Matrices and scaffolds for DNA delivery in tissue engineering

Abstract

Regenerative medicine aims to create functional tissue replacements, typically through creating a controlled environment that promotes and directs the differentiation of stem or progenitor cells, either endogenous or transplanted. Scaffolds serve a central role in many strategies by providing the means to control the local environment. Gene delivery from the scaffold represents a versatile approach to manipulating the local environment for directing cell function. Research at the interface of biomaterials, gene therapy, and drug delivery has identified several design parameters for the vector and the biomaterial scaffold that must be satisfied. Progress has been made towards achieving gene delivery within a tissue engineering scaffold, though the design principles for the materials and vectors that produce efficient delivery require further development. Nevertheless, these advances in obtaining transgene expression with the scaffold have created opportunities to develop greater control of either delivery or expression and to identify the best practices for promoting tissue formation. Strategies to achieve controlled, localized expression within the tissue engineering scaffold will have broad application to the regeneration of many tissues, with great promise for clinical therapies.

Figure 1

The rate of DNA release from hydrogels (A) and scaffolds (B) results from a combination of diffusion and material degradation. An initial burst may occur for vectors that are surface associated. Degradation of the biomaterial opens paths through the scaffold to allow for vector diffusion through the pores.

Figure 2

A) Viral and non-viral vectors can interact with polymeric biomaterials through non-specific mechanisms, including hydrophobic, electrostatic, and van der Waals interactions, and more specific interactions, regulated by avidin/biotin or antibody/antigen interactions. B) An immobilized vector can be released by desorption for non-specifically immobilized complexes, or covalently coupled vectors may require degradation of either the tether or the biomaterial for release.

Figure 3

Spatially patterned transgene expression: A) Pattern created by controlled cell adhesion in a micropatterned hyaluronic acid-collagen hydrogel, scale bar: 20 $m [111], Reprinted from Biomaterials, 26, T. Segura, P. H. Chung, L. D. Shea, DNA delivery from hyaluronic acid-collagen hydrogels via a substrate-mediated approach, 1575–1584, Copyright (2005), with permission from Elsevier. B) Pattern created by pinning aqueous solutions to hydrophilic regions on SAMs. Image demonstrates transfection within two circles. scale bar: 500 $m [153], Reprinted from Acta Biomaterialia, 1, A. K. Pannier, B. C. Anderson, L. D. Shea, Substrate-mediated delivery from self-assembled monolayers: effect of surface ionization, hydrophilicity, and patterning, 511–522, Copyright (2005), with permission from Elsevier. C) Pattern created by lipoplex deposition on a polystyrene surface using soft lithography microfluidics, the microchannels are respectively 500, 250, and 100 $m wide, scale bar: 500 $m [156]. Reprinted from Molecular Therapy, in press, T. L. Houchin, K. J. Whittlesey, L. D. Shea, Spatially patterned gene delivery for localized neuron survival and neurite extension, Copyright (2007), with permission from Nature. $=μ