Matrix-based gene delivery for tissue repair

• We present a detailed description of gene loaded scaffold design for tissue repair.
• Infiltrating cells are transfected through released DNA or matrix residing DNA.
• Surface associated DNA via nonspecific adsorption is a popular current technique.
• Biochemical cues may be used to ‘prime’ cells for transgene expression.

Scaffolds for tissue repair must provide structural and biochemical cues to initiate the complex cascade of events that lead to proper tissue formation. Incorporating genes into these scaffolds is an attractive alternative to protein delivery since gene delivery can be tunable to any DNA sequence and genes utilize the cells’ machinery to continuously produce therapeutic proteins, leading to longer lasting transgene expression and activation of autocrine and paracrine signaling that are not activated with bulk protein delivery. In this review, we discuss the importance of scaffold design and the impact of its design parameters (e.g. material, architecture, vector incorporation, biochemical cue presentation) on transgene expression and tissue repair.

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