[Biomaterials or Donor Tissue - What is the Future of Tissue Engenieering for Cornea Reconstruction?] / Keratin, Kollagen oder doch Spendergewebe ­ wo liegt die Zukunft in der Entwicklung neuer Biomaterialien zur Hornhautrekonstruktion?

For the replacement of corneal tissue, corneal grafts or amniotic membrane are still used as a standard material. Since this is biological tissue, there is only a limited standardization regarding preparation, tissue properties and behaviour after transplantation. In addition, there is a risk of disease transmission, and the availability of both human corneas and amniotic membrane is insufficient in many regions of the world, which is why alternative biomaterials have been explored for many years now. Among the natural biomaterials, materials based on collagen or keratin provide characteristics that make them good candidates for corneal tissue replacement. However, there are still many unsolved problems, particularly regarding the degradation after implantation and the seam strength of the materials. Initial clinical studies with different biomaterials based on collagen prove their good biocompatibility to integrate and their low immunogenicity. Currently, there is no biomaterial that meets the requirements in every situation. It can be assumed that different biomaterials will be available in the future, which, depending on the underlying corneal disease, will fulfill different functions and thus make a patient- and disease-specific care possible.

Towards artificial tissue models: past, present, and future of 3D bioprinting.

Regenerative medicine and tissue engineering have seen unprecedented growth in the past decade, driving the field of artificial tissue models towards a revolution in future medicine. Major progress has been achieved through the development of innovative biomanufacturing strategies to pattern and assemble cells and extracellular matrix (ECM) in three-dimensions (3D) to create functional tissue constructs. Bioprinting has emerged as a promising 3D biomanufacturing technology, enabling precise control over spatial and temporal distribution of cells and ECM. Bioprinting technology can be used to engineer artificial tissues and organs by producing scaffolds with controlled spatial heterogeneity of physical properties, cellular composition, and ECM organization. This innovative approach is increasingly utilized in biomedicine, and has potential to create artificial functional constructs for drug screening and toxicology research, as well as tissue and organ transplantation. Herein, we review the recent advances in bioprinting technologies and discuss current markets, approaches, and biomedical applications. We also present current challenges and provide future directions for bioprinting research.

Biofabrication: reappraising the definition of an evolving field.

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.

Bioengineering for Organ Transplantation: Progress and Challenges.

Organ transplantation can offer a curative option for patients with end stage organ failure. Unfortunately the treatment is severely limited by the availability of donor organs. Organ bioengineering could provide a solution to the worldwide critical organ shortage. The majority of protocols to date have employed the use of decellularization-recellularization technology of naturally occurring tissues and organs with promising results in heart, lung, liver, pancreas, intestine and kidney engineering. Successful decellularization has provided researchers with suitable scaffolds to attempt cell reseeding. Future work will need to focus on the optimization of organ specific recellularization techniques before organ bioengineering can become clinically translatable. This review will examine the current progress in organ bioengineering and highlight future challenges in the field.

Producción de órganos bioartificiales / Artificial organs production

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Whole-organ bioengineering: current tales of modern alchemy.

End-stage organ disease affects millions of people around the world, to whom organ transplantation is the only definitive cure available. However, persistent organ shortage and the resulting widespread transplant backlog are part of a disturbing reality and a common burden felt by thousands of patients on waiting lists in almost every country where organ transplants are performed. Several alternatives and potential solutions to this problem have been sought in past decades, but one seems particularly promising now: whole-organ bioengineering. This review describes briefly the evolution of organ transplantation and the development of decellularized organ scaffolds and their application to organ bioengineering. This modern alchemy of generating whole-organ scaffolds and recellularizing them with multiple cell types in perfusion bioreactors is paving the way for a new revolution in transplantation medicine. Furthermore, although the first generation of bioengineered organs still lacks true clinical value, it has created a number of novel tissue and organ model platforms with direct application in other areas of science (eg, developmental biology and stem cell biology, drug discovery, physiology and metabolism). In this review, we describe the current status and numerous applications of whole-organ bioengineering, focusing also on the multiple challenges that researchers have to overcome to translate these novel technologies fully into transplantation medicine.

