Abstract
Osteochondral defects in joints require surgical intervention to relieve pain and restore function. However, no current treatment enables a complete reconstitution of the articular surface. It is known that both mechanical and biological factors play a key role on osteochondral defect healing, however the underlying principles and how they can be used in the design of treatment strategies remain largely unknown. To unravel the underlying principles of mechanobiology in osteochondral defect healing, i.e., how mechanical stimuli can guide biological tissue formation, we employed a computational approach investigating the scaffold-associated mechanical and architectural properties that would enable a guided defect healing. A previous computer model of the knee joint was further developed to simulate healing of an empty osteochondral defect. Then, scaffolds were implanted in the defect and their architectures and material properties were systematically varied to identify their relevance in osteochondral defect healing. Scaffold mechanical and architectural properties were capable of influencing osteochondral defect healing. Specifically, scaffold material elastic modulus values in the range of cancellous bone (low GPa range) and a scaffold architecture that provided stability, i.e., resistance against displacement, in both the main loading direction and perpendicular to it supported the repair process. The here presented model, despite its simplifications, is regarded as a powerful tool to screen for promising properties of novel scaffold candidates fostering osteochondral defect regeneration prior to their implementation in vivo.
Highlights
Articular cartilage is a connective tissue found in joints, where it enables low-friction relative movements between bones (Kheir and Shaw, 2009)
Prediction of tissue formation based on the mechanical stimulus (S) showed that the mechanical environment at early time points favored the formation of cartilage in the defect, with traces of fibrous tissue confined to areas neighboring the cartilage-subchondral bone interface (Figure 4B)
After 20 days, a region with mechanical stimulus favorable to fibrous tissue formation, with thickness comparable to the healthy cartilage, was predicted to form at the articular interface. This layer of fibrous tissue, the peripheral part of the defect experienced a mechanical environment that fostered the formation of bone, while a region favorable to bone resorption was predicted in the central part. This situation was maintained until the completion of the repair process (50 days), with the region favorable to bone resorption only partially substituted by a region where the mechanical stimulus promoted bone formation and a very small region favorable to cartilage formation located between fibrous tissue and an underlying bone resorption area
Summary
Articular cartilage is a connective tissue found in joints, where it enables low-friction relative movements between bones (Kheir and Shaw, 2009). Despite the better biological potential of tissue engineering or other restorative strategies, no present clinical treatment enables a full restoration of intact articular interfaces. Some of these strategies are even associated with substantial drawbacks, such as the need for multiple surgeries (Nukavarapu and Dorcemus, 2013) or the triggering of further tissue degeneration in areas of the joint far from the original defect (Hunziker et al, 2015)
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