Recent advances in hydrogel-based 3D-printed bioinks for bone regeneration and potential applications in osteoporosis

Osteoporosis is a systemic skeletal disease characterized by impairment of bone remodeling, reduced bone strength, and fragility fractures. Despite active exploration of hydrogel-enabled 3D printing and bioprinting as tools for engineering bone tissue, the therapeutic implications for osteoporosis are still debated since most of the available data derive from general bone defect and osteochondral repair models. The purpose of this review is to discuss the role of bone remodeling in osteoporosis and analyse recent advances in hydrogel-based 3D-printed bioinks for bone regeneration. Particular attention is paid to their material composition and printability, mechanical properties, crosslinking strategies, biological performance, and ability to deliver a therapeutically relevant payload. The reviewed studies are classified according to the applied model and divided into general bone regeneration, osteoporosis-related bone-defect repair, localized therapy, and systemically active treatment. The limitations in terms of mechanical properties, vascularization, biodegradation, biosafety, and the lack of relevant in vivo preclinical models are discussed. This review aims to highlight the opportunities of hydrogel-based 3D-printed constructs for the regeneration and local or systemic treatment of osteoporotic bone while emphasizing the need for disease-specific and clinically relevant approaches.