CRISPR-Cas13: Pioneering RNA Editing for Nucleic Acid Therapeutics.

The CRISPR-Cas13 system has emerged as a revolutionary tool for RNA editing, offering new opportunities for the development of nucleic acid therapeutics. Unlike DNA-targeting CRISPR-Cas9, Cas13 targets and cleaves RNA, enabling gene silencing and preventing genomic instability. Its applications include suppressing disease-causing genes, correcting splicing errors, and modulating immune responses. Despite these advances, challenges persist, such as the need to refine specificity, mitigate off-target impacts, and ensure effective delivery. This review provides an overview of the CRISPR-Cas13 mechanism, elucidating its role in RNA-targeted therapies and its transformative potential for disease treatment. Furthermore, it addresses the ongoing challenges that the scientific community is striving to overcome.

Compact RNA editors with natural miniature Cas13j nucleases.

Clustered regularly interspaced short palindromic repeats-Cas13 effectors are used for RNA editing but the adeno-associated virus (AAV) packaging limitations because of their big sizes hinder their therapeutic application. Here we report the identification of the Cas13j family, with LepCas13j (529 aa) and ChiCas13j (424 aa) being the smallest and most highly efficient variants for RNA interference. The miniaturized Cas13j proteins enable the development of compact RNA base editors. Chi-RESCUE-S, by fusing dChiCas13j with hADAR2dd, demonstrates high efficiency and specificity in A-to-G and C-to-U conversions. Importantly, this system is compatible with single-AAV packaging without the need for protein sequence truncation. It successfully corrected pathogenic mutations, such as APOC3D65N and SCN9AR896Q, to the wild-type forms. In addition, we developed an optimized system, Chi-RESCUE-S-mini3, which pioneered efficient in vivo C-to-U RNA editing of PCSK9 in mice through single-AAV delivery, resulting in reduced total cholesterol levels. These results highlight the potential of Cas13j to treat human diseases.

Vaccination Shortens the Negative Nucleic Acid Conversion Time of the Older Population: A Retrospective Cohort Study of 73,456 Asymptomatic and Mild Patients with COVID-19 in Shanghai.

Purpose: To explore the influencing factors to predict the negative nucleic acid conversion time and ORF1ab gene CT value changes in patients with asymptomatic and mild COVID-19. Patients and Methods: A total of 73,456 patients with asymptomatic and mild COVID-19 admitted to the Mobile Cabin Hospital in Shanghai from April 3 to April 23, 2022 were selected as the research objects. Epidemiological, clinical, and laboratory data were collected. Correlation analysis was performed. Results: In patients <18 years old and ≥65 years old, COVID-19 vaccine can shorten the negative nucleic acid conversion time, which is reflected in the lower median or 75% quantile (P<0.001, P<0.05). In patients with underlying diseases, the negative nucleic acid conversion time of booster vaccination and complete vaccination was lower than that of non-vaccinated group (P<0.001, P<0.05). In patients ≤18 years of age or >65 years of age, patients with comorbidity and patients with symptoms, compared with patients 18-65 years of age, patients without comorbidity and patients without symptoms, there was a greater difference in the rate of rise of CT values between vaccinated and unvaccinated patients (P<0.05). Conclusion: The time of nucleic acid conversion to negative in patients with asymptomatic and mild COVID-19 is affected by age, comorbidity, and first nucleic acid CT value. Vaccination could shorten the negative nucleic acid conversion time of the older population, those with complications or symptoms. The vaccination of older patients does not increase the risk of symptoms.

Electrolytic Graphene Encapsulated CeO2 for Lithium-Sulfur Battery Interlayer Separator.

