3D nanofiber scaffolds from 2D electrospun membranes boost cell penetration and positive host response for regenerative medicine.

The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 µm). It was found that scaffolds with a mesh size of 500 µm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration.

Advancements in nonthermal physical field technologies for prefabricated aquatic food: A comprehensive review.

Aquatic foods are nutritious, enjoyable, and highly favored by consumers. In recent years, young consumers have shown a preference for prefabricated food due to its convenience, nutritional value, safety, and increasing market share. However, aquatic foods are prone to microbial spoilage due to their high moisture content, protein content, and unsaturated fatty acids. Furthermore, traditional processing methods of aquatic foods can lead to issues such as protein denaturation, lipid peroxidation, and other food safety and nutritional health problems. Therefore, there is a growing interest in exploring new technologies that can achieve a balance between antimicrobial efficiency and food quality. This review examines the mechanisms of cold plasma, high-pressure processing, photodynamic inactivation, pulsed electric field treatment, and ultraviolet irradiation. It also summarizes the research progress in nonthermal physical field technologies and their application combined with other technologies in prefabricated aquatic food. Additionally, the review discusses the current trends and developments in the field of prefabricated aquatic foods. The aim of this paper is to provide a theoretical basis for the development of new technologies and their implementation in the industrial production of prefabricated aquatic food.

Mild Photothermal-Stimulation Based on Injectable and Photocurable Hydrogels Orchestrates Immunomodulation and Osteogenesis for High-Performance Bone Regeneration.

A photoactivated bone scaffold integrated with minimally invasive implantation and mild thermal-stimulation capability shows great promise in the repair and regeneration of irregularly damaged bone tissues. Developing multifunctional photothermal biomaterials that can simultaneously serve as both controllable thermal stimulators and biodegradable engineering scaffolds for integrated immunomodulation, infection therapy, and impaired bone repair remains an enormous challenge. Herein, an injectable and photocurable hydrogel therapeutic platform (AMAD/MP) based on alginate methacrylate, alginate-graft-dopamine, and polydopamine (PDA)-functionalized Ti3C2 MXene (MXene@PDA) nanosheets is rationally designed for near-infrared (NIR)-mediated bone regeneration synergistic immunomodulation, osteogenesis, and bacterial elimination. The optimized AMAD/MP hydrogel exhibits favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro. The proper immune microenvironment provided by AMAD/MP could further modulate the balance of M1/M2 phenotypes of macrophages, thereby suppressing reactive oxygen species-induced inflammatory status. Significantly, this multifunctional hydrogel platform with mild thermal stimulation efficiently attenuates local immune reactions and further promotes new bone formation without the addition of exogenous cells, cytokines, or growth factors. This work highlights the potential application of an advanced multifunctional hydrogel providing photoactivated on-demand thermal cues for bone tissue engineering and regenerative medicine.

The potential role of extracellular vesicles in bioactive compound-based therapy: A review of recent developments.

Recent studies have explored the field of extracellular vesicles (EVs), driving an increasing interest in their application to human health. EVs have unique physicochemical traits to participate in intercellular communication, thus fostering the idea of using EVs to yield synergistic, preventive, and therapeutic effects. Many reports have shown that EVs contain natural bioactive compounds, such as lipids, proteins, RNA, and other active components that regulate biological processes, thereby contributing to human health. Therefore, in this review, we comprehensively elucidate various facets of the relationship between EVs and bioactive compounds that modulate EVs contents, including RNAs and proteins, discussing different forms of biological regulation. The use of EVs for cargo-loading bioactive compounds to exert biological functions and methods to load bioactive compounds into EVs are also discussed. This review highlighted the effect of EV-delivered bioactive compounds on several therapeutic mechanisms and applications, providing new insight into nutrition and pharmacology.

Genome-wide association study and transcriptome of olecranon-type traits in peach (Prunus persica L.) germplasm.

