In-vitro-Herstellung von Knorpeltransplantaten zur Anwendung bei der laryngotrachealen Rekonstruktion im Tiermodell
Zusammenfassung der Projektergebnisse
Laryngotracheal and tracheal can be difficult to treat and in some cases a permanent tracheostoma is the only option. Engineered cartilage may have an answer to this problem. Scaffolds are commonly used for tissue engineering. In a rabbit model, nasal, tracheal, costal, articular and auricular chondrocyts were researched for its potential to form suitable cartilage implants for laryngotracheal reconstruction (LTR). Preliminary data have shown that articular and auricular chondrocytes had the highest capacity to form cartilage and were therefore used to study the effect of a various growth factors on expansion and redifferentiation. Auricular chondrocytes were used to generate cartilage implants for LTR in a rabbit model. Cells were seeded onto a hyaluronic acid based scaffold (Hyalograft C) and the cultured for 3weeks. Several weeks following LTR, a foreign body reaction, which was directed towards the scaffold material, lead to failure of all engineered implants. As a result, research was directed towards finding alternative ways to engineer cartilage to avoid an immune rejection of the implants. A novel strategy was developed in this laboratory, which allowed fabrication of large scaffold free cartilage sheets, which after further optimization, were used for fabrication of a neotracheal construct. Prefabrication techniques were used to generate a fully vascularised neotrachea in the abdomen of rabbits, which in regards to shape, size and mechanical properties was comparable to that of a native rabbit trachea. The long-term biocompatibility of the scaffold free implants was excellent with no notable immune rejection. Following the DFG funded research period, neotracheas have been used for segmental tracheal reconstruction in rabbits and proofed to have sufficient mechanical stability with good integration. Ongoing research is directed towards using human chondrocytes for generating scaffold free cartilage using our newly designed bioreactor system and growth factor conditions. These sheets will be used to generate neotracheal constructs with human-sized dimensions, which will be implanted in athymic rat hosts.
Projektbezogene Publikationen (Auswahl)
- Fabrication of a vascularised composite neotrachea in a rabbit model Midwest Tissue Engineering Consortium, Ann Arbor, MI (2007)
Weidenbecher M, Awadallah A, Dennis JE
- Hyaluronan-based scaffolds to tissue-engineer cartilage implants for laryngotracheal reconstruction. Laryngoscope. 2007 Oct;117(10):1745-9
Weidenbecher M, Henderson JH, Tucker HM, Baskin JZ, Awadallah A, Dennis JE
- Tissue engineered implants for laryngotracheal reconstruction using Hyalograft C: An animal study. 78th annual meeting of the German Association of Otorhinolaryngology, Munich, Germany (2007)
Weidenbecher M, Henderson JH, Tucker HM, Dennis JE
- Tissue engineering of cartilage implants for laryngotracheal reconstruction. Third Annual Resident, Research Day, Department of Otolaryngology - Head & Neck Surgery, Case Western Reserve University, Cleveland, OH (2007)
Weidenbecher M, Jarchow A, Dennis JE
- Fabrication of a neotrachea using engineered cartilage. Laryngoscope. 2008 Apr;118(4):593-8
Weidenbecher M, Tucker HM, Awadallah A, Dennis JE
- Fabrication of a tissue engineered neotrachea. 79th annual meeting of the German Association of Otorhinolaryngology, Bonn, Germany (2008)
Weidenbecher M, Tucker HM, Dennis JE
