Design of a Fibrin Microthread-Based Composite Layer for Use in a Cardiac Patch

Chrobak, Megan O'Brien; Hansen, Katrina J.; Gershlak, Joshua R.; Vratsanos, Maria; Kanellias, Marianne; Gaudette, Glenn R.; Pins, George D.

doi:10.1021/acsbiomaterials.6b00547

Cited by 26 publications

(34 citation statements)

References 57 publications

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“…Scaffolds composed of fibers *400 mm apart would ensure that no cell in the fiber plane is more than 200 mm from a fiber with a high degree of homogeneity. Conversely, targeting 200 mm spacing with the approach described herein would ensure that a majority of cells are within 100 mm of a fiber (shown to increase cellular alignment 35 ) at the cost of overall mesh uniformity. The impact (positive or negative) of this heterogeneity will depend largely on the intended application and associated tolerances.…”

Section: Discussionmentioning

confidence: 99%

“…33,34 Overlapping sets of natural polymer microfibers have also been used to create more sophisticated fibrous tissue scaffolds and therapeutic biomaterials with unique and tunable properties. 35,36 However, fabrication of natural polymer fibrous networks more complex than overlapping aligned fibers, as well as broader adoption of these scaffolds and biomaterials by other research laboratories, has been hindered by technical challenges related to the characteristic fragility of these natural polymers, leading to processes that require significant manual labor at bench scale. Without automation, fabrication has been restrained to simple patterns, low throughput, and low fiber density.…”

Section: Introductionmentioning

confidence: 99%

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Digital Design and Automated Fabrication of Bespoke Collagen Microfiber Scaffolds

Kaiser

Bellows

Kant

et al. 2019

Tissue Engineering Part C: Methods

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A great variety of natural and synthetic polymer materials have been utilized in soft tissue engineering as extracellular matrix (ECM) materials. Natural polymers, such as collagen and fibrin hydrogels, have experienced especially broad adoption due to the high density of cell adhesion sites compared to their synthetic counterparts, ready availability, and ease of use. However, these and other hydrogels lack the structural and mechanical anisotropy that define the ECM in many tissues, such as skeletal and cardiac muscle, tendon, and cartilage. Herein, we present a facile, low-cost, and automated method of preparing collagen microfibers, organizing these fibers into precisely controlled mesh designs, and embedding these meshes in a bulk hydrogel, creating a composite biomaterial suitable for a wide variety of tissue engineering and regenerative medicine applications. With the assistance of custom software tools described herein, mesh patterns are designed by a digital graphical user interface and translated into protocols that are executed by a custom mesh collection and organization device. We demonstrate a high degree of precision and reproducibility in both fiber and mesh fabrication, evaluate single fiber mechanical properties, and provide evidence of collagen self-assembly in the microfibers under standard cell culture conditions. This work offers a powerful, flexible platform for the study of tissue engineering and cell material interactions, as well as the development of therapeutic biomaterials in the form of custom collagen microfiber patterns that will be accessible to all through the methods and techniques described here.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Digital Design and Automated Fabrication of Bespoke Collagen Microfiber Scaffolds

Kaiser

Bellows

Kant

et al. 2019

Tissue Engineering Part C: Methods

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“…The studies by McDevitt and Ribeiro were done on glass coverslips, however cardiomyocytes exist in a 3D environment and thus it is important to consider the effects of alignment and stiffness in an environment that better mimics myocardium. Chrobak et al examined cardiomyocyte function using an unaligned fibrin gel with a modulus of approximately 0.25 kPa ( 44 ). They demonstrated contractile strains decreased over time suggesting that in a soft unaligned environment cardiomyocytes are unable to increase strains over time.…”

Section: Discussionmentioning

confidence: 99%

Development of a Contractile Cardiac Fiber From Pluripotent Stem Cell Derived Cardiomyocytes

Hansen

Laflamme

Gaudette

2018

Front. Cardiovasc. Med.