Rare earth elements and graphene composites exhibit better catalytic properties in energy storage materials. The introduction of rare earth oxide and graphene composites as functional layers into the separator to seal the "shuttle effect" formed by polysulfides during the discharge process has proven to be effective. In this study, we prepared CeO2/graphene composites (labeled as CeG) by intercalation exfoliation and in situ electrodeposition methods simultaneously, in which CeO2 was encapsulated in large folds of graphene, which exhibited good defect levels (ID/IG < 1) and its intrinsically superior physical structure acted as a shielding layer to hinder the shuttle of polysulfides, improving the cycling stability and rate of cell performance. The separator cell with CeG achieves an initial discharge specific capacity of 1133.5 mAh/g at 0.5C, excellent rate performance (978.5 mAh/g at 2C), and long cycling (790 mAh/g after 400 cycles).

Network Pharmacology Study of Bioactive Components and Molecular Mechanisms of the Glycoside Fraction from Picrorhiza scrophulariiflora Against Experimental Colitis.

Purpose: To explore the potential mechanism of glycosidic fraction of Picrorhiza scrophulariiflora Pennell (GPS) extract for the treatment of colitis using UPLC-QTOF-MS analysis, network pharmacology and experimental research. Methods: The active components of GPS extract were identified by UPLC-QTOF-MS analysis and extracted their targets from the databases, which was used for network pharmacology analysis. Kyoto Encyclopedia of genes and genomes (KEGG) pathway analysis was performed to discover potential therapeutic mechanisms, and the network pharmacology results were then validated by in vivo and in vitro experiments. Results: The results showed that GPS extract significantly alleviated the clinical signs of colitis, including body weight, disease activity index, colon shortening, and colon tissue damage, and inhibited the transcription and production of colonic IL-1ß and IL-6 in DSS-induced colitis mice. In vitro, GPS extract also significantly suppressed nitric oxide (NO) production, iNOS expression, IL-1ß and IL-6 transcription of LPS-activated RAW 264.7 cells. Network pharmacology integrated with experimental validation identified that GPS extract significantly suppressed Akt, p38, ERK, and JNK phosphorylation in vivo and in vitro, and luteolin, apocynin, caffeic acid, caffeic acid methyl ester, luteoloside, picroside II, aucubin, cinnamic acid, vanillic acid, and sweroside were the main components responsible for the anti-inflammatory effect of GPS. These findings demonstrate that the potential anti-inflammatory effect of GPS extract against colitis is achieved through suppressing PI3K/Akt and MAPK pathways, and that the abovementioned active components mainly exerted its anti-inflammatory effect. Conclusion: The therapeutic effect of GPS extract on colitis is related to PI3K/Akt and MAPK pathways, which is a promising remedy for colitis therapy.

A Facile Crystallization Strategy to Turn Calcium Bisphosphonates into Novel Osteogenesis-Inducing Biomaterials.

Insoluble metal bisphosphonates (BPs) are considered an ideal alternative to the soluble counterparts in regenerative medicine due to their increased BP release profile, but still present undesired properties (e.g., low stability, uncontrolled degradation, and poor biocompatibility). Through a simple crystallization on a solid calcium hydroxyapatite (HA)-based substrate from a BP precursor solution in 30 days, a series of insoluble calcium BP (CaBP) crystals are developed. These crystals, including calcium alendronate (CaAln), calcium pamidronate (CaPam), calcium incadronate (CaInc), calcium risedronate (CaRis), calcium zoledronate (CaZol), and calcium di-minodronate (Ca(Min)2 ), present high purity, regular morphologies and excellent biodegradability. It is demonstrated that these CaBPs can induce osteogenic differentiation of adipose-derived mesenchymal stem cells in vitro in the absence of other osteogenic inducers. It is further found that CaBP induces bone formation more effectively in a femur defect rabbit model in three months but with a lower in vivo hematotoxicity than the clinically used HA during osteogenesis. It is believed that these desired biological properties arise from the capability of the insoluble CaBPs in releasing BPs in a sustained manner for stimulating osteogenesis. This work provides a significant strategy for turning CaBPs into novel biomaterials for tissue regeneration and demonstrates their great potential in the clinic.

Fabrication of Ti3Al-Based Intermetallic Alloy by Laser Powder Bed Fusion Using a Powder Mixture.

