Insulin Like Growth Factor-1 Improve Functional Recovery In Novel Rat And Non-human Primate Peripheral Nerve Injury Models
Thomas Harris, MBChB, Karim Sarhane, MD, Chenhu Qiu, BS, Philip Hanwright, MD, Connor Glass, MD, Alison Wong, MD, Nicholas von Guionneau, MBBS, Harsha Malapati, BS, Nicholas Hricz, BS, Matthew Generoso, BS, Sai Pinni, BS, Erica Lee, BS, Richard Redett III, MD, Kara Segna, MD, Ahmet Hoke, MD, PhD, Hai-Quan Mao, PhD, Sami Tuffaha, MD.
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Purpose: Insulin-like growth factor 1 (IGF-1) improves nerve regeneration and ameliorates the deleterious effects of chronic denervation. Local delivery is limited by its short half-life. The aim was to encapsulate IGF-1 within biodegradable nanoparticles (NPs) for sustained local delivery; develop a nanofiber hydrogel composite (NHC) carrier to maintain NPs at target tissue; assess the efficacy of the IGF-1 NP-NHC in rodent and non-human primate (NHP) peripheral nerve injury (PNI) models. Methods: The IGF-1 NP-NHC was assessed in rat and NHP median nerve injury models. The primary outcome measure in both models was stimulated grip strength testing. Nerve regeneration and end organ reinnervation and atrophy were evaluated histologically. Results: Sustained release of IGF-1 for 6 weeks was confirmed in rats and NHP. IGF-1 NP/NHC resulted in a two-fold increase in the number of regenerative axons compared to the saline treated control (5377 vs 2704, respectively) and reinnervation of glabrous skin (Figure 1). The IGF-1 treated NHP exhibited a 31.0% increase in functional recovery 71 weeks after nerve repair, consistent with the rat study outcomes (Figure 2). Conclusions: The IGF-1 NP-NHC provides sustained release of bioactive IGF-1 and thereby improves axonal regeneration and functional recovery in rat and NHP.
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