The osteochondral interface (OCI) is a structurally and functionally complex tissue whose degeneration or injury often results in poor healing and joint dysfunction due to its avascular and hypocellular nature. Conventional surgical treatments remain suboptimal, prompting growing interest in regenerative approaches, particularly with the utilization of hydrogel-based biomaterials that can mimic the extracellular matrix and support osteochondral regeneration. This study reviewed types of hydrogels, scaffold processing techniques, and animal models for OCI regeneration. Our search demonstrated that gelatin, alginate, chitosan, and hyaluronic acid were the most frequently investigated hydrogels. Layered constructs dominated current scaffold designs, while advanced methods such as 3D printing and extrusion demonstrated unique potential to create graded architectures resembling the native OCI. Rabbits were the most widely used in vivo models, though translation will require larger animal studies with clinically relevant defect sizes. Future efforts should focus on developing mechanically reinforced, biologically active, and continuously graded hydrogels, supported by standardized preclinical validation in large-animal models, to accelerate translation toward clinical solutions for osteochondral regeneration.
Bone exhibits hierarchical structural gradients that optimize mechanical performance and regenerative potential. Longitudinal and radial variations in cortical porosity and canal architecture influence load distribution, vascularization, and remodeling. Understanding these gradients is essential for designing scaffolds and implants that mimic native bone structure and function. This study quantified longitudinal and radial microgradients in cortical porosity and canal diameter along the rabbit femur and explored their implications for bone regeneration and repair implant design. Rabbit femora were divided into proximal, mid-shaft, and distal regions. High-resolution micro-computed tomography quantified cortical thickness, porosity, and canal diameter along radial and longitudinal axes in micron-scale resolutions. Compressive mechanical testing of cortical slices determined local moduli, which were correlated with microstructural parameters to establish structure-function relationships. Cortical thickness peaked at the mid-shaft and decreased toward both ends. Porosity and canal diameter increased radially toward the medullary cavity and longitudinally toward the bone ends. Upto 500 micron cortical thickness from the outer surface toward modullary cavity, porosity and canal diameter ranged, respectively, from ~5% and 40 micron at the mid-shaft to ~40% and 110 micron at the ends. At 750 micron cortical thickness, porosity and canal diameter ranged, respectively, from ~5% and 50 micron at the mid-shaft to ~80% and 200 micron at the ends. As expected, compressive moduli declined linearly with increasing porosity and canal size. The mid-shaft, with the lowest porosity and smallest canals, exhibited the highest modulus of around 15MPa, which decreased to 5MPa toward the ends. The rabbit femur displays distinct longitudinal and radial microgradients in porosity and canal architecture that govern local stiffness. These gradients define structural benchmarks for designing functionally graded tissue engineering scaffolds and bone implants that replicate native tissue structure and stiffness transitions to promote osteoconduction, osteoinduction, osteogenesis in bone regeneration and improve osseointegration of bone implants.