Advances in engineering hydrogels Zhang, Yu Shrike; Khademhosseini, Ali
Science,
05/2017, Letnik:
356, Številka:
6337
Journal Article
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Hydrogels are formed from hydrophilic polymer chains surrounded by a water-rich environment. They have widespread applications in various fields such as biomedicine, soft electronics, sensors, and ...actuators. Conventional hydrogels usually possess limited mechanical strength and are prone to permanent breakage. Further, the lack of dynamic cues and structural complexity within the hydrogels has limited their functions. Recent developments include engineering hydrogels that possess improved physicochemical properties, ranging from designs of innovative chemistries and compositions to integration of dynamic modulation and sophisticated architectures. We review major advances in designing and engineering hydrogels and strategies targeting precise manipulation of their properties across multiple scales.
Three‐dimensional porous scaffolds play a pivotal role in tissue engineering and regenerative medicine by functioning as biomimetic substrates to manipulate cellular behaviors. While many techniques ...have been developed to fabricate porous scaffolds, most of them rely on stochastic processes that typically result in scaffolds with pores uncontrolled in terms of size, structure, and interconnectivity, greatly limiting their use in tissue regeneration. Inverse opal scaffolds, in contrast, possess uniform pores inheriting from the template comprised of a closely packed lattice of monodispersed microspheres. The key parameters of such scaffolds, including architecture, pore structure, porosity, and interconnectivity, can all be made uniform across the same sample and among different samples. In conjunction with a tight control over pore sizes, inverse opal scaffolds have found widespread use in biomedical applications. In this review, we provide a detailed discussion on this new class of advanced materials. After a brief introduction to their history and fabrication, we highlight the unique advantages of inverse opal scaffolds over their non‐uniform counterparts. We then showcase their broad applications in tissue engineering and regenerative medicine, followed by a summary and perspective on future directions.
Inverse opal scaffolds are characterized by a highly ordered array of uniform and interconnected pores. This new class of advanced materials offers unique opportunities for a broad spectrum of applications in tissue regeneration by serving as biomimetic substrates with precisely controlled properties.
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Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. ...This inefficiency largely originates from the lack of appropriate tissue-engineered artificial matrices that can replace the damaged regions and promote tissue regeneration. Hydrogels are emerging as a promising class of biomaterials for both soft and hard tissue regeneration. Many critical properties of hydrogels, such as mechanical stiffness, elasticity, water content, bioactivity, and degradation, can be rationally designed and conveniently tuned by proper selection of the material and chemistry. Particularly, advances in the development of cell-laden hydrogels have opened up new possibilities for cell therapy. In this article, we describe the problems encountered in this field and review recent progress in designing cell-hydrogel hybrid constructs for promoting the reestablishment of osteochondral/cartilage tissues. Our focus centers on the effects of hydrogel type, cell type, and growth factor delivery on achieving efficient chondrogenesis and osteogenesis. We give our perspective on developing next-generation matrices with improved physical and biological properties for osteochondral/cartilage tissue engineering. We also highlight recent advances in biomanufacturing technologies (e.g. molding, bioprinting, and assembly) for fabrication of hydrogel-based osteochondral and cartilage constructs with complex compositions and microarchitectures to mimic their native counterparts.
Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue-engineered biomaterials that replace the damaged regions and promote tissue regeneration. Cell-laden hydrogel systems have emerged as a promising tissue-engineering platform to address this issue. In this article, we describe the fundamental problems encountered in this field and review recent progress in designing cell-hydrogel constructs for promoting the reestablishment of osteochondral/cartilage tissues. Our focus centers on the effects of hydrogel composition, cell type, and growth factor delivery on achieving efficient chondrogenesis and osteogenesis. We give our perspective on developing next-generation hydrogel/inorganic particle/stem cell hybrid composites with improved physical and biological properties for osteochondral/cartilage tissue engineering. We also highlight recent advances in biomanufacturing and bioengineering technologies (e.g. 3D bioprinting) for fabrication of hydrogel-based osteochondral and cartilage constructs.
