IGF-1 Nanoparticles To Improve Functional Recovery After Peripheral Nerve Injury
Philip Hanwright, MD1, Chenhu Qiu, BS2, Jennifer Rath, BS1, Nicholas von Guionneau, MBBS1, Karim Sarhane, MD1, Thomas Harris, BS1, Harsha Malapati, BS1, Ahmet Hoke, MD, PhD3, Hai-Quan Mao, PhD2, Sami Tuffaha, MD1.
1Johns Hopkins Department of Plastic Surgery, Baltimore, MD, USA, 2Johns Hopkins School of Engineering, Baltimore, MD, USA, 3Johns Hopkins School of Medicine, Baltimore, MD, USA.
PURPOSE: Insulin-like growth factor 1 (IGF-1) is a potent mitogen with well-described trophic and anti-apoptotic effects on neurons, myocytes, and Schwann cells (SCs). The aims of this study are to (1) encapsulate IGF-1 into biodegradable nanoparticles (NP) to enable sustained release at target tissue sites; and (2) assess the efficacy of locally delivered IGF-1 NPs to improve functional recovery following.
METHODS: (1) NP Fabrication: Varying ratios of IGF-1:polymer were evaluated. Loading efficiency and in vitro NP release kinetics were evaluated and mitogenic activity of released IGF-1 was assessed. (2) The effects of locally-delivered IGF-1 NPs. The effects of IGF-1 NP treatment on axonal regeneration, muscle atrophy and reinnervation, and recovery of forepaw motor function were assessed in vivol.
RESULTS: (1) An encapsulation efficiency of 83.2% was achieved. The 1:5 PEG5k-PCL40k formulation yielded optimal release of IGF-1 with near-zero-order release of IGF-1 for at least 70 days. Released IGF-1 exhibits comparable bioactivity to native IGF-1. (2) IGF-1 treated animals recovered significantly more forceful grip strength compared to negative controls (Fig. 1). IGF-1 treatment limits muscle atrophy during periods of denervation compared to negative controls (620 vs. 340um2; p <0.05) and enhances neuromuscular junction reinnervation (41 vs. 27%, p <0.05).
CONCLUSION: Sustained release of bioactive IGF-1 was achieved. IGF-1 NP treatment in vivo limits muscle atrophy during denervation and improves functional recovery of forelimb grip strength.
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