During development cells and tissues undergo changes in pattern and form that employ a wider range of physical mechanisms than at any other time in an organism's life. This book shows how physics can ...be used to analyze these biological phenomena. Written to be accessible to both biologists and physicists, major stages and components of the biological development process are introduced and then analyzed from the viewpoint of physics. The presentation of physical models requires no mathematics beyond basic calculus. Physical concepts introduced include diffusion, viscosity and elasticity, adhesion, dynamical systems, electrical potential, percolation, fractals, reaction-diffusion systems, and cellular automata. With full-color figures throughout, this comprehensive textbook teaches biophysics by application to developmental biology and is suitable for graduate and upper-undergraduate courses in physics and biology.
...adding the cells to the biomaterials with the interactions necessary to have the right environment for tissue formation in bioreactors and incubators adds yet another level of complexity to the ...process. By the time the general public became aware of bioprinting, 3D printing with inanimate materials had already produced a myriad of useful products expeditiously. ...many could expect that bioprinting, being a specific application of the more general technology, would deliver equally versatile and easy‐to‐manufacture living biological products; the field of 3D bioprinting quickly captured the public's imagination. Bioprinted tissues can be interconnected (e.g., liver, heart, kidney, etc.) to test drugs on a body‐on‐a‐chip model before the start of human clinical trials. Tissues printed with gene‐edited cells from the diseased patient to achieve a normal endpoint or combination of extended bioprinted tissue units functionally interconnected similarly to that in the human body are examples that could lead to unforeseen progress in regenerative medicine.
Biofabrication holds the potential to generate constructs that more closely recapitulate the complexity and heterogeneity of tissues and organs than do currently available regenerative medicine ...therapies. Such constructs can be applied for tissue regeneration or as in vitro 3D models. Biofabrication is maturing and growing, and scientists with different backgrounds are joining this field, underscoring the need for unity regarding the use of terminology. We therefore believe that there is a compelling need to clarify the relationship between the different concepts, technologies, and descriptions of biofabrication that are often used interchangeably or inconsistently in the current literature. Our objective is to provide a guide to the terminology for different technologies in the field which may serve as a reference for the biofabrication community.
Biofabrication holds great potential in the fields of regenerative medicine and physiological 3D in vitro models by allowing the manufacture of complex tissue constructs with a higher degree of biomimicry to native tissues than do current biomedical solutions.
As the number of biofabrication technologies being developed continues to expand, it is of paramount importance to adopt a concerted terminology framework and avoid generalizations.
The ratio between the spatial resolution and the timescale of manufacture could be considered as a reliable measure to aid in the selection of an appropriate biofabrication technology for a desired application.
Tissue engineering is emerging as a possible alternative to methods aimed at alleviating the growing demand for replacement tissues and organs. A major pillar of most tissue engineering approaches is ...the scaffold, a biocompatible network of synthetic or natural polymers, which serves as an extracellular matrix mimic for cells. When the scaffold is seeded with cells it is supposed to provide the appropriate biomechanical and biochemical conditions for cell proliferation and eventual tissue formation. Numerous approaches have been used to fabricate scaffolds with ever-growing complexity. Recently, novel approaches have been pursued that do not rely on artificial scaffolds. The most promising ones utilize matrices of decellularized organs or methods based on multicellular self-assembly, such as sheet-based and bioprinting-based technologies. We briefly overview some of the scaffold-free approaches and detail one that employs biological self-assembly and bioprinting. We describe the technology and its specific applications to engineer vascular and nerve grafts.
Biofabrication is an evolving research field that has recently received significant attention. In particular, the adoption of Biofabrication concepts within the field of Tissue Engineering and ...Regenerative Medicine has grown tremendously, and has been accompanied by a growing inconsistency in terminology. This article aims at clarifying the position of Biofabrication as a research field with a special focus on its relation to and application for Tissue Engineering and Regenerative Medicine. Within this context, we propose a refined working definition of Biofabrication, including Bioprinting and Bioassembly as complementary strategies within Biofabrication.
