Tissue engineering a fetal membrane

The aim of this study was to construct an artificial fetal membrane (FM) by combination of human amniotic epithelial stem cells (hAESCs) and a mechanically enhanced collagen scaffold containing encapsulated human amniotic stromal fibroblasts (hASFs). Such a tissue-engineered FM may have the potential to plug structural defects in the amniotic sac after antenatal interventions, or to prevent preterm premature rupture of the FM. The hAESCs and hASFs were isolated from human fetal amniotic membrane (AM). Magnetic cell sorting was used to enrich the hAESCs by positive ATP-binding cassette G2 selection. We investigated the use of a laminin/fibronectin (1:1)-coated compressed collagen gel as a novel scaffold to support the growth of hAESCs. A type I collagen gel was dehydrated to form a material mimicking the mechanical properties and ultra-structure of human AM. hAESCs successfully adhered to and formed a monolayer upon the biomimetic collagen scaffold. The resulting artificial membrane shared a high degree of similarity in cell morphology, protein expression profiles, and structure to normal fetal AM. This study provides the first line of evidence that a compacted collagen gel containing hASFs could adequately support hAESCs adhesion and differentiation to a degree that is comparable to the normal human fetal AM in terms of structure and maintenance of cell phenotype

A Tissue Engineering product development pathway

Tissue engineering is a field of inquiry and research that uses engineering techniques and principles of biological sciences to develop functional substitutes for reconstruction of damaged organs. Commercial translation of tissue engineering products is currently in progress all over the world. Many companies are moving their interest towards this market segment that grows by 6% per year. Aim of this thesis is to probe the possibility of developing tissue engineering products in the most cost-effective way, minimizing the industrial risk and developing a specific fund raising model. Tissue engineering is based on three main features: cells, scaffolds and bioreactors. Cells are seeded on a scaffold and cultured in a bioreactor in order to obtain a tissue engineering product. Nevertheless, developing cell carrying products is hampered by certification claims ("advanced therapies" certification rules) that unbearably increase R&D and certification costs and can be faced by either big companies or start-ups of big companies and spin-offs of complex aggregates of research centers involved in advanced cell research. On the other hand, scaffolds (certification class IIb) and bioreactors for tissue engineering (certification class I) can be developed with a lower economic effort, being the competition based on innovation, since their market is in the "growth phase" for scaffolds and in the "introduction phase" for bioreactors in the Levitt's product life cycle theory. Purpose of this thesis is to basically study scaffold and bioreactor features, then to preliminarily design some models of bioreactors and, eventually, to set a business model, based on private and public fund raising, aimed to the development of scaffolds for dental implantology and of bioreactors for cardiovascular and bone tissue engineering. Finally, a business plan of a company being spin-off of Politecnico di Torino and industrial start-up has been elaborate

Bioactive composites for bone tissue engineering

One of the major challenges of bone tissue engineering is the production of a suitable scaffold material. In this review the current composite materials options available are considered covering both the methods of both production and assessing the scaffolds. A range of production routes have been investigated ranging from the use of porogens to produce the porosity through to controlled deposition methods. The testing regimes have included mechanical testing of the materials produced through to in vivo testing of the scaffolds. While the ideal scaffold material has not yet been produced, progress is being made

Mathematical modelling of tissue-engineering angiogenesis

We present a mathematical model for the vascularisation of a porous scaffold following implantation in vivo. The model is given as a set of coupled non-linear ordinary differential equations (ODEs) which describe the evolution in time of the amounts of the different tissue constituents inside the scaffold. Bifurcation analyses reveal how the extent of scaffold vascularisation changes as a function of the parameter values. For example, it is shown how the loss of seeded cells arising from slow infiltration of vascular tissue can be overcome using a prevascularisation strategy consisting of seeding the scaffold with vascular cells. Using certain assumptions it is shown how the system can be simplified to one which is partially tractable and for which some analysis is given. Limited comparison is also given of the model solutions with experimental data from the chick chorioallantoic membrane (CAM) assay

Big bottlenecks in cardiovascular tissue engineering.

Although tissue engineering using human-induced pluripotent stem cells is a promising approach for treatment of cardiovascular diseases, some limiting factors include the survival, electrical integration, maturity, scalability, and immune response of three-dimensional (3D) engineered tissues. Here we discuss these important roadblocks facing the tissue engineering field and suggest potential approaches to overcome these challenges

Angiogenesis in tissue engineering : Breathing life into constructed tissue substitutes

Long-term function of three-dimensional (3D) tissue constructs depends on adequate vascularization after implantation. Accordingly, research in tissue engineering has focused on the analysis of angiogenesis. For this purpose, 2 sophisticated in vivo models (the chorioallantoic membrane and the dorsal skinfold chamber) have recently been introduced in tissue engineering research, allowing a more detailed analysis of angiogenic dysfunction and engraftment failure. To achieve vascularization of tissue constructs, several approaches are currently under investigation. These include the modification of biomaterial properties of scaffolds and the stimulation of blood vessel development and maturation by different growth factors using slow-release devices through pre-encapsulated microspheres. Moreover, new microvascular networks in tissue substitutes can be engineered by using endothelial cells and stem cells or by creating arteriovenous shunt loops. Nonetheless, the currently used techniques are not sufficient to induce the rapid vascularization necessary for an adequate cellular oxygen supply. Thus, future directions of research should focus on the creation of microvascular networks within 3D tissue constructs in vitro before implantation or by co-stimulation of angiogenesis and parenchymal cell proliferation to engineer the vascularized tissue substitute in situ

A mechanistic approach to design smart scaffolds for tissue engineering

This thesis describes a library of novel 3D scaffolds designed and optimized for tissue engineering and regenerative medicine applications. Tissue engineering aims at restoring or regenerating a deamaged tissue by combining cells, derived from a patient biopsy, with a 3D porous matrix, functioning as a scaffold. After isolation\ud and eventual in vitro expansion, cells are seeded on the 3D scaffolds and, depending on the strategy, implanted directly or at a later stage in the patient¿s body

Design and Fabrication of Three-Dimensional Scaffolds for Tissue Engineering of Human Heart Valves

We developed a new fabrication technique for 3-dimensional scaffolds for tissue engineering of human heart valve tissue. A human aortic homograft was scanned with an X-ray computer tomograph. The data derived from the X-ray computed tomogram were processed by a computer-aided design program to reconstruct a human heart valve 3-dimensionally. Based on this stereolithographic model, a silicone valve model resembling a human aortic valve was generated. By taking advantage of the thermoplastic properties of polyglycolic acid as scaffold material, we molded a 3-dimensional scaffold for tissue engineering of human heart valves. The valve scaffold showed a deviation of only +/- 3-4% in height, length and inner diameter compared with the homograft. The newly developed technique allows fabricating custom-made, patient-specific polymeric cardiovascular scaffolds for tissue engineering without requiring any suture materials. Copyright (c) 2008 S. Karger AG, Base