Reconstructive transplantation studies by Karim Sarhane today? One-fifth to one-third of patients with traumatic injuries to their arms and legs experience nerve injury, which can be devastating. It can result in muscle weakness or numbness, prevent walking or using the arms, and reduce the ability to perform daily activities. Even with surgery, some nerve injuries never recover, and currently there are not many medical options to address this problem. In 2022, the researchers plan to perform this research on more primates to triple the size of the original group. The study can then move into phase I clinical trials for humans.
Dr. Sarhane is published in top-ranked bioengineering, neuroscience, and surgery journals. He holds a patent for a novel Nanofiber Nerve Wrap that he developed with his colleagues at the Johns Hopkins Institute for NanoBioTechnology and the Johns Hopkins Department of Neuroscience (US Patent # 10500305, December 2019). He is the recipient of many research grants and research awards, including the Best Basic Science Paper at the Johns Hopkins Residents Research Symposium, the Basic Science Research Grant Prize from the American Foundation for Surgery of the Hand, the Research Pilot Grant Prize from the Plastic Surgery Foundation, and a Scholarship Award from the American College of Surgeons. He has authored to date 46 peer-reviewed articles, 11 book chapters, 45 peer-reviewed abstracts, and has 28 national presentations. He is an elected member of the Plastic Surgery Research Council, the American Society for Reconstructive Microsurgery, the American Society for Reconstructive Transplantation, and the American Society for Peripheral Nerves.
The use of hydrogels encapsulated with varying concentrations of IGF-1 allows for a prolonged and potentially tunable release in vivo (Yuan et al., 2000; Mathonnet et al., 2001; Kikkawa et al., 2014; Bayrak et al., 2017). The specific hydrogel formulations that have been evaluated vary with regards to IGF-1 release kinetics, degradation rate, and biocompatibility. Despite differences in study design, the majority of hydrogel studies included in Table 6 used a water-soluble polymer oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel with encapsulated gelatin microparticles (Yuan et al., 2000; Holland et al., 2005; Kikkawa et al., 2014; Bayrak et al., 2017). The extent of crosslinking within the OPF hydrogel as well as the use of encapsulated gelatin particles with variable isoelectric points allows for tunability of IGF-1 release. The cumulative release of IGF-1 by this hydrogel formulation was reported to be 95.2% ± 2.9% by Day 28, with some studies achieving a similar cumulative release within 48 h (Yuan et al., 2000; Kikkawa et al., 2014).
Recovery with 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.
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).
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.
