Three‐Dimensional Microfluidic Tissue‐Engineering Scaffolds Using a Flexible Biodegradable Polymer

Bettinger, Christopher J.; Weinberg, Eli J.; Kulig, Katherine M.; Vacanti, Joseph P.; Wang, Yadong; Borenstein, Jeffrey T.; Langer, Robert

doi:10.1002/adma.200500438

Cited by 270 publications

(215 citation statements)

References 34 publications

(26 reference statements)

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“…A variety of polymeric materials have been patterned in 3-D using microfabrication and similar technologies, based on designs established by computational fluid dynamics. Early work using micropatterned silicon (47) evolved into micromolded polymer networks (48), which could be stacked into macroscopic 3-D networks (49,50). Such devices have been made with relatively hydrophobic polymers such as PLGA (49), as well as with hydrogels such as calcium alginate (51).…”

Section: Three-dimensional Polymeric Matricesmentioning

confidence: 99%

Polymeric Biomaterials in Tissue Engineering

2008

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Polymeric biomaterials are one of the cornerstones of tissue engineering. A wide range of materials has been used. Approaches have shown increasing sophistication over recent years employing drug delivery functionality, micropatterning, microfluidics, and other technologies. Challenges such as producing threedimensional matrixes and rendering them deliverable through minimally invasive techniques have been addressed. A major recent development is the design of biomaterials for tissue engineering matrices to achieve specific biologic effects on cells, and vice versa.

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Section: Three-dimensional Polymeric Matricesmentioning

confidence: 99%

Polymeric Biomaterials in Tissue Engineering

2008

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“…Construction of 3D biodegradable structures with microchannels has relied on soft lithographic techniques. For example, PDMS molds with micro-patterns have been prepared to construct microchannels into biodegradable thermoplastic materials such as PLGA (King et al, 2004) or elastomers such as poly(glycerol sebacate) (Bettinger et al, 2006). Microfluidic channels have also been generated by patterning temperature-sensitive gelatin as a sacrificial element within hydrogel scaffold (Golden and Tien, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Controllable dissociation/biodegradation of hydrogel materials in physiological environments also makes hydrogels useful materials in tissue engineering (Bettinger et al, 2006). Furthermore, hydrogels can uniquely provide the necessary three-dimensional (3D) cell culture environments for chondrocytes or hepatocytes (Choi et al, 2007;Fedorovich et al, 2007;Glicklis et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…These include constructing poly(dimethylsiloxane) (PDMS) capillary networks (Borenstein et al, 2002;Kaihara et al, 2000;Leclerc et al, 2003), culturing cells on a permeable membrane (Vernon et al, 2005), and embedding microfluidic channels directly onto or within the hydrogel materials (Arcaute et al, 2006;Bettinger et al, 2006;Choi et al, 2007;Golden and Tien, 2007). Microfluidic channels, created within synthetic as well as naturally derived hydrogel materials, are typically produced by soft-lithographic procedures whereby the channels resembling physiological capillary networks are molded or imprinted.…”

Section: Introductionmentioning

confidence: 99%

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On‐demand three‐dimensional freeform fabrication of multi‐layered hydrogel scaffold with fluidic channels

Lee

Polio

et al. 2010

Biotech & Bioengineering

202

147

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One of the challenges in tissue engineering is to provide adequate supplies of oxygen and nutrients to cells within the engineered tissue construct. Soft-lithographic techniques have allowed the generation of hydrogel scaffolds containing a network of fluidic channels, but at the cost of complicated and often time-consuming manufacturing steps. We report a three-dimensional (3D) direct printing technique to construct hydrogel scaffolds containing fluidic channels. Cells can also be printed on to and embedded in the scaffold with this technique. Collagen hydrogel precursor was printed and subsequently crosslinked via nebulized sodium bicarbonate solution. A heated gelatin solution, which served as a sacrificial element for the fluidic channels, was printed between the collagen layers. The process was repeated layer-by-layer to form a 3D hydrogel block. The printed hydrogel block was heated to 378C, which allowed the gelatin to be selectively liquefied and drained, generating a hollow channel within the collagen scaffold. The dermal fibroblasts grown in a scaffold containing fluidic channels showed significantly elevated cell viability compared to the ones without any channels. The on-demand capability to print fluidic channel structures and cells in a 3D hydrogel scaffold offers flexibility in generating perfusable 3D artificial tissue composites.

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“…Top-down approaches aim to control the microscale features of large constructs. Some significant advances have been made by use of top-down techniques, and it has been demonstrated that microvasculature can be engineered in biomaterials and hydrogels by using micromolding (10,13,84). Bottom-up approaches, on the other hand, aim at generating large-scale tissues by assembling small building blocks.…”

Section: Emerging Trends and Opportunities In Lung Tissue Engineeringmentioning

confidence: 99%

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

Patel

Gauvin

Absar

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Development of lung models for testing a drug substance or delivery system has been an intensive area of research. However, a model that mimics physiological and anatomical features of human lungs is yet to be established. Although in vitro lung models, developed and fine-tuned over the past few decades, were instrumental for the development of many commercially available drugs, they are suboptimal in reproducing the physiological microenvironment and complex anatomy of human lungs. Similarly, intersubject variability and high costs have been major limitations of using animals in the development and discovery of drugs used in the treatment of respiratory disorders. To address the complexity and limitations associated with in vivo and in vitro models, attempts have been made to develop in silico and tissue-engineered lung models that allow incorporation of various mechanical and biological factors that are otherwise difficult to reproduce in conventional cell or organ-based systems. The in silico models utilize the information obtained from in vitro and in vivo models and apply computational algorithms to incorporate multiple physiological parameters that can affect drug deposition, distribution, and disposition upon administration via the lungs. Bioengineered lungs, on the other hand, exhibit significant promise due to recent advances in stem or progenitor cell technologies. However, bioengineered approaches have met with limited success in terms of development of various components of the human respiratory system. In this review, we summarize the approaches used and advancements made toward the development of in silico and tissue-engineered lung models and discuss potential challenges associated with the development and efficacy of these models. bioengineered lung; computational modeling; in silico; lung models; tissue engineering LUNG DISEASES ARE THE THIRD leading cause of deaths in the United States that translate into one in six deaths. More than 400,000 Americans die of lung disease every year and around 35 million are now living with chronic lung problems (1). Therefore, there is an important need to understand as to how a new drug entity or a novel formulation may influence the anatomy, physiology, and pathogenesis of lungs and vice versa.The human lung has an approximate volume of six liters, contains about 300 million alveoli, and provides a total surface area of 100 square meters as blood-air interface, which is packed into an elastic dynamic structure responsible for gas exchange (159). The human airway wall is a connective tissue that includes smooth muscle cells (SMC), mucus glands, blood vessels, and fibroblasts surrounded by a collagen-rich extracellular matrix (ECM). Epithelial cells, responsible for the efficient oxygen and carbon dioxide transfer, are at the interface between air and the connective tissue and are attached to an underlying basement membrane. The respiratory system is the site of a variety of pulmonary diseases such as asthma, bronchitis, pneumonia, cystic fibrosis, emphysema, a...

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Three‐Dimensional Microfluidic Tissue‐Engineering Scaffolds Using a Flexible Biodegradable Polymer

Cited by 270 publications

References 34 publications

Polymeric Biomaterials in Tissue Engineering

Polymeric Biomaterials in Tissue Engineering

On‐demand three‐dimensional freeform fabrication of multi‐layered hydrogel scaffold with fluidic channels

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

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