Part 1: a process view of nature. Multifunctional integration and the role of the construction agent

This is the first of two linked articles which draw s on emerging understanding in the field of biology and seeks to communicate it to those of construction, engineering and design. Its insight is that nature 'works' at the process level, where neither function nor form are distinctions, and materialisation is both the act of negotiating limited resource and encoding matter as 'memory', to sustain and integrate processes through time. It explores how biological agents derive work by creating 'interfaces' between adjacent locations as membranes, through feedback. Through the tension between simultaneous aggregation and disaggregation of matter by agents with opposing objectives, many functions are integrated into an interface as it unfolds. Significantly, biological agents induce flow and counterflow conditions within biological interfaces, by inducing phase transition responses in the matte r or energy passing through them, driving steep gradients from weak potentials (i.e. shorter distances and larger surfaces). As with biological agents, computing, programming and, increasingly digital sensor and effector technologies share the same 'agency' and are thus convergent

Liver organoids: from basic research to therapeutic applications.

Organoid cultures have emerged as an alternative in vitro system to recapitulate tissues in a dish. While mouse models and cell lines have furthered our understanding of liver biology and associated diseases, they suffer in replicating key aspects of human liver tissue, in particular its complex architecture and metabolic functions. Liver organoids have now been established for multiple species from induced pluripotent stem cells, embryonic stem cells, hepatoblasts and adult tissue-derived cells. These represent a promising addition to our toolbox to gain a deeper understanding of this complex organ. In this perspective we will review the advances in the liver organoid field, its limitations and potential for biomedical applications.Acknowledgements M.H. is a Wellcome Trust Sir Henry Dale Fellow and is jointly funded by the Wellcome Trust and the Royal Society (104151/Z/14/Z). This work was partially funded by a H2020 LSMF4LIFE awarded to M.H. PI is funded by the NC3Rs (NC/R001162/1). The authors acknowledge core funding to the Gurdon Institute from the Wellcome Trust (092096) and CRUK (C6946/A14492)

Flora Robotica – Mixed Societies of Symbiotic Robot-Plant Bio-Hybrids

Besides the life-as-it-could-be driver of artificial life research there is also the concept of extending natural life by creating hybrids or mixed societies that are built from both natural and artificial components. In this paper, we motivate and present the research program of the project flora robotica. We present our concepts of control, hardware de-sign, modeling, and human interaction along with preliminary experiments. Our objective is to develop and to investigate closely linked symbiotic relationships between robots and natural plants and to explore the potentials of a plant-robot society able to produce archi-tectural artifacts and living spaces. These robot-plant bio-hybrids create synergies that allow for new functions of plants and robots. They also create novel design opportunities for an architecture that fuses the design and construction phase. The bio-hybrid is an example of mixed societies between ‘hard artificial and ‘wet natural life, which enables an interaction between natural and artificial ecologies. They form an embodied, self-organizing, and distributed cognitive system which is supposed to grow and develop over long periods of time resulting in the creation of meaningful architectural structures. A key idea is to assign equal roles to robots and plants in order to create a highly integrated, symbiotic system. Besides the gain of knowledge, this project has the objective to cre-ate a bio-hybrid system with a defined function and application – growing architectural artifacts

Informing the Cannabis Conjecture: From Life’s Beginnings to Mitochondria, Membranes and the Electrome - A Review

Before the late 1980s, ideas around how the lipophilic phytocannabinoids might be working involved membranes and bioenergetics as these disciplines were “in vogue”. However, as interest in genetics and pharmacology grew, interest in mitochondria (and membranes) waned. The discovery of the cognate receptor for tetrahydrocannabinol (THC) led to the classification of the endocannabinoid system (ECS) and the conjecture that phytocannabinoids might be “working” through this system. However, the how and the “why” they might be beneficial, especially for compounds like CBD, remains unclear. Given the centrality of membranes and mitochondria in complex organisms, and their evolutionary heritage from the beginnings of life, revisiting phytocannabinoid action in this light could be enlightening. For example, life can be described as a self-organising and replicating far from equilibrium dissipating system, which is defined by the movement of charge across a membrane. Hence the building evidence, at least in animals, that THC and CBD modulate mitochondrial function could be highly informative. In this paper, we offer a unique perspective to the question, why and how do compounds like CBD potentially work as medicines in so many different conditions? The answer, we suggest, is that they can modulate membrane fluidity in a number of ways and thus dissipation and engender homeostasis, particularly under stress. To understand this, we need to embrace origins of life theories, the role of mitochondria in plants and explanations of disease and ageing from an adaptive thermodynamic perspective, as well as quantum mechanics

