Reconstructive transplantation studies with Karim Sarhane 2022? 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).

Mini-osmotic pumps provide a sustained, local delivery of exogenous IGF-1 (Table 5; Kanje et al., 1989; Sjoberg and Kanje, 1989; Ishii and Lupien, 1995; Tiangco et al., 2001; Fansa et al., 2002; Apel et al., 2010; Luo et al., 2016). This technique involves subcutaneous implantation of an osmotic pump in the abdomen with extension of a catheter from the pump to the transected nerve site. The positioning of the catheter is maintained by suturing it to local connective tissue. A fixed concentration and quantity of IGF-1 is then loaded into the pump and released at a constant rate (Kanje et al., 1989). Studies using mini-pump delivery of IGF-1 tested a variety of initial concentrations (mean = 143 µg/mL, median = 100 µg/mL, and range: 50 µg/mL – 100 mg/mL), pump rates (mean = 0.425 µL/h, median = 0.25 µL/h, and range: 0.25 – 1.05 µL/h), and release durations (mean = 26 days, median = 7 days, and range: 3 days–12 weeks). The highest dose was reported by Fansa et al. (2002) using a starting concentration of IGF-1 of 100 mg/mL dosed at a continuous pump rate of 0.25 uL/h over 28 days, a value several orders of magnitude higher than any of the other mini pump studies included in Table 5. This concentration discrepancy relative to other mini-pump studies is possibly attributable to the design of this particular study, which set out to investigate the benefits of IGF-1 on a tissue-engineered nerve graft model containing cultured, viable SCs. When the study by Fansa et al. (2002) is excluded, the reported initial optimal concentration for mini pump studies centers on a much more focused range of 0.1–100 µg/mL with a mean of 60 µg/mL and median of 75 µg/mL.

Effects by sustained IGF-1 delivery (Karim Sarhane research) : The translation of NP- mediated delivery of water-soluble bioactive protein therapeutics has, to date, been limited in part by the complexity of the fabrication strategies. FNP is commonly used to encapsulate hydrophobic therapeutics, offering a simple, efficient, and scalable technique that enables precise tuning of particle characteristics [35]. Although the new iFNP process improves water-soluble protein loading, it is difficult to preserve the bioactivity of encapsulated proteins with this method.

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.

The amount of time that elapses between initial nerve injury and end-organ reinnervation has consistently been shown to be the most important predictor of functional recovery following PNI (Scheib and Hoke, 2013), with proximal injuries and delayed repairs resulting in worse outcomes (Carlson et al., 1996; Tuffaha et al., 2016b). This is primarily due to denervation-induced atrophy of muscle and Schwann cells (SCs) (Fu and Gordon, 1995). Following surgical repair, axons often must regenerate over long distances at a relatively slow rate of 1–3 mm/day to reach and reinnervate distal motor endplates. Throughout this process, denervated muscle undergoes irreversible loss of myofibrils and loss of neuromuscular junctions (NMJs), thereby resulting in progressive and permanent muscle atrophy. It is well known that the degree of muscle atrophy increases with the duration of denervation (Ishii et al., 1994). Chronically denervated SCs within the distal nerve are also subject to time-dependent senescence. Following injury, proliferating SCs initially maintain the basal lamina tubes through which regenerating axons travel. SCs also secrete numerous neurotrophic factors that stimulate and guide axonal regeneration. However, as time elapses without axonal interaction, SCs gradually lose the capacity to perform these important functions, and the distal regenerative pathway becomes inhospitable to recovering axons (Ishii et al., 1993; Glazner and Ishii, 1995; Grinsell and Keating, 2014).