BACKGROUND: The top of the olecranon honey peach (Prunus persica L.) fruit appears similar to an eagle's beak. In this study, a single olecranon honey peach with a round-type fruit was observed in our fruit orchard. To explore the genetic mechanism of olecranon formation, we performed full-length transcriptome sequencing analysis of olecranon and round peaches as well as a genome-wide association study of the association of olecranon-type trait loci. RESULTS: The gene locus was 26,924,482 base pairs in NC_034014.1. Transcriptome sequencing showed that the clean sequencing data of each sample reached 7.10GB, with 14,360 genes and 23,167 transcripts expressed in both the olecranon honey peach and round peach. Among the 11 differentially expressed genes selected as candidate genes, six were highly expressed in olecranon peach and named as LOC18775282, LOC18772209, LOC18773929, LOC18772013, LOC18773401, and ONT.13798.5. Five genes were highly expressed in round peach and named as LOC18773079, LOC18773525, LOC18773067, LOC18775244, and LOC18772236. Notably, ONT.13798.5 was not previously identified. The genes were within 1 Mb up- or down-stream of the main genome-wide association study locus for olecranon-type traits. CONCLUSIONS: This study revealed loci associated with olecranon and provides useful information for analysis and breeding of olecranon honey peach.

Tirapazamine suppress osteosarcoma cells in part through SLC7A11 mediated ferroptosis.

Osteosarcoma is the most common primary orthopedic malignant bone tumor in adolescents. However, the traditional neoadjuvant chemotherapy regimen has reached the bottleneck. TPZ is a hypoxic prodrug that has a powerful anti-tumor effect in the hypoxic microenvironment of tumors. And ferroptosis is a newly discovered cell death in 2012, and ferroptosis inducers have been used in anti-tumor therapy research in recent decades. Though, the role of TPZ and ferroptosis in osteosarcoma remains unclear. The aim of this study was to investigate the role of TPZ in osteosarcoma and the specific mechanism. MTT assay showed the extraordinary inhibition of TPZ on three osteosarcoma cells under hypoxia. And fluorescence of Fe2+ staining was enhanced by TPZ. Western blotting showed decreased expression of SLC7A11 and GPX4. Lipid peroxidation was confirmed by MDA assay and C11 BODIPY 581/591 staining. SLC7A11 overexpression could restored the proliferation and migration abilities inhibited by TPZ. Thus, we for the first time demonstrated that TPZ could inhibit the proliferation and migration of osteosarcoma cells, and induce ferroptosis in part through inhibiting SLC7A11.

Polysaccharide extract from pomelo fruitlet ameliorates diet-induced nonalcoholic fatty liver disease in hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀).

Nonalcoholic fatty liver disease (NAFLD) is common in farmed fish fed a high-fat diet (HFD), which disrupts lipid metabolism, inhibits growth performance, and poses a serious threat to sustainable aquaculture. This study explored the anti-NAFLD effect and hepatoprotective mechanism of YZW-A, a water-soluble heteroglycan extracted from the pomelo fruitlet (Citrus maxima), in hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀). Hybrid grouper were fed an HFD, with 15% lipid, supplemented with YZW-A for 56 days. In vivo, addition of YZW-A resulted in improved growth performance and feed utilization, while it reduced whole body and muscle lipid content, viscerosomatic and hepatosomatic indexes, and lipid deposition in the hepatocytes. Lipogenesis-related genes were downregulated while lipolysis-related genes were upregulated in grouper supplemented with YZW-A. Additionally, destructive morphological changes in the liver tissue cells detected in HFD-fed grouper were normalized after treatment with YZW-A. In vitro, YZW-A improved lipid emulsion-induced hepatic steatosis by modulating key factors of lipid metabolism, achieved by triggering the AMP-activated protein kinase (AMPK) pathway in the hepatocytes and activating the AMPK/Nrf2/ARE axis. These results demonstrated the therapeutic effect of YZW-A on diet-induced NAFLD in hybrid grouper and elucidated a possible mechanism underlying NAFLD prevention and suppression of further deterioration by YZW-A.

Formation of volatiles in response to tea green leafhopper (Empoasca onukii Matsuda) herbivory in tea plants: a multi-omics study.