Rupture of a nerve is a debilitating injury with devastating consequences for the individual's quality of life. The gold standard of repair is the use of an autologous graft to bridge the severed ...nerve ends. Such repair however involves risks due to secondary surgery at the donor site and may result in morbidity and infection. Thus the clinical approach to repair often involves non-cellular solutions, grafts composed of synthetic or natural materials. Here we report on a novel approach to biofabricate fully biological grafts composed exclusively of cells and cell secreted material. To reproducibly and reliably build such grafts of composite geometry we use bioprinting. We test our grafts in a rat sciatic nerve injury model for both motor and sensory function. In particular we compare the regenerative capacity of the biofabricated grafts with that of autologous grafts and grafts made of hollow collagen tubes by measuring the compound action potential (for motor function) and the change in mean arterial blood pressure as consequence of electrically eliciting the somatic pressor reflex. Our results provide evidence that bioprinting is a promising approach to nerve graft fabrication and as a consequence to nerve regeneration.
Cellular particle dynamics
(CPD) is an effective computational method to describe the shape evolution and biomechanical relaxation processes in systems composed of micro tissues such as multicellular ...aggregates. Therefore, CPD is a useful tool to predict the outcome of postprinting structure formation in bioprinting. The predictive power of CPD has been demonstrated for multicellular systems composed of identical volume-conserving spherical and cylindrical bioink units. Experiments and computer simulations were related through an independently developed theoretical formalism based on continuum mechanics. Here we generalize the CPD formalism to (i) include non-identical bioink particles often used in specific bioprinting applications, (ii) describe the more realistic experimental situation in which during the post-printing structure formation
via
the fusion of spherical bioink units the volume of the system decreases, and (iii) directly connect CPD simulations to the corresponding experiments without the need of the intermediate continuum theory inherently based on simplifying assumptions.
Cellular particle dynamics
(CPD) is an effective computational method to describe the shape evolution and biomechanical relaxation processes in systems composed of micro tissues such as multicellular aggregates.
The outcome of a bioprinting process depends on both the deposition of the discrete bioink units and their ability to self-assemble into the desired structure following deposition. Post-printing ...structure formation is an autonomous process governed by fundamental biological organizing principles. As the quantitative formulation of such principles is notoriously difficult, bioprinting remains largely a trial and error approach. To address this problem, specifically in extrusion bioprinting, we have recently developed an effective computational method, the cellular particle dynamics (CPDs). We have demonstrated the predictive power of CPD in cases of simple printed constructs prepared with spherical multicellular bioink units. Here we generalize CPD to the important practical case of tubular grafts printed with cylindrical bioink units by taking into account the realistic experimental situation in which the length and the volume of the cylinders decrease post-printing. Based on our results, we provide a set of instructions for the use of CPD simulations to directly predict tubular graft formation without the need to carry out the corresponding complex and expensive control experiments. Using these instructions allows the efficient and timely biofabrication of tubular organ structures. A particularly instructive outcome of our analysis is that building tubular organ structures, such as vascular grafts by bioprinting can be done considerably faster by using cylindrical rather than spherical bionk units.
Tissue engineering technology promises to solve the organ transplantation crisis. However, assembly of vascularized 3D soft organs remains a big challenge. Organ printing, which we define as ...computer-aided, jet-based 3D tissue-engineering of living human organs, offers a possible solution. Organ printing involves three sequential steps: pre-processing or development of ‘blueprints’ for organs; processing or actual organ printing; and postprocessing or organ conditioning and accelerated organ maturation. A cell printer that can print gels, single cells and cell aggregates has been developed. Layer-by-layer sequentially placed and solidified thin layers of a thermo-reversible gel could serve as ‘printing paper’. Combination of an engineering approach with the developmental biology concept of embryonic tissue fluidity enables the creation of a new rapid prototyping 3D organ printing technology, which will dramatically accelerate and optimize tissue and organ assembly.
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