Abstract
Background: Osteochondral defects (OCD) can affect the articular cartilage and subchondral bone tissues, which requires superior therapies for the simultaneous and full restoration of such structurally and biologically different tissues. Methods: Tissue engineered OC grafts were prepared using a horseradish peroxidase (HRP) approach to crosslink silk fibroin (HRP-SF) as the articular cartilage-like layer and an underlying HRP-SF/ZnSrTCP subchondral bone-like layer (HRP-SF/dTCP), through salt-leaching/freeze-drying methodologies. In vivo OC regeneration was assessed by implantating the hierarchical scaffolds in rabbit critical size OC defects, during 8 weeks. A comparative analysis was performed using hierarchical OC grafts made of pure β-TCP (HRP-SF/TCP). Results: The hierarchical scaffolds showed good integration into the host tissue and no signs of acute inflammatory reaction, after 8 weeks of implantation. The histological analyses revealed positive collagen type II and glycosaminoglycans’ formation in the articular cartilage-like layer. New bone ingrowth’s and blood vessels infiltration were detected in the subchondral bone-like layers. Conclusions: The proposed hierarchical scaffolds presented an adequate in vivo response with cartilage tissue regeneration and calcified tissue formation specially promoted by the ionic incorporation into the subchondral bone layer, confirming the hierarchical structures as suitable for OCD regeneration.
Highlights
Orthopedic surgeons have been facing major limitations in the development of personalized therapies to treat and regenerate osteochondral defects (OCD)
The proposed hierarchical scaffolds presented an adequate in vivo response with cartilage tissue regeneration and calcified tissue formation specially promoted by the ionic incorporation into the subchondral bone layer, confirming the hierarchical structures as suitable for Osteochondral defects (OCD) regeneration
From the 3D reconstructions it is not distinguishable if the calcified component belongs to the tricalcium phosphate (TCP) in the scaffolds or to the calcified tissue in the new bone, based on the scanning parameters chosen for these assays and on the calcified component identified in the native subchondral bone tissue of the rabbit models, we believe that a high amount of the detected Calcium phosphates (CaPs) may came from the newly formed subchondral bone
Summary
Orthopedic surgeons have been facing major limitations in the development of personalized therapies to treat and regenerate osteochondral defects (OCD) These pathologies can simultaneously affect the articular cartilage and the subchondral bone, which implies advanced technological solutions to ensure the complete restoration of the two different tissues [1]. The development of more complex and stratified heterogeneous structures was recognized as a better solution to treat OCD considering its hierarchical structure that contain specific mechanical properties and biological composition from the top articular cartilage layer to the underlying subchondral bone layer Another important consideration for scaffolds design relies in the interface region between the articular cartilage and subchondral bone, called as calcified cartilage [8].
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