Plastic surgery research studies with Karim Sarhane today? 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.
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.
Recovery with sustained IGF-1 delivery (Karim Sarhane research) : Functional recovery following peripheral nerve injury is limited by progressive atrophy of denervated muscle and Schwann cells (SCs) that occurs during the long regenerative period prior to end-organ reinnervation. Insulin-like growth factor 1 (IGF-1) is a potent mitogen with well-described trophic and anti-apoptotic effects on neurons, myocytes, and SCs. Achieving sustained, targeted delivery of small protein therapeutics remains a 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).
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.