KEY MESSAGE: Combined transcriptome and metabolome analysis of fresh leaf infestation by tea green leafhoppers (Empoasca (Matsumurasca) onukii Matsuda) suggests roles for alternative pre-mRNA splicing and mRNAs in the regulation of aroma formation in tea plants. Oriental Beauty is a high-grade, oolong tea with a pronounced honey-like aroma and rich ripe fruit flavor that develops primarily as a result of the infestation of the fresh leaves by tea green leafhoppers (Empoasca (Matsumurasca) onukii Matsuda). Here, we used PacBio Iso-Seq and RNA-seq analyses to determine the full-length transcripts and gene expression profiles of fresh tea leaves in response to E. (M.) onukii herbivory. We investigated the relationship between RNA-seq, tea metabolites, and aroma response mechanisms in leaves infested by leafhoppers. We found 3644 differentially expressed genes, of which 2552 were up- and 1092 were down-regulated. A total of 49,913 alternative splicing events were predicted, including 324 differential AS events. Moreover, 3105 differentially expressed transcripts were also identified, of which 2295 were up- and 810 were down-regulated. The characterization of expression patterns of the key gene transcript isoforms involved in the aroma formation pathways identified 130 differentially expressed metabolites, 97 of which were up- and 33 were down-regulated. Two key aroma compounds (phenylacetaldehyde and 4-hydroxybenzaldehyde) were highly correlated with genes of the aroma formation pathways. Our results revealed that pre-mRNA AS plays a crucial role in the metabolic regulation surrounding aroma formation under leafhopper herbivory in tea plants.

Quantitative Structure-Activity Relationship Model to Predict Antioxidant Effects of the Peptide Fraction Extracted from a Co-Culture System of Chlorella pyrenoidosa and Yarrowia lipolytica.

In this study, the antioxidant components in co-culture of Chlorella pyrenoidosa and Yarrowia lipolytica (3:1 ratio) were confirmed as trypsin-hydrolyzed peptides (EHPs). The EHPs were composed of 836 different peptides with molecular weights ranging from 639 to 3531 Da and were mainly composed of hydrophobic amino acids (48.1%). These peptides showed remarkable protective effects against oxidative stress in HepG2, which may be attributed to their structures. Furthermore, the mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly lower in the peptide-treated group than in the control group, suggesting that the antioxidant enzyme-coding genes were not activated. The EC50 value of three peptides in the EHPs were in the order of AGYSPIGFVR (0.04 ± 0.002 mg/mL) > VLDELTLAR (0.09 ± 0.001 mg/mL) > LFDPVYLFDQG (0.41 ± 0.03 mg/mL); these results agreed with the prediction of the model (R2 > 0.9, Q2 > 0.5). Thus, EHPs show potential as potent new antioxidant agents.

Characterization and relationship analysis of antioxidant and anti-inflammatory peptides in pomelo fruitlet albumin.

Several macromolecules from the pomelo fruitlet (PF) have demonstrated functional potential in previous research. In this study, pomelo fruitlet albumin (PFA) was extracted from PF, its anti-inflammatory and antioxidant properties were assessed using enzyme-linked immunosorbent assays, and its capacity to clear free radicals was measured. Meanwhile, we hypothesize that the amino acid sequence may affect the anti-inflammatory and antioxidant properties, and the two may rely on common significant sites within the amino acid sequence. Therefore, we analyzed the amino acid sequence using a quantitative structure-activity relationship model to explore the connection between the antioxidant and anti-inflammatory capacities of PFA. Both capacities were closely associated with six sites within the amino acid sequence. Collectively, this study illustrates that PFA exhibits both anti-inflammatory and antioxidant capacities, with six specific sites identified as significantly affecting both activities.

Bioinspired soft-hard combined system with mild photothermal therapeutic activity promotes diabetic bone defect healing via synergetic effects of immune activation and angiogenesis.

Background: The comprehensive management of diabetic bone defects remains a substantial clinical challenge due to the hostile regenerative microenvironment characterized by aggravated inflammation, excessive reactive oxygen species (ROS), bacterial infection, impaired angiogenesis, and unbalanced bone homeostasis. Thus, an advanced multifunctional therapeutic platform capable of simultaneously achieving immune regulation, bacterial elimination, and tissue regeneration is urgently designed for augmented bone regeneration under diabetic pathological milieu. Methods and Results: Herein, a photoactivated soft-hard combined scaffold system (PGCZ) was engineered by introducing polydopamine-modified zeolitic imidazolate framework-8-loaded double-network hydrogel (soft matrix component) into 3D-printed poly(ε-caprolactone) (PCL) scaffold (hard matrix component). The versatile PGCZ scaffold based on double-network hydrogel and 3D-printed PCL was thus prepared and features highly extracellular matrix-mimicking microstructure, suitable biodegradability and mechanical properties, and excellent photothermal performance, allowing long-term structural stability and mechanical support for bone regeneration. Under periodic near-infrared (NIR) irradiation, the localized photothermal effect of PGCZ triggers the on-demand release of Zn2+, which, together with repeated mild hyperthermia, collectively accelerates the proliferation and osteogenic differentiation of preosteoblasts and potently inhibits bacterial growth and biofilm formation. Additionally, the photoactivated PGCZ system also presents outstanding immunomodulatory and ROS scavenging capacities, which regulate M2 polarization of macrophages and drive functional cytokine secretion, thus leading to a pro-regenerative microenvironment in situ with enhanced vascularization. In vivo experiments further demonstrated that the PGCZ platform in conjunction with mild photothermal therapeutic activity remarkably attenuated the local inflammatory cascade, initiated endogenous stem cell recruitment and neovascularization, and orchestrated the osteoblast/osteoclast balance, ultimately accelerating diabetic bone regeneration. Conclusions: This work highlights the potential application of a photoactivated soft-hard combined system that provides long-term biophysical (mild photothermal stimulation) and biochemical (on-demand ion delivery) cues for accelerated healing of diabetic bone defects.

