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    Biomaterials

    (B-72) An Insulin-Like Growth Factor Receptor Targeting Peptide Hydrogel for Peripheral Artery Disease

    Friday, October 13, 2023
    9:30 AM – 10:30 AM PDT
    Location: Exhibit Hall - Row B - Poster # 72

      Presenting Author(s)

    • SP

      Siya Patel

      Undergraduate student
      New Jersey Institute of Technology, United States

      • Co-Author(s)

    • AR

      Abhishek Roy

      Graduate student
      New Jersey Institute of Technology
      Newark, New Jersey, United States

    • GG

      Gelavizh Gharati (she/her/hers)

      Graduate student
      New Jersey Institute of Technology
      Harrison, New Jersey, United States

      • Primary Investigator(s)

    • Vivek Kumar, PhD (he/him/his)

      Associate Professor
      New Jersey Institute of Technology
      Newark, New Jersey, United States

    Introduction:: Peripheral Artery Disease (PAD) is characterized by blockage, narrowing, and thickening of arteries from the heart to the extremities due to buildup of plaque, also known as atherosclerosis [1]. A prevalent and common disease, PAD can cause ischemia to the lower extremities and can result in many fatal conditions such as myocardial infarctions or the loss of motor function to those areas of the body. Current therapies for PAD include stent placement within the artery and angioplasty to remove the current blockage but decreased blood flow may still remain [2]. The objective of this study is to determine the angiogenic nature of a self-assembling peptide hydrogel (SAPH) with a self-assembling domain and IGF-1c mimic, termed SLIGF. This SAPH will be studied through an in vitro tube formation assay and in vivo study using a Hind Limb Ischemia (HLI) animal model.

    Materials and Methods:: The peptide was prepared in a Liberty Blue Solid Phase peptide synthesizer utilizing Fmoc chemistry. The lyophilized peptide was formulated in 1xPBS. In the tube formation assay, human umbilical vein endothelial cells (HUVECs) were combined with conditioned media and plated on a matrigel matrix for 8 hours. Quantitative analysis of the nodes and total tube formation was conducted and compared to cells with suramin treatment. In the in vivo study, HLI was induced in C57BL/6 mice via unilaterally ligating the femoral artery through an initial surgery. SLIGF hydrogel at 10 mg/ml concentration was compared to PBS control which was injected intramuscularly (IM) in the gastrocnemius muscle and the quadriceps of the ischemic limb. The animals were closely monitored and Laser Doppler Perfusion Imaging (LDPI) was used to analyze the blood reperfusion over time points of 0, 1, 2, 3, 5, 7, 14, 21, 28 days.

    Results, Conclusions, and Discussions:: In previous studies, similar hydrogels have shown angiogenic properties and response through subcutaneous implantation in rats [3]. This study aims to further investigate those properties by introducing it to a HLI model. This study aims to promote revascularization, once injected in the mouse model, and motor function in the ischemic limb. The tube formation assay was conducted and SLIGF, similar to IGF-1, showed a significant increase in nodes and total tube length compared to suramin control. An initial 28 day pilot study on an HLI model was performed and the SAPH showed promising results in promoting blood vessel formation.

    We introduce a SAPH with an angiogenic response to promote tube formation in an in vitro assay and revascularization and functional limb use in an HLI model. In the future, we aim to increase the efficacy of the SAPH via computationally modifying the bioactive mimic for a greater angiogenic response.


    Acknowledgements (Optional): :

    References (Optional): :


    1. Centers for Disease Control and Prevention. (2022, December 19). Peripheral arterial disease (PAD). Centers for Disease Control and Prevention. https://www.cdc.gov/heartdisease/PAD.htm#:~:text=Peripheral%20arterial%20disease%20(PAD)%20in,arteries%2C%20which%20is%20called%20atherosclerosis. 




    2. U.S. Department of Health and Human Services. (n.d.). Peripheral Artery Disease Treatment. National Heart Lung and Blood Institute. https://www.nhlbi.nih.gov/health/peripheral-artery-disease/treatment 




    3. Siddiqui Z;Sarkar B;Kim KK;Kadincesme N;Paul R;Kumar A;Kobayashi Y;Roy A;Choudhury M;Yang J;Shimizu E;Kumar VA; (n.d.-b). Angiogenic hydrogels for dental pulp revascularization. Acta biomaterialia. https://pubmed.ncbi.nlm.nih.gov/33689817/