer length,^10,11 water content,¹² mechanical and chemical properties, etc.^13–15 However, natural hydrogels have the strong advantage of being biocompatible^16–19 and biodegradable.^20–22

1.2.Classify hydrogels based on their formation

Yet another way to classify hydrogels is by how they are synthesized. The hydrogel research field is quite diverse. Here we will briefly discuss two new very exciting developments. One, smart hydrogels are materials that change their properties in response to a change to external stimuli or inputs.^23,24 Some possible inputs are changes in pH,^25,26 temperature,^27,28 salt content,^29–31 chemical or biochemical contents, etc.^32,33 Possible outputs or changes in the hydrogel properties include changes in mechanical properties,^34,35 shapes, swelling, etc.^23,36 These “smart” properties can be exploited for many important industrial and biochemical applications. For example, drug-laden hydrogels microparticles can be allowed to circulate the blood stream to only release upon encountering particular temperature,³⁷ pH or biochemical situations.³⁸ Second, self-healing hydrogels are materials that can automatically “repair” themselves when defects such as cracks, changes in mechanical properties, etc. are encountered.^39–41 Typically, such healing occurs because of spontaneous formation of new bonds.⁴² Intuitively, it is not hard to envision the utility of such self-healing materials in tissue engineering, organ regeneration, etc.^43,44

Due to their high water content, hydrogels has wide ranging applications in a variety of areas. In a research setting, hydrogels have been used for cell culture and tissue scaffold bioengineering.^45–47 In the medical area, hydrogels have been used as drug delivery systems, wound dressing scaffolds, biosensors, etc.^48–50 Moreover, hydrogels are used widely in diapers^51,52 and contact lens.^53–55 As a rule of thumb, natural hydrogels are biocompatible and are rapidly finding more and more uses in the biomedical setting.

2.Hydrogel Synthesis

In this chapter, we describe methods that are most commonly used to synthesis hydrogels. In general, physical and radiation crosslink techniques are prefer in medical application compare with chemical crosslink and grafting techniques due to non-toxicity in preparation process.

2.1.Physical crosslink

2.1.1.Heating or cooling process

A sol-gel formation bases on temperature alteration of polymer solution is a process without using chemical crosslink agents. Phase transition occurs at a distinct temperature of polymer solution is called low critical solution temperature (LCST) and form a reversible hydrogels. Natural polymers such as agarose⁵⁶ or polyethylene glycol (PEG)–polylactic acid⁵⁷ dissolve in water as random coils, and then form helix structure if solution temperature is lower than LCST and reversible. Upon cooling the structure aggregates to form a rigid hydrogels (Fig. 1). A similar example is from Yoshioka group that dissolved gelatin in warm water at 37^oC and form hydrogels at 27°C.⁵⁸

2.1.2.Ionic interaction

Ionic interaction occurs between ionic polymer chains containing opposite charges with multivalent ions that plays a role as crosslinkers.⁵⁹ In the case of chitosan, ammonium groups with positively charges on chitosan form ionic bonds with Pt (II) which is commonly used as crosslinker (Fig. 2).⁶⁰

2.1.3.Complex coacervation

The interaction between an anionic polymer solutions with a cationic polymer solution forms a complex coacervation gel (Fig. 3). Gotoh group developed alginate-chitosan hybrid gels by mixed anionic polysaccharide alginate acid, which contains carboxyl group, and cationic polysaccharide chitosan, which contains amino groups in neutral aqueous solution. The polyelectrolyte complexes were synthesized provide a good substance to absorb Cu (II), Co (II), and Cd (II) in drug delivery system.⁶¹

Fig. 1.Gel formation due to phase transition upon changing temperature.

Fig. 2.Gelation based on ion interaction between charged ammonium groups of chitosan with divalent Platinum ions.

Fig. 3.Schematic of complex coacervation process.

2.1.4.Freeze-thaw process

Freeze-thaw is one of the gelation techniques occur in mild condition without chemically crosslink agents. Polymeric solution is frozen and thawed to form cryogels. The method was first reported on a...