Due to their light weight and outstanding mechanical properties at high temperatures, Ti3Al-based intermetallic alloys have driven increasing interest from both academia and industry; however, when additive manufacturing (AM) is applied to them, the outcome is hardly satisfying. In this work, we report a crack-free Ti3Al-based alloy fabrication by laser powder bed fusion (LPBF) using a mixture of a commercial Ti-48Al-2Cr-2Nb powder and a pure Ti powder. With the aid of a high cooling rate during LPBF, the as-built sample shows a ductile ß phase with some partially-melted particles. After the heat treatment, partially-melted particles were dissolved, and the sample showed equiaxed α2 precipitates in the ß matrix. The hardness was 515 ± 38 HV in the as-built sample and 475 ± 37 HV in the heat-treated sample. This study shows a novel strategy to fabricate crack-free Ti3Al-based alloy using LPBF from powder blends.

[Alveolar macrophages in rats with chronic obstructive pulmonary disease (COPD) promotes proliferation, mucin and inflammatory factors secretion of airway epithelial cells and its mechanism].

Objective To explore how alveolar macrophages from chronic obstructive pulmonary disease (COPD)-model rats affect proliferation and secretion of 16HBE human bronchial epithelial cells and investigate the associated mechanism. Methods Alveolar macrophages were extracted from COPD rats induced by cigarette smoke exposure and LPS instillation through bronchoalveolar lavage, then co-cultured with 16HBE cells in vitro. Exosomes were extracted from alveolar macrophages of rats with exosome isolation kit. The differentially expressed miRNA in exosomes derived from macrophages of rats in COPD group and control group was detected by PCR. miR-380 was overexpressed with miR-380 mimic while the expression of cystic fibrosis transmembrane transduction regulator (CFTR) was knocked down with siRNA in 16HBE cells. The proliferation of 16HBE cells was detected with CCK-8 assay. The migration ability of 16HBE cells was evaluated with TranswellTM migration assay. The levels of mucins (MUC5AC, MUC5B, MUC2) and CFTR expressed by 16HBE cells were detected with Western blot analysis. The expression of TNF-α and IL-6 in the supernatant of 16HBE cells was detected with ELISA. Results The alveolar macrophages from COPD rats enhanced the proliferation and migration of 16HBE cells. The production of mucins and TNF-α as well as IL-6 in 16HBE cells were increased by COPD macrophages. The expression of miR-380 was significantly elevated in exosomes derived from COPD alveolar macrophages. Both overexpression of miR-380 and inhibition of CFTR decreased the expression of CFTR, resulting in the significantly enhanced proliferation and migration of 16HBE cells as well as increased expression of MUC5AC, MUC5B, MUC2 and TNF-α, IL-6. Conclusion The alveolar macrophages from COPD rats can enhance the proliferation and mucin expression as well as inflammatory cytokine secretion of 16HBE cells. This process may be involved with abnormal expression of miR-380 in exosomes of COPD alveolar macrophages and down-regulation of CFTR in bronchial epithelial cells.

Effect of High-Current Pulsed Electron Beam on Properties of Graphene-Modified Aluminum Titanium Carbide Composites.

High-current pulse electron beam (HCPEB) is an advanced surface modification technology developed in recent decades. This paper focuses on the effect of 0.3 wt.% graphene on the electrical conductivity and microhardness of HCPEB-treated Al-20TiC composites. The SEM results show that the titanium carbide was uniformly distributed in the aluminum matrix of the initial sample. Conversely, the graphene showed a small aggregation, and there were holes and cracks on the top surface of the sample. After HCPEB modification, the agglomeration of graphene gradually improved, and the number of surface pores reduced. The X-ray diffraction results show that after HCPEB treatment, the aluminum diffraction peak widened and shifted to a higher angle and the grain was significantly refined. Compared with the initial Al-20TiC composite samples, the conductivity of graphene-modified HCPEB-treated sample increased by 94.3%. The microhardness test results show that the microhardness of the graphene-modified HCPEB-treated sample increased by 18.4%, compared with the initial Al-20TiC composite samples. This enhancement of microhardness is attributed to the joint effects of fine grain strengthening, dispersion strengthening of the second phase, solution strengthening and dislocation strengthening. In brief, HCPEB has good application prospects for powder metallurgy in future.

