Contrast-enhanced computed tomography is an emerging diagnostic technique for osteoarthritis. However, the effects of increased water content, as well as decreased collagen and proteoglycan concentrations due to cartilage degeneration, on the diffusion of cationic and nonionic agents, are not fully understood. We hypothesize that for a cationic agent, these variations increase the diffusion rate while decreasing partition, whereas, for a nonionic agent, these changes increase both the rate of diffusion and partition. Thus, we examine the diffusion of cationic and nonionic contrast agents within degraded tissue in time- and depth-dependent manners. Osteochondral plugs (N = 15, d = 8 mm) were extracted from human cadaver knee joints, immersed in a mixture of cationic CA4+ and nonionic gadoteridol contrast agents, and imaged at multiple time-points, using the dual-contrast method. Water content, and collagen and proteoglycan concentrations were determined using lyophilization, infrared spectroscopy, and digital densitometry, respectively. Superficial to mid (0%-60% depth) cartilage CA4+ partitions correlated with water content (R < −0.521, P <.05), whereas in deeper (40%-100%) cartilage, CA4+ correlated only with proteoglycans (R > 0.671, P <.01). Gadoteridol partition correlated inversely with collagen concentration (0%-100%, R < −0.514, P <.05). Cartilage degeneration substantially increased the time for CA4+ compared with healthy tissue (248 ± 171 vs 175 ± 95 minute) to reach the bone-cartilage interface, whereas for gadoteridol the time (111 ± 63 vs 179 ± 163 minute) decreased. The work clarifies the diffusion mechanisms of two different contrast agents and presents depth and time-dependent effects resulting from articular cartilage constituents. The results will inform the development of new contrast agents and optimal timing between agent administration and joint imaging.

The unprecedented properties of meta-biomaterials could pave the way for the development of life-lasting orthopedic implants. Here, we used non-auxetic meta-biomaterials to address the shortcomings of the current treatment options in acetabular revision surgery. Due to the severe bone deficiencies and poor bone quality, it can be very challenging to acquire adequate initial implant stability and long-term fixation. More advanced treatments, such as patient-specific implants, do guarantee the initial stability, but are formidably expensive and may eventually fail due to stress shielding. We, therefore, developed meta-implants furnished with a deformable porous outer layer. Upon implantation, this layer plastically deforms into the defects, thereby improving the initial stability and homogeneously stimulating the surrounding bone. We first studied the space-filling behavior of additively manufactured pure titanium lattices, based on six different unit cells, in a compression test complemented with full-field strain measurements. The diamond, body-centered cubic, and rhombic dodecahedron unit cells were eventually selected for the design of the deformable porous outer layer. Each design came in three different relative density profiles, namely maximum (MAX), functionally graded (FG), and minimum (MIN). After their compression in bone-mimicking molds with simulated acetabular defects, the space-filling behavior of the implants was evaluated using load-displacement curves, micro-CT images, and 3D reconstructions. The meta-implants with an FG diamond infill exhibited the most promising space-filling behavior. However, the required push-in forces exceed the impact forces currently applied in surgery. Future research should, therefore, focus on design optimization, to improve the space-filling behavior and to facilitate the implantation process for orthopedic surgeons. Statement of significance: Ideally, orthopedic implants would last for the entire lifetime of the patient. Unfortunately, they rarely do. Critically sized defects are a common sight in the revision of acetabular cups, and rather difficult to treat. The permanent deformation of lattice structures can be used to create shape-morphing implants that would fill up the defect site, and thereby restore the physiological loading conditions. Bending-dominated structures were incorporated in the porous outer layer of the space-filling meta-implants for their considerable lateral expansion in response to axial compression. A functionally graded density offered structural integrity at the joint while enhancing the deformability at the bone-implant interface. With the use of a more ductile metal, CP-Ti, these meta-implants could be deformed without strut failure.

Recent insights suggest that the osteochondral interface plays a central role in maintaining healthy articulating joints. Uncovering the underlying transport mechanisms is key to the understanding of the cross-talk between articular cartilage and subchondral bone. Here, we describe the mechanisms that facilitate transport at the osteochondral interface. Using scanning electron microscopy (SEM), we found a continuous transition of mineralization architecture from the non-calcified cartilage towards the calcified cartilage. This refurbishes the classical picture of the so-called tidemark; a well-defined discontinuity at the osteochondral interface. Using focused-ion-beam SEM (FIB-SEM) on one osteochondral plug derived from a human cadaveric knee, we elucidated that the pore structure gradually varies from the calcified cartilage towards the subchondral bone plate. We identified nano-pores with radius of 10.71 ± 6.45 nm in calcified cartilage to 39.1 ± 26.17 nm in the subchondral bone plate. The extracted pore sizes were used to construct 3D pore-scale numerical models to explore the effect of pore sizes and connectivity among different pores. Results indicated that connectivity of nano-pores in calcified cartilage is highly compromised compared to the subchondral bone plate. Flow simulations showed a permeability decrease by about 2000-fold and solute transport simulations using a tracer (iodixanol, 1.5 kDa with a free diffusivity of 2.5 × 10⁻¹⁰ m²/s) showed diffusivity decrease by a factor of 1.5. Taken together, architecture of the nano-pores and the complex mineralization pattern in the osteochondral interface considerably impacts the cross-talk between cartilage and bone.

Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P <.05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent.