Hydrogels for tissue engineering: scaffold design variables and applications

Abstract

Polymer scaffolds have many different functions in the field of tissue engineering. They are applied as space filling agents, as delivery vehicles for bioactive molecules, and as three-dimensional structures that organize cells and present stimuli to direct the formation of a desired tissue. Much of the success of scaffolds in these roles hinges on finding an appropriate material to address the critical physical, mass transport, and biological design variables inherent to each application. Hydrogels are an appealing scaffold material because they are structurally similar to the extracellular matrix of many tissues, can often be processed under relatively mild conditions, and may be delivered in a minimally invasive manner. Consequently, hydrogels have been utilized as scaffold materials for drug and growth factor delivery, engineering tissue replacements, and a variety of other applications.

Introduction

The field of tissue engineering has developed to meet the tremendous need for organs and tissues [1], [2], [3], [4]. In the most general sense, tissue engineering seeks to fabricate, living replacement parts for the body [5]. The necessity of tissue engineering is illustrated by the ever-widening supply and demand mismatch of organs and tissues for transplantation (Fig. 1) [6]. This trend persists, as demonstrated by the fact that only 23,407 people received transplants from July 2000 to July 2001, while 79,902 people awaited them [7].

Numerous strategies currently used to engineer tissues depend on employing a material scaffold. These scaffolds serve as a synthetic extracellular matrix (ECM) to organize cells into a three-dimensional architecture and to present stimuli, which direct the growth and formation of a desired tissue [8]. Depending on the tissue of interest and the specific application, the required scaffold material and its properties will be quite different. Common scaffold materials include poly(lactide-co-glycolide) (PLG). PLG are hydrolytically degradable polymers that are FDA approved for use in the body and mechanically strong [9], [10]. However, they are hydrophobic and typically processed under relatively severe conditions, which makes factor incorporation and entrapment of viable cells potentially a challenge. As an alternative, a variety of hydrogels, a class of highly hydrated polymer materials (water content ⩾30% by weight) [11], are being employed as scaffold materials. They are composed of hydrophilic polymer chains, which are either synthetic or natural in origin. The structural integrity of hydrogels depends on crosslinks formed between polymer chains via various chemical bonds and physical interactions. Hydrogels used in these applications are typically degradable, can be processed under relatively mild conditions, have mechanical and structural properties similar to many tissues and the ECM, and can be delivered in a minimally invasive manner [12].

This review will focus on the use of hydrogels as scaffolds for tissues engineering. Adequate scaffold design and material selection for each specific application depend on several variables, including physical properties (e.g. mechanics, degradation, gel formation), mass transport properties (e.g. diffusion), and biological properties (e.g. cell adhesion and signaling). We have identified three categories of scaffolds applications in this review: space filling agents, bioactive molecule delivery, and cell/tissue delivery. The materials available for use in hydrogel formation are first discussed along with a description of the pertinent design variables. The current use of hydrogels for each of the major categories of applications will subsequently be reviewed.