Umbilical cord cells as a source of cardiovascular tissue engineering

There is increasing scientific evidence that human umbilical cord cells are a valuable source of adult stem cells that can be used for various implications including regenerative medicine and tissue engineering. The review describes the role of progenitor cells (mesenchymal, endothelial, prenatal) for the use in cardiovascular tissue engineering, i.e., the formation of large vessels and heart valves from umbilical cord cells. Currently used replacements in cardiovascular surgery are made of foreign materials with well known drawbacks such as thrombo-embolic complications, infection, loss of functional and biological properties, and others. Especially in the field of replacements in congenital cardiac defects, there would be a need of materials which have the advantage of optimal biological and mechanical properties. In the case of human umbilical cord cells, autologous cells can be used by minimally invasive procedures. The cells have excellent growth capacities and form a neo-matrix with excellent mechanical properties. For optimal growth and modeling, scaffolds are required with high biocompatibility and biodegradability, which allow cell attachment, ingrowth, and organization. Nutrients and waste must be easily transported and cells should be in entire contact with host's body. Finally, regenerated materials can be fully incorporated and the scaffold is completely replaced. Besides these cell and scaffold requirements, feto-maternal conditions and risk factors concerning deriving stem cells are of major interest. There are still many open questions concerning whether and how maternal conditions such as infection (viral or bacterial) or gestational age of the newborn influence stem cell harvesting and quality. If these cells will be used for the construction of replacement materials, it is clear that very strict criteria and protocols be introduced enabling the promising step from isolated cells to a therapeutic device such as a new heart valve. It is hoped that it will be only a question of time until human umbilical cord cells will be used frequently as the source of cardiovascular tissues among others in the clinical setting of treating congenital heart defect

Quality Assurance in Biobanking for Pre-Clinical Research

It is estimated that not less than USD 28 billion are spent each year in the USA alone on irreproducible pre-clinical research, which is not only a fundamental loss of investment and resources but also a strong inhibitor of efficiency for upstream processes regarding the translation towards clinical applications and therapies. The issues and cost of irreproducibility has mainly been published on pre-clinical research. In contrast to pre-clinical research, test material is often being transferred into humans in clinical research. To protect treated human subjects and guarantee a defined quality standard in the field of clinical research, the manufacturing and processing infrastructures have to strictly follow and adhere to certain (inter-)national quality standards. It is assumed and suggested by the authors that by an implementation of certain quality standards within the area of pre-clinical research, billions of USD might be saved and the translation phase of promising pre-clinical results towards clinical applications may substantially be improved. In this review, we discuss how an implementation of a quality assurance (QA) management system might positively improve sample quality and sustainability within pre-clinically focused biobank infrastructures. Biobanks are frequently positioned at the very beginning of the biomedical research value chain, and, since almost every research material has been stored in a biobank during the investigated life cycle, biobanking seems to be of substantial importance from this perspective. The role model of a QA-regulated biobank structure can be found in biobanks within the context of clinical research organizations such as in regenerative medicine clusters

Tissue-engineered trachea: History, problems and the future

This review tries to summarize the efforts over the past 20 years to construct a tissue-engineered trachea. After illustrating the main technical bottlenecks faced nowadays, we discuss what might be the solutions to these bottlenecks. You may find out why the focus in this research field shifts dramatically from the construction of a tubular cartilage tissue to reepithelialization and revascularization of the prosthesis. In the end we propose a novel concept of ‘in vivo bioreactor', defined as the design of a perfusion system inside the scaffold, and explain its potential application in the construction of a tissue-engineered trache

Tissue engineering on matrix: future of autologous tissue replacement

Tissue engineering aims at the creation of living neo-tissues identical or close to their native human counterparts. As basis of this approach, temporary biodegradable supporter matrices are fabricated in the shape of a desired construct, which promote tissue strength and provide functionality until sufficient neo-tissue is formed. Besides fully synthetic polymer-based scaffolds, decellularized biological tissue of xenogenic or homogenic origin can be used. In a second step, these scaffolds are seeded with autologous cells attaching to the scaffold microstructure. In order to promote neo-tissue formation and maturation, the seeded scaffolds are exposed to different forms of stimulation. In cardiovascular tissue engineering, this "conditioning” can be achieved via culture media and biomimetic in vitro exposure, e.g., using flow bioreactors. This aims at adequate cellular differentiation, proliferation, and extracellular matrix production to form a living tissue called the construct. These living autologous constructs, such as heart valves or vascular grafts, are created in vitro, comprising a viable interstitium with repair and remodeling capabilities already prior to implantation. In situ further in vivo remodeling is intended to recapitulate physiological vascular architecture and function. The remodeling mechanisms were shown to be dominated by monocytic infiltration and chemotactic host-cell attraction leading into a multifaceted inflammatory process and neo-tissue formation. Key molecules of these processes can be integrated into the scaffold matrix to direct cell and tissue fate in viv

Tissue Engineering of Human Heart Valve Leaflets: A Novel Bioreactor for a Strain-Based Conditioning Approach

Current mechanical conditioning approaches for heart valve tissue engineering concentrate on mimicking the opening and closing behavior of the leaflets, either or not in combination with tissue straining. This study describes a novel approach by mimicking only the diastolic phase of the cardiac cycle, resulting in tissue straining. A novel, yet simplified, bioreactor system was developed for this purpose by applying a dynamic pressure difference over a closed tissue engineered valve, thereby inducing dynamic strains within the leaflets. Besides the use of dynamic strains, the developing leaflet tissues were exposed to prestrain induced by the use of a stented geometry. To demonstrate the feasibility of this strain-based conditioning approach, human heart valve leaflets were engineered and their mechanial behavior evaluated. The actual dynamic strain magnitude in the leaflets over time was estimated using numerical analyses. Preliminary results showed superior tissue formation and non-linear tissue-like mechanical properties in the strained valves when compared to non-loaded tissue strips. In conclusion, the strain-based conditioning approach, using both prestrain and dynamic strains, offers new possibilities for bioreactor design and optimization of tissue properties towards a tissue-engineered aortic human heart valve replacemen