Collagen/glycosaminoglycan coatings enhance new bone formation in a critical size bone defect - A pilot study in rats

Bone regeneration in critical size bone defects still represents an important but unsolved clinical problem. Glycosaminoglycans (GAGs) like chondroitin sulfate (CS) or hyaluronan (HA) are important multifunctional components of the extracellular matrix (ECM) in bone and may stimulate bone healing by recruitment of mesenchymal stromal cells and by supporting their differentiation. Sulfation of GAGs affects their biological activity and thus their interactions with growth factors and/or cells involved in the bone healing process. The aim of this pilot study was to evaluate the osteogenic capacity of chemically high-sulfated chondroitin sulfate (sCS3) and hyaluronan (sHA3) with an average degree of sulfation DS≈3 on bone healing. Titanium-coated polyetheretherketone (Ti-PEEK) plates were coated with collagen type I (col), collagen-based artificial ECMs containing CS or HA and compared to col/sCS3 and col/sHA3 coatings bridging a critical size bone defect in rat femur. After 4weeks the gap size of 5.1mm±0.1mm following surgery was significantly reduced to 1.4mm±0.9mm for col/sHA3 and to 0.9mm±0.7mm for col/CS. The highest amount of newly formed bone was detected for col/CS (79%±30%) and col/sHA3 (36%±20%) compared to uncoated plates (13%±3%) or col-coated plates (18%±16%). Enchondral ossification could be confirmed for col/CS, col/HA, and col/sHA3 by positive staining for Alcian blue and collagen type II. These results suggest that an artificial ECM has osteogenic effects and is able to enhance bone healing in critical situations.