A morphospace for synthetic organs and organoids: the possible and the actual (original) (raw)

Middle-out methods for spatiotemporal tissue engineering of organoids

Nature Reviews Bioengineering

Organoids recapitulate many aspects of the complex three-dimensional (3D) organization found within native tissues and even display tissue and organ-level functionality. Traditional approaches to organoid culture have largely employed a top-down tissue engineering strategy, whereby cells are encapsulated in a 3D matrix, such as Matrigel, alongside well-defined biochemical cues that direct morphogenesis. However, the lack of spatiotemporal control over niche properties renders cellular processes largely stochastic. Therefore, bottom-up tissue engineering approaches have evolved to address some of these limitations and focus on strategies to assemble tissue building blocks with defined multi-scale spatial organization. However, bottom-up design reduces the capacity for self-organization that underpins organoid morphogenesis. Here, we introduce an emerging framework, which we term middle-out strategies, that relies on existing design principles and combines top-down design of defined synthetic matrices that support proliferation and self-organization with bottom-up modular engineered intervention to limit the degrees of freedom in the dynamic process of organoid morphogenesis. We posit that this strategy will provide key advances to guide the growth of organoids with precise geometries, structures and function, thereby facilitating an unprecedented level of biomimicry to accelerate the utility of organoids to more translationally relevant applications. Sections • Top-down, scaffold-based tissue engineering approaches allow for macroscale control over organoid geometry and are amenable to cell-based remodelling and self-organization but suffer from a lack of spatiotemporal control of niche properties. • Bottom-up, modular tissue engineering approaches allow for precise control over cellular and extracellular tissue building blocks for precision engineering but at the cost of minimizing the capacity for cellular self-organization. • Middle-out, interventional tissue engineering approaches combine aspects of top-down and bottom-up tissue engineering methods to enable precise spatiotemporal control of engineered cell niches, thereby enabling deterministic control of cellular self-organization. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author selfarchiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Modularity in Developmental Biology and Artificial Organs: A Missing Concept in Tissue Engineering

Artificial Organs, 2011

Tissue engineering is reviving itself, adopting the concept of biomimetics of in vivo tissue development. A basic concept of developmental biology is the modularity of the tissue architecture according to which intermediates in tissue development constitute semiautonomous entities. Both engineering and nature have chosen the modular architecture to optimize the product or organism development and evolution. Bioartificial tissues do not have a modular architecture. On the contrary, artificial organs of modular architecture have been already developed in the field of artificial organs. Therefore the conceptual support of tissue engineering by the field of artificial organs becomes critical in its new endeavor of recapitulating in vitro the in vivo tissue development.

Synthetic tissue biology: Tissue engineering meets synthetic biology

Birth Defects Research Part C: Embryo Today: Reviews, 2007

We propose the term ''synthetic tissue biology'' to describe the use of engineered tissues to form biological systems with metazoan-like complexity. The increasing maturity of tissue engineering is beginning to render this goal attainable. As in other synthetic biology approaches, the perspective is bottom-up; here, the premise is that complex functional phenotypes (on par with those in whole metazoan organisms) can be effected by engineering biology at the tissue level. To be successful, current efforts to understand and engineer multicellular systems must continue, and new efforts to integrate different tissues into a coherent structure will need to emerge. The fruits of this research may include improved understanding of how tissue systems can be integrated, as well as useful biomedical technologies not traditionally considered in tissue engineering, such as autonomous devices, sensors, and manufacturing. Birth Defects Research (Part C) 81:354-361,

(2009) Control of organogenesis: towards effective tissue engineering

Fundamentals of Tissue Engineering …, 2009

(There is no abstract: this is the first paragraph) The word “Organogenesis” is defined as “the production and development of the organs of an animal or plant” [1]. In the context of medical research, it has traditionally been applied to the natural processes of foetal development but it is now beginning to be applied also to the creation of living organs, or organ substitutes, by artificial means. It is this latter meaning that is most relevant to this book and most of this chapter will therefore focus on artificial organogenesis. It will be helpful, though, to review the basic features of natural organogenesis first, because the most successful methods of artificial organogenesis tend to build on them.

Organoids: inception and utilization of 3D organ models

2020

Over the previous decade, one of the most exciting advancements in stem cell technology has been the development of organoid culture system. Organoids are new research tools created in-vitro, to form self-organizing 3-Dimensional structures that encompass some of the crucial characteristics of the represented organ. Organoids are grown from stem cells from an organ of interest. There are potentially as many types of organoids as there are different tissues and organs in a body. It is challenging for scientists to understand the underlying mechanism of biological processes with complex spatial cellular organization and tissue dynamics. Also, how they are disrupted in a disease is impossible to study in-vivo, but discovery of organoids is revolutionizing the fields of biology. Since success in these platforms will be restricted without the proficiency to alter the genomic content, genome engineering was also applied in recently discovered organoid cultures for correcting mutations. Th...

Engineered materials for organoid systems

Nature Reviews Materials, 2019

Organoids are 3D cell culture systems that are formed through cell differentiation and self-organization of pluripotent stem cells or tissue-derived progenitor cells, which can contain supporting stromal elements. The foundation of tissue culture was laid in 1907, when Harrison et al. cultured dissected frog neural tubes 1. Cell culture studies were continued throughout the 20th century to describe the embryonic development of organs by observing tissue reorganization after dissociation 2,3 (Fig. 1), which led to the identification of cell sorting and cell-fate specification during organogenesis and the powerful innate ability of cells to spontaneously organize into complex structures in vitro. Organoids are a class of microphysiological systems that provide platforms to model the features of organs and tissues in an in vitro setting 4. The terminology in the field remains to be universally defined 5 and terms such as organoid, organotypic culture, spheroid, enteroid and assembloid are used by different communities for different 3D cell culture systems. For example, for gastrointestinal tissues, the term organoid has been suggested for cultures that contain both epithelial and mesenchymal or stromal components, whereas the term enteroid has been used for 3D cultures that contain only epithelial cells 6. By contrast, spheroid has been used to describe either aggregates of cells or region-specific brain organoids 7. In this Review, the term organoid is used to describe all of these complex, multicellular systems.

Next generation organoids for biomedical research and applications

Biotechnology advances

Organoids are in vitro cultures of miniature fetal or adult organ-like structures. Their potentials for use in tissue and organ replacement, disease modeling, toxicology studies, and drug discovery are tremendous. Currently, major challenges facing human organoid technology include (i) improving the range of cellular heterogeneity for a particular organoid system, (ii) mimicking the native micro- and matrix-environment encountered by cells within organoids, and (iii) developing robust protocols for the in vitro maturation of organoids that remain mostly fetal-like in cultures. To tackle these challenges, we advocate the principle of reverse engineering that replicates the inner workings of in vivo systems with the goal of achieving functionality and maturation of the resulting organoid structures with the input of minimal intrinsic (cellular) and environmental (matrix and niche) constituents. Here, we present an overview of organoid technology development in several systems that emp...