Syndecan-4 proteoliposomes enhance revascularization in a rabbit hind limb ischemia model of peripheral ischemia.

Autor: Sligar AD; Department of Biomedical Engineering, University of Texas at Austin, 1 University Station, BME 5.202D, C0800, Austin, TX 78712, USA., Howe G; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Texas Medical School at Houston, TX, USA., Goldman J; Center for Laboratory Animal Medicine and Care, UT Health Science Center at Houston, USA., Felli P; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Texas Medical School at Houston, TX, USA., Gómez-Hernández A; Department of Biochemistry and Molecular Biology, School of Pharmacy, Complutense University of Madrid, Madrid, Spain., Takematsu E; Department of Biomedical Engineering, University of Texas at Austin, 1 University Station, BME 5.202D, C0800, Austin, TX 78712, USA., Veith A; Department of Biomedical Engineering, University of Texas at Austin, 1 University Station, BME 5.202D, C0800, Austin, TX 78712, USA., Desai S; Department of Biomedical Engineering, University of Texas at Austin, 1 University Station, BME 5.202D, C0800, Austin, TX 78712, USA., Riley WJ; Department of Biomedical Engineering, University of Texas at Austin, 1 University Station, BME 5.202D, C0800, Austin, TX 78712, USA., Singeetham R; Department of Biomedical Engineering, University of Texas at Austin, 1 University Station, BME 5.202D, C0800, Austin, TX 78712, USA., Mei L; Department of Biomedical Engineering, University of Texas at Austin, 1 University Station, BME 5.202D, C0800, Austin, TX 78712, USA., Callahan G; Department of Biomedical Engineering, University of Texas at Austin, 1 University Station, BME 5.202D, C0800, Austin, TX 78712, USA., Ashirov D; Department of Biomedical Engineering, University of Texas at Austin, 1 University Station, BME 5.202D, C0800, Austin, TX 78712, USA., Smalling R; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Texas Medical School at Houston, TX, USA; Memorial Hermann Heart and Vascular Institute, Houston, TX, USA., Baker AB; Department of Biomedical Engineering, University of Texas at Austin, 1 University Station, BME 5.202D, C0800, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA; The Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, TX, USA; Institute for Biomaterials, Drug Delivery and Regenerative Medicine, University of Texas at Austin, Austin, TX, USA. Electronic address: abbaker@austin.utexas.edu.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2023 Sep 01; Vol. 167, pp. 425-435. Date of Electronic Publication: 2023 Jun 13.
DOI: 10.1016/j.actbio.2023.06.006
Abstrakt: Regenerative therapeutics for treating peripheral arterial disease are an appealing strategy for creating more durable solutions for limb ischemia. In this work, we performed preclinical testing of an injectable formulation of syndecan-4 proteoliposomes combined with growth factors as treatment for peripheral ischemia delivered in an alginate hydrogel. We tested this therapy in an advanced model of hindlimb ischemia in rabbits with diabetes and hyperlipidemia. Our studies demonstrate enhancement in vascularity and new blood vessel growth with treatment with syndecan-4 proteoliposomes in combination with FGF-2 or FGF-2/PDGF-BB. The effects of the treatments were particularly effective in enhancing vascularity in the lower limb with a 2-4 increase in blood vessels in the treatment group in comparison to the control group. In addition, we demonstrate that the syndecan-4 proteoliposomes have stability for at least 28 days when stored at 4°C to allow transport and use in the hospital environment. In addition, we performed toxicity studies in the mice and found no toxic effects even when injected at high concentration. Overall, our studies support that syndecan-4 proteoliposomes markedly enhance the therapeutic potential of growth factors in the context of disease and may be promising therapeutics for inducing vascular regeneration in peripheral ischemia. STATEMENT OF SIGNIFICANCE: Peripheral ischemia is a common condition in which there is a lack of blood flow to the lower limbs. This condition can lead to pain while walking and, in severe cases, critical limb ischemia and limb loss. In this study, we demonstrate the safety and efficacy of a novel injectable therapy for enhancing revascularization in peripheral ischemia using an advanced large animal model of peripheral vascular disease using rabbits with hyperlipidemia and diabetes.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The senior author (ABB) has a US patent on the technology in this manuscript.
(Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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