Functional barrier principle for growth-factor-based articular cartilage repair.
OBJECTIVE
Induction of growth-factor-based repair in full-thickness articular cartilage defects can be impaired by the upgrowth of blood vessels and new bone into the cartilaginous compartment. We postulated that if an antiangiogenic factor (suramin) is included in the chondrogenic matrix applied to the cartilaginous compartment of a full-thickness defect, vascular upgrowth and therefore bone formation will be inhibited (functional barrier principle).


METHODS
Full-thickness defects were created in miniature pigs and the bony portion filled with a chondrogenic matrix. The cartilaginous compartment was filled with the same matrix which additionally contained suramin, either in a free form or in free and liposome-encapsulated forms. Animals were sacrificed 8 weeks after surgery and the extent to which bone tissue had encroached on the cartilaginous compartment was graded semiquantitatively using light microscopy.


RESULTS
In 63% of the control defects, bone represented more than 50% of the repair tissue present. In 10% of the defects treated with free suramin, bone upgrowth was completely inhibited; in 55%, osseous tissue occupied 1-10% of the cartilaginous space and in the other 35%, it represented 11-50% of the repair tissue present in this compartment. In 69% of the defects treated with free and liposome-encapsulated suramin, bone upgrowth into the cartilaginous compartment was completely inhibited; in the remaining 31%, osseous tissue occupied no more than 1-10% of this space.


CONCLUSIONS
To be effective, an antiangiogenic factor needs to be present at a sustained level throughout the chondrogenic treatment course.
Hunziker
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EB
ITI Research Institute for Dental and Skeletal Biology, University of Bern, Murtenstrasse 35, P.O. Box 54, CH-3010 Bern, Switzerland. ernst.hunziger@iti.unibe.ch
Driesang
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IM
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D002358:Cartilage, Articular / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries; D002455:Cell Division / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects; D020219:Chondrogenesis / Q000502:physiology*; D004195:Disease Models, Animal; D005780:Gelatin / Q000032:analysis / Q000494:pharmacology; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology; D008081:Liposomes; D009389:Neovascularization, Pathologic; D010012:Osteogenesis / Q000187:drug effects; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013498:Suramin / Q000008:administration & dosage* / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature / Q000502:physiology*
D020533:Angiogenesis Inhibitors; D006133:Growth Substances; D008081:Liposomes; D011506:Proteins; D013498:Suramin; D005780:Gelatin