The bioartificial kidney: current status and future promise.

The rapid understanding of the cellular and molecular bases of organ function and disease processes will be translated in the next decade into new therapeutic approaches to a wide range of clinical disorders, including acute and chronic renal failure. Central to these new therapies are the developing technologies of cell therapy and tissue engineering, which are based on the ability to expand stem or progenitor cells in tissue culture to perform differentiated tasks and to introduce these cells into the patient either via extracorporeal circuits or as implantable constructs. Cell therapy devices are currently being developed to replace the filtrative, metabolic, and endocrinologic functions of the kidney lost in both acute and chronic renal failure. This review summarizes the current state of development of a wearable or implantable bioartificial kidney. These devices have the promise to be combined to produce a wearable or implantable bioartificial kidney for full renal replacement therapy that may significantly diminish morbidity and mortality in patients with acute or chronic kidney disease.

Regeneration and bioengineering of the kidney: current status and future challenges.

The prevalence of chronic kidney disease continues to outpace the development of effective treatment strategies. For patients with advanced disease, renal replacement therapies approximate the filtration functions of the kidney at considerable cost and inconvenience, while failing to restore the resorptive and endocrine functions. Allogeneic transplantation remains the only restorative treatment, but donor shortage, surgical morbidity and the need for lifelong immunosuppression significantly limit clinical application. Emerging technologies in the fields of regenerative medicine and tissue engineering strive to address these limitations. We review recent advances in cell-based therapies, primordial allografts, bio-artificial organs and whole-organ bioengineering as they apply to renal regeneration. Collaborative efforts across these fields aim to produce a bioengineered kidney capable of restoring renal function in patients with end-stage disease.

The use of bioreactors as in vitro models in pharmaceutical research.

Bringing a new drug to market is costly in terms of capital and time investments, and any development issues encountered during late-stage clinical trials can often be the result of in vitro-in vivo extrapolations (IVIVE) not accurately reflecting clinical outcome. In the discipline of drug metabolism and pharmacokinetics (DMPK), current in vitro cellular methods do not provide the 3D structure and function of organs found in vivo; therefore, new dynamic methods need to be established to aid improvement of IVIVE. In this review, we highlight the importance of model progression into dynamic systems for use within drug development, focusing on devices developed currently in the areas of the liver and blood-brain barrier (BBB), and the potential to develop models for other organ systems, such as the kidney. We discuss the development of dynamic 3D bioreactor-based systems as in vitro models for use in DMPK studies.

Ingeniería tisular cardiaca y corazón bioartificial / Cardiac tissue engineering and the bioartificial heart

La insuficiencia cardiaca es la etapa final de muchas enfermedades cardiovasculares, como el infarto agudo de miocardio, y sigue siendo uno de los retos más atractivos para la medicina regenerativa debido a su alta incidencia y prevalencia. A lo largo de los últimos 20 años, la cardiomioplastia, basada en la administración aislada de células con capacidad regenerativa, ha focalizado la mayoría de estudios que han perseguido regenerar el corazón. No obstante, aunque esta terapia se ha mostrado factible en el ámbito clínico, el grado de regeneración del miocardio infartado y de mejoría de la función cardiaca es muy limitado. Ante tal escenario ha emergido la ingeniería tisular cardiaca como una novedosa tecnología basada en el uso de células con capacidad regenerativa, materiales biológicos y/o sintéticos, factores de crecimiento, diferenciación y proangiogénicos, y sistemas de registro online para inducir la regeneración de un órgano o tejido dañado. Un paso más, según algunos estudios pioneros realizados en animales, consiste en la generación de corazones bioartificiales de novo descelularizándolos y preservando sus estructuras de soporte para posteriormente repoblarlos con nuevo tejido muscular contráctil y vascular. Este nuevo abordaje comportaría, finalmente, el trasplante del corazón «reconstruido» restableciendo la función cardiaca del receptor (AU)

