Tissue Engineering von Knorpelersatzgewebe – Mechanische Stimulation in der In-vitro-Kultivierung von humanen Chondrozyten

Zusammenfassung

Die Behandlung von Knorpeldefekten stellt noch immer ein großes Problem in der Orthopädie dar. Eine vielversprechende Alternative zu konventionellen Methoden ist die Reimplantierung von in vitro vorkultivierten Chondrozyten im Rahmen des Tissue Engineering von Knorpel. Die bei diesen Verfahren verwendeten zellbesiedelten Biomaterialien können durch mechanische Stimulation in ihren Regenerateigenschaften verbessert werden. Eine Modulation der Chondrozytenfunktion und dadurch der biologischen und biomechanischen Eigenschaften des Knorpelersatzgewebes lässt sich durch Scher-, Perfusions-, hydrostatische Druck- und direkte Krafteinleitungssysteme erzielen, die beispielhaft und primär in ihren biologischen Auswirkungen vorgestellt werden. Vor dem Hintergrund der trotz günstiger Voraussetzungen und aussichtsreicher Ansätze bisher noch nicht gelungenen In-vitro-Kultivierung von mechanisch und biologisch vollwertigem funktionellem Knorpelersatz werden die Grundlagen, Ergebnisse, Chancen und Probleme der jeweiligen Kultivierungsmodalität beleuchtet und zukünftige Ansätze vorgestellt.

Abstract

The treatment of cartilage defects remains a major problem in orthopaedics. With regard to cartilage tissue engineering, the reimplantation of pre-cultivated chondrocytes in the form of a chondrocyte graft is a promising alternative to conventional methods. Clinical practice requires this MACT procedure (matrix-associated autologous chondrocyte transplantation) to produce a biocompatible replacement tissue with adequate mechanical properties. Mechanical stimulation has the capacity to improve the quality of these cell-seeded biomaterials. By altering chondrocytes' cellular activities, the biological and biomechanical properties of cartilage replacement tissue can be modulated. Different systems are used for this purpose, e.g. shear, perfusion, hydrostatic pressure or compression. The mechanisms, biological effects, chances and problems of the techniques are presented and assessed. Among the stimulating techniques considered are systems that apply indirect and direct shear forces such as spinner flasks, rotating-wall bioreactors, direct tissue shear and perfusion culture systems. The application of hydrostatic pressure or compression may be brought about by either static or dynamic loading systems. Compressive loading is considered in the light of both its short- and long-term effects; additionally two exemplified systems are discussed in detail. However, despite promising approaches and seemingly favourable tissue characteristics, the in vitro culturing of functional cartilage replacement tissue with cartilage-like mechanical and biological characteristics still remains elusive. Furthermore, controlling, monitoring and regulating culturing conditions are general biotechnological requirements of a standardised in vitro cultivation. Among these, different aspects such as aseptic operation, media supplementation, nutrient and gas exchange, temperature and humidity control are considered.

Schlüsselwörter

Tissue Engineering von Gelenkknorpel - zellbesiedelte Matrix - Bioreaktorsystem - Knorpelregeneratgewebe - zyklische Kompression

Key words

tissue engineering of articular cartilage - cell‐seeded scaffold - bioreactor - cartilage replacement tissue - dynamic loading

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