Page 101 - Tailoring Electrospinning Techniques for Regenerative Medicine - Marc Simonet

Tissue engineering is an emerging interdisciplinary field, applying the principles and methods of engineering to the development of biological substitutes that can restore, maintain or improve tissue function.10 In the conventional tissue engineering paradigm, cells are isolated from the patient and expanded, subsequently seeded onto an appropriate sca old material, a er which the cells are stimulated to form tissue in bioreactor systems. These tissues can then be implanted into the patient from whom the cells were taken to serve as autologous living implants. The use of this paradigm to render living semilunar heart valve substitutes has been extensively studied using various cell sources and sca old materials. The most obvious choice for a heart valve sca old material is a homogra or xenogra depleted of cells, to render so-called decellularized matrices. Though these may provide the most natural template for valve remodeling and growth, homogra s are of limited availability, while xenogra s su er from the risk of zoonoses. In addition, successful ingrowth of cells and recapitulation of tissue growth and remodeling has not yet been proven in humans. The use of synthetic sca old materials represents a promising alternative approach, allowing the tissue to develop while the sca old degrades, without supply limitations and risk of zoonoses. Commonly used synthetic sca old materials for heart valve tissue engineering are poly(glycolic acid) (PGA), poly(lactic acid) (PLA), poly(4-hydroxybutyrate)
(P4HB), poly(hydroxyalkanoate) (PHA) and poly(hydroxyoctanoates) (PHO). The promise of
heart valve tissue engineering using synthetic
sca olds was demonstrated in sheep by replacement
of a single pulmonary valve leaflet with a tissue
engineered equivalent based on rapid degrading
synthetic sca olds.11,12 Later, full trileaflet valves
were fabricated based on rapid degrading synthetic
sca olds, which demonstrated remodeling potential
into native valve mimicking structures in sheep.13–16
Though the approach seems promising, it is obvious
that the remodeling initially occurs via thickening
of the engineered tissues.17 This thickening may be
a result of non-physiological valve characteristics
at the time of implantation and might benefit from improvements in sca old development to closer 5 mimic the native valve. Growth of tissue engineered
prostheses based on synthetic sca olds has been demonstrated for large blood vessel substitutes18 and should be further explored for tissue engineered heart valves.
To reduce mortality and morbidity risks with conventional heart valve replacement surgery, minimally invasive valve replacement techniques have rapidly evolved as an alternative treatment option.19,20 Feasibility of the use of tissue engineered heart valves based on rapid degrading synthetic sca olds integrated into self-expanding nitinol stents and implanted via a minimally invasive valve implantation technique was recently demonstrated in sheep.21
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