Articular cartilage is crucial in human physiology, and its degeneration poses a significant public health challenge. While recent advancements in 3D bioprinting and tissue engineering show promise for cartilage regeneration, there remains a gap between research findings and clinical application. This review critically examines the mechanical and biological properties of hyaline cartilage, along with current 3D manufacturing methods and analysis techniques. Moreover, we provide a quantitative synthesis of bioink properties used in cartilage tissue engineering. After screening 181 initial works, 33 studies using extrusion bioprinting were analyzed and synthesized, presenting results that indicate the main materials, cells, and methods utilized for mechanical and biological evaluation. Altogether, this review motivates the standardization of mechanical analyses and biomaterial assessments of 3D bioprinted constructs to clarify their chondrogenic potential.

Articular cartilage morphology and composition are essential factors in joint biomechanics, and their alteration is a crucial aspect of osteoarthritis (OA), a prevalent disease that causes pain and functional loss. This research focuses on developing patient-specific synthetic cartilage using innovative Digital Anatomy polymers. The objectives include investigating the morphology, characterizing the mechanical properties, and replicating the architecture of natural cartilage. This approach offers potential alternatives to traditional manufacturing methods and reduces the need for expensive in vivo experiments. Finite Element Analysis (FEA) validates a novel patient-specific measurement setup. It provides insights into the role of morphology in the distribution of stress and strain within cartilage. CAD design is also utilized to create standardized fiber-reinforced samples that mimic the layered micro-architecture of natural cartilage, allowing for the study of their contribution to the overall mechanical properties. The results demonstrate that 3D-printed polymers can effectively replicate the elastic properties of cartilage. The proposed patient-specific simulator produces reliable results, which have been validated through FEM analysis. While the recreated microstructure closely resembles biological cartilage samples, the elastic properties are slightly underestimated. In conclusion, designing an in silico knee joint is a feasible approach that offers numerous advantages for further development. The Young’s modulus values of our synthetic cartilage modules range from $2.43$ MPa to $7.24$ MPa, within the range reported in the literature. Moreover, Young´s modulus at the micro level shows the differences between surface $1.74$ MPa and internal substrate $1.83$ MPa depending on the fiber orientation. Finally, our model proves to be mechanically and morphologically accurate at both the macro and micro levels.

Articular cartilage degeneration poses a significant public health challenge; techniques such as 3D bioprinting are being explored for its regeneration in vitro. Gelatin-based hydrogels represent one of the most promising biopolymers used in cartilage tissue engineering, especially for its collagen composition and tunable mechanical properties. However, there are no standard protocols that define process parameters such as the crosslinking method to apply. To this aim, a reproducible study was conducted for exploring the influence of different crosslinking methods on 3D bioprinted gelatin structures. This study assessed mechanical properties and cell viability in relation to various crosslinking techniques, revealing promising results particularly for dual (photo + ionic) crosslinking methods, which achieved high cell viability and tunable stiffness. These findings offer new insights into the effects of crosslinking methods on 3D bioprinted gelatin for cartilage applications. For example, ionic and photo-crosslinking methods provide softer materials, with photo-crosslinking supporting cell stretching and diffusion, while ionic crosslinking preserves a spherical stem cell morphology. On the other hand, dual crosslinking provides a stiffer, optimized solution for creating stable cartilage-like constructs. The results of this study offer a new perspective on the standardization of gelatin for cartilage bioprinting, bridging the gap between research and clinical applications.

Tissue-engineered bone tissue grafts are a promising alternative to the more conventional use of natural donor bone grafts. However, choosing an appropriate biomaterial/scaffold to sustain cell survival, proliferation, and differentiation in a 3D environment remains one of the most critical issues in this domain. Recently, chitosan/gelatin/genipin (CGG) hybrid scaffolds have been proven as a more suitable environment to induce osteogenic commitment in undifferentiated cells when doped with graphene oxide (GO). Some concern is, however, raised towards the use of graphene and graphene-related material in medical applications. The purpose of this work was thus to check if the osteogenic potential of CGG scaffolds without added GO could be increased by improving the medium diffusion in a 3D culture of differentiating cells. To this aim, the level of extracellular matrix (ECM) mineralization was evaluated in human bone-marrow-derived stem cell (hBMSC)-seeded 3D CGG scaffolds upon culture under a perfusion flow in a dedicated custom-made bioreactor system. One week after initiating dynamic culture, histological/histochemical evaluations of CGG scaffolds were carried out to analyze the early osteogenic commitment of the culture. The analyses show the enhanced ECM mineralization of the 3D perfused culture compared to the static counterpart. The results of this investigation reveal a new perspective on more efficient clinical applications of CGG scaffolds without added GO.

