Preface

Chapter 8 **Development of PVA/Fe3O4 as Smart Magnetic Hydrogels for**

Puspita Sari, Yanurita Dwihapsari and Darminto

Chapter 9 **Hyaluronic-Based Antibacterial Hydrogel Coating for**

**Basic Research to Clinical Applications 179**

Malik Anjelh Baqiya, Ahmad Taufiq, Sunaryono, Munaji, Dita

**Implantable Biomaterials in Orthopedics and Trauma: From**

Maraldi Susanna, Scarponi Sara and Romanò Carlo Luca

Giammona Gaetano, Pitarresi Giuseppe, Palumbo Fabio Salvatore,

**Biomedical Applications 159**

**VI** Contents

Hydrogels are swollen polymer networks holding water in their structures. By definition, water must constitute at least 10% of the total weight (or volume) for a material to be a hy‐ drogel. However, hydrogels are capable to retain 90% water in their structure. Due to their high water holding capacity, hydrogels have potential applications in processes ranging from industrial to biological fields. Some of the more focused fields include oil reserve treat‐ ment, tissue engineering, implants and controlled drug release. Literature on these subjects is expanding. Recently, hydrogels have been explored as potential plugs to control the ani‐ sotropic permeability profile of heterogeneous oil reservoirs. Drug delivery systems and tis‐ sue engineering implants are the other most studied areas, where hydrogels have been used as 3D materials in dried form. Nonetheless, hydrogels are unique materials and there is al‐ ways space for more research. A number of original papers, reviews, monographs and tech‐ nical reports are focusing on the technological aspects of hydrogels to make them more acceptable as a multidisciplinary material. With its distinguished editor and an international team of contributors, the book *Hydrogels* is an outstanding reference for academia, industry and regenerative medicine and environment research scientists.

**Dr. Sajjad Haider**

Chemical Engineering Department College of Engineering King Saud University Riyadh, Saudi Arabia

**Dr. Adnan Haider** Kohat University of Science and Technology KPK, Kohat, Pakistan

**Section 1**

**Bio and Synthetic Hydrogels**

**Bio and Synthetic Hydrogels**

**Chapter 1**

**Provisional chapter**

**Decellularized ECM-Derived Hydrogels: Modification**

**Decellularized ECM-Derived Hydrogels: Modification** 

Extracellular matrix (ECM) hydrogels are water-swollen fibrillary three-dimensional (3D) networks where collagen type I is the major component. The hierarchical network formed by the polymerization of tropocollagen molecules with enhanced properties is an attractive template for generating biomaterials. The mammalian tissue source from which collagen is extracted and its consequent modification are variables that impact the physicochemical and biological properties of the collagen network. This chapter has the purpose to provide a review of the research of different strategies to modify and characterize the properties of decellularized ECM-derived hydrogels in the context of

Hydrogels are water-swollen polymeric materials with specific three-dimensional (3D) structure. During the last years, hydrogels have been investigated for enhancing biomedical applications. These biomaterials offer a moist environment that can be enriched to provide protection against infections, regulate the inflammation process, promote tissue regeneration, and remove wound exudates [1]. ECM-based hydrogels are promising materials for tissue engineering and regenerative medicine application due to the balance of biochemical and physical characteristics that can be achieved by their modification. Collagen is the main structural protein of the mammalian ECM. It has a favorable impact on blood coagulation, promoting the aggregation

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: 10.5772/intechopen.78331

**and Properties**

**Abstract**

**1. Introduction**

**and Properties**

Jesús A. Claudio-Rizo, Jorge Delgado,

Jesús A. Claudio-Rizo, Jorge Delgado,

http://dx.doi.org/10.5772/intechopen.78331

Birzabith Mendoza-Novelo

Birzabith Mendoza-Novelo

Iraís A. Quintero-Ortega, José L. Mata-Mata and

Iraís A. Quintero-Ortega, José L. Mata-Mata and

safe biomaterials with immunomodulatory properties.

**Keywords:** ECM, collagen, hydrogel, cross-linking, properties

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

#### **Decellularized ECM-Derived Hydrogels: Modification and Properties Decellularized ECM-Derived Hydrogels: Modification and Properties**

DOI: 10.5772/intechopen.78331

Jesús A. Claudio-Rizo, Jorge Delgado, Iraís A. Quintero-Ortega, José L. Mata-Mata and Birzabith Mendoza-Novelo Jesús A. Claudio-Rizo, Jorge Delgado, Iraís A. Quintero-Ortega, José L. Mata-Mata and Birzabith Mendoza-Novelo

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.78331

#### **Abstract**

Extracellular matrix (ECM) hydrogels are water-swollen fibrillary three-dimensional (3D) networks where collagen type I is the major component. The hierarchical network formed by the polymerization of tropocollagen molecules with enhanced properties is an attractive template for generating biomaterials. The mammalian tissue source from which collagen is extracted and its consequent modification are variables that impact the physicochemical and biological properties of the collagen network. This chapter has the purpose to provide a review of the research of different strategies to modify and characterize the properties of decellularized ECM-derived hydrogels in the context of safe biomaterials with immunomodulatory properties.

