Functional Hydrogels as Biomaterials

Tissue engineering aims to regenerate, repair and replace dysfunctional or deceased tissue/organ and is an attractive solution to the current issues faced with organ transplantation. Most research strategies for engineering a functional tissue involve the encapsulation of cells within three dimensional (3D) matrices. Hydrogels, which are a class of polymers that are capable of absorbing water, have arisen as potential candidates for cell encapsulation matrices due to their similarity to the native extracellular matrix (ECM) surrounding cells in the body. Moreover, this highly hydrated environment also allows good permeability and diffusion of nutrients and oxygen through the network to the encapsulated cells, as well as waste products released from the cells to the environment. In this chapter, the advantages and disadvantages of hydrogels fabricated from various materials will be reviewed, with highlights on biosynthetic hydrogels. These hydrogels which are designed to have tailorable physical properties as well as the desired biological attributes are potentially suitable as cell encapsulation matrices.

Endothelial cells have presented a wide variety of applications including tissue engineering, artificial organs, and pharmaceutical drug screening. The new insight in exploring synthetic hydrogels which are suitable for expansion of endothelial cells and keeping their original functions will open a new era of soft and wet biomaterials as active templates for cell expansion. In this chapter, we introduce a cell culture system based on protein-free synthetic hydrogels for expansion of endothelial cells. The negatively charged synthetic hydrogels, such as PNaAMPS and PNaSS, can promote endothelial cell proliferation to form a monolayer, without surface modification of any cell-adhesive proteins or peptides, under the environment of serum-containing medium. Moreover, the synthetic hydrogels can maintain the original functions of the expanded cells. In the sections of the effect of chemical structure and zeta potential on cell behaviors, we introduce the effect of physicochemical properties of fully synthetic hydrogels, i.e., chemical structure, charge density, and surface topography, on static cell behaviors (adhesion, spreading, morphology, proliferation, cytoskeletal structure, and focal adhesion) and dynamic cell behaviors (migration velocity, morphology oscillation). In addition, the effect of hydrogel properties on cell behaviors is correlated well with the adsorption of protein derived from cell culture medium. In the section of application of protein-free hydrogels in biomedical field, the platelet compatibility and surface friction of endothelial cell monolayers cultured on hydrogel templates, selective cell adhesion and proliferation on micro-patterned hydrogel surfaces, as well as proliferation of endothelial cells on tough hydrogels are introduced.

Thanks to their tunable physical and biochemical properties, hydrogels are an attractive tool for tissue engineering applications. This review highlights the design parameters that have been shown to influence stem cell behaviour when cultured on or within hydrogels and presents the various types of materials and crosslinking methods currently used to produce hydrogels suitable for stem cell-based tissue engineering. We also focus on new generations of hydrogels with spatially and dynamically controllable physical and biochemical properties, which open up new perspectives in the study of stem cell behaviour and in the development of therapeutic solutions in regenerative medicine. In line with the current need for more tunable and dynamic properties, polyrotaxane hydrogels can be used to create spatially flexible structures at the molecular scale and are therefore emerging as a new player in the field of tissue engineering.

Hydrogel is a three-dimensionally cross-linked material made of water-soluble polymers. Here, we describe the use of cross-linked biological components, including polysaccharide, proteins, and cells, for stem cell culture matrices. The cross-linked materials can be conveniently prepared and stably stored until utilization.

Cell encapsulation and cell delivery have been proposed as an alternative approach to treat various diseases since they allow localized and controlled delivery of therapeutic cells to specific physiological sites to restore the lost functions, which can overcome many current limitations in the present therapeutic technologies. In particular, great interests have been attracted in utilizing stem cell as the cell source for cell encapsulation and therapy in the recent years. This chapter provides an overview of cell encapsulation technology based on hydrogel biomaterials, with a focus on stem cell encapsulation and some recent developments of such strategy for its use in treatment of diabetes. It is well established that stem cell encapsulation can be a promising approach for therapy of diabetes, especially in cases where limited cells are available for differentiation and expansion. Several potential stem cell candidates and their differentiation protocols have been examined and developed. The authors believe that stem cell encapsulation may see exciting improvement in the next few decades. However, a few challenges have to be addressed such as safety and efficacy of this approach for treatment of diabetes and scale-up of manufacturing process under Good Manufacturing Practice conditions before the technology can enter human clinical trials and become a real clinical therapeutic strategy.

The concept of dynamic supramolecular surfaces and its performance as the functional biomaterials surfaces are introduced in this chapter. In order to provide the dynamic nature on substrate surfaces, supramolecular architecture of polyrotaxanes (PRXs) is introduced into designing block copolymers. In the PRX segment, many cyclodextrins are threaded onto a linear poly(ethylene glycol) chain capped both terminals with bulky endo-groups. The molecular mobility at surfaces in aqueous media could be controlled via changing the number of threaded CDs. By adopting the mobile supramolecular PRX platform, conformational change of adsorbed fibrinogen molecules is greatly suppressed, and the subsequent platelet adhesion is reduced. Further, introducing RGD sequence into the PRX platform can induce fast cellular response but reduce the later cellular metabolic response. These novel concepts of dynamic cell-adhesive surfaces are expected to provide a promising way to develop functional biomaterials that is able to induce selective cell adhesion, rapid cellular recognition, or suppression of differentiation.

The supramolecular self-assembly formed between cyclodextrins (CDs) and polymers has inspired interesting development of many novel supramolecular hydrogels as injectable delivery systems for sustained drug or gene release due to their thixotropic nature, thermoreversible properties, and biocompatibility. A large number of supramolecular hydrogels have been formed between CDs and poly(ethylene oxide) or its block copolymers with a hydrophobic segment. The intermolecular interactions by the hydrophobic blocks further strengthen and stabilize the supramolecular network, opening up a new approach for designing long-term sustained delivery systems. Recent advances in this field have greatly improved the rheological and delivery properties of the supramolecular hydrogels, making them more suitable for biomedical applications. Novel supramolecular structures based on pseudoblock copolymers formed by host-guest inclusion complexation with new stimuli-responsive properties have also been developed, forming “smart” supramolecular hydrogels with more desired and promising properties for controlled release applications.