Suppression of adverse angiogenesis in an albumin-based hydrogel for articular cartilage and intervertebral disc regeneration.
An injectable polyethylene glycol-crosslinked albumin gel (AG) supplemented with hyaluronic acid as a matrix for autologous chondrocyte implantation was evaluated with regard to its impact on angiogenesis. Healthy articular cartilage and intervertebral discs (IVD) are devoid of blood vessels, whereas pathological blood vessel formation augments degeneration of both theses tissues. In contrast to human endothelial cells, primary human articular chondrocytes encapsulated in the AG retained their viability. Endothelial cells did not adhere to the gel surface to a significant extent nor did they proliferate in vitro. The AG did not release any diffusible toxic components. Contrary to Matrigel employed as positive control, the AG prevented endothelial chemoinvasion in Transwell filter assays even in the presence of a chemotactic gradient of vascular endothelial growth factor. In ovo, the AG exhibited a barrier function for blood vessels of the chick chorioallantoic membrane. Subcutaneous implantation of human IVD chondrocytes enclosed in the albumin gel into immunodeficient mice revealed a complete lack of angiogenesis inside the gel after two weeks. At the same time, the IVD chondrocytes within the gel remained vital and displayed a characteristic gene expression pattern as judged from aggrecan, collagen type I and type II mRNA levels. In summary, aiming at articular cartilage and IVD regeneration the albumin gel promises to be a beneficial implant matrix for chondrocytes simultaneously exhibiting non-permissive properties for adverse endothelial cells.
Scholz
B
B
NMI Natural and Medical Sciences Institute at the University of Tubingen, Markwiesenstrasse 55, D-72770 Reutlingen, Germany.
Kinzelmann
C
C
Benz
K
K
Mollenhauer
J
J
Wurst
H
H
Schlosshauer
B
B
D000368:Aged; D000418:Albumins / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000737:chemistry; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D018919:Neovascularization, Physiologic; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D012038:Regeneration
D000418:Albumins; D001672:Biocompatible Materials; D024042:Collagen Type I; D024043:Collagen Type II; D020100:Hydrogels; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid