Instructive Nanofiber Scaffolds with VEGF Create a Microenvironment for Arteriogenesis and Cardiac Repair

Lin, Yi; Luo, Chwan Yau; Hu, Yu; Yeh, Ming Long; Hsueh, Ying Chang; Chang, Meng-Wei; Tsai, Da Ching; Wang, Jieh Neng; Tang, Ming Jer; Wei, Erika I. H.; Springer, Matthew L.; Hsieh, Patrick C.

doi:10.1126/scitranslmed.3003841

Cited by 129 publications

(103 citation statements)

References 57 publications

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“…Moreover, while liposomes have been shown to accumulate experimentally in areas of MI [30,35,36], their clinical application has been hindered because they are unstable and readily interact with high-density lipoproteins in blood. Also, self-assembling nanofiber scaffolds coated with VEGF were recently shown to improve cardiac function in rat and pig models of MI by inducing arteriogenesis and recruitment of endogenous myofibroblasts and cardiomyocyte-like cells [37]. In contrast to some of these systems, PLGA MPs are advantageous because they allow local drug delivery over an extended period of time.…”

Section: Discussionmentioning

confidence: 99%

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration

Formiga

Pelacho

Garbayo

et al. 2014

Journal of Controlled Release

102

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Acidic fibroblast growth factor (FGF1) and neuregulin-1 (NRG1) are growth factors involved in cardiac development and regeneration. Microparticles (MPs) mediate cytokine sustained release, and can be utilized to overcome issues related to the limited therapeutic protein stability during systemic administration. We sought to examine whether the administration of microparticles (MPs) containing FGF1 and NRG1 could promote cardiac regeneration in a myocardial infarction (MI) rat model. We investigated the possible underlying mechanisms contributing to the beneficial effects of this therapy, especially those linked to endogenous regeneration. FGF1-and NRG1-loaded MPs were prepared using a multiple emulsion solvent evaporation technique. Seventy-three female Sprague-Dawley rats underwent permanent left anterior descending coronary artery occlusion, and MPs were intramyocardially injected in the peri-infarcted zone four days later. Cardiac function, heart tissue remodeling, revascularization, apoptosis, cardiomyocyte proliferation, and stem cell homing were evaluated one week and three months after treatment. MPs were shown to efficiently encapsulate FGF1 and NRG1, releasing the bioactive proteins in a sustained manner. Three months after treatment, a statistically significant improvement in cardiac function was detected in rats treated with growth factor-loaded MPs (FGF1, NRG1, or FGF1/NRG1). The therapy led to inhibition of cardiac remodeling with smaller infarct size, a lower fibrosis degree and induction of tissue revascularization. Cardiomyocyte proliferation and progenitor cell recruitment was detected. Our data support the therapeutic benefit of NRG1 and FGF1 when combined with protein delivery systems for cardiac regeneration. This approach could be scaled up for use in preclinical and clinical studies.

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Section: Discussionmentioning

confidence: 99%

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration

Formiga

Pelacho

Garbayo

et al. 2014

Journal of Controlled Release

102

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“…Rapid regeneration of new coronary blood vessels is essential for prolonging survival of the injured myocardium (2). Unraveling new sources of vascular endothelial cells in the heart provides important insights into therapeutic deployment for cardiac regeneration (3).…”

Section: Introductionmentioning

confidence: 99%

Preexisting endothelial cells mediate cardiac neovascularization after injury

Huang

Kanisicak

et al. 2017

Journal of Clinical Investigation

162

125

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“…Furthermore, a study by Lin et al concluded that in a porcine model the peptide nanofiber scaffold was not only a passive delivery vehicle but also improved diastolic function post-MI through reduction of fibrosis, neo-capillary formation and reduced ventricular remodeling (Lin et al, 2010). Similar studies in small animal models showed positive, yet non-significant, effects of nanofibers alone; however, combined with the incorporation of GFs or endogenous stem cell recruitment factors significantly improved cardiac function was achieved (Davis et al, 2006;Lin et al, 2012). Peptide nanofiber-based scaffolds represent a bottom-up approach to fiber formation where small, chemically synthesized oligopeptides are the building blocks.…”

Section: Nanofibrous Materials For Cardiac Tissue Repairingmentioning

confidence: 89%

Nano-Engineered Biomaterials for Tissue Regeneration: What Has Been Achieved So Far?

et al. 2016

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Nanomaterials have attracted the interest of tissue engineers for the last two decades. Their unique properties make them promising for de novo fabrication of bio-inspired hybrid/composite materials with improved regenerative properties, including, for example, the capacity for electric conductivity and the provision of antimicrobial properties. However, to this day, the use of such materials in medical applications is rather limited and most of the studies have only reached the archetypical proof-of-concept stage. Herein, we present a review on the use of nanomaterials in tissue engineering for regenerative therapies of heart, skin, eye, skeletal muscle, and nervous system. The advantages and limitations of nano-engineering materials are presented in this review alongside with the future challenges and milestones nanotechnology must overcome to make an impact in biomedical applications.

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Instructive Nanofiber Scaffolds with VEGF Create a Microenvironment for Arteriogenesis and Cardiac Repair

Abstract: An intramyocardial microenvironment was created using nanofibers and VEGF for endogenous cardiac repair after infarction.

Cited by 129 publications

References 57 publications

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration

Preexisting endothelial cells mediate cardiac neovascularization after injury

Nano-Engineered Biomaterials for Tissue Regeneration: What Has Been Achieved So Far?

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