Injectable hydrogels in bone tissue engineering: from bench to bedside

Abstract

Abstract Large segmental bone defects resulting from trauma, tumor resection, infection, or congenital abnormalities often exceed the innate regenerative capacity of bone, necessitating effective therapeutic strategies. Conventional treatments, such as autografts and allografts, are associated with significant limitations, including donor site morbidity, immunogenicity, limited availability, and risk of disease transmission. Bone tissue engineering (BTE) has emerged as a promising alternative, integrating scaffolds, bioactive molecules, and stem cells to promote bone regeneration. Among various scaffold systems, injectable hydrogels have gained considerable attention due to their excellent biocompatibility, adaptability to irregular defect sites, and tunable physicochemical properties. These hydrogels provide a three-dimensional, biomimetic microenvironment that is conducive to cellular adhesion, proliferation, differentiation, and tissue integration. Moreover, their ability to encapsulate and deliver therapeutic agents and stem cells in a controlled and localized manner further enhances their regenerative potential. Recent advancements, including the incorporation of bioactive nanoparticles, osteoinductive factors, and the development of smart, stimuli-responsive, and self-healing systems, have significantly expanded the functional capabilities of injectable hydrogels in bone repair. This review provides a comprehensive overview of recent progress in the design and application of injectable hydrogels for bone tissue engineering, with a focus on material innovations, gelation mechanisms, and biological performance. Graphical AbstractInfographic on injectable hydrogels for bone tissue engineering, covering clinical needs, benefits, composition, mechanisms, and clinical translation.This infographic presents a detailed exploration of injectable hydrogels for bone tissue engineering. It highlights unmet clinical needs such as critical-sized bone defects and the limitations of conventional therapies. The concept of injectable hydrogels is illustrated with a syringe injecting a liquid precursor, which gels to form a scaffold. Key benefits are shown, including minimally invasive procedures and controlled delivery. The composition of hydrogels is categorized into natural, synthetic, and composite types. Advanced innovations like bioactive nanoparticles and self-healing properties are discussed. A mechanism of action section outlines steps from a 3D microenvironment to new bone formation. Finally, a section on clinical translation details the pathway from lab studies to successful patient applications.