John A Walker1, Gianni Rossini2, Michelle W Thompson3, Joseph C Wenke4, David Baer4. 1. Department of Radiology, The University of Texas Health Science Center, School of Medicine, San Antonio, TX; email:walkerja@livemail.uthscsa.edu. 2. Department of Biochemistry & Biomaterials, Southwest Research Institute, San Antonio, TX. 3. Department of Pathology, Tri-Service Research Laboratory, San Antonio, TX. 4. Regenerative Medicine Task Area, United States Army Institute of Surgical Research, San Antonio, TX.
Abstract
UNLABELLED: In vitro and in vivo assessments suggest that proteasome inhibitors may be useful for modulating wound healing. METHODS: Proteasome Inhibitor I was used to assess the potential utility of proteasome inhibitors in improving wound healing in a standard rat model. Bilateral, 6 cm incisions were made 1 cm lateral to the spine of adult male Sprague Dawley rats. Animals were randomly assigned to 1 of 3 groups: no treatment (n = 15), low concentration (1% w/v, n = 15), or high concentration (5% w/v, n = 15). Treatments were applied to the left side incision at 0 hours, 24 hours, and 48 hours. Right-side incisionsreceived a vehicle, dimethyl sulfoxide, alone and independent of the assigned group, serving as both external and internal controls. Rats were sacrificed at days 7, 14, and 28 (n = 5 per group) and wounds subjected to mechanical testing and histology. RESULTS: No significant intergroup difference existed at 7 and 14 days. On day 28, a dosedependent increase in tensile strength with increasing Proteasome Inhibitor I was observed. CONCLUSION: Results suggest dimethyl sulfoxide was not the ideal vehicle and additional improvement may be realized by optimizing the delivery method.
UNLABELLED: In vitro and in vivo assessments suggest that proteasome inhibitors may be useful for modulating wound healing. METHODS: Proteasome Inhibitor I was used to assess the potential utility of proteasome inhibitors in improving wound healing in a standard rat model. Bilateral, 6 cm incisions were made 1 cm lateral to the spine of adult male Sprague Dawley rats. Animals were randomly assigned to 1 of 3 groups: no treatment (n = 15), low concentration (1% w/v, n = 15), or high concentration (5% w/v, n = 15). Treatments were applied to the left side incision at 0 hours, 24 hours, and 48 hours. Right-side incisionsreceived a vehicle, dimethyl sulfoxide, alone and independent of the assigned group, serving as both external and internal controls. Rats were sacrificed at days 7, 14, and 28 (n = 5 per group) and wounds subjected to mechanical testing and histology. RESULTS: No significant intergroup difference existed at 7 and 14 days. On day 28, a dosedependent increase in tensile strength with increasing Proteasome Inhibitor I was observed. CONCLUSION: Results suggest dimethyl sulfoxide was not the ideal vehicle and additional improvement may be realized by optimizing the delivery method.