Smart-Responsive Multifunctional Therapeutic System for Improved Regenerative Microenvironment and Accelerated Bone Regeneration via Mild Photothermal Therapy.

The treatment of bone defects remains a substantial clinical challenge due to the lack of spatiotemporal management of the immune microenvironment, revascularization, and osteogenic differentiation. Herein, deferoxamine (DFO)-loaded black phosphorus nanosheets decorated by polydopamine layer are prepared (BPPD) and compounded into gelatin methacrylate/sodium alginate methacrylate (GA) hybrid hydrogel as a smart-responsive therapeutic system (GA/BPPD) for accelerated bone regeneration. The BPPD nanocomposites served as bioactive components and near-infrared (NIR) photothermal agents, which conferred the hydrogel with excellent NIR/pH dual-responsive properties, realizing the stimuli-responsive release of DFO and PO4 3 - during bone regeneration. Under the action of NIR-triggered mild photothermal therapy, the GA/BPPD hydrogel exhibited a positive effect on promoting osteogenesis and angiogenesis, eliminating excessive reactive oxygen species, and inducing macrophage polarization to the M2 phenotype. More significantly, through macrophage M2 polarization-induced osteoimmune microenvironment, this hydrogel platform could also drive functional cytokine secretion for enhanced angiogenesis and osteogenesis. In vivo experiments further demonstrated that the GA/BPPD system could facilitate bone healing by attenuating the local inflammatory response, increasing the secretion of pro-healing factors, stimulating endogenous cell recruitment, and accelerating revascularization. Collectively, the proposed intelligent photothermal hydrogel platform provides a promising strategy to reshape the damaged tissue microenvironment for augmented bone regeneration.

The deubiquitinase OTUD1 deubiquitinates TIPE2 and plays a protective role in sepsis-induced lung injury by targeting TAK1-mediated MAPK and NF-κB signaling.

Ovarian tumor domain-containing protease 1 (OTUD1) is a critical negative regulator that promotes innate immune homeostasis and is extensively involved in the pathogenesis of sepsis. In this study, we performed a powerful integration of multiomics analysis and an experimental mechanistic investigation to elucidate the immunoregulatory role of OTUD1 in sepsis at the clinical, animal and cellular levels. Our study revealed the upregulation of OTUD1 expression and the related distinctive alterations observed via multiomics profiling in clinical and experimental sepsis. Importantly, in vivo and in vitro, OTUD1 was shown to negatively regulate inflammatory responses and play a protective role in sepsis-induced pathological lung injury by mechanistically inhibiting the activation of the transforming growth factor-beta-activated kinase 1 (TAK1)-mediated mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in the present study. Subsequently, we probed the molecular mechanisms underlying OTUD1's regulation of NF-κB and MAPK pathways by pinpointing the target proteins that OTUD1 can deubiquitinate. Drawing upon prior research conducted in our laboratory, it has been demonstrated that tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) performs a protective function in septic lung injury and septic encephalopathy by suppressing the NF-κB and MAPK pathways. Hence, we hypothesized that TIPE2 might be a target protein of OTUD1. Additional experiments, including Co-IP, immunofluorescence co-localization, and Western blotting, revealed that OTUD1 indeed has the ability to deubiquitinate TIPE2. In summary, OTUD1 holds potential as an immunoregulatory and inflammatory checkpoint agent, and could serve as a promising therapeutic target for sepsis-induced lung injury.

Preparation of Dendrobium officinale Polysaccharide by Lactic Acid Bacterium Fermentation and Its Protective Mechanism against Alcoholic Liver Damage in Mice.

