Optics-Free, In Situ Swelling Monitoring of Articular Cartilage with Graphene Strain Sensors.

Abstract

Articular cartilage derives its load-bearing strength from the mechanical and physiochemical coupling between the collagen network and negatively charged proteoglycans, respectively. Current disease modeling approaches and treatment strategies primarily focus on cartilage stiffness, partly because indentation tests are readily accessible. However, stiffness measurements via indentation alone cannot discriminate between proteoglycan degradation versus collagen degradation, and there is a lack of methods to monitor physiochemical contributors in full-stack tissue. To decouple these contributions, here, we developed a platform that measures tissue swelling in full-depth equine cartilage explants using piezoresistive graphene strain sensors. These piezoresistive strain sensors are embedded within an elastomer bulk and have sufficient sensitivity to resolve minute, real-time changes in swelling. By relying on simple DC resistance measurements over optical techniques, our platform can analyze multiple samples in parallel. Using these devices, we found that cartilage explants under enzymatic digestion showed distinctive swelling responses to a hypotonic challenge and established average equilibrium swelling strains in healthy cartilage (4.6%), cartilage with proteoglycan loss (0.5%), and in cartilage with both collagen and proteoglycan loss (-2.6%). Combined with histology, we decoupled the pathologic swelling responses as originating either from reduced fixed charge density or from loss of intrinsic stiffness of the collagen matrix in the superficial zone. By providing scalable and in situ monitoring of cartilage swelling, our platform could facilitate regenerative medicine approaches aimed at restoring osmotic function in osteoarthritic cartilage or could be used to validate physiologically relevant swelling behavior in synthetic hydrogels.