Freeze-dried tendon allograft loaded with a gene therapy proves effective in early studies

Allografts loaded with Gdf5 served as tissue-engineered scaffolds that produced significantly fewer adhesions compared to autografts.

A new graft technique involving gene therapy shows potential in pre-clinical studies for creating a framework around which flexor tendon tissue can reorganize as it heals, according to a study published in the journal Molecular Therapy.

Hani Awad, PhD, and colleagues at the University of Rochester Medical Center investigated the use of freeze-dried tendon allografts loaded with a recombinant adeno-associated vector (rAAV) expressing the gene that codes for the building of growth and differentiation factor 5 (Gdf5). The researchers implanted the graft into the distal flexor digitorum longus (FDL) tendons of mice.

Investigators compared functional recovery for these mice to a control group implanted with allograft loaded with a non-therapeutic gene (lacZ).

The results show that the allografts served as tissue-engineered scaffolds, with significantly fewer adhesions compared to autografts. The allografts also delivered the solution of gene therapy vectors into the graft site, which directed cells to accept the graft and remodel it into living tissue, according to a press release from the university.

The researchers also found that animals that received the freeze-dried FDL allografts loaded with rAAV Gdf5 recovered two-times more range of motion compared to control animals at 14 days postsurgery. At 28 days, the allograft group had reached nearly 65% of the normal range of motion while the control group had recovered only 35% of normal, according to the release.

"Orthopedic surgeons have been searching for the perfect material to replace tendon, one with the right mix of strength and elasticity and would not cause adhesion," Awad stated in the release.

"We believe the only material to meet these strict requirements is non-living, but structurally intact tendon. We were surprised to find that no one had tried combining it with gene therapy or other drug delivery techniques to overcome its limitations," he said.

One limitation of the study is that the allografts used were so small that the tendon had to be immobilized during the healing process to prevent tearing. Thus, overall healing of the two groups — GDF-treated and control — proceeded at the same rate over the first 84 days after reconstruction.

In larger animals and in humans, where allografts should be able to benefit from the force of motion as they heal, Awad noted that he expects that gene-therapy-loaded allografts will heal at a much faster rate than autografts or synthetic grafts.

For more information:
Basile P, Dadali T, Jacobson J, et al. Freeze-dried tendon allografts as tissue-engineering scaffolds for Gdf5 gene delivery. Mol Ther. 2008. Published online ahead of print January 8, 2008. Available at http://www.nature.com/mt/index.html.