Article
Treatment of cartilage defects by in vitro engineered autologous micro-tissue - A pilot animal study
Behandlung von Knorpeldefekten mittels in vitro hergestelltem autologem Knorpelgewebe - eine Pilottierstudie
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Authors
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J. Libera
- co.don AG, Dpt. Research & Development, Teltow, Germany
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A. Büchter
- Clinic for Cranio-Maxillofacial Surgery, University Hospital, Münster, Germany
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H.-P. Wiesmann
- Clinic for Cranio-Maxillofacial Surgery, University Hospital, Münster, Germany
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U. Meyer
- Clinic for Maxillofacial & Facial Plastic Surgery, University Hospital, Düsseldorf, Germany
| Published: | September 28, 2006 |
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Outline
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Advances in the understanding of in vitro cartilage formation are recently applied to improve tissue engineering strategies. In this pilot mini-pig study we tested feasibility, safety and a simple operative technique of/for transplantation of in vitro engineered autologous cartilaginous tissue as well as studied short time effects on cartilage regeneration in full thickness cartilage defects.
Autologous chondrocytes isolated from biopsies of the talocrural joint were multiplicated in culture and transferred into a 3D aggregate culture without using a scaffold and any growth factors. 4 mm cartilage defects were surgically introduced into the tibia-femoral joints of five minipigs. The in vitro formed tissue constructs were transplanted by simple dropping into three of the defects. Two defects without construct transplantation served as a control. After three months defects were analysed by gross pathology as well as histology and immunohistochemistry.
In vitro cultured chondrocytes using aggregate culture led to the formation of a micro-tissue containing chondrocytes in a self assembled cartilaginous extracellular matrix. Chondrocytes developed a speroidal solid micro-tissue with diameters around 600µm. Dropping of chondrocyte spheroids into the created cartilage defects lead to an adhesion of micro-tissues within 20 min avoiding any fixation of cartilage transplant. After a healing period of 3 months the gross pathological inspection of the treated defect areas demonstrated a defect filling and a well integrated repair tissue with no hypertrophy, whereas control defects showed irregular fibrous tissue formation and deformation of joint anatomy. The transplanted chondrospheres appeared to form hyaline cartilage as confirmed by histological and immunohistochemical analyses for SafraninO, collagen type I and II, and S100.
These results indicate that in vitro expanded articular chondrocytes are able to form a micro-tissue capable of repairing full thickness cartilage defects in vivo. The biologic process of transplant adhesion avoids any separate fixation and would allow an arthroscopic application of these autologous transplants. The pilot study revealed the feasibility and safety of the selected animal model, the operative technique and the autologous tissue transplant as well as revealed, even after a short follow up, the regenerative capacity of the presented in vitro engineered cartilaginous tissue. Within next studies, long-term efficiency will be evaluated.