In medicine, nanotechnology has sparked a rapidly growing interest as it promises to solve a number of issues associated with conventional therapeutic agents, including their poor water solubility ...(at least, for most anticancer drugs), lack of targeting capability, nonspecific distribution, systemic toxicity, and low therapeutic index. Over the past several decades, remarkable progress has been made in the development and application of engineered nanoparticles to treat cancer more effectively. For example, therapeutic agents have been integrated with nanoparticles engineered with optimal sizes, shapes, and surface properties to increase their solubility, prolong their circulation half‐life, improve their biodistribution, and reduce their immunogenicity. Nanoparticles and their payloads have also been favorably delivered into tumors by taking advantage of the pathophysiological conditions, such as the enhanced permeability and retention effect, and the spatial variations in the pH value. Additionally, targeting ligands (e.g., small organic molecules, peptides, antibodies, and nucleic acids) have been added to the surface of nanoparticles to specifically target cancerous cells through selective binding to the receptors overexpressed on their surface. Furthermore, it has been demonstrated that multiple types of therapeutic drugs and/or diagnostic agents (e.g., contrast agents) could be delivered through the same carrier to enable combination therapy with a potential to overcome multidrug resistance, and real‐time readout on the treatment efficacy. It is anticipated that precisely engineered nanoparticles will emerge as the next‐generation platform for cancer therapy and many other biomedical applications.
On the way to nanomedicine: Considerable advances in the development of nanoparticles for cancer therapy have been made in recent years. Nanoparticle‐based drug‐delivery systems offer advantages with regard to multidrug resistance, systemic delivery, and clearance, and enable for example specific tumor targeting and controlled release of therapeutic agents.
Glioblastoma‐associated macrophages (GAMs) play a crucial role in the progression and invasiveness of glioblastoma multiforme (GBM); however, the exact crosstalk between GAMs and glioblastoma cells ...is not fully understood. Furthermore, there is a lack of relevant in vitro models to mimic their interactions. Here, novel 3D‐bioprinted mini‐brains consisting of glioblastoma cells and macrophages are presented as tool to study the interactions between these two cell types and to test therapeutics that target this interaction. It is demonstrated that in the mini‐brains, glioblastoma cells actively recruit macrophages and polarize them into a GAM‐specific phenotype, showing clinical relevance to transcriptomic and patient survival data. Furthermore, it is shown that macrophages induce glioblastoma cell progression and invasiveness in the mini‐brains. Finally, it is demonstrated how therapeutics can inhibit the interaction between GAMs and tumor cells resulting in reduced tumor growth and more sensitivity to chemotherapy. It is envisioned that this 3D‐bioprinted tumor model is used to improve the understanding of tumor biology and for evaluating novel cancer therapeutics.
A novel 3D bioprinted model recapitulating the microenvironment of glioblastoma multiforme is presented. The interaction between glioblastoma cells and glioma‐associated macrophages is investigated, demonstrating clinically relevant cell phenotypes, polarization and invasion of cancer cells and macrophages. Moreover, this model is able to mimic the responsiveness to chemotherapy and immunotherapy similar to the clinical situation.
Over the last decades, the fabrication of 3D tissues has become commonplace in tissue engineering and regenerative medicine. However, conventional 3D biofabrication techniques such as scaffolding, ...microengineering, and fiber and cell sheet engineering are limited in their capacity to fabricate complex tissue constructs with the required precision and controllability that is needed to replicate biologically relevant tissues. To this end, 3D bioprinting offers great versatility to fabricate biomimetic, volumetric tissues that are structurally and functionally relevant. It enables precise control of the composition, spatial distribution, and architecture of resulting constructs facilitating the recapitulation of the delicate shapes and structures of targeted organs and tissues. This Review systematically covers the history of bioprinting and the most recent advances in instrumentation and methods. It then focuses on the requirements for bioinks and cells to achieve optimal fabrication of biomimetic constructs. Next, emerging evolutions and future directions of bioprinting are discussed, such as freeform, high‐resolution, multimaterial, and 4D bioprinting. Finally, the translational potential of bioprinting and bioprinted tissues of various categories are presented and the Review is concluded by exemplifying commercially available bioprinting platforms.
