Background: Molecular and cellular-based enhancements of healing combined with conventional methods may yield better outcomes after the surgical management of tendon injury. We examined the histological and biomechanical effects of adenovirus-mediated transgene expression of bone morphogenetic protein-14 (BMP-14) on healing in a rat Achilles tendon laceration model. Specifically, we hypothesized that this delivery system for gene therapy would hasten the restoration of the normal histological appearance and tensile strength of a surgically repaired tendon. Methods: The right Achilles tendon of ninety male Sprague-Dawley rats was transected, repaired, and immediately infected with adenovirus expressing either the gene for green fluorescent protein (AdGFP) or the gene for human BMP-14 and green fluorescent protein (AdBMP-14). A sham control group received no viral-mediated infection after repair. Animals from each of the three groups were killed at one, two, and three weeks after surgery. The retrieved tendons were inspected, examined under light and fluorescent microscopy, and tested to determine their tensile strength. Results: Tendons transduced with BMP-14 exhibited less visible gapping, a greater number of neotenocytes at the site of healing, and 70% greater tensile strength than did either those transduced with GFP or the sham controls at two weeks after repair. Histological examination revealed no inflammatory response to the adenovirus in tendons transduced with BMP-14 or GFP. No ectopic bone or cartilage formed in the tendons transduced with BMP-14. Conclusions: Adenovirus-mediated gene therapy with BMP-14 expedites tendon-healing in this animal model. No adverse immunological response to the adenoviral vector was detected in the host tissue, and the local production of BMP-14 did not induce unwelcome bone or cartilage formation within the healing tendon. Clinical Relevance: The results of this animal study suggest that gene therapy with BMPs may improve the capacity of injured musculoskeletal tissue to heal.
BACKGROUND CONTEXT: We have recently demonstrated that BMP-9 is one of the most osteogenic BMPs both in vitro and in vivo. Although comparisons of carriers combined with recombinant BMP-2 have been performed previously, no comparison of carriers for cell-based gene therapy has been performed. In order for further development of gene therapy to occur, it is essential to define the ideal carrier for this application.
BACKGROUND CONTEXT: Anterior plate fixation is frequently used after anterior cervical and discectomy and fusion (ACDF). Although good results with few complications have been reported with plates across a single level, less consistent results have been reported with plates spanning multiple disc levels. Recently, dynamic plates that allow for controlled settling across the construct have been popularized to allow for loading of the graft to promote fusion. To date these proposed benefits have been largely theoretical and there are no studies confirming any benefits over more traditional static plates.