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Journal ArticleDOI

Translational Application of Microfluidics and Bioprinting for Stem Cell-Based Cartilage Repair

TL;DR: This work discusses the use of microfluidics and bioprinting approaches for the translation of stem cell-based therapy for cartilage repair in clinics, and focuses on the optimization of hydrogel-based materials to mimic the articular cartilage triggered by their use as bioinks in 3D biopprinting applications.
Abstract: Cartilage defects can impair the most elementary daily activities and, if not properly treated, can lead to the complete loss of articular function. The limitations of standard treatments for cartilage repair have triggered the development of stem cell-based therapies. In this scenario, the development of efficient cell differentiation protocols and the design of proper biomaterial-based supports to deliver cells to the injury site need to be addressed through basic and applied research to fully exploit the potential of stem cells. Here, we discuss the use of microfluidics and bioprinting approaches for the translation of stem cell-based therapy for cartilage repair in clinics. In particular, we will focus on the optimization of hydrogel-based materials to mimic the articular cartilage triggered by their use as bioinks in 3D bioprinting applications, on the screening of biochemical and biophysical factors through microfluidic devices to enhance stem cell chondrogenesis, and on the use of microfluidic technology to generate implantable constructs with a complex geometry. Finally, we will describe some new bioprinting applications that pave the way to the clinical use of stem cell-based therapies, such as scaffold-free bioprinting and the development of a 3D handheld device for the in situ repair of cartilage defects.

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Citations
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01 Jun 2017
TL;DR: Bioprinting is a technology with the prospect to change the way many diseases are treated, by replacing the damaged tissues with live de novo created biosimilar constructs as mentioned in this paper.
Abstract: Bioprinting is a technology with the prospect to change the way many diseases are treated, by replacing the damaged tissues with live de novo created biosimilar constructs. However, after more than...

90 citations

01 Sep 2012
TL;DR: Common hydrogels and their crosslinking methods are introduced and the latest microscale approaches for generation of cell containing gel particles are reviewed, specifically on microfluidics-based methods and on techniques such as micromolding and electrospinning.
Abstract: Hydrogels in which cells are encapsulated are of great potential interest for tissue engineering applications. These gels provide a structure inside which cells can spread and proliferate. Such structures benefit from controlled microarchitectures that can affect the behavior of the enclosed cells. Microfabrication-based techniques are emerging as powerful approaches to generate such cell-encapsulating hydrogel structures. In this paper we introduce common hydrogels and their crosslinking methods and review the latest microscale approaches for generation of cell containing gel particles. We specifically focus on microfluidics-based methods and on techniques such as micromolding and electrospinning.

81 citations

Journal ArticleDOI
Longfa Kou1, Xue Jiang1, Shuyi Xiao1, Ying-Zheng Zhao1, Qing Yao1, Ruijie Chen1 
TL;DR: The traditional intervention methods for the prevention of IUAs, as well as novel therapeutics and delivery strategies that will most likely change the treatment paradigms for better clinical outcomes are discussed.

64 citations

Journal ArticleDOI
TL;DR: This paper aims to draw attention to technological advancements made in 3D bioprinting that target the lack of multi-material, and/or multi cell-type, printing capabilities of most current devices.
Abstract: To assist the transition of 3D bioprinting technology from simple lab-based tissue fabrication, to fully functional and implantable organs, the technology must not only provide shape control, but also functional control. This can be accomplished by replicating the cellular composition of the native tissue at the microscale, such that cell types interact to provide the desired function. There is therefore a need for precise, controllable, multi-material printing that could allow for high, possibly even single cell, resolution. This paper aims to draw attention to technological advancements made in 3D bioprinting that target the lack of multi-material, and/or multi cell-type, printing capabilities of most current devices. Unlike other reviews in the field, which largely focus on variations in single-material 3D bioprinting involving the standard methods of extrusion-based, droplet-based, laser-based, or stereolithographic methods; this review concentrates on sophisticated multi-material 3D bioprinting using multi-cartridge printheads, co-axial nozzles and microfluidic-enhanced printing nozzles.

51 citations

Journal ArticleDOI
TL;DR: This review introduces scaffold-free based bioinks, including living cell-only aggregations without any biomaterial carrier for functional tissue formation, and the current advantages and disadvantages of scaffolding-free bioink, as well as the future prospects to overcome the limitations.

32 citations

References
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Journal ArticleDOI
27 Jul 2006-Nature
TL;DR: The manipulation of fluids in channels with dimensions of tens of micrometres — microfluidics — has emerged as a distinct new field that has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology.
Abstract: The manipulation of fluids in channels with dimensions of tens of micrometres--microfluidics--has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.

8,260 citations


"Translational Application of Microf..." refers background in this paper

  • ...Indeed, microfluidic technology enables the precise control over fluids at the microscale, thus allowing mimicking of the natural cell microenvironment by continuous perfusion culture or by creating chemical gradients [14]....

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Journal ArticleDOI
TL;DR: Cultured autologous chondrocytes can be used to repair deep cartilage defects in the femorotibial articular surface of the knee joint.
Abstract: Background Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee. Methods The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site. Results Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and s...

5,375 citations


"Translational Application of Microf..." refers background in this paper

  • ...Autologous chondrocyte implantation (ACI) has been the first cell-based approach to treat cartilage defects [2, 3], and more lately, stem cells have been proposed as an alternative cell source for cell-based cartilage repair [4, 5]....

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Journal ArticleDOI
TL;DR: A microfluidic cell culture device created with microchip manufacturing methods that contains continuously perfused chambers inhabited by living cells arranged to simulate tissue- and organ-level physiology has great potential to advance the study of tissue development, organ physiology and disease etiology.
Abstract: Organ-level physiology is recapitulated in vitro by culturing cells in perfused, microfluidic devices.

2,339 citations


"Translational Application of Microf..." refers background in this paper

  • ...Furthermore, microfluidic devices can be used to develop organotypic models of the whole articular joint capable to recapitulate either a physiological or a pathological environment [81], perfectly matching the concept of organs-on-chips for the study of tissue development, organ physiology, and disease etiology [82, 83]....

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Journal ArticleDOI
TL;DR: The use of both synthetic and natural hydrogels as scaffolds for three-dimensional cell culture as well as synthetic hydrogel hybrids that incorporate sophisticated biochemical and mechanical cues as mimics of the native extracellular matrix are discussed.
Abstract: Methods for culturing mammalian cells ex vivo are increasingly needed to study cell and tissue physiology and to grow replacement tissue for regenerative medicine. Two-dimensional culture has been the paradigm for typical in vitro cell culture; however, it has been demonstrated that cells behave more natively when cultured in three-dimensional environments. Permissive, synthetic hydrogels and promoting, natural hydrogels have become popular as three-dimensional cell culture platforms; yet, both of these systems possess limitations. In this perspective, we discuss the use of both synthetic and natural hydrogels as scaffolds for three-dimensional cell culture as well as synthetic hydrogels that incorporate sophisticated biochemical and mechanical cues as mimics of the native extracellular matrix. Ultimately, advances in synthetic-biologic hydrogel hybrids are needed to provide robust platforms for investigating cell physiology and fabricating tissue outside of the organism.

2,298 citations


"Translational Application of Microf..." refers background in this paper

  • ...Furthermore, hydrogels can be easily tailored in different geometries and, if properly designed, can provide the cells with an environment similar to that of native cartilage [36, 37]....

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Journal ArticleDOI
27 Jul 2006-Nature
TL;DR: Highly integrated microdevices show great promise for basic biomedical and pharmaceutical research, and robust and portable point-of-care devices could be used in clinical settings, in both the developed and the developing world.
Abstract: Microsystems create new opportunities for the spatial and temporal control of cell growth and stimuli by combining surfaces that mimic complex biochemistries and geometries of the extracellular matrix with microfluidic channels that regulate transport of fluids and soluble factors. Further integration with bioanalytic microsystems results in multifunctional platforms for basic biological insights into cells and tissues, as well as for cell-based sensors with biochemical, biomedical and environmental functions. Highly integrated microdevices show great promise for basic biomedical and pharmaceutical research, and robust and portable point-of-care devices could be used in clinical settings, in both the developed and the developing world.

2,082 citations


"Translational Application of Microf..." refers background in this paper

  • ...Indeed, the controlled perfusion of the culture medium within microchannels allows maintaining more uniform culture conditions than standard static approaches, providing the stable supply of nutrients and growth factors as well as the removal of waste products [13, 53]....

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  • ...In this scenario, microfluidic systems have attracted significant interest implementing platforms, in which the control of local environmental conditions, including biochemical and biophysical parameters, is exploited to study and direct stem cell fate [12, 13]....

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