Development of 3D Microvascular Networks Within Gelatin Hydrogels Using Thermoresponsive Sacrificial Microfibers

Lee, Jung Bok; Wang, Xintong; Faley, Shannon; Baer, Bradly; Balikov, Daniel A.; Sung, Hak‐Joon; Bellan, Leon M.

doi:10.1002/adhm.201500792

Cited by 94 publications

(80 citation statements)

References 44 publications

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“…The mechanism by which the 3D structure is rendered depends on the nature of the gelation www.advancedsciencenews.com www.advhealthmat.de chemistry used for the hydrogel inks, which may be templated or free-form (Figure 2). In templated systems, the gel is deposited around a pre-printed sacrificial template [86] or printed as a liquid that is subsequently polymerized in situ; [87] in either case, template removal results in the desired microporous structure. However, due to the requirement for templating, the same limitations associated with the use of porogens (i.e., the need to complete removal of the sacrificial template/unreacted monomer, and fabrication speed) also apply to templated 3D printing, albeit without the likelihood of producing isolated pores unless intentionally designed.…”

Section: D Printingmentioning

confidence: 99%

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities

Hoare

2017

Adv Healthcare Materials

178

168

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Structured macroporous hydrogels that have controllable porosities on both the nanoscale and the microscale offer both the swelling and interfacial properties of bulk hydrogels as well as the transport properties of “hard” macroporous materials. While a variety of techniques such as solvent casting, freeze drying, gas foaming, and phase separation have been developed to fabricate structured macroporous hydrogels, the typically weak mechanics and isotropic pore structures achieved as well as the required use of solvent/additives in the preparation process all limit the potential applications of these materials, particularly in biomedical contexts. This review highlights recent developments in the field of structured macroporous hydrogels aiming to increase network strength, create anisotropy and directionality within the networks, and utilize solvent‐free or additive‐free fabrication methods. Such functional materials are well suited for not only biomedical applications like tissue engineering and drug delivery but also selective filtration, environmental sorption, and the physical templating of secondary networks.

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Section: D Printingmentioning

confidence: 99%

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities

Hoare

2017

Adv Healthcare Materials

178

168

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“…In previous reports, it has been frequently discussed that the dissolving of sacrificial templates inside the cell-laden gel may hurt the cells. 29,31,33,50 However, continuous efforts until now have not yet fully addressed this common problem, probably because of the inherent drawback of the strategy that involves microfabrication process in the presence of the live cells. For instance, in a recent report, Huang and his co-workers tried to reduce the damage to cells caused by the fabrication process by using a biocompatible sacrificial template made of sodium alginate; however, the reagent used for dissolving the template, ethylenediaminetetraacetic acid (EDTA), is not biocompatible.…”

Section: Resultsmentioning

confidence: 99%

“…26,[30][31][32][33][34] However, these methods are still unsuitable for constructing the vascular structures needed for supporting a 3-D culture for the following reasons: (1) for those strategies based on the casting-and-bonding scheme, multiple layers of channels and complicated connections have to be fabricated and stacked carefully to realize a certain thickness of the culture; (2) the bioactive hydrogels that are suitable for embedding cells are usually very soft, making it difficult to 3-D print such gels with sufficient resolution to match the scale of capillary blood vessels; and (3) the low mechanical strength of bioactive hydrogels and limited methods for sealing the channels make channels apt to leak and difficult to connect to tubes. [31][32][33] More importantly, some of the microfabrication processes involved in these aforementioned techniques, such as heating, photopolymerization, metal coordination, and dissolving of sacrificial template, are often harmful to the embedded cells; also, the fabrication methods are not universal, meaning that each method only supports very limited types of hydrogels.…”

Section: Introductionmentioning

confidence: 99%

Freestanding 3-D microvascular networks made of alginate hydrogel as a universal tool to create microchannels inside hydrogels

