Osteoporotic bone defect (OBD) is a serious bone defect resulting from the disruption of the bone structural integrity due to fractures in osteoporotic conditions. OBD not only leads to increased risk of fractures, delayed bone healing, functional loss, and chronic pain, but also reduces patients′ quality of life and even elevates the risk of death. Currently, OBD is primarily treated with systemic medications and local bone grafting. However, drug therapy is often associated with serious side effects, low bioavailability and poor bone targeting performance, while bone grafting is limited by high infection rate in donor areas, scarce bone source and severe immune rejection. Therefore, there is an urgent need for new bone repair materials to improve the bone microenvironment and stimulate bone regeneration. Bioactive molecules have shown great potential in modulating OBD treatment, but their application in organisms is hindered by their low bioavailability and short half-life. Hydrogels have emerged as an ideal vehicle to address these limitations by prolonging the retention time and half-life of bioactive molecules at the site of injury, reducing side effects and promoting cell adhesion under physiological conditions. All these advantages promote osteoblast proliferation and differentiation, providing a promising solution for OBD treatment. However, hydrogels still face challenges such as uncontrolled degradation rate, inadequate mechanical properties and poor osseointegration ability. To this end, the authors systematically elucidated the challenges of hydrogels in OBD treatment and proposed countermeasures, aiming to provide a reference for the research and clinical application of hydrogels.

Osteoporotic bone defect (OBD) is a serious bone defect resulting from the disruption of the bone structural integrity due to fractures in osteoporotic conditions. OBD not only leads to increased risk of fractures, delayed bone healing, functional loss, and chronic pain, but also reduces patients′ quality of life and even elevates the risk of death. Currently, OBD is primarily treated with systemic medications and local bone grafting. However, drug therapy is often associated with serious side effects, low bioavailability and poor bone targeting performance, while bone grafting is limited by high infection rate in donor areas, scarce bone source and severe immune rejection. Therefore, there is an urgent need for new bone repair materials to improve the bone microenvironment and stimulate bone regeneration. Bioactive molecules have shown great potential in modulating OBD treatment, but their application in organisms is hindered by their low bioavailability and short half-life. Hydrogels have emerged as an ideal vehicle to address these limitations by prolonging the retention time and half-life of bioactive molecules at the site of injury, reducing side effects and promoting cell adhesion under physiological conditions. All these advantages promote osteoblast proliferation and differentiation, providing a promising solution for OBD treatment. However, hydrogels still face challenges such as uncontrolled degradation rate, inadequate mechanical properties and poor osseointegration ability. To this end, the authors systematically elucidated the challenges of hydrogels in OBD treatment and proposed countermeasures, aiming to provide a reference for the research and clinical application of hydrogels.