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Development of a novel tissue engineered/gene therapy approach to the treatment of rotator cuff tears in a rat model

Authors: J.S. Dines, C. Uggen, D. Grande, R. Razzano, D.M. Dines

References: SECEC, Rome 2005

Abstract
AIMS: Endogenous healing is poor or insufficient in many rotator cuff repairs. This study evaluates a new cell-polymer construct of tendon cells transduced with either IGF-1 or PDGFb for their ability to augment rotator cuff tendon healing in vivo.

MATERIAL: Rat tendon fibroblasts were transduced with the genes for either PDGFb or IGF-1 by retroviral vectors. After selection and expansion, they were seeded onto a polymer scaffold and further cultured. The supraspinatus tendon of 33 rats were surgically transsected and allowed to undergo an inflammatory phase of healing for two weeks (mimicking the clinical setting of a chronic rotator cuff tear). a second surgery was then performed to repair the original tear. repair involved standard suture realignment as a control or suture repair with an addition of a gene modified tendon tissue construct (experimental groups). Experimental repair utilized a tendon cell construct on PGA scaffold incorporated with the gene for promoting repair (PDGFb in one group; IGF-1 in the other). Repaired tissue was harvested at 12 weeks post repair and prepared for histological examination and mechanical testing via servo-hydraulic dynastat mechanical spectrometer with special grips. Toughness, stiffness, load to failure, and maximum deformation were tested.

RESULTS: Rotator cuffs repaired by standard suture repair resulted in a range from poor or no repair to incomplete restoration of tendon architecture. Experimental group repairs resulted in near complete to full restoration of the torn tendon architecture. Histologic analysis demonstrated restoration of the normal crimp patterning and collagen bundle alignment in the experimental groups. Repair of the rotator cuff tears with tendon cells transduced with the gene for IGF-1 improved the mechanical properties of the repair site when compared with suture repair alone. PDGFb did not yield significant differences in mechanical properties from the control group.

CONCLUSION: This study supports our hypothesis that gene modified constructs can augment tendon repair in a rat model of rotator cuff injury. IGF-1 delivered locally by gene therapy and tissue engineering methods improved the histological and mechanical properties of repaired tendons compared to the PDGFb repair group.

This study demonstrates the efficacy of a new type of bioactive implant for repair of rotator cuff injuries.

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