Perspectives on engineering organs in vitro: overcoming oxygen supply limitations (original) (raw)

Tissue Engineering: A Boon to Tissue Regeneration

Inventi Rapid: Pharm Biotech & Microbio, 2018

The artificial generation of tissues, organs or even more complex living organisms was throughout the history of mankind a matter of myth and dream. During the last decades this vision became feasible and has been recently introduced in clinical medicine. Tissue engineering and regenerative medicine are terms in biomedical field that deal with the transformations. Tissue Engineering (TE) is a scientific field mainly focused on the development of tissue and organ substitutes by controlling biological, biophysical and/or biomechanical parameters in the laboratory. This results in elaboration of threedimensional cellular constructs with properties more similar to natural tissues than classical monolayer cultures. These systems enable the in-vitro study of human physiology and physiopathology more accurately, while providing a set of biomedical tools with potential applicability in toxicology, medical devices, tissue replacement, repair and regeneration. To succeed in these purposes, TE uses nature as an inspiration source for the generation of extracellular matrix analogues (scaffolds), either from natural or synthetic origin as well as bioreactors and bio-devices to mimic natural physiological conditions of particular tissues. These scaffolds embed cells in a three dimensional milieu that display signals critical for the determination of cellular fate, in terms of proliferation, differentiation and migration, among others. The aim of this review is to analyze the state of the art of TE and some of its application fields.

Challenges in tissue engineering

Journal of The Royal Society Interface - J R SOC INTERFACE, 2006

Almost 30 years have passed since a term 'tissue engineering' was created to represent a new concept that focuses on regeneration of neotissues from cells with the support of biomaterials and growth factors. This interdisciplinary engineering has attracted much attention as a new therapeutic means that may overcome the drawbacks involved in the current artificial organs and organ transplantation that have been also aiming at replacing lost or severely damaged tissues or organs. However, the tissues regenerated by this tissue engineering and widely applied to patients are still very limited, including skin, bone, cartilage, capillary and periodontal tissues. What are the reasons for such slow advances in clinical applications of tissue engineering? This article gives the brief overview on the current tissue engineering, covering the fundamentals and applications. The fundamentals of tissue engineering involve the cell sources, scaffolds for cell expansion and differentiation and carriers for growth factors. Animal and human trials are the major part of the applications. Based on these results, some critical problems to be resolved for the advances of tissue engineering are addressed from the engineering point of view, emphasizing the close collaboration between medical doctors and biomaterials scientists.

Tissue Engineering; Current Status & Futuristic Scope

Journal of Medicine and Life, 2019

Almost 30 years have passed since the term ‘tissue engineering’ was created to represent a new concept that focuses on the regeneration of neotissues from cells with the support of biomaterials and growth factors. This interdisciplinary engineering has attracted much attention as a new therapeutic means that may overcome the drawbacks involved in the current artificial organs and organ transplantation that have also been aiming at replacing lost or severely damaged tissues or organs. However, the tissues regenerated by tissue engineering and widely applied to patients are still minimal, including skin, bone, cartilage, capillary, and periodontal tissues. What are the reasons for such slow advances in clinical applications of tissue engineering? This article gives a brief overview of the current state of tissue engineering, covering the fundamentals and applications. The fundamentals of tissue engineering involve cell sources, scaffolds for cell expansion and differentiation, as well...

Biological and synthetic scaffold: an extra cellular matrix for constructive tissue engineering

International Journal of Medical Research and Review, 2016

Worldwide many people suffering from tissue dysfunctions or damages need rapid transplantation. Tissue engineering has attracted attention as therapeutic modality aiming at repairing lost or damaged tissues. Critical step in tissue engineering is fabrication of three dimensional scaffolds which mimic the extracellular matrix of tissues and promote tissue regeneration process. Extensive research has been carried out to develop a compatible scaffold which mimic the anatomical site of injury and as well as accessing the stem cells and growth factors to home on the injured site. The present article provides an overview on different scaffold approaches and materials used to fabricate scaffolds, with their properties and associated advantages and disadvantages. In particular, the therapeutic potential of amniotic membrane and collagen scaffold has been extensively reviewed in here.

From In Vitro to In Situ Tissue Engineering

2014

In vitro tissue engineering enables the fabrication of functional tissues for tissue replacement. In addition, it allows us to build useful physiological and pathological models for mechanistic studies. However, the translation of in vitro tissue engineering into clinical therapies presents a number of technical and regulatory challenges. It is possible to circumvent the complexity of developing functional tissues in vitro by taking an in situ tissue engineering approach that uses the body as a native bioreactor to regenerate tissues. This approach harnesses the innate regenerative potential of the body and directs the appropriate cells to the site of injury. This review surveys the biomaterial-, cell-, and chemical factor-based strategies to engineer tissue in vitro and in situ.