Dendrobium officinale polysaccharide (DP) was prepared with lactic acid bacterium fermentation to overcome the large molecular weight and complex structure of traditional DP for improving its functional activity and application range in this work. The structure was analyzed, and then the functional activity was evaluated using a mouse model of alcoholic liver damage. The monosaccharide compositions were composed of four monosaccharides: arabinose (0.13%), galactose (0.50%), glucose (24.38%), and mannose (74.98%) with a molecular weight of 2.13 kDa. The connection types of glycosidic bonds in fermented D. officinale (KFDP) were →4)-ß-D-Manp(1→, →4)-ß-Glcp(1→, ß-D-Manp(1→, and ß-D-Glcp(1→. KFDP exhibited an excellent protective effect on alcoholic-induced liver damage at a dose of 80 mg/kg compared with polysaccharide separated and purified from D. officinale without fermentation (KDP), which increased the activity of GSH, GSH-Px, and GR and decreased the content of MDA, AST, T-AOC, and ALT, as well as regulated the level of IL-6, TNF-α, and IL-1ß to maintain the normal functional structure of hepatocytes and retard the apoptosis rate of hepatocytes. The results proved that fermentation degradation is beneficial to improving the biological activity of polysaccharides. The potential mechanism of KFDP in protecting alcoholic liver damage was inhibiting the expression of miRNA-150-5p and targeting to promote the expression of Pik3r1. This study provides an important basis for the development of functional foods.

Mendelian randomization analysis reveals causal associations of serum metabolites with sepsis and 28-day mortality.

Metabolic disorder has been found to be an important factor in the pathogenesis and progression of sepsis. However, the causation of such an association between serum metabolites and sepsis has not been established. We conducted a two-sample Mendelian randomization (MR) study. A genome-wide association study of 486 human serum metabolites was used as the exposure, whereas sepsis and sepsis mortality within 28 days were set as the outcomes. In MR analysis, 6 serum metabolites were identified to be associated with an increased risk of sepsis, and 6 serum metabolites were found to be related to a reduced risk of sepsis. Furthermore, there were 9 metabolites positively associated with sepsis-related mortality, and 8 metabolites were negatively correlated with sepsis mortality. In addition, "glycolysis/gluconeogenesis" (p = 0.001), and "pyruvate metabolism" (p = 0.042) two metabolic pathways were associated with the incidence of sepsis. This MR study suggested that serum metabolites played significant roles in the pathogenesis of sepsis, which may provide helpful biomarkers for early disease diagnosis, therapeutic interventions, and prognostic assessments for sepsis.

Phenolic amides (avenanthramides) in oats - an update review.

Oats (Avena sativa L.) are one of the worldwide cereal crops. Avenanthramides (AVNs), the unique plant alkaloids of secondary metabolites found in oats, are nutritionally important for humans and animals. Numerous bioactivities of AVNs have been investigated and demonstrated in vivo and in vitro. Despite all these, researchers from all over the world are taking efforts to learn more knowledge about AVNs. In this work, we highlighted the recent updated findings that have increased our understanding of AVNs bioactivity, distribution, and especially the AVNs biosynthesis. Since the limits content of AVNs in oats strictly hinders the demand, understanding the mechanisms underlying AVN biosynthesis is important not only for developing a renewable, sustainable, and environmentally friendly source in both plants and microorganisms but also for designing effective strategies for enhancing their production via induction and metabolic engineering. Future directions for improving AVN production in native producers and heterologous systems for food and feed use are also discussed. This summary will provide a broad view of these specific natural products from oats.

• Avenanthramides are unique nutritional alkaloids in oats• AVN bioactivity, distribution, and the potential AVNs biosynthesis are discussed• AVNs can be produced via induction and metabolic engineering.

Involvement of branched RG-I pectin with hemicellulose in cell-cell adhesion of tomato during fruit softening.

