Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

3D bioprinting of tissues and organs

An overview of tissue and whole organ decellularization processes.

MUCKE aims to mine a large volume of images, to structure them conceptually and to use this conceptual structuring in order to improve large-scale image retrieval. The last decade witnessed important progress concerning low-level image representations. However, there are a number problems which need to be solved in order to unleash the full potential of image mining in applications. The central problem with low-level representations is the mismatch between them and the human interpretation of image content. This problem can be instantiated, for instance, by the incapability of existing descriptors to capture spatial relationships between the concepts represented or by their incapability to convey an explanation of why two images are similar in a content-based image retrieval framework. We start by assessing existing local descriptors for image classification and by proposing to use co-occurrence matrices to better capture spatial relationships in images. The main focus in MUCKE is on cleaning large scale Web image corpora and on proposing image representations which are closer to the human interpretation of images. Consequently, we introduce methods which tackle these two problems and compare results to state of the art methods. Note: some aspects of this deliverable are withheld at this time as they are pending review. Please contact the authors for a preview.

http://ieeexplore.ieee.org/iel2/4524/12820/00592460.pdf

Image Processing

Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

The molecular and physical information coded within the extracellular milieu is informing the development of a new generation of biomaterials for tissue engineering. Several powerful extracellular influences have already found their way into cell-instructive scaffolds, while others remain largely unexplored. Yet for commercial success tissue engineering products must be not only efficacious but also cost-effective, introducing a potential dichotomy between the need for sophistication and ease of production. This is spurring interest in recreating extracellular influences in simplified forms, from the reduction of biopolymers into short functional domains, to the use of basic chemistries to manipulate cell fate. In the future these exciting developments are likely to help reconcile the clinical and commercial pressures on tissue engineering.

Complexity in biomaterials for tissue engineering

Zebrafish and newt heart regeneration has been demonstrated to be the result of cardiomyocyte proliferation, which has suggested the feasibility of maintaining the proliferation capacity of native mammalian neonatal cardiomyocytes. Recent experiments demonstrating that stem cells are highly depolarized while terminally differentiated cells are hyperpolarized have indicated a potential role of membrane potential in maintaining a proliferative phenotype. In this study, we used titrated potassium gluconate and ouabain to depolarize primary neonatal rat cardiomyocytes and demonstrated the concomitant proliferative effect between postpartum day 3 (P3) and post partum day 7 (P7). After isolation, the cells were cultured for one day in normal media and before replacing the media with titrated depolarizing agents for four days. The effect of depolarization was validated by DiBAC, a slow-acting voltage-sensitive fluorescence dye. Total nuclei count and cardiomyocyte percentage were evaluated by microscopic cytometry. Cell cycle was analyzed by propidium iodide on flow cytometry. Both treatment groups had a dose dependent effect on cardiomyocyte percentage and induced proliferation at specific range of concentrations before eventually reaching toxic levels. A study of cell cycle showed increased populations of non-G0/G1 phase cardiomyocytes with treatment. Conclusion: We concluded that the control of membrane potential could modulate the proliferation of neonatal rat cardiomyocytes.

http://ieeexplore.ieee.org/iel7/6954316/6972691/06972849.pdf

Alterations in membrane potential promote neonatal cardiomyocyte proliferation

You might find this additional info useful...This article cites 32 articles, 15 of which can be accessed free at:http://jap.physiology.org/content/98/4/1434.full.html#ref-list-1 This article has been cited by 4 other HighWire hosted articles€[Abstract] [Full Text] [PDF] J Appl Physiol, September 1, 2007; 103 (3): 803-811.Rajiv Jesudason, Lauren Black, Arnab Majumdar, Phillip Stone and Bela Sukimechanical properties of extracellular matricesDifferential effects of static and cyclic stretching during elastase digestion on the€[Abstract] [Full Text] [PDF] PNAS, January 27, 2009; 106 (4): 1081-1086.Buczek-Thomas, Phillip J. Stone, Matthew A. Nugent and Bela SukiMichael C. Ritter, Rajiv Jesudason, Arnab Majumdar, Dimitrije Stamenovic, Jo AnnA zipper network model of the failure mechanics of extracellular matrices€[Abstract] [Full Text] [PDF] Am J Physiol Lung Cell Mol Physiol 2009; 296 (3): L534-L546.Elma Kurtagic, Mark P. Jedrychowski and Matthew A. NugentNeutrophil elastase cleaves VEGF to generate a VEGF fragment with altered activity€[Abstract] [Full Text] [PDF] PNAS, June 7, 2011; 108 (23): 9414-9419.Matthew A. Nugent and Bela SukiAscânio D. Araujo, Arnab Majumdar, Harikrishnan Parameswaran, Eunice Yi, Jean L. Spencer,Dynamics of enzymatic digestion of elastic fibers and networks under tensionUpdated information and services including high resolution figures, can be found at:http://jap.physiology.org/content/98/4/1434.full.html Additional material and information about Journal of Applied Physiology can be found at:http://www.the-aps.org/publications/japplThis infomation is current as of October 7, 2011.€

Lauren D. Black

Papers

Alterations in membrane potential promote neonatal cardiomyocyte proliferation

properties of engineered elastin-rich matrices Effects of elastase on the mechanical and failure