Injectable matrices and scaffolds for drug delivery in tissue engineering

Abstract

Injectable matrices and depots have been the subject of much research in the field of drug delivery. The classical tissue engineering paradigm includes a matrix or scaffold to facilitate tissue growth and provide structural support, cells, and the delivery of bioactive molecules. As both tissue engineering and drug delivery techniques benefit from the use of injectable materials due to the minimal invasiveness of an injection, significant crossover should be observed between injectable materials in both fields. This review aims to outline injectable materials and processing techniques used in both tissue engineering and drug delivery and to describe methods by which current injectable materials in the field of drug delivery can be adapted for use as injectable scaffolds for tissue engineering.

Introduction

Injectable biomaterials are widely researched and hold great promise in both the fields of drug delivery and tissue engineering, largely due to the minimally invasive nature with which they can be delivered. Injectable systems in drug delivery can be used both for parenteral drug delivery or localized injection to an affected site. Drug release kinetics can be varied via altering the character and processing of the injectable biomaterial matrix or depot, and the properties (size, hydrophobicity, etc.) of the drug to be released often have a large effect on release kinetics. For a patient, injectable delivery systems offer the advantage of avoiding surgical procedures and the host of potential complications thereof to implant the drug depot or, in the case of long term drug delivery, an elimination of the need for repeated doctors visits or potentially dangerous indwelling percutaneous lines. Thus a long term drug delivery system deliverable via a simple injection holds multiple benefits for patient safety and quality of life.

Tissue engineering is a relatively new field that seeks to regenerate human tissues through the use of some combination of cells, bioactive molecules such as drugs or growth factors, and a biomaterial support system or scaffold. The need for such technology is readily apparent — with the continued aging of the population, the current shortage in donor organ availability will likely only grow, and strategies to address the shortage through increased donation are fraught with medical [1], [2] and ethical concerns [3], [4], [5], [6], [7]. The ability to regenerate damaged tissues and organs to a healthy and functional state using the body's own healing capabilities and without the need for long term immune suppression represents a near ideal solution to this growing problem. Injectable materials for use in tissue engineering share the same advantages as those used in drug delivery. Additionally, in tissue engineering applications, injectable biomaterials that form scaffolds in situ have the advantage of being able to take the shape of a tissue defect, avoiding the need for patient specific scaffold prefabrication. There are, however, additional considerations necessary when developing injectable systems for tissue engineering; for many applications the system must also able to support a suspended cell population prior to injection and throughout the solidification process.

With these considerations in mind, an examination of injectable systems for both drug delivery and tissue engineering is warranted, including an overview of necessary characteristics for tissue engineering scaffolds and how current injectable systems for drug delivery applications could be modified to facilitate their use as injectable tissue engineering scaffolds.