Hydrogels for cardiac tissue engineering

Camci‐Unal, Gulden; Annabi, Nasim; Dokmeci, Mehmet R.; Liao, Ronglih; Khademhosseini, Ali

doi:10.1038/am.2014.19

Cited by 147 publications

(115 citation statements)

References 103 publications

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“…In this framework, induced pluripotent stem cells (iPSCs) hold great promise, due to their wide availability and the possibility to differentiate into multiple cell lineages including cardiomyocytes [3,11,15,16]. Second, the alignment of cardiomyocytes and their organization into bundles characterized by spontaneous and synchronous contraction further complicate the development of biologically relevant cardiac tissues [1–3,17,18]. Third, the generation of thick (cardiac) tissue constructs requires the introduction of microvascular networks in order to provide oxygen and nutrients, remove waste products, and eventually promote vessel anastomosis with the host vasculature [3,19,20].…”

Section: Introductionmentioning

confidence: 99%

Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip

et al. 2016

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Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium. Together with controlled anisotropy, this 3D endothelial bed was then seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction. We further embedded the organoids into a specially designed microfluidic perfusion bioreactor to complete the endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity evaluation. Finally, we demonstrated that such a technique could be translated to human cardiomyocytes derived from induced pluripotent stem cells to construct endothelialized human myocardium. We believe that our method for generation of endothelialized organoids fabricated through an innovative 3D bioprinting technology may find widespread applications in regenerative medicine, drug screening, and potentially disease modeling.

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Section: Introductionmentioning

confidence: 99%

Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip

et al. 2016

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“…5, 6 The versatile features of hydrogels ranges from finely tunable mechanical, chemical properties to ease in fabrication of spatially controlled microstructures for tissue engineering applications. 7-9 Naturally derived polymers, such as gelatin, have the inherent properties of providing cell binding motifs, biodegradability and ability to be tethered with complex biofunctional molecules. 5, 7 Approaches that integrate stem cells with hydrogels for bone tissue regeneration applications offer immense potential to address the problems associated with currently available regeneration therapy methods.…”

Section: Introductionmentioning

confidence: 99%

Nanoengineered biomimetic hydrogels for guiding human stem cell osteogenesis in three dimensional microenvironments

et al. 2016

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The ability to modulate stem cell differentiation in a three dimensional (3D) microenvironment for bone tissue engineering in absence of exogenous pharmaceutical agents such as bone morphogenic protein (BMP-2) remains a challenge. In this study, we introduce extracellular matrix (ECM)-mimicking nanocomposite hydrogels to induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) for bone regeneration in absence of any osteoinducting factors. In particular, we have reinforced photocrosslinkable collagen-based matrix (gelatin methacryloyl, GelMA) used disk-shaped nanosilicates (nSi), a new class of two-dimensional (2D) nanomaterials. We show that nanoengineered hydrogels supported migration and proliferation of encapsulated hMSCs, with no signs of cell apoptosis or inflammatory cytokine responses. The addition of nSi significantly enhances osteogenic differentiation of encapsulated hMSCs as evident by the increase in alkaline phosphates (ALP) activity and deposition of biomineralized matrix compared to GelMA without nSi. We also show that microfabricated nanoengineered microgels can be used to pattern and control cellular behaviour. Furthermore, we also show that nanoengineered hydrogel have high biocompatibility as determined by in vivo experiments using immunocompetent rat model. Specifically, the hydrogels showed minimum localized immune responses, indicating it ability for tissue engineering applications. Overall, we showed the ability of nanoengineered hydrogels loaded with 2D nanosilicates for osteogenic differentiation of stem cells in vitro, in absence of any growth factors such as BMP-2. Our in vivo studies show high biocompatibility of nanocomposites and show the potential for growth factor free bone regeneration.

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“…9 However, cell therapy faces several limitations, such as low rate of cell survival and poor retention of transplanted cells in the injured tissue; in addition, the cell source, the route of administration, and cell post-transplantation arrhythmias are other major limitations that affect the treatment success. 10−12 …”

Section: Introductionmentioning

confidence: 99%

Biomimetic Polymers for Cardiac Tissue Engineering

et al. 2016

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Heart failure is a morbid disorder characterized by progressive cardiomyocyte (CM) dysfunction and death. Interest in cell-based therapies is growing, but sustainability of injected CMs remains a challenge. To mitigate this, we developed an injectable biomimetic Reverse Thermal Gel (RTG) specifically engineered to support long-term CM survival. This RTG biopolymer provided a solution-based delivery vehicle of CMs, which transitioned to a gel-based matrix shortly after reaching body temperature. In this study we tested the suitability of this biopolymer to sustain CM viability. The RTG was biomolecule-functionalized with poly-l-lysine or laminin. Neonatal rat ventricular myocytes (NRVM) and adult rat ventricular myocytes (ARVM) were cultured in plain-RTG and biomolecule-functionalized-RTG both under 3-dimensional (3D) conditions. Traditional 2D biomolecule-coated dishes were used as controls. We found that the RTG-lysine stimulated NRVM to spread and form heart-like functional syncytia. Regarding cell contraction, in both RTG and RTG-lysine, beating cells were recorded after 21 days. Additionally, more than 50% (p value < 0.05; n = 5) viable ARVMs, characterized by a well-defined cardiac phenotype represented by sarcomeric cross-striations, were found in the RTG-laminin after 8 days. These results exhibit the tremendous potential of a minimally invasive CM transplantation through our designed RTG-cell therapy platform.

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Hydrogels for cardiac tissue engineering

Cited by 147 publications

References 103 publications

Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip

Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip

Nanoengineered biomimetic hydrogels for guiding human stem cell osteogenesis in three dimensional microenvironments

Biomimetic Polymers for Cardiac Tissue Engineering

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