scholarly journals Three-dimensional bioprinting and tissue fabrication: prospects for drug discovery and regenerative medicine

2015 ◽  
pp. 23 ◽  
Author(s):  
Guohao Dai ◽  
Vivian Lee
Keyword(s):  
Drug Discovery ◽  
Regenerative Medicine ◽  
Three Dimensional

scholarly journals 3D Bioprinting: The Roller Coaster Ride to Commercialization

2020 ◽  
Vol 6 (3) ◽  
Author(s):  
Anton Elemoso ◽  
Grigoriy Shalunov ◽  
Yakov M. Balakhovsky ◽  
Alexander Yu. Ostrovskiy ◽  
Yusef D. Khesuani
Keyword(s):  
Drug Discovery ◽  
Regenerative Medicine ◽  
Food Industry ◽  
Three Dimensional ◽  
3D Bioprinting ◽  
Roller Coaster ◽  
Practical Applications

Three-dimensional (3D) bioprinting as a technology is being researched and applied since 2003. It is actually several technologies (inkjet, extrusion, laser, magnetic bioprinting, etc.) under an umbrella term “3D bioprinting.” The versatility of this technology allows widespread applications in several; however, after almost 20 years of research, there is still a limited number of cases of commercialized applications. This article discusses the potential for 3D bioprinting in regenerative medicine, drug discovery, and food industry, as well as the existing cases of companies that create commercialized products and services in the aforementioned areas and even in fashion, including their go-to-market route and financing received. We also address the main barriers to creating practical applications of 3D bioprinting within each sphere the technology that is being studied for.

scholarly journals Advancing Drug Discovery for Neurological Disorders Using iPSC-Derived Neural Organoids

2021 ◽  
Vol 22 (5) ◽  
pp. 2659
Author(s):  
Gianluca Costamagna ◽  
Giacomo Pietro Comi ◽  
Stefania Corti
Keyword(s):  
Drug Discovery ◽  
Drug Screening ◽  
Neural Development ◽  
Neurological Disorders ◽  
Large Scale ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Cellular Level ◽  
Complex Data ◽  
Complex Data Sets

In the last decade, different research groups in the academic setting have developed induced pluripotent stem cell-based protocols to generate three-dimensional, multicellular, neural organoids. Their use to model brain biology, early neural development, and human diseases has provided new insights into the pathophysiology of neuropsychiatric and neurological disorders, including microcephaly, autism, Parkinson’s disease, and Alzheimer’s disease. However, the adoption of organoid technology for large-scale drug screening in the industry has been hampered by challenges with reproducibility, scalability, and translatability to human disease. Potential technical solutions to expand their use in drug discovery pipelines include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to create isogenic models, single-cell RNA sequencing to characterize the model at a cellular level, and machine learning to analyze complex data sets. In addition, high-content imaging, automated liquid handling, and standardized assays represent other valuable tools toward this goal. Though several open issues still hamper the full implementation of the organoid technology outside academia, rapid progress in this field will help to prompt its translation toward large-scale drug screening for neurological disorders.

scholarly journals Special Issue: Application of Extracellular Matrix in Regenerative Medicine

2021 ◽  
Vol 11 (7) ◽  
pp. 3262
Author(s):  
Neill J. Turner
Keyword(s):  
Extracellular Matrix ◽  
Regenerative Medicine ◽  
Wound Repair ◽  
Three Dimensional ◽  
Dynamic Structure ◽  
Scaffold Material ◽  
Special Issue ◽  
Organ Regeneration ◽  
Scaffold Materials ◽  
The Many

The present Special Issue comprises a collection of articles addressing the many ways in which extracellular matrix (ECM), or its components parts, can be used in regenerative medicine applications. ECM is a dynamic structure, composed of a three-dimensional architecture of fibrous proteins, proteoglycans, and glycosaminoglycans, synthesized by the resident cells. Consequently, ECM can be considered as nature’s ideal biologic scaffold material. The articles in this Special Issue cover a range of topics from the use of ECM components to manufacture scaffold materials, understanding how changes in ECM composition can lead to the development of disease, and how decellularization techniques can be used to develop tissue-derived ECM scaffolds for whole organ regeneration and wound repair. This editorial briefly summarizes the most interesting aspects of these articles.

scholarly journals Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery

2021 ◽  
Vol 22 (3) ◽  
pp. 1203
Author(s):  
Lu Qian ◽  
Julia TCW
Keyword(s):  
Drug Discovery ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Structural Complexity ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Central Nerve System ◽  
Human Ipscs ◽  
Nerve System

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients’ CNS and serve as a platform for therapeutic development and personalized precision medicine.

scholarly journals Reversal of senescence-associated beta-galactosidase expression during in vitro three-dimensional tissue-engineering of human chondrocytes in a polymer scaffold

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shojiro Katoh ◽  
Atsuki Fujimaru ◽  
Masaru Iwasaki ◽  
Hiroshi Yoshioka ◽  
Rajappa Senthilkumar ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Replicative Senescence ◽  
Cultured Cells ◽  
Three Dimensional ◽  
Human Chondrocytes ◽  
Cartilage Tissue ◽  
Optimal Method ◽  
Beta Galactosidase