Recent advances in translating 3D bioprinting to the clinics are reviewed, including developments in bioprinting strategies, innovations in bioinks for bioprinting, advances in bioprinting of complex architectures, and the translational potential of bioprinted tissue‐like structures. Commercially available bioprinting platforms are briefly discussed toward the end.
3D printing and bioprinting have become a key component in precision medicine. They have been used toward the fabrication of medical devices with patient‐specific shapes, production of engineered ...tissues for in vivo regeneration, and preparation of in vitro tissue models used for screening therapeutics. In particular, vat polymerization‐based 3D (bio)printing as a unique strategy enables more sophisticated architectures to be rapidly built. This progress report aims to emphasize the recent advances made in vat polymerization‐based 3D printing and bioprinting, including new biomaterial ink formulations and novel vat polymerization system designs. While some of these approaches have not been utilized toward the combination with biomaterial inks, it is anticipated their rapid translation into biomedical applications.
Recent advances in vat polymerization‐based 3D printing and bioprinting are discussed, including new biomaterial ink formulations and novel vat polymerization system designs. While some of these approaches have not been utilized toward the combination with biomaterial inks, their rapid translation into biomedical applications is anticipated.
The field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and ...microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development.
3D bioprinting technology provides programmable and customizable platforms to engineer cell‐laden constructs mimicking human tissues for a wide range of biomedical applications. However, the ...encapsulated cells are often restricted in spreading and proliferation by dense biomaterial networks from gelation of bioinks. Herein, a cell‐benign approach is reported to directly bioprint porous‐structured hydrogel constructs by using an aqueous two‐phase emulsion bioink. The bioink, which contains two immiscible aqueous phases of cell/gelatin methacryloyl (GelMA) mixture and poly(ethylene oxide) (PEO), is photocrosslinked to fabricate predesigned cell‐laden hydrogel constructs by extrusion bioprinting or digital micromirror device‐based stereolithographic bioprinting. The porous structure of the 3D‐bioprinted hydrogel construct is formed by subsequently removing the PEO phase from the photocrosslinked GelMA hydrogel. Three different cell types (human hepatocellular carcinoma cells, human umbilical vein endothelial cells, and NIH/3T3 mouse embryonic fibroblasts) within the 3D‐bioprinted porous hydrogel patterns show enhanced cell viability, spreading, and proliferation compared to the standard (i.e., nonporous) hydrogel constructs. The 3D bioprinting strategy is believed to provide a robust and versatile platform to engineer porous‐structured tissue constructs and their models for a variety of applications in tissue engineering, regenerative medicine, drug development, and personalized therapeutics.
An aqueous two‐phase emulsion bioink is developed to create bioprinted porous‐structured hydrogel constructs. Interconnected micropores within the bioprinted hydrogel constructs enhance the growth, spreading, and proliferation of encapsulated living cells.
Recent advancements in bioprinting techniques have enabled convenient fabrication of micro-tissues in organ-on-a-chip platforms. In a sense, the success of bioprinted micro-tissues depends on how ...close their architectures are to the anatomical features of their native counterparts. The bioprinting resolution largely relates to the technical specifications of the bioprinter platforms and the physicochemical properties of the bioinks. In this article, we compare inkjet, extrusion, and light-assisted bioprinting technologies for fabrication of micro-tissues towards construction of biomimetic organ-on-a-chip platforms. Our theoretical analyses reveal that for a given printhead diameter, surface contact angle dominates inkjet bioprinting resolution, while nozzle moving speed and the nonlinearity of viscosity for bioinks regulate extrusion bioprinting resolution. The resolution of light-assisted bioprinting is strongly affected by the photocrosslinking behavior and light characteristics. Our tutorial guideline for optimizing bioprinting resolution would potentially help model the complex microenvironment of biological tissues in organ-on-a-chip platforms.
We compare current bioprinting technologies for their effective resolutions in the fabrication of micro-tissues towards construction of biomimetic microphysiological systems.
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