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Patients with diabetes mellitus (DM) suffer from a high risk of fractures and poor bone healing ability. Surprisingly, no effective therapy is available to treat diabetic bone defect in clinic. Here, a 3D printed enzyme‐functionalized scaffold with multiple bioactivities including osteogenesis, angiogenesis, and anti‐inflammation in diabetic conditions is proposed. The as‐prepared multifunctional scaffold is constituted with alginate, glucose oxidase (GOx), and catalase‐assisted biomineralized calcium phosphate nanosheets (CaP@CAT NSs). The GOx inside scaffolds can alleviate the hyperglycemia environment by catalyzing glucose and oxygen into gluconic acid and hydrogen peroxide (H2O2). Both the generated H2O2 as well as the overproduced H2O2 in DM can be scavenged by CaP@CAT NSs, while the initiated hypoxic microenvironment stimulates neovascularization. Moreover, the incorporation of CaP@CAT NSs not only enhance the mechanical property of the scaffolds, but also facilitate bone regeneration by the degraded Ca2+ and PO43− ions. The remarkable in vitro and in vivo outcomes demonstrate that enzymes functionalized scaffolds can be an effective strategy for enhancing bone tissue regeneration in diabetic conditions, underpinning the potential of multifunctional scaffolds for diabetic bone regeneration. [ABSTRACT FROM AUTHOR]

Various bifunctional scaffolds have recently been developed to address the reconstruction of tumor‐initiated bone defects. Such scaffolds are usually composed of a near‐infrared (NIR) photothermal conversion agent and a conventional bone scaffold for photothermal therapy (PTT) and long‐term bone regeneration. However, the reported photothermal conversion agents are mainly restricted to the first biological window (NIR‐I) with intrinsic poor tissue penetration depth. Also, most of these agents are non‐bioactive materials, which induced potential systemic side toxicity after implantation. Herein, a NIR‐II photothermal conversion agent (Wesselsite [SrCuSi4O10] nanosheets, SC NSs) with tremendous osteogenic and angiogenic bioactivity, is rationally integrated with polycaprolactone (PCL) via 3D printing. The as‐designed 3D composite scaffolds not only trigger osteosarcoma ablation through NIR‐II light generated extensive hyperthermia, but also promote in vitro cellular proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs), respectively, and the ultimate enhancement of vascularized bone regeneration in vivo owing to the controlled and sustained release of bioactive ions (Sr, Cu, and Si). The authors' study provides a new avenue to prepare multifunctional bone scaffolds based on therapeutic bioceramics for repairing tumor‐induced bone defects. [ABSTRACT FROM AUTHOR]

• 3D printed PCL/CS scaffolds were developed with excellent bioactive compositions and controllable porous structures. • Alkaline phosphatase (ALP)-responsive scaffolds were developed through the combination of a hemicyanine dye and PCL/CS scaffolds. • The combination of near-infrared (NIR) fluorescence and photoacoustic imaging was achieved. • Non-invasive, real-time visualization of enhanced bone formation was achieved both in vitro and in vivo. Although numerous biomaterials have been fabricated as scaffolds for the application of tissue engineering, real-time non-invasive monitoring of in vivo bone regeneration is still a big challenge. Particularly, the early osteogenesis is difficult to detect using conventional imaging modalities, such as X-ray computed tomography (CT) and magnetic resonance imaging (MRI) due to the limited amount of neo-bone tissue. Herein we report on alkaline phosphatase (ALP)-responsive scaffolds, which are composed of a turn-on hemicyanine dye (LET-3) and a typical three dimensional (3D) printed bone tissue engineering scaffold (polycaprolactone/calcium silicate, PCL/CS), for real-time non-invasive monitoring of in vivo bone regeneration by near-infrared fluorescence (NIR-FL) and photoacoustic (PA) duplex imaging. ALP, an early-stage biomarker of bone formation, turns "on" the NIR-FL/PA signals of LET-3 in scaffolds both in vitro and in vivo. Thus, the osteogenic-associated bioactivity of LET-3 labeled scaffolds could be visualized by NIR-FL/PA dual-modal imaging. Our results provide a promising strategy for detecting neo-bone formation by the combination of ALP prober and bone tissue engineering scaffolds, which holds great potential for traceable tissue engineering. [ABSTRACT FROM AUTHOR]