Abstract
Bone defects combined with tumors, infections, or other bone diseases are challenging in clinical practice. Autologous and allogeneic grafts are two main traditional remedies, but they can cause a series of complications. To address this problem, researchers have constructed various implantable biomaterials. However, the original pathological microenvironment of bone defects, such as residual tumors, severe infection, or other bone diseases, could further affect bone regeneration. Thus, the rational design of versatile biomaterials with integrated bone therapy and regeneration functions is in great demand. Many strategies have been applied to fabricate smart stimuli-responsive materials for bone therapy and regeneration, with stimuli related to external physical triggers or endogenous disease microenvironments or involving multiple integrated strategies. Typical external physical triggers include light irradiation, electric and magnetic fields, ultrasound, and mechanical stimuli. These stimuli can transform the internal atomic packing arrangements of materials and affect cell fate, thus enhancing bone tissue therapy and regeneration. In addition to the external stimuli-responsive strategy, some specific pathological microenvironments, such as excess reactive oxygen species and mild acidity in tumors, specific pH reduction and enzymes secreted by bacteria in severe infection, and electronegative potential in bone defect sites, could be used as biochemical triggers to activate bone disease therapy and bone regeneration. Herein, we summarize and discuss the rational construction of versatile biomaterials with bone therapeutic and regenerative functions. The specific mechanisms, clinical applications, and existing limitations of the newly designed biomaterials are also clarified.
Highlights
Severe infection, osteoporosis, osteonecrosis, and some congenital malformations can cause large bone defects, which remain challenging in clinical practice.[1]
Specific mild acidity in tumors,[23,24] specific pH reduction and enzymes secreted by bacteria in severe infection,[25,26,27] and electronegative potentials in bone defect sites.[28]
In contrast to photodynamic therapy (PDT), sonodynamic therapy (SDT) is initiated by ultrasound with a tissue penetration depth of over 10 cm, which has been widely applied in clinical practice for several years in ablating deepseated tumors.[62]
Summary
Severe infection, osteoporosis, osteonecrosis, and some congenital malformations can cause large bone defects, which remain challenging in clinical practice.[1]. In contrast to PDT, SDT is initiated by ultrasound with a tissue penetration depth of over 10 cm, which has been widely applied in clinical practice for several years in ablating deepseated tumors.[62] In addition to tumor ablation, ultrasound was proven to enhance bone regeneration since it could enhance the mRNA level of vascular endothelial growth factor A (VEGF-A) and stimulate cartilage cell proliferation, accelerating the maturation of newly formed bone and expediting cell mineralization.[63,64] With in-depth research, this technique was extended to the infection field for the clinical treatment of bone defects and severe bacterial infection.[27,31,65] Crasto et al.[66] fabricated novel liposome-rhBMP-2 nanocomplexes that can release rhBMP-2 after exposure to nonthermogenic clinical diagnostic ultrasound.
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