Bioreactors for tendon tissue engineering: challenging mechanical demands towards tendon regeneration

Tendon tissues have very important load-bearing and load-transfer functions, and are also very prone to injuries that can dramatically affect patientâ s quality of life and which are difficult to manage successfully with current available therapies. Regenerative approaches following tendon tissue engineering (TTE) principles have sought to augment the injured tendon with stem cells, scaffolds and mechanical stimulus to improve natural healing response. In fact, combinatorial tenogenic cues may involve adequate topographical, biochemical and mechanical signals for recapitulating native cellular microenvironment and thus promote regeneration. Hence, for the successful implementation of TTE therapies, all aspects of tendon function and requirements should be taken into account in the in vitro maturation of constructs prior implantation. In this sense, bioreactor systems represent attractive tools to provide biomechanical signaling to cells-laden constructs under closely monitored and tightly controlled environments. This chapter discusses specific roles of biomechanical stimulation in tendons and the most frequently used bioreactor systems in tendon tissue engineering field

3D-organoid cultures

In vitro three-dimensional (3D) cultures are emerging as novel systems with which to study tissue development, organogenesis and stem cell behavior ex vivo. When grown in a 3D environment, embryonic stem cells (ESCs) self-organize into organoids and acquire the right tissue patterning to develop into several endoderm- and ectoderm-derived tissues, mimicking their in vivo counterparts. Tissue-resident adult stem cells (AdSCs) also form organoids when grown in 3D and can be propagated in vitro for long periods of time. In this Review, we discuss recent advances in the generation of pluripotent stem cell- and AdSC-derived organoids, highlighting their potential for enhancing our understanding of human development. We will also explore how this new culture system allows disease modeling and gene repair for a personalized regenerative medicine approach.M.H. is a Wellcome Trust Sir Henry Dale Fellow and is jointly funded by the Wellcome Trust and the Royal Society. B.-K.K. is supported by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society.This is the author accepted manuscript. The final version is available from the Company of Biologists via http://dx.doi.org/10.1242/dev.11857

Polarity during tissue repair, a multiscale problem

Tissue repair is essential for all organisms, as it protects the integrity and function of tissues and prevents infections and diseases. It takes place at multiple scales, from macroscopic to microscopic levels. Most mechanisms driving tissue repair rely on the correct polarisation of collective cell behaviours, such as migration and proliferation, and polarisation of cytoskeletal and junctional components. Furthermore, re-establishment and maintenance of cell polarity are fundamental for a tissue to be fully repaired and for withstanding mechanical stress during homeostasis and repair. Recent evidence highlights an important role for the interplay between cell polarity and tissue mechanics that are critical in tissue repair

Designing for emergence and innovation: Redesigning design

We reveal the surprising and counterintuitive truth that the design process, in and of itself, is not always on the forefront of innovation. Design is a necessary but not a sufficient condition for the success of new products and services. We intuitively sense a connection between innovative design and emergence. The nature of design, emergence and innovation to understand their interrelationships and interdependencies is examined. We propose that design must harness the process of emergence; for it is only through the bottom-up and massively iterative unfolding of emergence that new and improved products and services are successfully refined, introduced and diffused into the marketplace. The relationships among design, emergence and innovation are developed. What designers can learn from nature about emergence and evolution that will impact the design process is explored. We examine the roles that design and emergence play in innovation. How innovative organizations can incorporate emergence into their design process is explored. We demarcate the boundary between invention and innovation. We also articulate the similarities and differences of design and emergence. We then develop the following three hypotheses: Hypothesis 1: “An innovative design is an emergent design.” Hypothesis 2: “A homeostatic relationship between design and emergence is a required condition for innovation.”Hypothesis 3: “Since design is a cultural activity and culture is an emergent phenomenon, it follows that design leading to innovation is also an emergent phenomenon” We provide a number of examples of how design and emergence have worked together and led to innovation. Examples include the tool making of early man; the evolutionary chain of the six languages speech, writing, math, science, computing and the Internet; the Gutenberg printing press and techniques of collaborative filtering associated with the Internet. We close by describing the relationship between human and naturally “designed” systems and the notion a key element of a design is its purpose as is the case with a living organism