Regenerative technologies to bed side: Evolving the regulatory framework.
Ontology highlight
ABSTRACT:
SUBMITTER: Sakai D
PROVIDER: S-EPMC5822969 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The role of biomechanical stimuli, or mechanotransduction, in normal bone homeostasis and repair is understood to facilitate effective osteogenesis of mesenchymal stem cells (MSCs) in vitro. Mechanotransduction has been integrated into a multitude of in vitro bone tissue engineering strategies and provides an effective means of controlling cell behaviour towards therapeutic outcomes. However, the delivery of mechanical stimuli to exogenous MSC populations, post implantation, poses a significant translational hurdle. Here, we describe an innovative bio-magnetic strategy, MICA, where magnetic nanoparticles (MNPs) are used to remotely deliver mechanical stimuli to the mechano-receptor, TREK-1, resulting in activation and downstream signalling via an external magnetic array. In these studies, we have translated MICA to a pre-clinical ovine model of bone injury to evaluate functional bone repair. We describe the development of a magnetic array capable of in vivo MNP manipulation and subsequent osteogenesis at equivalent field strengths in vitro. We further demonstrate that the viability of MICA-activated MSCs in vivo is unaffected 48?h post implantation. We present evidence to support early accelerated repair and preliminary enhanced bone growth in MICA-activated defects within individuals compared to internal controls. The variability in donor responses to MICA-activation was evaluated in vitro revealing that donors with poor osteogenic potential were most improved by MICA-activation. Our results demonstrate a clear relationship between responders to MICA in vitro and in vivo. These unique experiments offer exciting clinical applications for cell-based therapies as a practical in vivo source of dynamic loading, in real-time, in the absence of pharmacological agents.
| S-EPMC5904134 | biostudies-literature
Project description:Design and implementation of robust network modules is essential for construction of complex biological systems through hierarchical assembly of 'parts' and 'devices'. The robustness of gene regulatory networks (GRNs) is ascribed chiefly to the underlying topology. The automatic designing capability of GRN topology that can exhibit robust behavior can dramatically change the current practice in synthetic biology. A recent study shows that Darwinian evolution can gradually develop higher topological robustness. Subsequently, this work presents an evolutionary algorithm that simulates natural evolution in silico, for identifying network topologies that are robust to perturbations. We present a Monte Carlo based method for quantifying topological robustness and designed a fitness approximation approach for efficient calculation of topological robustness which is computationally very intensive. The proposed framework was verified using two classic GRN behaviors: oscillation and bistability, although the framework is generalized for evolving other types of responses. The algorithm identified robust GRN architectures which were verified using different analysis and comparison. Analysis of the results also shed light on the relationship among robustness, cooperativity and complexity. This study also shows that nature has already evolved very robust architectures for its crucial systems; hence simulation of this natural process can be very valuable for designing robust biological systems.
| S-EPMC4304830 | biostudies-literature
Project description:Organ and tissue shortage are known as a crucially important public health problem as unfortunately a small percentage of patients receive transplants. In the context of emerging regenerative medicine, researchers are trying to regenerate and replace different organs and tissues such as the liver, heart, skin, and kidney. Liver tissue engineering (TE) enables us to reproduce and restore liver functions, fully or partially, which could be used in the treatment of acute or chronic liver disorders and/or generate an appropriate functional organ which can be transplanted or employed as an extracorporeal device. In this regard, a variety of techniques (e.g., fabrication technologies, cell-based technologies, microfluidic systems and, extracorporeal liver devices) could be applied in tissue engineering in liver regenerative medicine. Common TE techniques are based on allocating stem cell-derived hepatocyte-like cells or primary hepatocytes within a three-dimensional structure which leads to the improvement of their survival rate and functional phenotype. Taken together, new findings indicated that developing liver tissue engineering-based techniques could pave the way for better treatment of liver-related disorders. Herein, we summarized novel technologies used in liver regenerative medicine and their future applications in clinical settings.
| S-EPMC7072533 | biostudies-literature
Project description:Regenerative medicine aims to tackle a panoply of challenges from repairing focal damage to articular cartilage to preventing pathological tissue remodeling after myocardial infarction. Hydrogels are water-swollen networks formed from synthetic or naturally derived polymers and are emerging as important tools to address these challenges. Recent advances in hydrogel chemistries are enabling researchers to create hydrogels that can act as 3D ex vivo tissue models, allowing them to explore fundamental questions in cell biology by replicating tissues' dynamic and nonlinear physical properties. Enabled by cutting edge techniques such as 3D bioprinting, cell-laden hydrogels are also being developed with highly controlled tissue-specific architectures, vasculature, and biological functions that together can direct tissue repair. Moreover, advanced in situ forming and acellular hydrogels are increasingly finding use as delivery vehicles for bioactive compounds and in mediating host cell response. Here, advances in the design and fabrication of hydrogels for regenerative medicine are reviewed. It is also addressed how controlled chemistries are allowing for precise engineering of spatial and time-dependent properties in hydrogels with a look to how these materials will eventually translate to clinical applications.
