Research Progress of Injectable Hydrogels Targeting Specific Pathogenesis for Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) remains a significant clinical challenge in orthopedics, characterized by the poor self-regenerative ability of necrotic bone tissue. Without timely and effective intervention, over 70% of affected patients will eventually suffer from femoral head collapse and require total hip arthroplasty(THA). ONFH arises from different pathways and causes, including traumatic vascular disruption and nontraumatic factors such as steroid-induced ONFH(SONFH) and alcohol-induced ONFH(AIONFH) . Based on these complex pathways, injectable hydrogels have emerged as a minimally invasive therapeutic option for targeted treatment. Herein, this review systematically assesses the strategically designed hydrogels targeting specific pathogenic pathways of ONFH to prevent structural collapse. This review mainly discusses the advantages of injectable hydrogel in stimulating angiogenesis and neovascularization to restore blood supply; facilitating anti-inflammatory modulation to foster a pro-regenerative microenvironment; enhancing bone mineralization through osteoconduction-osteoinduction mechanism; and regulating bone resorption. Additionally, it analyzes various injectabl hydrogel formulations for targeting distinct etiologies, along with their associated clinical studies, and offers recommendations for the future. This review establishes a targeted design for hydrogels that mimic ONFH pathological characteristics, providing a framework for developing effective, minimally invasive strategies that prevent or delay joint replacement.