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Rat Sciatic Nerve Regeneration Using IGF- 1 Enriched White Adipose Tissue Flap as a Biologic Scaffold
Rebecca A. Rajfer, BS; Ayhan Kilic; Bukola Ojo, BS; Geoffrey Konopka; Daniel Hagg; Eugene Jang; Yelena Akelina; Jeremy Mao; Melvin P. Rosenwasser; Peter Tang
Columbia University College of Physicians & Surgeons, New York, NY, USA
Background: White adipose tissue (WAT) and insulin-like growth factor-1 (IGF-1) have shown potential to enhance peripheral nerve regeneration. We hypothesized that white adipose tissue flap (WATF) enriched with IGF-1 as an in vivo biologic scaffold would provide functional and histological benefits in a sciatic nerve crush injury model.
Methods: Forty male Sprague-Dawley rats were divided into four arms. All rats underwent a crush injury to one sciatic nerve and received a pedicled WATF, controlled local release of IGF-1, both, or no treatment at the lesion area for 4 weeks. The WATF was composed of adipose tissue derived from the inguinal region. IGF-1 was delivered from polylactic-co-glycolic acid (PLGA) microspheres embedded in fibrin gel adjacent to the crush injury. Tibialis anterior (TA) muscle weights and maximum isometric tetanic force (ITF) of the TA muscle normalized to the contralateral side were recorded. Histological sections 1mm distal to the lesion were histomorphometrically analyzed. Data were analyzed utilizing Student’s t-test and two-way ANOVA.
Results: At 4 weeks, the mean normalized ITFs were as follows: WATF 51.9±12.3%, IGF-1 33.5±5.7%, WATF/IGF-1 46.7±22.8%, and control 44.8±12.8%. The presence of the WATF as a main effect resulted in a statistically significant 26.1% increase in normalized ITF (p<0.05). There was a statistically significant 11.3% increase in myelin thickness and 13.1% increase in total axon count in the WATF-only group versus control (p<0.01). The TA muscle weights were similar across all groups. Both functional and histomorphometric data suggest that the presence of IGF-1 suppressed the effect of the WATF rather than enhanced it.
Conclusions: We induced a sciatic nerve axonotmesis experimental model in rats, which yielded promising functional and histomorphometrical results utilizing a pedicled WATF. IGF-1 does not appear to enhance the regenerative effect of the WATF.
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