Growth factor delivery-based tissue engineering: general approaches and a review of recent developments

Abstract

The identification and production of recombinant morphogens and growth factors that play key roles in tissue regeneration have generated much enthusiasm and numerous clinical trials, but the results of many of these trials have been largely disappointing. Interestingly, the trials that have shown benefit all contain a common denominator, the presence of a material carrier, suggesting strongly that spatio-temporal control over the location and bioactivity of factors after introduction into the body is crucial to achieve tangible therapeutic effect. Sophisticated materials systems that regulate the biological presentation of growth factors represent an attractive new generation of therapeutic agents for the treatment of a wide variety of diseases. This review provides an overview of growth factor delivery in tissue engineering. Certain fundamental issues and design strategies relevant to the material carriers that are being actively pursued to address specific technical objectives are discussed. Recent progress highlights the importance of materials science and engineering in growth factor delivery approaches to regenerative medicine.

Figure 1.

Cross talk between cells mediated by growth factors and ECM. The producer cell secretes soluble growth factors that bind to target cell receptors. The instructions are translated into the cell through complex signal transduction networks resulting in a specific biological cellular response. Insert illustrates how ECM can control growth factor presentation in a temporal and spatial fashion. Cell migration towards gradients of growth factors, bonded to ECM, can also be ECM mediated, whereas cells will use integrin machinery to follow growth factor gradients. Upon degradation, ECM growth factors become available for cell binding via cell membrane growth factor receptors and will ultimately induce a specific biological cellular response.

Figure 2.

Illustration displays spatio-temporal delivery of distinct factors. A material system loaded with different bioactive factors can be tailored to display a sequential delivery of these factors over time, resulting in controlled sequential waves of factor delivery over extended periods of time.

Figure 3.

Schematic of two tissue engineering approaches using synthetic ECMs to present growth factors to tissues. (a) Physically encapsulated bioactive factors can be released from synthetic ECMs to target specific cell populations to migrate and direct tissue regeneration. (b) Alternatively, growth factors can be chemically bound to the material system, making them available to cells that infiltrate the material.

Figure 4.

Sophisticated material systems capable of using growth factors to programme native cells. Polymer systems can be functionalized to recruit specific subsets of cells, where the cells are programmed to execute a specific task after leaving the material that can be to maintain, regenerate or even to destroy a particular tissue or subset of cells at a local or distant site.