Cell adhesion of four cultivars of tomato fruit, "Micro Tom (MT)", "Heinz 1706 (H1706)", "Money Maker (MM)", "Ailsa Craig (AC)" were evaluated and cell walls were analyzed in order to assess the possible contribution of pectic and hemicellulosic polysaccharides to the softening and altered cell adhesion at two different stages of ripeness. Cell wall material (CWM) and solubilised fractions of green and red ripe fruit were analyzed by chemical, enzymatic techniques. In comparison with the four cultivars of tomato fruits, H1706 and MM are harder than MT and AC at both green and red ripe stage. The ripening-associated solubilisation of rhamnogalacturonan-riched pectic polysaccharides was reduced in H1706 and MM, and the content of side -chain sugars from RG-I reduced by more than 50% in MT and AC. In addition to recognized pectic modifying enzymes, RGase had a good effect on cell separation of H1706 and MM fruit at red ripe stage. The higher RG-I content and branching degree have been associated with increased cell adhesion and reduced cell wall porosity, thus maintained fruit firmness.

Enhanced nitrogen removal via Yarrowia lipolytica-mediated nitrogen and related metabolism of Chlorella pyrenoidosa from wastewater.

We investigated the optimum co-culture ratio with the highest biological nitrogen removal rate, revealing that chemical oxygen demand, total nitrogen (TN), and ammoniacal nitrogen (NH3-N) removal was increased in the Chlorella pyrenoidosa and Yarrowia lipolytica co-culture system at a 3:1 ratio. Compared with the control, TN and NH3-N content in the co-incubated system was decreased within 2-6 days. We investigated mRNA/microRNA (miRNA) expression in the C. pyrenoidosa and Y. lipolytica co-culture after 3 and 5 days, identifying 9885 and 3976 differentially expressed genes (DEGs), respectively. Sixty-five DEGs were associated with Y. lipolytica nitrogen, amino acid, photosynthetic, and carbon metabolism after 3 days. Eleven differentially expressed miRNAs were discovered after 3 days, of which two were differentially expressed and their target mRNA expressions negatively correlated with each other. One of these miRNAs regulates gene expression of cysteine dioxygenase, hypothetical protein, and histone-lysine N-methyltransferase SETD1, thereby reducing amino acid metabolic capacity; the other miRNA may promote upregulation of genes encoding the ATP-binding cassette, subfamily C (CFTR/MRP), member 10 (ABCC10), thereby promoting nitrogen and carbon transport in C. pyrenoidosa. These miRNAs may further contribute to the activation of target mRNAs. miRNA/mRNA expression profiles confirmed the synergistic effects of a co-culture system on pollutant disposal.

Bioinspired Piezoelectric Periosteum to Augment Bone Regeneration via Synergistic Immunomodulation and Osteogenesis.

Ideal periosteum materials are required to participate in a sequence of bone repair-related physiological events, including the initial immune response, endogenous stem cell recruitment, angiogenesis, and osteogenesis. However, conventional tissue-engineered periosteal materials have difficulty achieving these functions by simply mimicking the periosteum via structural design or by loading exogenous stem cells, cytokines, or growth factors. Herein, we present a novel biomimetic periosteum preparation strategy to comprehensively enhance the bone regeneration effect using functionalized piezoelectric materials. The resulting biomimetic periosteum possessing an excellent piezoelectric effect and improved physicochemical properties was prepared using a biocompatible and biodegradable poly(3-hydroxybutyric acid-co-3-hydrovaleric acid) (PHBV) polymer matrix, antioxidized polydopamine-modified hydroxyapatite (PHA), and barium titanate (PBT), which were further incorporated into the polymer matrix to fabricate a multifunctional piezoelectric periosteum by a simple one-step spin-coating method. The addition of PHA and PBT dramatically enhanced the physicochemical properties and biological functions of the piezoelectric periosteum, resulting in improved surface hydrophilicity and roughness, enhanced mechanical performance, tunable degradation behavior, and stable and desired endogenous electrical stimulations, which is conducive to accelerating bone regeneration. Benefiting from endogenous piezoelectric stimulation and bioactive components, the as-fabricated biomimetic periosteum demonstrated favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro, which not only promoted adhesion, proliferation, and spreading as well as osteogenesis of mesenchymal stem cells (MSCs) but also effectively induced M2 macrophage polarization, thereby suppressing reactive oxygen species (ROS)-induced inflammatory reactions. Through in vivo experiments, the biomimetic periosteum with endogenous piezoelectric stimulation synergistically accelerated the formation of new bone in a rat critical-sized cranial defect model. The whole defect was almost completely covered by new bone at 8 weeks post treatment, with a thickness close to that of the host bone. Collectively, with its favorable immunomodulatory and osteogenic properties, the biomimetic periosteum developed here represents a novel method to rapidly regenerate bone tissue using piezoelectric stimulation.