| S-EPMC5922416 | biostudies-literature
Project description:The human gastrointestinal microbiota (GIM) is a complex and diverse ecosystem that consists of community of fungi, viruses, protists and majorly bacteria. The association of several human illnesses, such as inflammatory bowel disease, allergy, metabolic syndrome and cancers, have been linked directly or indirectly to compromise in the integrity of the GIM, for which some medical interventions have been proposed or attempted. This review highlights and gives update on various technologies, including microfluidics, high-through-put sequencing, metabolomics, metatranscriptomics and culture in GIM research and their applications in gastrointestinal microbiota therapy, with a view to raise interest in the evaluation, validation and eventual use of these technologies in diagnosis and the incorporation of therapies in routine clinical practice.
| S-EPMC7464388 | biostudies-literature
Project description:Three-Dimensional (3D) printing technologies have been widely used in the medical sector for the production of medical assistance equipment and surgical guides, particularly 3D bio-printing that combines 3D printing technology with biocompatible materials and cells in field of tissue engineering and regenerative medicine. These additive manufacturing technologies can make patient-made production from medical image data. Thus, the application of 3D bio-printers with biocompatible materials has been increasing. Currently, 3D bio-printing technology is in the early stages of research and development but it has great potential in the fields of tissue and organ regeneration. The present paper discusses the history and types of 3D printers, the classification of 3D bio-printers, and the technology used to manufacture artificial tissues and organs.
| S-EPMC6170866 | biostudies-other
Project description:Simple Summary Despite significant strides in multimodal therapy, cancers still rank within the first three causes of death especially in industrial nations. A lack of individualized approaches and accurate preclinical models are amongst the major barriers that limit the development of novel therapeutic options and drugs. Recently, the 3D culture system of organoids was developed which stably retains the genetic and phenotypic characteristics of the original tissue, healthy as well as diseased. In this review, we summarize current data and evidence on the relevance and reliability of such organoid culture systems in cancer research, focusing on their role in drug investigations (in a personalized manner). Abstract Organoids are a new 3D ex vivo culture system that have been applied in various fields of biomedical research. First isolated from the murine small intestine, they have since been established from a wide range of organs and tissues, both in healthy and diseased states. Organoids genetically, functionally and phenotypically retain the characteristics of their tissue of origin even after multiple passages, making them a valuable tool in studying various physiologic and pathophysiologic processes. The finding that organoids can also be established from tumor tissue or can be engineered to recapitulate tumor tissue has dramatically increased their use in cancer research. In this review, we discuss the potential of organoids to close the gap between preclinical in vitro and in vivo models as well as clinical trials in cancer research focusing on drug investigation and development.
| S-EPMC8507862 | biostudies-literature
Project description:A mathematical model for the theoretical evaluation of microbial electrochemical technologies (METs) is presented that incorporates a detailed physico-chemical framework, includes multiple reactions (both at the electrodes and in the bulk phase) and involves a variety of microbial functional groups. The model is applied to two theoretical case studies: (i) A microbial electrolysis cell (MEC) for continuous anodic volatile fatty acids (VFA) oxidation and cathodic VFA reduction to alcohols, for which the theoretical system response to changes in applied voltage and VFA feed ratio (anode-to-cathode) as well as membrane type are investigated. This case involves multiple parallel electrode reactions in both anode and cathode compartments; (ii) A microbial fuel cell (MFC) for cathodic perchlorate reduction, in which the theoretical impact of feed flow rates and concentrations on the overall system performance are investigated. This case involves multiple electrode reactions in series in the cathode compartment. The model structure captures interactions between important system variables based on first principles and provides a platform for the dynamic description of METs involving electrode reactions both in parallel and in series and in both MFC and MEC configurations. Such a theoretical modelling approach, largely based on first principles, appears promising in the development and testing of MET control and optimization strategies.
| S-EPMC5297720 | biostudies-literature
Project description:Recent advances in high-throughput sequencing technologies and bioinformatics have generated huge new opportunities for discovering and diagnosing plant viruses and viroids. Plant virology has undoubtedly benefited from these new methodologies, but at the same time, faces now substantial bottlenecks, namely the biological characterization of the newly discovered viruses and the analysis of their impact at the biosecurity, commercial, regulatory, and scientific levels. This paper proposes a scaled and progressive scientific framework for efficient biological characterization and risk assessment when a previously known or a new plant virus is detected by next generation sequencing (NGS) technologies. Four case studies are also presented to illustrate the need for such a framework, and to discuss the scenarios.
| S-EPMC5258733 | biostudies-literature
Project description:In-depth understanding of microstructure development is required to fabricate high quality products by additive manufacturing (for example, 3D printing). Here we report the governing role of side-branching in the microstructure development of alloys by laser powder bed fusion. We show that perturbations on the sides of cells (or dendrites) facilitate crystals to change growth direction by side-branching along orthogonal directions in response to changes in local heat flux. While the continuous epitaxial growth is responsible for slender columnar grains confined to the centreline of melt pools, side-branching frequently happening on the sides of melt pools enables crystals to follow drastic changes in thermal gradient across adjacent melt pools, resulting in substantial broadening of grains. The variation of scan pattern can interrupt the vertical columnar microstructure, but promotes both in-layer and out-of-layer side-branching, in particular resulting in the helical growth of microstructure in a chessboard strategy with 67° rotation between layers.
| S-EPMC7004990 | biostudies-literature