Synthetic biocompatible cyclodextrin-based constructs for local gene delivery to improve cutaneous wound healing

Abstract

The localized, sustained delivery of growth factors for wound healing therapy is actively being explored by gene transfer to the wound site. Biocompatible matrices such as bovine collagen have demonstrated usefulness in sustaining gene therapy vectors that express growth factors in local sites for tissue repair. Here, new synthetic biocompatible materials are prepared and shown to deliver a protein to cultured cells via the use of an adenoviral delivery vector. The synthetic construct consists of a linear, beta-cyclodextrin-containing polymer and an adamantane-based cross-linking polymer. When the two polymers are combined, they create an extended network by the formation of inclusion complexes between the cyclodextrins and adamantanes. The properties of the network are altered by controlling the polymer molecular weights and the number of adamantanes on the cross-linking polymer, and these modifications and others such as replacement of the beta-cyclodextrin (host) and adamantane (guest) with other cyclodextrins (hosts such as alpha, gamma, and substituted members) and inclusion complex forming molecules (guests) provide the ability to rationally design network characteristics. Fibroblasts exposed to these synthetic constructs show proliferation rates and migration patterns similar to those obtained with collagen. Gene delivery (green fluorescent protein) to fibroblasts via the inclusion of adenoviral vectors in the synthetic construct is equivalent to levels observed with collagen. These in vitro results suggest that the synthetic constructs are suitable for in vivo tissue repair applications.