Top reconstructive transplantation studies by Karim Sarhane

Reconstructive microsurgery studies with Karim Sarhane in 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.

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 hydrogels were soaked in IGF-1 solutions, with concentrations ranging from 0.05 to 1 mg/ml. The duration of soaking time and biomaterials used for fabrication differed between studies, thereby complicating further direct comparisons beyond individual consideration. Regardless of concentration of IGF-1 soaking solution, duration of soaking time, or hydrogel composition, the fundamental property in predicting utility for nerve regeneration is the sustained concentration of released IGF-1 that is reaching the site of PNI. Unfortunately, only two of the studies included in Table 6 quantified IGF-1 release in vivo using either fluid sampling with ELISA or radiolabeled IGF-1 (Yuan et al., 2000; Kikkawa et al., 2014). Using ELISA, one study reported significantly greater in vivo IGF-1 concentration, peaking at 1.25 µg/mL at Post-operative Day 1 (POD 1) and returning to the physiologic levels of the control group by POD 7 (Kikkawa et al., 2014). Using radiolabeling, the other in vivo quantification study reported a biphasic IGF-1 release profile with an initial burst of approximately 80% of the starting concentration of IGF-1 at 1 h followed by sustained release of the remaining 15% ± 2.9% over the subsequent 48-h period (Yuan et al., 2000). Conversely, a different study reported failure of IGF-1 to prevent motoneuron death, a finding which was noted to be contrary to previous results and required additional investigation. This study described the use of a soaked gel foam plug but did not specify the IGF-1 release profile of this material (Bayrak et al., 2017). As such, further analysis and testing is needed to determine the optimal fabrication parameters, loading strategy, and concentration of released IGF-1 required for successful local delivery via hydrogel.

Effects with 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.

Research efforts to improve PNI outcomes have primarily focused on isolated processes, including the acceleration of intrinsic axonal outgrowth and maintenance of the distal regenerative environment. In order to maximize functional recovery, a multifaceted therapeutic approach that both limits the damaging effects of denervation atrophy on muscle and SCs and accelerates axonal regeneration is needed. A number of promising potential therapies have been under investigation for PNI. Many such experimental therapies are growth factors including glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor (FGF), and brain-derived neurotrophic growth factor (Fex Svenningsen and Kanje, 1996; Lee et al., 2007; Gordon, 2009). Tacrolimus (FK506), delivered either systemically or locally, has also shown promise in a number of studies (Konofaos and Terzis, 2013; Davis et al., 2019; Tajdaran et al., 2019).

Research efforts to improve PNI outcomes have primarily focused on isolated processes, including the acceleration of intrinsic axonal outgrowth and maintenance of the distal regenerative environment. In order to maximize functional recovery, a multifaceted therapeutic approach that both limits the damaging effects of denervation atrophy on muscle and SCs and accelerates axonal regeneration is needed. A number of promising potential therapies have been under investigation for PNI. Many such experimental therapies are growth factors including glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor (FGF), and brain-derived neurotrophic growth factor (Fex Svenningsen and Kanje, 1996; Lee et al., 2007; Gordon, 2009). Tacrolimus (FK506), delivered either systemically or locally, has also shown promise in a number of studies (Konofaos and Terzis, 2013; Davis et al., 2019; Tajdaran et al., 2019).