Int J Artif Organs 2017; 40(4): 133 - 135
Article Type: EDITORIAL
- • Accepted on 18/04/2017
- • Published in print on 09/05/2017
- • Available online on 10/05/2017
This article is available as full text PDF.
In the coming years, due to the aging of the population and the low availability of donor organs, there will be an urgent need for bioengineering solutions to assist, mimic or replace failing patient organs. These solutions can be offered by developing artificial or bioartificial organs as well as tissue-engineered organs.
Artificial organs are based on biomaterials and novel designs. Typical examples of these are artificial kidney devices for better and more continuous patient treatment (1-2-3-4) or artificial liver devices for blood detoxification (5-6-7).
Bioartificial organs combine biomaterials and biological cells. Typical examples include bioartificial kidney devices combining biomaterials and kidney epithelial cells for improved blood detoxification (8-9-10) or bioartificial pancreas devices for the treatment of diabetes (11).
Significant efforts have also been focused on constructing tissue-engineered organs as alternatives to direct transplantation of donor organs (12-13-14). An important component of these is the scaffold, a 3-dimensional (3D) construct that serves as a temporary support for isolated cells to grow into new tissue before they are transplanted back to the host tissue.
In these fields of research, the scientific and technological challenges are big. There is a need for new biomaterials, for better understanding and tailoring of the biomaterial–cell/tissue interaction, for better immune protection and mass transfer, as well as for the development of new concepts and designs. The complexity increases from artificial organs to bioartificial organs to tissue-engineered organs, and the engineering and regulatory demands are very high. In my opinion, to achieve significant advancements in this field engineering must be integrated with biology and medicine. Major advancements can only be achieved as a result of collaborative efforts with partners from a range of disciplines that provide a wide spectrum of different kinds of expertise. To stimulate this, in 2016 the European Society of Artificial organs (ESAO), established a new working group on “Bioartificial organs.” The group includes experts from all these disciplines and focuses on organizing symposia at various international conferences, training events for young researchers entering the field, as well as outreach activities to promote the field to a broad audience (see). This special issue also aims to highlight some important, recent developments in the field by bringing together some significant contributions.
Summary of contents
This issue contains two important contributions on bioartificial organs: one study on a bioartificial liver and one on a pancreas. Figaro et al focus on optimizing the fluidized bed bioreactor as an external bioartificial liver (15). The team had previously designed and validated a new bioartificial liver (BAL) based on a Prismaflex™ device, including fluidized bed bioreactors hosting alginate-encapsulated hepatocytes. In this contribution, they assess the impact of the bead production process, the bed fluidization, mass transfer and the bead mechanical properties on the cell viability and basic metabolic function. Based on their results, and the constraints of all the extracorporeal circulation (plasma flow rate, thermal exchange), a concentration of 2 mg (1% v/v) of microspheres for 15-20 million cells per milliliter of alginate solution appears to be the best configuration. The filling ratio for the beads in the bioreactors could reach 60%. Four 250-mL bioreactors represent approximately 15% of the hepatocytes in a liver, which is a reasonable target for extracorporeal liver supply.
Long et al focus on co-microencapsulation of bone marrow mesenchymal stem cells and mouse pancreatic β cells to treat diabetic mice (16). They found out that after 28 days of in vitro culture, the secretion of insulin following co-microencapsulation is higher than that observed for microencapsulated beta-TC-6 cells alone. On the 28th day after transplantation, the blood glucose level reach 6.86 mmol/L in the microencapsulated beta-TC-6 group. On the 14th day, the blood glucose level was 6.80 mmol/L in the co-microencapsulated BMSC/beta-TC-6 group, which is close to the normal blood glucose level of healthy mice. Their study indicates that combining microencapsulation technology and co-culture of stem cells and somatic cells has promise for the treatment of type I diabetes mellitus.
In this focus issue, one contribution on tissue engineering focuses on the effects of macroporous scaffold geometry on cell culture parameters, two others focus on scaffold development, and another on a translational animal model for evaluating tissue-engineered heart valves.
Eghbali et al uses a perfused bioreactor hosting a poly(ε-caprolactone) macroporous scaffold to investigate transport phenomena and culture parameters on cell growth (17). They actually set up an in silico multiphysics numerical model to study the fluid dynamics and the mass transport of the nutrients in the bioreactor. Their results show that the system can be a robust reference to systematically investigate and assess crucial culture parameters.
Alarake et al focus on the development of in situ cross-linking, cytocompatible, gelatin hydrogels by the use of transglutaminase as a cross-linker for potential application in the regeneration of tissues (18). They report that transglutaminase cross-linked gelatin hydrogels might be suitable as injectable hydrogels for engineering of musculoskeletal and other types of connective tissues.
Güney et al develop triblock copolymers based on ε-caprolactone and trimethylene carbonate for the 3D printing of tissue-engineering scaffolds (19). These block copolymers combine the low Glass Transition Temperature (GTT) of amorphous PTMC (approximately 20°C) and the semi-crystallinity of PCL (GTT approximately -60°C; melting temperature approximately 60°C). From these materials, porous structures are prepared by 3D printing using ethylene carbonate as crystalizable and water-extractable solvent. The rate of cooling is used for tailoring the pore size to the structures.
One of the recently developed techniques for tissue engineering involves decellularization of animal organs. The remaining scaffold, consisting of an extracellular matrix (ECM) of structural proteins such as collagen and elastin, growth factors, and glycosaminoglycans, can be re-populated with (autologous) cells, aiming at growing ex vivo a fully transplantable organ (20-21-22). In this special issue, two papers are focused on this technique.
Hussein et al review the cross-linking methods (including different cross-linking agents and methods of evaluation of cross-linking efficiency) to avoid enzymatic biodegradation of the organ in the host (23). The most important characteristic of the cross-linkers should be nontoxicity and ability to preserve the ECM components, especially glycosaminoglycans and associated growth factors for retention of scaffold bioactivity. Cross-linking reduces antigenicity and increases the storage properties. Fedecostante et al focus on the decellularization of the kidney with emphasis on scaffold decontamination (24). They also discuss critical aspects such as cell types and sources that can be used for recellularization, seeding strategies and possible applications beyond renal replacement.
Finally, Gallo et al review studies using a Vietnamese pig as animal model for tissue-engineered heart valves and provide a complete and exhaustive panel of physiological parameters and methodological information for related preclinical studies (25).
- Stamatialis, Dimitrios [PubMed] [Google Scholar] , * Corresponding Author (email@example.com)
Bioartificial Organs Group, Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede - The Netherlands