Actuation-Mediated Compression of a Mechanoresponsive Hydrogel by Soft Robotics to Control Release of Therapeutic Proteins

被引：0
作者：
Wallace, Eimear J. [1 ,2 ]
O'Dwyer, Joanne [3 ]
Dolan, Eimear B. [1 ,4 ,5 ]
Burke, Liam P. [1 ,6 ,7 ]
Wylie, Robert [1 ]
Bellavia, Gabriella [2 ]
Straino, Stefania [2 ]
Cianfarani, Francesca [2 ]
Ciotti, Gabriella [2 ]
Serini, Simona [8 ]
Calviello, Gabriella [8 ]
Roche, Ellen T. [9 ,10 ,11 ]
Mitra, Tapas [1 ,4 ]
Duffy, Garry P. [1 ,4 ,12 ,13 ]
机构：
[1] Univ Galway, Anat & Regenerat Med Inst REMEDI, Coll Med Nursing & Hlth Sci, Sch Med, Galway H91 W2TY, Ireland
[2] Explora Srl, Via G Peroni 386, I-00131 Rome, Italy
[3] Univ Galway, Anat & Regenerat Med Inst, Sch Med, Coll Med Nursing & Hlth Sci, Galway H91 W2TY, Ireland
[4] Univ Galway, SFI Res Ctr Med Devices, CURAM, Galway H91 W2TY, Ireland
[5] Univ Galway, Sch Engn, Galway H91 HX31, Ireland
[6] Univ Galway, Sch Med, Antimicrobial Resistance & Microbial Ecol Grp, Galway H91 DK59, Ireland
[7] Univ Galway, Ryan Inst, Ctr One Hlth, Galway H91 DK59, Ireland
[8] Univ Cattolica Sacro Cuore, Sch Med & Surg, Dept Translat Med & Surg, Sect Gen Pathol, I-00168 Rome, Italy
[9] MIT, Inst Med Engn & Sci, Cambridge, MA 01239 USA
[10] Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA
[11] MIT, Dept Mech Engn, Cambridge, MA 02139 USA
[12] Trinity Coll Dublin, Adv Mat Bioengn Res Ctr AMBER, Dublin D02 W9K7, Ireland
[13] Trinity Coll Dublin, BioEngn Res Ctr AMBER, Dublin D02 W9K7, Ireland
来源：
ADVANCED SCIENCE | 2025年 / 12卷 / 07期
基金：
爱尔兰科学基金会;
关键词：
actuation; controlled drug delivery; hydrogels; soft robotics; therapeutic proteins; GROWTH-FACTOR; IN-VITRO; NETWORK HYDROGELS; COLLOIDAL GELS; DELIVERY; ANGIOGENESIS; VEGF; SYSTEMS; VASCULARIZATION; MECHANISMS;
D O I：
10.1002/advs.202401744
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Therapeutic proteins, the fastest growing class of pharmaceuticals, are subject to rapid proteolytic degradation in vivo, rendering them inactive. Sophisticated drug delivery systems that maintain protein stability, prolong therapeutic effects, and reduce administration frequency are urgently required. Herein, a mechanoresponsive hydrogel is developed contained within a soft robotic drug delivery (SRDD) device. In a step-change from previously reported systems, pneumatic actuation of this system releases the cationic therapeutic protein Vascular Endothelial Growth Factor (VEGF) in a bioactive form which is required for therapeutic angiogenesis, the growth of new blood vessels, in numerous clinical conditions. The ability of the SRDD device to release bioactive VEGF in a spatiotemporal manner from the hydrogel is tested in diabetic rats - a model in which angiogenesis is difficult to stimulate. Daily actuation of the SRDD device in the diabetic rat model significantly increased cluster of differentiation 31+ (CD31+) blood vessel number (p = 0.0335) and the diameter of alpha-smooth muscle actin+ (alpha-SMA+) blood vessels (p = 0.0025) compared to passive release of VEGF from non-actuated devices. The SRDD device combined with the mechanoresponsive hydrogel offers the potential to deliver an array of bioactive therapeutics in a spatiotemporal manner to mimic their natural release in vivo.
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页数：15
相关论文
共 93 条
  • [1] Jain K.K., Drug Delivery Systems - An Overview: Methods in Molecular Biology, pp. 1-50, (2008)
  • [2] Bae Y.H., Park K., Adv. Drug Delivery Rev., 158, (2020)
  • [3] Kintzing J.R., Filsinger Interrante M.V., Cochran J.R., Trends Pharmacol. Sci., 37, (2016)
  • [4] Vaishya R., Khurana V., Patel S., Mitra A.K., Expert Opin. Drug Delivery, 12, (2015)
  • [5] Dimitrov D.S., Therapeutic Proteins: Methods in Molecular Biology, pp. 1-26, (2012)
  • [6] Mitragotri S., Burke P.A., Langer R., Nat. Rev. Drug Discovery, 13, (2014)
  • [7] Usmani S.S., Bedi G., Samuel J.S., Singh S., Kalra S., Kumar P., Ahuja A.A., Sharma M., Gautam A., Raghava G.P.S., PLoS One, 12, (2017)
  • [8] Shraddha M., Madhuvanti D., Onkar S., Protein Therapeutics Martket: Global Opportunity Analysis and Industry Forecast 2021–2030, (2022)
  • [9] Lee K.Y., Peters M.C., Anderson K.W., Mooney D.J., Nature, 408, (2000)
  • [10] Gu F., Amsden B., Neufeld R., J. Controlled Release, 96, (2004)
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