Local gene delivery from ECM coated poly (lactide co glycolide) multiple channel bridges after spinal cord injury

Biomaterials, 2009 · DOI: 10.1016/j.biomaterials.2008.12.051 · Published: April 1, 2009

Simple Explanation

The study explores delivering genes to injured spinal cords using tissue engineering scaffolds. These scaffolds, coated with extracellular matrix (ECM) and DNA, aim to promote tissue regeneration by directing cell function and influencing cellular responses through localized production of tissue inductive factors. The method involves surface immobilization of DNA complexed with lipids (lipoplexes) onto the scaffold. This approach can be applied to scaffolds with complex geometries and allows for precise control over where the DNA is placed, potentially creating gradients of inductive factors. The spinal cord bridges contain multiple linear guidance channels to support cell infiltration and integrate into the spinal cord, while the channels induced cell orientation along its major axis and supported and directed axons elongation across the channels.

Study Duration

3 weeks

Participants

40 female Long-Evans rats

Evidence Level

Not specified

Key Findings

1
Fibronectin, an ECM protein, produced greater gene expression levels and immobilization efficiencies compared with collagen and laminin.
2
Lipoplex incubation on ECM-coated PLG increased gene expression relative to drying methods, resulting in more homogeneously distributed lipoplexes and a higher number of transfected cells.
3
In a rat spinal cord injury model, lipoplexes immobilized to the bridge produced transgene expression levels two-fold greater than naked plasmid DNA, with expression persisting for at least three weeks.

Research Summary

This study investigates surface immobilization to deliver complexed DNA (lipoplexes) from a multiple channel bridge in order to promote transgene expression in the injured spinal cord using low quantities of DNA. In vitro studies revealed that fibronectin produced greater expression levels and immobilization efficiencies compared with collagen, laminin, and no coating. In addition, lipoplex incubation on ECM-coated PLG increased expression relative to either of the drying methods. In vivo, lipoplexes immobilized to the bridge produced transgene expression levels in a rat spinal cord hemisection model that were 2-fold greater than naked plasmid. Additionally, expression with lipoplexes persisted for at least three weeks.

Practical Implications

Enhanced Spinal Cord Regeneration

The combination of tissue engineering and gene therapy shows promise for spinal cord regeneration by delivering genes that can address multiple barriers to recovery, such as cell survival and axonal elongation.

Improved Gene Delivery Methods

Surface-mediated delivery of lipoplexes from fibronectin-coated bridges offers an efficient DNA delivery system after spinal cord injury, requiring only small amounts of DNA to induce transgene expression for an extended period.

Scaffold Design Optimization

The study highlights the importance of scaffold surface properties, particularly the use of fibronectin coating, in maximizing gene transfer and promoting tissue regeneration.

Study Limitations

1
The specific mechanism by which fibronectin enhances transgene expression remains unclear.
2
The spinal cord, however, is a challenging site for gene delivery due to the constant exchange of cerebrospinal fluid, which may lead to faster clearance of DNA relative to other sites.
3
Doubling the dose of lipoplexes incubated with the bridges did not enhance the expression levels.

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