A Study on the Effect of Graphene in Enhancing the Electrochemical Properties of SnO2-Fe2O3 Anode Materials.

To enhance the conductivity and volume expansion during the charging and discharging of transition metal oxide anode materials, rGO-SnO2-Fe2O3 composite materials with different contents of rGO were prepared by the in situ hydrothermal synthesis method. The SEM morphology revealed a sphere-like fluffy structure, particles of the 0.4%rGO-10%SnO2-Fe2O3 composite were smaller and more compact with a specific surface area of 223.19 m2/g, the first discharge capacity of 1423.75 mAh/g, and the specific capacity could be maintained at 687.60 mAh/g even after 100 cycles. It exhibited a good ratio performance and electrochemical reversibility, smaller charge transfer resistance, and contact resistance, which aided in lithium-ion transport. Its superior electrochemical performance was due to the addition of graphene, which made the spherical particle size distribution more uniform, effectively lowering the volume expansion during the process of charging and discharging and improving the electrochemical cycle stability of the anode materials.

A nano-preparation approach to enable the delivery of daphnoretin to potentiate the therapeutical efficacy in hepatocellular cancer.

Daphnoretin (DAP), isolated from a traditional Chinese medicine Wikstroemia indica (Linn. C. A. Meyer), could induce apoptosis of hepatocellular cancer (HCC) and inhibit tumor growth. However, the application of DAP in cancer therapies was hampered because to its poor solubility. Herein, this study aimed to design an approach of double-targeted nano-preparation to enable the delivery of DAP to potentiate the therapeutical efficacy in liver cancer via glycyrrhetinic acid-polyethylene glycol-block-poly (D,L-lactic acid)/polyethylene glycol-block-poly (D,L-lactic acid)-DAP (GPP/PP-DAP). In particular, the purity of separated DAP was up to 98.12% for preparation research. GPP/PP-DAP was successfully prepared by the thin-film hydration method. Subsequently, the GPP/PP-DAP was optimized by univariate analysis and the response surface methodology, producing a stable and systemically injectable nano-preparation. Impressively, on the one hand, cytotoxicity studies showed that the IC50 of the GPP/PP-DAP was lower than that of free DAP. On the other hand, the GPP/PP-DAP was more likely to be endocytosed by HepG2 cells and targeted to the liver with orthotopic tumors, potentiating the therapeutical efficacy in HCC. Collectively, both in vitro and in vivo results indicated the excellent tumor inhibition and liver targeting of GPP/PP-DAP, suggesting the nano-preparation could serve as a potential drug delivery system for natural ingredients with anti-hepatoma activity to lay the theoretical foundation for clinical application.

Diffusion-Induced Stress in Commercial Graphite Electrodes during Multiple Cycles Measured by an In Situ Method.

The cyclic stress evolution induced by repeated volume variation causes mechanical degradation and damage to electrodes, resulting in reduced performance and lifetime of LIBs. To probe the electro-chemo-mechanical coupled degradation, we conducted in situ measurements of Young's modulus and stress evolution of commercial used graphite electrodes during multiple cycles. A bilayer graphite electrode cantilever is cycled galvanostatically in a custom cell, while the bending deformation of the bilayer electrode is captured by a CCD optical system. Combined with a mechanical model, Li-concentration-dependent elastic modulus and stress are derived from the curvature of the cantilever electrode. The results show that modulus, stress and strain all increase with the lithium concentration, and the stress transforms from compression to tension in the thickness direction. During multiple cycles, the modulus decreases with an increase in the cycle number at the same concentration. The maximum stress/strain of each cycle is maintained at almost same level, exhibiting a threshold that results from the co-interaction of concentration and damage. These findings provide basic information for modeling the degradation of LIBs.

Molecular hydrogen alleviates asthma through inhibiting IL-33/ILC2 axis.