Biomaterials for Organ and Tissue Regeneration

2020

The ultimate goal of tissue engineering (TE) studies is to construct fully functional three-dimensional (3D) artificial tissues and organs by using a combination of cells, biomaterials, and signaling factors [1,2]. These signaling factors include biochemical ones, such as serum proteins, growth factors, and cytokines; physicochemical ones such as O 2 tension, pH, and CO 2 concentration; as well as physical ones such as mechanical cues, electromagnetic environment, and temperature. The main challenge that has kept tissue-engineered constructs (TECs) from being widely adopted to clinics is poor cell survival due to lack of proper vascularization and resulting poor integration in vivo for clinically relevant, thick constructs [3,4]. In static culture, mass transport of oxygen and nutrients, as well as removal of waste and metabolites, depends solely on passive diffusion. Depending on the cell type and the diffusivity properties of the scaffold, the diffusion for cell survival is limited to 100À200 μm distance [5], which is approximately the same size of the in vivo vascular network mesh that ensures the viability of our tissues [6]. Therefore maintenance of 3D, clinically relevant sizes of TECs, requires dynamic culture that introduces convection and perfusion, in addition to diffusion into the culture system. TE bioreactors are the keys to translate lab-grown constructs to clinically relevant, large scale, viable, and financially plausible tissues and organs by providing proper mass transport, as well as a strictly controlled culture environment for several important variables such as culture media contents, temperature, oxygen tension, and pH. A more recent, and possibly shorter term attainable role attributed to TE is the production of in vitro disease models that can serve to further improve our understanding of the cellular mechanisms of several diseases, as well as the effects of certain parameters (such as stress factors or environmental variables) on disease progression [7À9]. These models are extremely useful for developing novel therapeutic approaches, performing high-throughput preclinical drug screening, as well as personalizing treatment options by precision medicine approach [10,11]. These in vitro disease models also serve the purpose of reducing animal testing in consideration of the three Rs (reduction, refinement, and replacement) [12,13]. Biomaterials for Organ and Tissue Regeneration.

Biomaterials for Tissue Engineering

Advanced Engineering Materials, 2007

Biomaterials for the permanent replacement of lost tissue have offered a number of solutions for compelling clinical problems of the muscoskeletal system. But the limitations of the artificial replacement of a living tissue by a non living material are numerous, e.g. stress-shielding, allergic reactions, wear particles and chronic inflammatory reactions. No permanent device can substitute the full function of a lost tissue. The next step towards a reconstruction of a lost tissue function is the regeneration of the lost tissue in vitro with a subsequent implantation or, even better, the in vivo processed regeneration without any in vitro step. Both methods: tissue engineering (in vitro) or tissue regeneration (in vivo) need a biomaterial as a framework for single cells to build a vital and well functioning tissue. The challenge for the tissue engineering process is to find the best combination of cells, growth factors, culture conditions and biomaterials for a precise clinical problem. Many biomaterials used for tissue engineering purposes imitate in their composition and/or structure the native and physiological conditions for the tissue specific cells. These aspects are called biomimetic and they are enabled by means of nano(bio)technological methods. Biomaterials for tissue engineering applications are used in the form of carriers, hydrogels, vlies or scaffolds. Carrier materials enable adherent tissue constituents (e.g. cells or chondrons) the production of an extracellular matrix that embeds the tissue components in a as native tissue without any potentially marring framework substance. Hydrogels are water swell able highly negatively loaded polymers with a well defined pore size that allows diffusion of gas and nutrition to support and sustain the embedded cells (that reconstruct the tissue). Scaffolds are porous analogues of the extracelluar matrix of the tissue that has to be regenerated. These material forms serve as a delivery vehicle for the cells that reconstruct the lost tissue in the body. All of these materials and constructs serve as cell environment that has to establish optimal conditions for the proliferation and-as the more difficult step-the redifferentiation of the desired tissue cells. This paper will provide a survey about common characteristics of biomaterials that are used for regenerative medicine and tissue engineering applications. An overview over the current research prospects and the most promising future trends in the optimization of biomaterials for tissue engineering applications is given.

Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

Frontiers in bioengineering and biotechnology, 2017

In the tissue engineering (TE) paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D) microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D) models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the "3Rs" guiding principles for a more ethical resea...