AbstractRegenerative medicine applications require cells that are not inflicted with senescence after in vitro culture for an optimal in vivo outcome. Methods to overcome replicative senescence include genomic modifications which have their own disadvantages. We have evaluated a three-dimensional (3D) thermo-reversible gelation polymer (TGP) matrix environment for its capabilities to reverse cellular senescence. The expression of senescence-associated beta-galactosidase (SA-βgal) by human chondrocytes from osteoarthritis-affected cartilage tissue, grown in a conventional two-dimensional (2D) monolayer culture versus in 3D-TGP were compared. In 2D, the cells de-differentiated into fibroblasts, expressed higher SA-βgal and started degenerating at 25 days. SA-βgal levels decreased when the chondrocytes were transferred from the 2D to the 3D-TGP culture, with cells exhibiting a tissue-like growth until 42–45 days. Other senescence associated markers such as p16INK4a and p21 were also expressed only in 2D cultured cells but not in 3D-TGP tissue engineered cartilage. This is a first-of-its-kind report of a chemically synthesized and reproducible in vitro environment yielding an advantageous reversal of aging of human chondrocytes without any genomic modifications. The method is worth consideration as an optimal method for growing cells for regenerative medicine applications.

Poly-(lactic acid) and fibrin bioactive cellularized scaffold for use in bone regenerative medicine: Proof of concept

2021 ◽  
pp. 088391152199640
Author(s):  
Renata Aquino de Carvalho ◽  
Valmir Vieira Rocha Júnior ◽  
Antonio José Felix Carvalho ◽  
Heloisa Sobreiro Selistre de Araújo ◽  
Mônica Rosas Costa Iemma ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Regenerative Medicine ◽  
Platelet Rich Plasma ◽  
Three Dimensional ◽  
Culture Conditions ◽  
Infrapatellar Fat Pad ◽  
Dimensional Structure ◽  
Poly Lactic Acid ◽  
Proof Of Concept ◽  
Critical Bone Defects

Bone regenerative medicine (BRM) aims to overcome the limitations of conventional treatments for critical bone defects by developing therapeutic strategies, based on temporary bioactive substitutes, capable of stimulating, sustaining, and guiding tissue regeneration. The aim of this study was to validate the “proof of concept” of a cellularized bioactive scaffold and establish its potential for use in BRM. For this purpose, three-dimensional scaffolds of poly-(lactic acid) (PLA), produced by the additive manufacturing technique, were incorporated into a human platelet-rich plasma (PRP-h) fibrin matrix containing human infrapatellar fat pad mesenchymal stem cells (hIFPMSC). The scaffolds (PLA/finbrin-bioactive) were kept under ideal culture conditions in a medium free from fetal bovine serum and analyzed at 5 and 10 days by Scanning Electron Microscopy (SEM), Fourrier Transform Infrared (FTIR), Circular Dichroism and fluorescence microscopy. The results demonstrated the feasibility of obtaining a rigid, cytocompatible, and cellularized three-dimensional structure. In addition, PRP platelets and leukocytes were able to provide a bioactive environment capable of maintaining the viability of hIFPMSC into scaffolds. The results validate the concept of a customizable, bioactive, cellularized, and non-immunogenic strategy for application in BRM.

scholarly journals Induction of functional hypothalamus and pituitary tissues from pluripotent stem cells for regenerative medicine

2020 ◽  
Author(s):  
Mayuko Kano ◽  
Hidetaka Suga ◽  
Hiroshi Arima
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Hormone Replacement ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Hormone Deficiency ◽  
Adrenal Crisis ◽  
Mouse Escs

Abstract The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. However, exogenous drug administration cannot mimic the physiological changes that are a result of hormone requirements. Therefore, patients are at a high risk of severe hormone deficiency, including adrenal crisis. Pluripotent stem cells (PSCs) self-proliferate and differentiate into all types of cells. The generation of endocrine tissues from PSCs has been considered as another new treatment for hypopituitarism. Our colleagues established a three-dimensional culture method for embryonic stem cells (ESCs). In this culture, the ESC-derived aggregates exhibit self-organization and spontaneous formation of highly ordered patterning. Recent results have shown that strict removal of exogenous patterning factors during early differentiation efficiently induces rostral hypothalamic progenitors from mouse ESCs. These hypothalamic progenitors generate vasopressinergic neurons, which release neuropeptides upon exogenous stimulation. Subsequently, we reported adenohypophysis tissue self-formation in three-dimensional cultures of mouse ESCs. The ESCs were found to differentiate into both non-neural oral ectoderm and hypothalamic neuroectoderm in adjacent layers. Interactions between the two tissues appear to be critically important for in vitro induction of a Rathke's pouch-like developing embryo. Various endocrine cells were differentiated from non-neural ectoderm. The induced corticotrophs efficiently secreted adrenocorticotropic hormone when engrafted in vivo, which rescued hypopituitary hosts. For future regenerative medicine, generation of hypothalamic and pituitary tissues from human PSCs is necessary. We and other groups succeeded in establishing a differentiation method with the use of human PSCs. Researchers could use these methods for models of human diseases to elucidate disease pathology or screen potential therapeutics.

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