Future of local bone regeneration - Protein versus gene therapy

Abstract

The most promising attempts to achieve bone regeneration artificially are based on the application of mediators such as bone morphogenetic proteins (BMPs) directly to the deficient tissue site. BMPs, as promoters of the regenerative process, have the ability to induce de novo bone formation in various tissues, and many animal models have demonstrated their high potential for ectopic and orthotopic bone formation. However, the biological activity of the soluble factors that promote bone formation in vivo is limited by diffusion and degradation, leading to a short half-life. Local delivery remains a problem in clinical applications. Several materials, including hydroxyapatite, tricalcium phosphate, demineralised bone matrices, poly-lactic acid homo- and heterodimers, and collagen have been tested as carriers and delivery systems for these factors in a sustained and appropriate manner. Unfortunately these delivery vehicles often have limitations in terms of biodegradability, inflammatory and immunological rejection, disease transmission, and most importantly, an inability to provide a sustained, continuous release of these factors at the region of interest. In coping with these problems, new approaches have been established: genes encoding these growth factor proteins can be delivered to the target cells. In this way the transfected cells serve as local "bioreactors", as they express the exogenous genes and secrete the synthesised proteins into their vicinity. The purpose of this review is to present the different methods of gene versus growth factor delivery in tissue engineering. Our review focuses on these promising and innovative methods that are defined as regional gene therapy and provide an alternative to the direct application of growth factors. Various advantages and disadvantages of non-viral and viral vectors are discussed. This review identifies potential candidate genes and target cells, and in vivo as well as ex vivo approaches for cell transduction and transfection. In explaining the biological basis, this paper also refers to current experimental and clinical applications.