Background and Clinical Significance: Sarcopenia, characterized by muscle loss and fat infiltration, poses a significant health burden for aging populations. Quantitative Color 2D and 3D radiodensitometry provides a powerful tool to monitor muscle quality and quantity through CT imaging. This study assessed the impact of a ten-year-long home-bed gym exercise intervention on muscle quality in an elderly subject using CT-derived radiodensitometric analysis. The study involved two comparative analyses: Study A, which compared knee-to-ankle CT scans of the subject between 2013 and 2023; and Study B, which compared the subject’s 2023 thigh CT scan with a cohort of 2500 elderly Icelandic individuals from the AGES-Reykjavik study. Case Presentation: A 70-year-old male began a home-based Full-Body In-Bed Gym exercise program in 2013. Quantitative muscle volume and radiodensity measurements were performed using CT at baseline and after ten years. Results: Study A shows significant improvements in muscle volume observed in the knee-to-ankle region, while a slower decline in radiodensity was noted, indicating substantial preservation of muscle quality despite the expected decay of ten-year aging. For instance, muscle volume increased by 15% in the left Soleus muscle and by 6% in the right Soleus muscle, while the average radiodensity decreased by 12–17 HU. The subject’s thigh muscle quality at 80-years-old is above the AGES-Reykjavik’s cohort average, with reduced fat infiltration. Conclusions: Long-term home Full-Body In-Bed Gym, a low-impact exercise, can mitigate aging sarcopenia, as evidenced by improved tissue radiodensity and muscle mass substantial preservation. This suggests potential applications in personalized healthcare strategies to enhance muscle preservation among aging populations.

Platelet-derived products are increasingly investigated for cartilage regeneration because of their high content of bioactive factors. While rapid clearance after direct injection has been partly addressed by hydrogel encapsulation, many platelet-enriched hydrogels still rely on variably processed platelet derivatives, leaving challenges in standardization and storage stability. Here, we developed a gelatin-based hydrogel enriched with lyophilized, pathogen-inactivated human platelet lysate (L-PIPL) as an off-the-shelf platelet-derived reservoir for localized delivery of chondrogenic cues. L-PIPL was produced from expired pathogen-inactivated platelet units by freeze–thaw lysis and lyophilization, then incorporated into a gelatin-based hydrogel at 5, 10, and 15% (w/v). Composite hydrogels were characterized by scanning electron microscopy (SEM), attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), rheology, transforming growth factor beta 1 (TGF- β 1) release, and soluble protein analysis. Cytocompatibility and early chondrogenic response were assessed in extruded, crosslinked cell-laden constructs using C20A4 chondrocytes and adipose-derived mesenchymal stromal cells (AD-MSCs). L-PIPL preserved the core hydrogel chemistry while modulating microarchitecture and viscoelastic properties. Moderate enrichment, particularly 5%–10% (w/v), maintained gel-like behavior and cytocompatibility, whereas 15% L-PIPL reduced network stability and cell viability. Release of bioactive factors was dose-dependent, with an initial burst followed by slower release over time. In AD-MSC-laden constructs, L-PIPL increased metabolic activity, with the 10% formulation showing the highest activity, and the 5% formulation showing the most favorable early chondrogenic commitment. L-PIPL-enriched hydrogels provide a standardized, cytocompatible, and bioactive matrix for localized delivery of platelet-derived factors. Overall, 5% L-PIPL emerged as the most promising formulation for further development in cartilage tissue engineering.