Generation of cell-laden hydrogel microspheres using 3D printing-enabled microfluidics

Suvarnapathaki, Sanika; Ramos, Rafael; Sawyer, Stephen W.; McLoughlin, Shannon Theresa; Ramos, Andrew; Venn, Sarah; Soman, Pranav

doi:10.1557/jmr.2018.77

Cited by 24 publications

(17 citation statements)

References 29 publications

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“…Microfluidic techniques for the fabrication of vascular networks within 3D scaffolds also have allowed the guided development of blood vessels. Despite the in vitro success of microfluidic approaches, the resolution of microfabrication techniques was not optimal 34,35 . Other studies have attempted to incorporate angiogenic cells into scaffolding matrices to promote rapid neovascularization [36][37][38][39] .…”

Section: Current Strategies For the Survival Of Tissue-engineered Conmentioning

confidence: 99%

Breathing life into engineered tissues using oxygen-releasing biomaterials

et al. 2019

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Engineering three-dimensional (3D) tissues in clinically relevant sizes have demonstrated to be an effective solution to bridge the gap between organ demand and the dearth of compatible organ donors. A major challenge to the clinical translation of tissue-engineered constructs is the lack of vasculature to support an adequate supply of oxygen and nutrients post-implantation. Previous efforts to improve the vascularization of engineered tissues have not been commensurate to meeting the oxygen demands of implanted constructs during the process of homogeneous integration with the host. Maintaining cell viability and metabolic activity during this period is imperative to the survival and functionality of the engineered tissues. As a corollary, there has been a shift in the scientific impetus beyond improving vascularization. Strategies to engineer biomaterials that encapsulate cells and provide the sustained release of oxygen over time are now being explored. This review summarizes different types of oxygen-releasing biomaterials, strategies for their fabrication, and approaches to meet the oxygen requirements in various tissue engineering applications, including cardiac, skin, bone, cartilage, pancreas, and muscle regeneration.

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Section: Current Strategies For the Survival Of Tissue-engineered Conmentioning

confidence: 99%

Breathing life into engineered tissues using oxygen-releasing biomaterials

et al. 2019

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“…Despite relatively weak mechanical properties, hydrogels exhibit exceptional biomimetic properties and material tunability. [ 11,12 ] The spatial and temporal control found in hydrogel synthesis approaches also assists in generating modular mechanical and chemical properties. These aspects enable the generation of scaffolds that mimic the native tissue microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Hydroxyapatite‐Incorporated Composite Gels Improve Mechanical Properties and Bioactivity of Bone Scaffolds

Suvarnapathaki

Lantigua

et al. 2020

Macromolecular Bioscience

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require mechanically strong scaffolds to support cell differentiation and mineral deposition. [8-10] The commonly used biomaterials, such as ceramics and metals, are mechanically robust but are compatible with only certain cell cultures. Despite relatively weak mechanical properties, hydrogels exhibit exceptional biomimetic properties and material tunability. [11,12] The spatial and temporal control found in hydrogel synthesis approaches also assists in generating modular mechanical and chemical properties. These aspects enable the generation of scaffolds that mimic the native tissue microenvironment. [13,14] Across all human tissue types, cells are sensitive and responsive to mechanical stresses and stiffnesses, including compression, tension, and shear. [15] Typically, the stiffness of hydrogels can be modified by adjusting the prepolymer concentration and the cross-linking time. [16,17] These techniques can result in stiffer hydrogels but lead to limitations in the biological performance of the material. These limitations have necessitated innovative approaches such as reinforcing hydrogels with nano/microfibers in various weaving patterns. [18,19] Another approach to improve the mechanical and biological properties of hydrogels simultaneously is to process these composite materials at higher cross-linking densities. The mechanical properties have been demonstrated to affect cell migration and tissue morphogenesis within the material. [8] More recently, hydroxyapatite ((HA), Ca 10 (PO 4) 6 (OH) 2), silver, and gold nanoparticles have been incorporated into hydrogels to enhance the scaffold's mechanical capabilities and cytocompatibility. [20,21] In previous works, HA has been used as a filling material to fabricate biocompatible matrices in orthopedic and mineralized implants. [22-24] HA has a natural tendency to bind to osseous tissues and its physical properties are similar to that of the native minerals in the human body. [22,25-29] The success of HApolymer composite materials has offered advanced and desirable qualities in biomimetic and mechanically competent bone tissue engineering scaffolds. [30] In the past, different forms of tissue scaffolds were fabricated using HA, such as electrospun fibers, 3D printed thermoplastic polymers, and freeze-dried matrices. [31-34] In our work, we have generated HA-reinforced, hydrogel-based scaffolds which have high water content and have biomimetic properties. Reinforcing polymeric scaffolds with micro/nanoparticles improve their mechanical properties and render them bioactive. In this study, hydroxyapatite (HA) is incorporated into 5% (w/v) gelatin methacrylate (GelMA) hydrogels at 1, 5, and 20 mg mL −1 concentrations. The material properties of these composite gels are characterized through swelling, degradation, and compression tests. Using 3D cell encapsulation, the cytocompatibility and osteogenic differentiation of preosteoblasts are evaluated to assess the biological properties of the composite scaffolds. The in vitro assays demonstrate increasing cell prolife...

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“…Currently, one potential way to overcome this problem is by microfluidics, typically with the design of T‐junction microchannels for two phases: GelMA solution and oil. However, the output and the generating stability are the main concerns when applying this method to produce GelMA microdroplets.…”

Section: Introductionmentioning

confidence: 99%

Electro‐Assisted Bioprinting of Low‐Concentration GelMA Microdroplets

Xie

Gao

Zhao

et al. 2018

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Low‐concentration gelatin methacryloyl (GelMA) has excellent biocompatibility to cell‐laden structures. However, it is still a big challenge to stably fabricate organoids (even microdroplets) using this material due to its extremely low viscosity. Here, a promising electro‐assisted bioprinting method is developed, which can print low‐concentration pure GelMA microdroplets with low cost, low cell damage, and high efficiency. With the help of electrostatic attraction, uniform GelMA microdroplets measuring about 100 μm are rapidly printed. Due to the application of lower external forces to separate the droplets, cell damage during printing is negligible, which often happens in piezoelectric or thermal inkjet bioprinting. Different printing states and effects of printing parameters (voltages, gas pressure, nozzle size, etc.) on microdroplet diameter are also investigated. The fundamental properties of low‐concentration GelMA microspheres are subsequently studied. The results show that the printed microspheres with 5% w/v GelMA can provide a suitable microenvironment for laden bone marrow stem cells. Finally, it is demonstrated that the printed microdroplets can be used in building microspheroidal organoids, in drug controlled release, and in 3D bioprinting as biobricks. This method shows great potential use in cell therapy, drug delivery, and organoid building.

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Generation of cell-laden hydrogel microspheres using 3D printing-enabled microfluidics

Abstract: Abstract

Cited by 24 publications

References 29 publications

Breathing life into engineered tissues using oxygen-releasing biomaterials

Breathing life into engineered tissues using oxygen-releasing biomaterials

Hydroxyapatite‐Incorporated Composite Gels Improve Mechanical Properties and Bioactivity of Bone Scaffolds

Electro‐Assisted Bioprinting of Low‐Concentration GelMA Microdroplets

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