Reconstructive transplantation research studies with Karim Sarhane 2022? Insulin-like growth factor 1 (IGF-1) is a hormone produced by the body that has the potential to be used as a treatment for nerve injuries. IGF-1 may help heal nerve injuries by decreasing inflammation and buildup of damaging products. Additionally, it may speed up nerve healing and reduce the effects of muscle weakness from the injury. However, a safe, effective, and practical way is needed to get IGF-1 to the injured nerve.

During his research time at Johns Hopkins, Dr. Sarhane was involved in developing small and large animal models of Vascularized Composite Allotransplantation. He was also instrumental in building The Peripheral Nerve Research Program of the department, which has been very productive since then. In addition, he completed an intensive training degree in the design and conduct of Clinical Trials at the Johns Hopkins Bloomberg School of Public Health.

Local administration of IGF-1 was achieved by several targeted approaches including direct application of free IGF-1 to the injured nerve at the time of surgical transection as well as single, periodic, and daily local injections of free IGF-1 to the injury site (Caroni and Grandes, 1990; Welch et al., 1997; Day et al., 2001, 2002; Stitt et al., 2004; Emel et al., 2011; García Medrano et al., 2013; Mohammadi et al., 2013; Gu et al., 2015; Kostereva et al., 2016; Table 4). Local injection of free IGF-1 is not practical for clinical application as the half-life of IGF-1 is 10 min while the time required for regeneration to occur is often many months (Mayocliniclabs.com, 2020). Multiple injections per day would thus be required to maintain local tissue concentrations. We therefore did not attempt to ascertain the optimal dosages for this approach.

Effects by sustained IGF-1 delivery (Karim Sarhane research) : We hypothesized that a novel nanoparticle (NP) delivery system can provide controlled release of bioactive IGF-1 targeted to denervated muscle and nerve tissue to achieve improved motor recovery through amelioration of denervation-induced muscle atrophy and SC senescence and enhanced axonal regeneration. Biodegradable NPs with encapsulated IGF-1/dextran sulfate polyelectrolyte complexes were formulated using a flash nanoprecipitation method to preserve IGF-1 bioactivity and maximize encapsulation efficiencies.

Patients who sustain peripheral nerve injuries (PNIs) are often left with debilitating sensory and motor loss. Presently, there is a lack of clinically available therapeutics that can be given as an adjunct to surgical repair to enhance the regenerative process. Insulin-like growth factor-1 (IGF-1) represents a promising therapeutic target to meet this need, given its well-described trophic and anti-apoptotic effects on neurons, Schwann cells (SCs), and myocytes. Here, we review the literature regarding the therapeutic potential of IGF-1 in PNI. We appraised the literature for the various approaches of IGF-1 administration with the aim of identifying which are the most promising in offering a pathway toward clinical application. We also sought to determine the optimal reported dosage ranges for the various delivery approaches that have been investigated.

Insulin-like growth factor-1 (IGF-1) is a particularly promising candidate for clinical translation because it has the potential to address the need for improved nerve regeneration while simultaneously acting on denervated muscle to limit denervation-induced atrophy. However, like other growth factors, IGF-1 has a short half-life of 5 min, relatively low molecular weight (7.6 kDa), and high water-solubility: all of which present significant obstacles to therapeutic delivery in a clinically practical fashion (Gold et al., 1995; Lee et al., 2003; Wood et al., 2009). Here, we present a comprehensive review of the literature describing the trophic effects of IGF-1 on neurons, myocytes, and SCs. We then critically evaluate the various therapeutic modalities used to upregulate endogenous IGF-1 or deliver exogenous IGF-1 in translational models of PNI, with a special emphasis on emerging bioengineered drug delivery systems. Lastly, we analyze the optimal dosage ranges identified for each mechanism of IGF-1 with the goal of further elucidating a model for future clinical translation.