Total hip replacement (THR) is highly successful in restoring mobility after hip fracture, yet long-term complications such as aseptic loosening, periprosthetic fracture, wear-induced osteolysis, and stress shielding continue to limit implant longevity. These failure modes largely originate from the inability of monolithic implant designs to satisfy the heterogeneous mechanical and biological requirements of the proximal femur. Their uniform material properties and fixed architecture hinder physiological load transfer, compromise osseointegration, and accelerate bone loss. Functionally graded hip scaffold–implant hybrids (FG-HSIHs) have emerged as a promising next-generation solution, offering spatial control over stiffness, porosity, degradation behavior, and surface bioactivity within a single construct to better mimic the structure and function of healthy bone. This review synthesizes advances in clinical understanding, biomechanics, mechanobiology, and computational modeling relevant to the development of FG-HSIHs. We first examine the biological pathways and biomechanical mechanisms underlying major THR complications, highlighting the inherent conflicts among desired material and structural properties. These mechanistic insights form the basis for simulation-guided strategies that enable spatially adaptive design tailored to mitigate specific failure risks. We then evaluate current progress in mechanical modeling, mechanobiological simulation, multiphysics analysis, and multi-objective optimization, and assess how these components contribute to an integrated design workflow. Despite rapid progress, no existing framework fully unifies mechanical, biological, transport, and degradation processes or incorporates patient-specific biological factors. Key challenges remain in defining physiologically grounded grading targets, establishing predictive validation pipelines, and implementing multiphysics-driven design tools suitable for translational use. Overall, the purpose of this review is to assemble a coherent, field-wide perspective on the clinical, biomechanical, biological, and computational considerations relevant to FG-HSIH design, rather than cataloging all technical details. The framework presented in this review provides a structured pathway for translating functionally graded hip scaffold–implant hybrids from concept to clinically testable prototypes. By linking THR failure mechanisms with biomechanical requirements, biological pathways, and computational design strategies, the review identifies actionable targets for implant innovation and preclinical development. The synthesis of mechanical modeling, mechanobiology, and multiphysics optimization offers a roadmap for generating designs that more effectively integrate with host bone and reduce long-term revision risk. The identified translational gaps—including the lack of integrated mechanobiological–degradation models, limited patient-specific biological inputs, and insufficient validation pipelines—clarify priorities for future experimental studies, preclinical testing protocols, and multidisciplinary collaboration. Collectively, these insights support the development of next-generation hip implants that can improve long-term patient outcomes and reduce the burden of revision surgery.
Luo et al. (Fri,) studied this question.