Sun

Liu

et al. 2016

Biomicrofluidics

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The diffusion of molecules such as nutrients and oxygen through densely packed cells is impeded by blockage and consumption by cells, resulting in a limited depth of penetration. This has been a major hurdle to a bulk (3-D) culture. Great efforts have been made to develop methods for generating branched microchannels inside hydrogels to support mass exchange inside a bulk culture. These previous attempts faced a common obstacle: researchers tried to fabricate microchannels with gels already loaded with cells, but the fabrication procedures are often harmful to the embedded cells. Herein, we present a universal strategy to create microchannels in different types of hydrogels, which effectively avoids cell damage. This strategy is based on a freestanding alginate 3-D microvascular network prepared by in-situ generation of copper ions from a sacrificial copper template. This alginate network could be used as implants to create microchannels inside different types of hydrogels. This approach effectively addresses the issue of cell damage during microfabrication and made it possible to create microchannels inside different types of gels. The microvascular network produced with this method is (1) strong enough to allow handling, (2) biocompatible to allow cell culturing, and (3) appropriately permeable to allow diffusion of small molecules, while sufficiently dense to prevent blocking of channels when embedded in different types of gels. In addition, composite microtubules could be prepared by simply pre-loading other materials, e.g., particles and large biomolecules, in the hydrogel. Compared with other potential strategies to fabricate freestanding gel channel networks, our method is more rapid, low-cost and scalable due to parallel processing using an industrially massproducible template. We demonstrated the use of such vascular networks in creating microchannels in different hydrogels and composite gels, as well as with a cell culture in a nutrition gradient based on microfluidic diffusion. In this way, the freestanding hydrogel vascular network we produced is a universal functional unit that can be embedded in different types of hydrogel; users will be able to adopt this strategy to achieve vascular mass exchange in the bulk culture without changing their current protocol. The method is readily implementable to applications in vascular tissue regeneration, drug discovery, 3-D culture, etc. Published by AIP Publishing. [http://dx

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“…Hydroxyproline and proline maintain the tertiary structure of the collagen. Collagen is a major extracellular matrix (ECM) protein and controls all the cellular fate processes [82] . It is used as a scaffold material for various tissue engineering applications; however, its poor mechanical properties limits its suitability in bioprinting.…”

Section: ) Collagen and Gelatinmentioning

confidence: 99%

3D bioprinting technology for regenerative medicine applications

Sundaramurthi¹,

Rauf²,

Hauser³

2016

IJB

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Alternative strategies that overcome existing organ transplantation methods are of increasing importance because of ongoing demands and lack of adequate organ donors. Recent improvements in tissue engineering techniques offer improved solutions to this problem and will influence engineering and medicinal applications. Tissue engineering employs the synergy of cells, growth factors and scaffolds besides others with the aim to mimic the native extracellular matrix for tissue regeneration. Three-dimensional (3D) bioprinting has been explored to create organs for transplantation, medical implants, prosthetics, in vitro models and 3D tissue models for drug testing. In addition, it is emerging as a powerful technology to provide patients with severe disease conditions with personalized treatments. Challenges in tissue engineering include the development of 3D scaffolds that closely resemble native tissues. In this review, existing printing methods such as extrusion-based, robotic dispensing, cellular inkjet, laser-assisted printing and integrated tissue organ printing (ITOP) are examined. Also, natural and synthetic polymers and their blends as well as peptides that are exploited as bioinks are discussed with emphasis on regenerative medicine applications. Furthermore, applications of 3D bioprinting in regenerative medicine, evolving strategies and future perspectives are summarized.

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Development of 3D Microvascular Networks Within Gelatin Hydrogels Using Thermoresponsive Sacrificial Microfibers

Cited by 94 publications

References 44 publications

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities

Freestanding 3-D microvascular networks made of alginate hydrogel as a universal tool to create microchannels inside hydrogels

3D bioprinting technology for regenerative medicine applications

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