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Stem cell therapy has the potential to regenerate cardiac function after myocardial infarction. In this study, we sought to examine if fibrin microthread technology could be leveraged to develop a contractile fiber from human pluripotent stem cell derived cardiomyocytes (hPS-CM). hPS-CM seeded onto fibrin microthreads were able to adhere to the microthread and began to contract seven days after initial seeding. A digital speckle tracking algorithm was applied to high speed video data (>60 fps) to determine contraction behaviour including beat frequency, average and maximum contractile strain, and the principal angle of contraction of hPS-CM contracting on the microthreads over 21 days. At day 7, cells seeded on tissue culture plastic beat at 0.83 ± 0.25 beats/sec with an average contractile strain of 4.23±0.23%, which was significantly different from a beat frequency of 1.11 ± 0.45 beats/sec and an average contractile strain of 3.08±0.19% at day 21 (n = 18, p < 0.05). hPS-CM seeded on microthreads beat at 0.84 ± 0.15 beats/sec with an average contractile strain of 3.56±0.22%, which significantly increased to 1.03 ± 0.19 beats/sec and 4.47±0.29%, respectively, at 21 days (n = 18, p < 0.05). At day 7, 27% of the cells had a principle angle of contraction within 20 degrees of the microthread, whereas at day 21, 65% of hPS-CM were contracting within 20 degrees of the microthread (n = 17). Utilizing high speed calcium transient data (>300 fps) of Fluo-4AM loaded hPS-CM seeded microthreads, conduction velocities significantly increased from 3.69 ± 1.76 cm/s at day 7 to 24.26 ± 8.42 cm/s at day 21 (n = 5–6, p < 0.05). hPS-CM seeded microthreads exhibited positive expression for connexin 43, a gap junction protein, between cells. These data suggest that the fibrin microthread is a suitable scaffold for hPS-CM attachment and contraction. In addition, extended culture allows cells to contract in the direction of the thread, suggesting alignment of the cells in the microthread direction.

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“…Furthermore, the final material must support the contraction and cell orientation. Here, comprising aligned microthreads were distributed uniformly throughout a fibrin based hydrogel, with a significant impact in cell alignment and mechanical properties [38].…”

Section: Fibrinmentioning

confidence: 99%

Overview of natural hydrogels for regenerative medicine applications

Catoira

Fusaro

Francesco

et al. 2019

J Mater Sci: Mater Med

559

437

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Hydrogels from different materials can be used in biomedical field as an innovative approach in regenerative medicine. Depending on the origin source, hydrogels can be synthetized through chemical and physical methods. Hydrogel can be characterized through several physical parameters, such as size, elastic modulus, swelling and degradation rate. Lately, research is focused on hydrogels derived from biologic materials. These hydrogels can be derived from protein polymers, such as collage, elastin, and polysaccharide polymers like glycosaminoglycans or alginate among others. Introduction of decellularized tissues into hydrogels synthesis displays several advantages compared to natural or synthetic based hydrogels. Preservation of natural molecules such as growth factors, glycans, bioactive cryptic peptides and natural proteins can promote cell growth, function, differentiation, angiogenesis, anti-angiogenesis, antimicrobial effects, and chemotactic effects. Versatility of hydrogels make possible multiple applications and combinations with several molecules on order to obtain the adequate characteristic for each scope. In this context, a lot of molecules such as cross link agents, drugs, grow factors or cells can be used. This review focuses on the recent progress of hydrogels synthesis and applications in order to classify the most recent and relevant matters in biomedical field.

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Design of a Fibrin Microthread-Based Composite Layer for Use in a Cardiac Patch

Cited by 26 publications

References 57 publications

Digital Design and Automated Fabrication of Bespoke Collagen Microfiber Scaffolds

Digital Design and Automated Fabrication of Bespoke Collagen Microfiber Scaffolds

Development of a Contractile Cardiac Fiber From Pluripotent Stem Cell Derived Cardiomyocytes

Overview of natural hydrogels for regenerative medicine applications

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