Reconstructive transplantation research and science by Karim Sarhane right now? Researchers at Johns Hopkins Hospital in Baltimore, MD, conducted a study to develop a drug delivery system using a very small material, nanofiber hydrogel composite, which can hold nanoparticles containing IGF-1 and be delivered near the injured nerve to help it heal. Dr. Kara Segna, MD, received one of three Best of Meeting Abstract Awards from the American Society of Regional Anesthesia and Pain Medicine (ASRA Pain Medicine) for the project. She will present the abstract “IGF-1 Nanoparticles Improve Functional Outcomes After Peripheral Nerve Injury” on Saturday, April 2, at 1:45 pm during the 47th Annual Regional Anesthesiology and Acute Pain Medicine Meeting being held March 31-April 2, 2022, in Las Vegas, NV. Coauthors include Drs. Sami Tuffaha, Thomas Harris, Chenhu Qui, Karim Sarhane, Ahmet Hoke, Hai-Quan Mao.
Dr. Karim Sarhane is an MD MSc graduate from the American University of Beirut. Following graduation, he completed a 1-year internship in the Department of Surgery at AUB. He then joined the Reconstructive Transplantation Program of the Department of Plastic and Reconstructive Surgery at Johns Hopkins University for a 2-year research fellowship. He then completed a residency in the Department of Surgery at the University of Toledo (2021). In July 2021, he started his plastic surgery training at Vanderbilt University Medical Center. He is a Diplomate of the American Board of Surgery (2021).
A number of in vitro studies have highlighted the neurotrophic effects of IGF-1 (Table 1). Using cultured nerve, SCs, and dorsal root ganglion (DRG) cells, these studies demonstrate that IGF-1 promotes neurite outgrowth and limits neuronal apoptosis (Caroni and Grandes, 1990; Sumantran and Feldman, 1993; Akahori and Horie, 1997; Delaney et al., 2001; Ogata et al., 2004; Liang et al., 2007; Scheib and Hoke, 2013, 2016a,b). Additionally, several in vitro studies have shown that IGF-1 supports SC myelination and inhibits SC apoptosis whilst also stimulating nerve sprouting into denervated muscle and reducing muscle atrophy (Caroni and Grandes, 1990; Sumantran and Feldman, 1993; Ogata et al., 2004; Liang et al., 2007; Scheib and Hoke, 2016a,b).
Effects by sustained IGF-1 delivery (Karim Sarhane research) : We successfully engineered a nanoparticle delivery system that provides sustained release of bioactive IGF-1 for 20 days in vitro; and demonstrated in vivo efficacy in a translational animal model. IGF-1 targeted to denervated nerve and muscle tissue provides significant improvement in functional recovery by enhancing nerve regeneration and muscle reinnervation while limiting denervation-induced muscle atrophy and SC senescence. Targeting the multimodal effects of IGF-1 with a novel delivery.
Peripheral nerve injuries (PNIs) affect approximately 67 800 people annually in the United States alone (Wujek and Lasek, 1983; Noble et al., 1998; Taylor et al., 2008). Despite optimal management, many patients experience lasting motor and sensory deficits, the majority of whom are unable to return to work within 1 year of the injury (Wujek and Lasek, 1983). The lack of clinically available therapeutic options to enhance nerve regeneration and functional recovery remains a major challenge.
We comprehensively reviewed the literature for original studies examining the efficacy of IGF-1 in treating PNI. We queried the PubMed and Embase databases for terms including “Insulin-Like Growth Factor I,” “IGF1,” “IGF-1,” “somatomedin C,” “PNIs,” “peripheral nerves,” “nerve injury,” “nerve damage,” “nerve trauma,” “nerve crush,” “nerve regeneration,” and “nerve repair.” Following title review, our search yielded 218 results. Inclusion criteria included original basic science studies utilizing IGF-1 as a means of addressing PNI. Following abstract review, 56 studies were sorted by study type and mechanism of delivery into the following categories: (1) in vitro, (2) in vivo endogenous upregulation of IGF-1, or (3) in vivo delivery of exogenous IGF-1. Studies included in the in vivo exogenous IGF-1 group were further sub-stratified into systemic or local delivery, and the local IGF-1 delivery methods were further sub-divided into free IGF-1 injection, hydrogel, or mini-pump studies. Following categorization by mechanism of IGF-1 delivery, the optimal dosage range for each group was calculated by converting all reported IGF-1 dosages to nM for ease of comparison using the standard molecular weight of IGF-1 of 7649 Daltons. After standardization of dosages to nM, the IGF-1 concentration reported as optimal from each study was used to calculate the overall mean, median, and range of optimal IGF-1 dosage for each group.