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Traditional shape memory polymers (SMPs) could avoid large volume trauma during implantation; however, for bone repair, scaffolds with high porosity and biomineralization are essential to promote bone regeneration. A novel porous composite scaffold with high biomineralization activity was developed by sequential gas foaming and a freeze-drying method. The results showed that the cross-linked block structure of the polymer matrix presented excellent shape memory properties, and osteogenesis was promoted by citrate functionalized amorphous calcium phosphate (CCACP). CCACP improved the mechanical strength of the scaffold, and the synergistic effect of CCACP and PEG promotes hydrophilicity and further promoted cell adhesion. Bending experiments indicated that the shape-memory effect of the scaffolds could be varied by varying the CCACP content. In addition, hydroxyapatite deposition was sped up as CCACP accelerated the mineralization of the scaffolds. Moreover, the result of the CCK-8 assessment suggested that composite scaffolds exhibited high biocompatibility, and the cells extended out abundant filopodia to adhere onto the scaffolds. In rat bone defect models, the obtained scaffolds promoted new bone formation compared to the control group. The developed composite scaffolds show potential for minimally invasive bone repair application.

Enzymes play a key role in natural mineralization, but their function is disabling in bone metabolism when patients suffer severe degenerations like hypophosphatasia. To regulate bone homeostasis, a self‐activating phosphorus‐rich system is proposed on calcium glycerophosphate (CaGP) modified polyurethane (PU) fibrous substrate, wherein ample enzyme catalytic domains are imported with intestinal alkaline phosphatase (IALP) chelating and activating by calcium in situ that is testified by chemical potential evaluation. Therefore, Ca‐bonding IALP catalyzes organophosphate to phosphate locally to achieve a calcified symbiotic state, regulating mineralization and accelerating osteoinduction in vitro and in vivo. The self‐activating enzyme system promotes early osteogenic differentiation and angiogenesis, resulting in rapid healing of cranial defect with a "long‐tail" effect compared to an enzyme‐assisted system. Transcriptomic and metabolomic analyses demonstrate positive associations with neovascularization and calcium/phosphorus metabolism, specifically upregulated glycerophospholipids and calcium ions in favor of osteogenic differentiation under cytokine‐free conditions. These results provide a potential enzyme‐activating therapy in bone homeostasis and regeneration. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fabrication of electroactive fibrous membranes mimicking extracellular matrix. • Outstanding reactive oxygen species (ROS) clearance ability due to redox activity. • ROS alleviation mediated macrophage polarization and osteoimmune reprogramming. • Ca2+ elevation promoted MSCs proliferation and osteogenesis differentiation. • High performance in the progressive regeneration of calvarial defect of rats. Inspired by the endogenous electric field of natural bone tissue, fibrous aniline trimer (AT)-based polyurethane (FPAT) membranes have been fabricated with good electroactivity through electrospinning, which may serve to restore electrophysiological microenvironment and regulate site-specific cell behaviors to promote osteogenesis. By virtue of the redox activity, the electroactive FPAT membranes exhibited the progressive scavenging ability of reactive oxygen species (ROS) with increasing AT content. Furthermore, a systematic study of specific biomarkers was practiced to draw a comprehensive understanding of the bioelectrical stimulation, including in vitro cell experiments, in vivo RNA-sequencing, subcutaneous implantation, and bone defect repair. Focused on site-specific cell behaviors, both macrophages and mesenchymal stem cells (MSCs)were significantly regulated by the AT-based membranes on electrophysiological microenvironment. For macrophages, the AT-based membranes polarized macrophages to M2 phenotype by efficiently clearing excessive ROS to manipulate the osteoimmune microenvironment in vitro and in vivo. For MSCs, the FPAT membranes scavenged excessive intracellular ROS and elevated intracellular Ca2+ concentration, thereby promoting cell proliferation and driving osteogenesis differentiation. Histology results and gene expression profiles on a rat calvarial bone defect model discovered the efficacy of the AT-based membranes in immunomodulation and osteogenesis. Moreover, the upregulated genes at the RNA level and signaling pathways testified that the electroactive FPAT membranes were strongly involved in regulating macrophage polarization and bone repairing process. This work demonstrated an efficacious therapy of electroactive FPAT membranes from the regulatory mechanism, cellular to tissue levels in bone progressive regeneration, which could provide a legible evaluation system for conductive materials. [ABSTRACT FROM AUTHOR]