About the project
The clinical therapies currently available for bone tissue regeneration are based on the use of autologous or heterologous demineralized bone or bone substitutes, although these approaches have several drawbacks. Autologous bone is scarcely available due to the lack of donor sites and its harvesting often requires painful invasive surgery. On the other hand, transplant from a donor can be rejected and expose the patient to infective pathogens. Therefore, for the reconstruction of bone defects, a great benefit could be achieved from alternative sources and, in particular, from engineered constructs that can be integrated into the surrounding tissues.
To obtain a bone-engineered tissue, scaffolds should meet a number of essential requirements, and of primary importance is the presence of interconnected porosity, with pores of adequate size to allow chemotaxis, cell proliferation and differentiation. The use of synthetic or natural polymers for bone regeneration is extremely appealing in the clinical field, since they can be easily fabricated into three-dimensional (3-D) structures that fit well the defect size, presenting a large surface for cell adhesion and migration, and a controlled porosity that allows for an adequate diffusion of nutrients and waste products. Among the natural polymers, the most frequently used for tissue regeneration are alginate, collagen, hyaluronic acid and gelatin, while synthetic biodegradable polymers for bone tissue regeneration include poly(α-hydroxyesters), polydioxanone, polyorthoesters, polyanhydrides and some polyurethanes. However, an adequate balance between in vivo scaffold degradation and tissue regeneration is not easily achievable, because of a number of different variables that may occur in clinical conditions, such as the geometry of the bone defect to be filled, the different volumes of the material required and the functional loading, which affects bone apposition and remodeling. Therefore, biointegration is an appealing alternative to biodegradation, and it can be achieved by use of polymeric scaffolds with a very slow degradation rate, that can be designed to fulfill all the requirements of the specific application. Following this approach, scaffolds could be used effectively when there is a need to substitute bone defects, preventing tissue collapse and sustaining newly forming tissue. In this respect, the range of mechanical and morphological properties that can be obtained with polyurethanes (PU) is significantly larger than with commonly used medical-grade biodegradable polymers. In the last 10 years we have set up a process to obtain crosslinked PU foams with slow degradation rate and with a controlled range of pore size, open porosity and mechanical properties. PU foams with different hydrophilicity, surface-modified by a protein coating, and composites have also been developed and characterized.
Concerning the cells, stem cells will undoubtedly play a key role in the development of such strategies, due to their ability to differentiate into multiple cell phenotypes. Adult stem cells, in particular, have attracted considerable research interest because they pose few ethical dilemmas and limitations in terms of availability, in comparison to embryonic stem cells. Among them, mesenchymal stromal cells (MSCs) are particularly appealing because of their demonstrated tolerogenic properties and differentiation potential into osteoblasts, chondrocytes, myocytes, tenocytes, adipocytes and endothelial cells; in addition, they have been widely investigated in musculo-skeletal tissue regeneration. MSCs have been isolated from several tissues, including bone marrow (BM), umbilical cord blood peripheral blood and adipose tissue. While MSCs isolated from these tissues appear promising for clinical applications , in some cases limitations exist in terms of access to, and use of these sources. In particular, the procedures required to obtain the tissues for the isolation of the cells may be invasive, the cells number obtained can be low, and the differentiation potential may be dependent on the age of the donor . In this perspective, the attention of the researchers has been turned to the human term placenta as possible source of progenitor/stem cells . The fact that placental tissues originate during the first stages of embryological development supports the possibility that these tissues may contain cells which have retained the plasticity of the early embryonic cells. Furthermore, as the placenta is generally discarded after birth, it is available in large supply, the isolation of cells from this tissue does not involve any invasive procedure for the donor, and their use does not pose any ethical problem . These aspects make cells isolated from the fetal membranes of the placenta, in particular from amniotic and chorionic membranes, good candidates for possible use in cell therapy and tissue engineering approaches, with the possibility of providing cells that are capable of differentiating into multiple different cell types, and which also display immunological properties that would allow their use in an allo-transplantation setting.
The project was initiated in 2005 and has been funded by UiO, the Bavarian Research Fund combined with industrial collaboration with MediGlobe Gmbh, Achenmühle, Germany, and also by the Italian Institute of Technology.
- Julia Will, PhD, Universität Erlangen, Institute of Glass and Ceramics, Department of Materials Science and Engineering, University of Erlangen-Nürnberg,
Henkestr. 91, D-91052 Erlangen, Germany
- Prof. Dr. med. Dr.-Ing. habil. Erich Wintermantel,Lehrstuhl für Medizintechnik, Fakultät Maschinenwesen, Technische Universität München,
Gebäude 4, Boltzmannstrasse 15 , D-85748 Garching,
- Timothy Douglas, PhD, UMC Medical Centre Nijmegen,
- Serena Bertoldi, PhDBiomaterials Laboratory, Bioengineering Department, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133, Milan, Italy. Tools