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The concept of engineering living constructs that can be used to replace damaged, malfunctioning or failing tissues and organs has revolutionized the field of transplant surgery. Offering an answer to the persisting problem of donor organ shortage, tissue engineering integrates discoveries from multiple fields including cell, matrix and developmental biology, biochemistry and chemistry, materials sciences, physics, medicine and biotechnology with the aim to manufacture vital implants outside the body. One principal idea of tissue engineering is to create suitable, biocompatible three-dimensional (3D) scaffold materials that can be implanted as medical devices. Depending on the requirements, such scaffolds, may possess the capacity to remodel in vivo or they may need to be seeded with stem, progenitor or tissue-specific cells prior to implantation. The idea seems simple, but has taken almost two decades to refine and improve, and to date, we are still far away from a routine clinical application of tissue-engineered constructs to address the unmet needs of patients desperately waiting for critical replacement organs [1]. Despite the still unfulfilled expectation of off-the-shelf tissues and organs, tissue engineering has helped to advance our knowledge of human organ development and to make progress in cell culture practices, bioreactor and biomaterials design, non-invasive tissue monitoring, drug delivery strategies and surgical intervention.

One principal idea of tissue engineering is to create suitable, biocompatible 3D scaffold materials that can be implanted as medical devices.

This Special Issue on strategies in tissue engineering covers several areas relevant to the field. In their review article, Brauchle and Schenke-Layland [2] provide comprehensive insight to the current progress in non-invasive, marker-free monitoring of cells and tissues employing Raman spectroscopy. Raman spectroscopy is a laser-based technology that can be used to study changes in chemical bonds and molecular symmetry. Its various applications include the high-throughput screening of pharmaceutical products, real-time monitoring of gas mixtures and temperatures, the characterization of materials, and the detection of explosives. In recent years, Raman microspectroscopy has become a technology of interest for the life sciences. The review focuses on the use of Raman spectroscopy for the analysis of cellular phenotypes, as well as tissue and organ structures.

In recent years, Raman microspectroscopy has become a technology of interest for the life sciences.

Hansmann and colleagues [3] review the accomplishments made in the field of bioreactor design for cell and tissue culture applications, with special emphasis on challenges when expanding this technology to the field of musculoskeletal applications. In general, it has been established that the controlled exposure of tissue-engineered constructs to defined biophysical signals within tailored bioreactors leads to improved cellular ingrowth, proper tissue formation and physiological remodeling. When aiming to generate de novo-vascularized tissues in vitro, improved tissue culture conditions are necessary to ensure the transport of oxygen and nutrients to the cells. Groeber et al. [4] report the development of a bioreactor system that allows the physiological culture of 3D vascularized skin equivalents by dynamically perfusing the vasculature, while facilitating an air-liquid interface that is necessary for the appropriate culture of skin cells. The authors conclude that the combination of the novel bioreactor system with the enzymatically decellularized 3D scaffold called “BioVaSc” may serve as platform technology in the future to further increase the complexity of skin equivalents such as the integration of sweat glands or hair follicles [5]. To improve current tissue culture protocols for the establishment of skin equivalents is also the focus of the study by Sommer et al. [6]. The authors determined that exposure to a defined concentration of transforming growth factor beta 1 (TGF-β1) instructs human neonatal dermal fibroblasts to form 3D elastic fibers, which are crucial extracellular matrix components in many tissues, including the skin. We congratulate the authors for their pioneering discovery since this study is, to date, the first report on the possibility of normal, primary isolated human neonatal dermal fibroblasts to assemble mature and cross-linked elastic fibers ex vivo. The described protocol will enable future in-depth studies aiming to further investigate elastic fiber development.

Kleinhans and colleagues [7] report the suitability of plasma treatment for the cost-effective and reproducible functionalization of cell cultureware. The authors show that ammonia plasma-treated polystyrene surfaces increases the proliferative capacity of human bone marrow-derived mesenchymal stem cells and dermal microvascular endothelial cells, a feature that can be ultimately used for the functionalization of implant materials.

When aiming for the generation of neo-tissues and organs, it is important to understand the mechanisms that lead to normal and pathological tissue development. In many cases human development has become the blueprint for tissue engineering and regenerative medicine efforts. However, the investigation of human developmental patterns is often hampered due to the scarcity of appropriate tissue samples. In their study, Votteler et al. [8] demonstrate an improved processing procedure that allows the analysis of human fetal and adult cardiovascular tissues from different sources, preserved using varying methods. The authors further disclose a tissue-processing protocol to obtain RNA from formalin-fixed, paraffin-embedded (FFPE) fetal tissues that is suitable for global gene expression profiling.

We are confident that these papers will contribute to further advancements in tissue engineering.

The Ross operation is a highly complex surgical procedure performed to replace a patient's aortic valve with the pulmonary autograft, which is then replaced by a homograft. However, valve homograft scarcity forces surgeons to search for alternative prostheses. Since the development of a tissue-engineered heart valve construct is still in its infancy, Weimar and colleagues [9] explored the possibility of using porcine stentless prostheses as alternative pulmonary substitutes, revealing an unexpected disappointing performance of the xenografts. The important findings of this study implicate the necessity to refine and optimize biological valve substitutes for young adolescent patients, as further highlighted by the commentary of Prof. Dr. Ulrich A. Stock [10], which will also have an important impact on the future design of tissue-engineered heart valves.

This Special Issue consists of some papers presented at the “3rd International Conference on Strategies in Tissue Engineering” held in Würzburg, Germany in 2012. As shown by these papers, much progress has been made, and we are confident that these will contribute to further advancements in tissue engineering.

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Prof. Katja Schenke-Layland, University Women's Hospital of the Eberhard Karls University Tübingen and Inter-University Centre for Medical Technology Stuttgart-Tübingen (IZST), Germany

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Prof. Heike Walles, University Hospital of the Julius-Maximillians-University Würzburg, Institute of Tissue Engineering and Regenerative Medicine, Germany


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