**Keywords:** ECM, collagen, hydrogel, cross-linking, properties

#### **1. Introduction**

Hydrogels are water-swollen polymeric materials with specific three-dimensional (3D) structure. During the last years, hydrogels have been investigated for enhancing biomedical applications. These biomaterials offer a moist environment that can be enriched to provide protection against infections, regulate the inflammation process, promote tissue regeneration, and remove wound exudates [1]. ECM-based hydrogels are promising materials for tissue engineering and regenerative medicine application due to the balance of biochemical and physical characteristics that can be achieved by their modification. Collagen is the main structural protein of the mammalian ECM. It has a favorable impact on blood coagulation, promoting the aggregation

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

of platelets, and the absorption of fluid, and regulating the deposition of other ECM's proteins such as fibrin, laminin, elastin, and fibronectin [2]. Besides, collagen can induce processes of the cell signalization involved in the growth, proliferation, migration, and differentiation of cells. Low inflammatory and cytotoxic responses and high biodegradability are other attractive properties of collagen [3]. The collagen can be extracted from diverse ECMs using acid hydrolysis assisted by proteolytic enzymes. The extracted collagen can be subsequently polymerized under physiological conditions (pH 7, 37°C) to generate a highly hydrated 3D network [4].

nanoparticles, and matrices for 3D cell culture. They are also investigated for tissue engineering including skin replacement, bone substitutes, and artificial blood vessels and heart valves [7]. In this chapter, a review of the state of the art of different strategies to modify and characterize the properties of natural ECM hydrogels in the context of the biomedical applications is presented. The chapter emphasizes the chemical and physical methods intended to enhance physicochemical properties and immunomodulatory applications of the ECM hydrogels.

Decellularized ECM-Derived Hydrogels: Modification and Properties

http://dx.doi.org/10.5772/intechopen.78331

5

The versatility of collagen to generate biomedical hydrogels is primarily associated with its complex hierarchical structure originated from its amino acid molecular sequence and the formation of triple helical structures [8]. The collagen polymerization is a self-assembly process of long fibrillar structures, regulated by both electrostatic and hydrophobic interactions that promote the collagen fibers cross-linking [9]. This process is influenced by parameters such as temperature, pH, collagen concentration, and the presence of other biomolecules or polymers [10]. The macroscopic result of the in vitro collagen fibrillogenesis is a 3D water-swollen network. ECM hydrogels are very suitable materials for biomedical applications due to their good interaction with living tissues, biocompatibility, soft and elastic consistency, high water content, and ECM remaining composition [11]. The swelling in liquid medium gives them the capacity to absorb, retain and release under controlled conditions amounts of water; regulating their structural conformation [12]. The ECM residual composition and the methods of modification of the hydrogels determinate the water uptake capacity and influence their biological and physicochemical properties. This section is dedicated to the discussion of the

**2. Methods of preparation of natural ECM-based hydrogels**

main characteristics of strategies for the modification of collagen in hydrogel state.

network in close association with the surface of the cells that produced them [14].

The ECM is the noncellular component present within all tissues and organs that provides not only essential physical scaffolding for the cellular constituents but also initiates crucial biochemical and biomechanical cues, which are required for tissue morphogenesis, differentiation, and homeostasis [13]. As shown in **Figure 2**, this matrix is composed of a variety of proteins and polysaccharides that are locally secreted and assembled into an organized

Collagen is the main component of the ECM [15]. The collagen is extracted from diverse ECM by multistep processes including the tissue decellularization and acid hydrolysis assisted with proteases. Among others, collagen has been extracted from porcine dermis [16], bovine pericardium [17], porcine urinary bladder [18], porcine small intestine submucosa [19], bovine Achilles tendon [20], and rat tail tendon [21]. The polymerization of the extracted collagen under physiological conditions (37°C, pH 7) has allowed to develop biomedical hydrogels mimicking the structure and function of the ECM in vitro. The polymerization kinetics and the structural characteristics of the fibrillar collagen gel network are influenced by the residual composition of the ECM. Consequently, the swelling, mechanics, degradation, and biological

**2.1. Importance of the tissue source in the natural ECM-based hydrogels**

The ECM-based hydrogels maintain the biocompatibility and biodegradability associated with the collagen. Diverse authors use to refer ECM hydrogels like collagen hydrogels, as the collagen is the major component inside ECM. However, these biomaterials have poor mechanical properties and fast degradation rate, limiting the range of use in applications such as the loading, encapsulating and controlled delivery of cells or drugs, or as wound care dressings [5]. The structure and mechanics of the ECM hydrogels can be modified by chemical cross-linking (using glutaraldehyde, genipin, carbodiimides, acrylates, oligourethanes, and among others); and/or by physical cross-linking (using freeze-drying cycles, forming interpenetrated networks (IPN) with other proteins or polymers). The selection of the cross-linking strategy has to consider the impact upon the structure-property relationships. After modification, several advances have been reported in the design of ECM-based hydrogels. The delivery of cells and biomolecules, the enhancing of the stiffness, the regulation of the cell-material interactions, the control of the cell fate and function, and the modulation of the environment of both normal and injured/diseased tissues are among them [6]. As shown in **Figure 1**, ECM hydrogels have been studied as substrates for ophthalmology, sponges for burns/wounds, systems for controlled delivery of functional molecules or

**Figure 1.** Schematic representation of the biomedical applications of collagen-based hydrogels.

nanoparticles, and matrices for 3D cell culture. They are also investigated for tissue engineering including skin replacement, bone substitutes, and artificial blood vessels and heart valves [7].

In this chapter, a review of the state of the art of different strategies to modify and characterize the properties of natural ECM hydrogels in the context of the biomedical applications is presented. The chapter emphasizes the chemical and physical methods intended to enhance physicochemical properties and immunomodulatory applications of the ECM hydrogels.
