Osteoarthritis is a common form of arthritis that affects 100 million individuals in the world today. As the disease progresses, lesions within the cartilage grow and eventually the subchondral bone is exposed. This degeneration of articular cartilage leads to a loss of mobility, severe and debilitating pain, and a reduction in the overall quality of life for the patients. Depending on the severity of the disease, the current clinical treatments include the chronic use of anti-inflammatory drugs, abrasion, mosaicoplasty, microfracture surgery, or chondrocyte transplantation. The last resort for OA patients is total joint replacement, but this treatment is costly and traumatic. Yet, these approaches have had varied successes due to the lack of a vascular and lymphatic system hindering the regenerative capacity of native cartilage. Consequently, there is significant clinical interest in creating a therapy based on tissue-engineering principles to restore function to the damaged cartilage tissue site.
Given our interest in dendritic macromers and hydrogels, we evaluated the photocrosslinkable derivatives of the poly(glycerol-succinic acid)-polyethylene glycol dendritic –linear copolymers (PGLSA-OH)2-PEG as scaffolds for cartilage tissue engineering. Chondrocyte -hydrogel constructs were prepared, and it was found that the 7.5 wt% hydrogel scaffolds were supportive of significant cartilaginous extracellular matrix synthesis. However, this hydrogel quickly degraded. In order to slow the degradation rate of the hydrogel scaffold but still retain the favorable characteristics of the 7.5 wt% hydrogel scaffold in terms of matrix accumulation, we prepared a new macromer which contained ester as well as carbamate linkages. Specifically, we prepared a first generation dendritic macromolecule composed of glycerol, succinic acid, ß-alanine, and poly(ethylene glycol) using a divergent method as shown in in the figure. The hydrogels displayed a range of mechanical properties based on their structure, generation size and concentration in solution. All of the hydrogels showed minimal swelling characteristics. The dendrimer solutions were then photo-crosslinked in situ in an ex vivo rabbit osteochondral defect (3 mm diameter and 10 mm depth), and the resulting hydrogels were subjected to physiologically relevant dynamic loads. Magnetic resonance imaging (MRI) showed the hydrogels to be fixated in the defect site after the repetitive loading regimen. The ([G1]-PGLBA-MA)2-PEG hydrogel was chosen for the 6 month pilot in vivo rabbit study because this hydrogel scaffold could be prepared at low polymer weight (10wt%) and possessed the largest compressive modulus of the 10% formulations, a low swelling ratio, and contained carbamate linkages which are more hydrolytically stable than the ester linkages. The hydrogel treated osteochondral defects showed good attachment in the defect site and histological analysis showed the presence of collagen II and glycosaminoglycans (GAGs) in the treated defects. By contrast, the contralateral unfilled defects showed poor healing and negligible GAG or collagen II production. Good mechanical properties, low swelling, good attachment to the defect site, and positive in vivo results illustrate the potential of these dendrimer-based hydrogels as scaffolds for osteochondral defect repair