Heart failure is the end-stage of many cardiovascular diseases—such as acute myocardial infarction—and remains one of the most appealing challenges for regenerative medicine because of its high incidence and prevalence. Over the last 20 years, cardiomyoplasty, based on the isolated administration of cells with regenerative capacity, has been the focal point of most studies aimed at regenerating the heart. Although this therapy has proved feasible in the clinical setting, the degree of infarcted myocardium regenerated and of improved cardiac function are at best modest. Hence, tissue engineering has emerged as a novel technology using cells with regenerative capacity, biological and/or synthetic materials, growth, proangiogenic and differentiation factors, and online registry systems, to induce the regeneration of whole organs or locally damaged tissue. The next step, seen recently in pioneering animal studies, is de novo generation of bioartificial hearts by decellularization and preservation of supporting structures for their subsequent repopulation with new contractile, vascular muscle tissue. Ultimately, this new approach would entail transplantation of the “rebuilt” heart, reestablishing cardiac function in the recipient (AU)

Recent advances in electronic and bioelectronic noses and their biomedical applications.

Significant effort has been made in the development of an artificial nose system for various applications. Advances in sensor technology have facilitated the development of high-performance electronic and bioelectronic noses. Numerous articles describe the advantages of artificial nose systems for biomedical applications. Recent advances in the development of electronic and bioelectronic noses and their biomedical applications are reviewed in this article.

Ex situ bioengineering of bioartificial endocrine glands: a new frontier in regenerative medicine of soft tissue organs.

Ex situ bioengineering is one of the most promising perspectives in the field of regenerative medicine allowing for organ reconstruction outside the living body; i.e. on the laboratory bench. A number of hollow viscera of the cardiovascular, respiratory, genitourinary, and digestive systems have been successfully bioengineered ex situ, exploiting biocompatible scaffolds with a 3D morphology that recapitulates that of the native organ (organomorphic scaffold). In contrast, bioengineering of entire soft tissue organs and, in particular endocrine glands still remains a substantial challenge. Primary reasons are that no organomorphic scaffolding for endocrine viscera have as yet been entirely assembled using biocompatible materials, nor is there a bioreactor performance capable of supporting growth within the thickness range of the regenerating cell mass which has proven to be reliable enough to ensure formation of a complete macroscopic gland ex situ. Current technical options for reconstruction of endocrine viscera include either biocompatible 3D reticular scaffolds lacking any organomorphic geometry, or allogenic/xenogenic acellular 3D matrices derived from a gland similar to that to be bioengineered, eventually recellularized by autologous/heterologous cells. In 2007, our group designed, using biocompatible material, an organomorphic scaffold-bioreactor unit for bioengineering ex situ the human thyroid gland, chosen as a model for its simple anatomical organization (repetitive follicular cavities). This unit reproduces both the 3D native geometry of the human thyroid stromal/vascular scaffold, and the natural thyrocyte/vascular interface. It is now under intense investigation as an experimental tool to test cellular 3D auto-assembly of thyroid tissue and its related vascular system up to the ex situ generation of a 3D macroscopic thyroid gland. We believe that these studies will lay the groundwork for a new concept in regenerative medicine of soft tissue and endocrine organs; i.e. that the organomorphism of a biocompatible scaffold-bioreactor complex is essential to both the 3D organization of seeded stem cells/precursor cells and their phenotypic fate as glandular/parenchymal/vascular elements, eventually leading to a physiologically competent and immuno-tolerant bioconstruct, macroscopically suitable for transplantation and clinical applications.

Modularity in developmental biology and artificial organs: a missing concept in tissue engineering.

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.