A combined cell therapy and in-situ tissue-engineering approach for myocardial repair

Habib, Manhal; Shapira-Schweitzer, Keren; Caspi, Oren; Gepstein, Amira; Arbel, Gil; Aronson, Doron; Seliktar, Dror; Gepstein, Lior

doi:10.1016/j.biomaterials.2011.06.049

Cited by 82 publications

(55 citation statements)

References 37 publications

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“…It is this inflammatory response and hydrogel clearance-usually in combination with the secretion of cytokines and growth factors-that leads to functional tissue regeneration (44)(45)(46). These observations were also in agreement with our previous studies using PF plugs in a bone segmental defect model as well as with injectable PF hydrogels in a cardiac myocardial infarction model (47,48). Our findings thus concur that mode of implantation can play an important role not only in the degradation and resorption properties of the materials, but also in subsequent tissue repair processes.…”

Section: Significancesupporting

confidence: 92%

Using bimodal MRI/fluorescence imaging to identify host angiogenic response to implants

Berdichevski

Yameen

Dafni³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Therapies that promote angiogenesis have been successfully applied using various combinations of proangiogenic factors together with a biodegradable delivery vehicle. In this study we used bimodal noninvasive monitoring to show that the host response to a proangiogenic biomaterial can be drastically affected by the mode of implantation and the surface area-to-volume ratio of the implant material. Fluorescence/MRI probes were covalently conjugated to VEGF-bearing biodegradable PEG-fibrinogen hydrogel implants and used to document the in vivo degradation and liberation of bioactive constituents in an s.c. rat implantation model. The hydrogel biodegradation and angiogenic host response with three types of VEGFbearing implant configurations were compared: preformed cylindrical plugs, preformed injectable microbeads, and hydrogel precursor, injected and polymerized in situ. Although all three were made with identical amounts of precursor constituents, the MRI data revealed that in situ polymerized hydrogels were fully degraded within 2 wk; microbead degradation was more moderate, and plugs degraded significantly more slowly than the other configurations. The presence of hydrogel degradation products containing the fluorescent label in the surrounding tissues revealed a distinct biphasic release profile for each type of implant configuration. The purported in vivo VEGF release profile from the microbeads resulted in highly vascularized s.c. tissue containing up to 16-fold more capillaries in comparison with controls. These findings demonstrate that the configuration of an implant can play an important role not only in the degradation and resorption properties of the materials, but also in consequent host angiogenic response.biomaterial scaffold | angiogenesis | hydrogel | contrast agents | tissue regeneration W ith progress in the field of regenerative medicine relying more on approaches that deliver cells and/or bioactive factors using minimally invasive procedures, functional donor-tohost integration remains a critical challenge. In this context, biodegradable hydrogel scaffolds provide certain advantages, such as excellent tissue compatibility, temporary protection from host inflammation, and controlled resorption based on cell-mediated degradation (1). Effective transport properties to and within an implanted hydrogel are critical in the design of cell-seeded scaffolds, where the delivery of nutrients and removal of waste products from regions deep within the implant can severely limit the use of a patch for only the smallest of grafts (i.e., <0.5 mm) (2-4). Therefore, a great deal of research in the field of regenerative medicine has been devoted to ameliorate the survival of the cells and tissues with implants that use proangiogenic factors.One strategy is to enhance the localized formation of vascularized networks to improve the perfusion of oxygen and nutrients to the intended region in the body (2, 4, 5). This process is regulated by a number of different growth factors that stimulate a complex angiogenic res...

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Section: Significancesupporting

confidence: 92%

Using bimodal MRI/fluorescence imaging to identify host angiogenic response to implants

Berdichevski

Yameen

Dafni³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…The combination of CMC and hydrogels resulted in a favorable effect on cardiac remodeling with a significant increase in FS and functional outcomes 30 days after treatment administration. Higher anterior wall thickness was also detected in the CMC-hydrogel group when compared to controls, and transplanted CMC were detected one month after administration inside the infarcted region [57]. In another approach Bearzi C. et al synthesized a PEG-fibrinogen hydrogel using PEG-diacrylate as crosslinker and the photoinitiator Irgacure 2959 to control gelation.…”

Section: Hydrogels In Cell-based Therapiesmentioning

confidence: 99%

Heart regeneration after myocardial infarction using synthetic biomaterials

Pascual-Gil

Garbayo

Díaz-Herráez

et al. 2015

Journal of Controlled Release

116

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Abstract:Myocardial infarction causes almost 7.3 million deaths each year worldwide. However, current treatments are more palliative than curative. Presently, cell and protein therapies are considered the most promising alternative treatments. Clinical trials performed until now have demonstrated that these therapies are limited by protein short half-life and by low transplanted cell survival rate, prompting the development of novel cell and protein delivery systems able to overcome such limitations. In this review we discuss the advances made in the last 10 years in the emerging field of cardiac repair using biomaterial-based delivery systems with focus on the progress made on preclinical in vivo studies. Then, we focus in cardiac tissue engineering approaches, and how the incorporation of both cells and proteins together into biomaterials has opened new horizons in the myocardial infarction treatment. Finally, the ongoing challenges and the perspectives for future work in cardiac tissue engineering will also be discussed.

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“…[79][80][81] Recently, both 2D and 3D cardiac patches were fabricated by differentiating human ESCs into cardiomyocytes in fibrin-based matrices. 79 After 2 weeks of culture, highly functionalized cardiac tissues were formed by the alignment of ESCs in microfabricated hydrogel matrices containing staggered elliptical pores (Figure 4).…”

Section: Directing Stem Cell Differentiation Into Cardiac Lineagementioning

confidence: 99%

“…84 In another study, photocrosslinkable PEGylated-fibrinogen was used to transplant human ESC-derived cardiomyocytes. 81 Cell-loaded gels were delivered into the hearts of rats using a MI model. The post-MI ventricular performance significantly improved 30 days after delivery, demonstrating the capability of the hydrogel to act as a cardiomyocyte carrier without inducing unfavorable cardiac remodeling.…”

Section: Directing Stem Cell Differentiation Into Cardiac Lineagementioning

confidence: 99%