BACKGROUND: Asthma is one of the most common noninfectious chronic diseases characterized by type II inflammation. This study aimed to investigate the effects of molecular hydrogen on the pathogenesis of asthma. METHODS: OVA sensitized asthma mouse model and house dust mite treated 16HBE cellular model were established and hydrogen/oxygen mixture was used to treat asthmatic mice and 16HBE cells. Serum and BALF cytokines were measured with specific ELISA assays. E-cadherin and ZO-1 were detected by immunohistochemical staining and expression of caspase 3 and 9, NF-κB, IL-33 and ST2 was assessed by quantitative real-time PCR, western blot and/or immunofluorescence. IL-33 promoter activity was analyzed by dual-luciferase assay. ILC2 population was assayed by flow cytometry and differentially expressed miRNAs were detected using miRNA array. RESULTS: Serum and BALF levels of IL-33 and other alarmin and type II cytokines were greatly increased by OVA and inhibited by H2 in asthmatic mice. The expression of NF-κB (p65) and ST2 was upregulated by OVA and suppressed by H2. ILC2 population was markedly increased in OVA-induced asthmatic mice, and such increase was inhibited by H2. E-cadherin and ZO-1 levels in airway tissues of asthmatic mice were significantly lower than that of control mice, and the reduction was recovered by H2 treatment. H2 alleviated HDM induced apoptosis of 16HBE cells, upregulation of IL-33 and ST2, and elevation of IL-33 promoter activity. A group of miRNAs differentially expressed in HDM and HDM + H2 treated 16HBE cells were identified. CONCLUSIONS: These data demonstrated that H2 is efficient in suppressing allergen-induced asthma and could be developed as a therapeutics for asthma and other conditions of type II inflammation.

Effects of smartphone-based interventions and monitoring on bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Recently, there has been a range of studies about smartphone-based interventions and monitoring for reducing symptoms of bipolar disorder (BD). However, their efficacy for BD remains unclear. AIM: To compare the effect of smartphone-based interventions and monitoring with control methods in treating patients with BD. METHODS: A systematic literature search was performed on PubMed, Embase, Clinical trials, psycINFO, Web of Science, and Cochrane Library. Randomized clinical trials (RCTs) or single-group trials in which smartphone-based interventions and monitoring were compared with control methods or baseline in patients with symptoms of BD were included. Data were synthesized using a random-effects or a fixed-effects model to analyze the effects of psychological interventions and monitoring delivered via smartphone on psychiatric symptoms in patients with BD. The primary outcome measures were set for mania and depression symptoms. Subgroups were created to explore which aspects of smartphone interventions are relevant to the greater or lesser efficacy of treating symptoms. RESULTS: We identified ten articles, including seven RCTs (985 participants) and three single-group trials (169 participants). Analysis of the between-group study showed that smartphone-based interventions were effective in reducing manic [g = -0.19, 95% confidence interval (CI): -0.33 to -0.04, P = 0.01] and depressive (g = -0.28, 95%CI: -0.55 to -0.01, P < 0.05) symptoms. In within-group analysis, smartphone-based interventions significantly reduced manic (g = 0.17, 95%CI: 0.04 to 0.30, P < 0.01) and depressive (g = 0.48, 95%CI: 0.18 to 0.78) symptoms compared to the baseline. Nevertheless, smartphone-based monitoring systems significantly reduced manic (g = 0.27, 95%CI: 0.02 to 0.51, P < 0.05) but not depressive symptoms. Subgroup analysis indicated that the interventions with psychoeducation had positive effects on depressive (g = -0.62, 95%CI: -0.81 to -0.43, P < 0.01) and manic (g = -0.24, 95%CI: -0.43 to -0.06, P = 0.01) symptoms compared to the controlled conditions, while the interventions without psychoeducation did not (P > 0.05). The contacts between therapists and patients that contributed to the implementation of psychological therapy reduced depression symptoms (g = -0.47, 95%CI: -0.75 to -0.18, P = 0.01). CONCLUSION: Smartphone-based interventions and monitoring have a significant positive impact on depressive and manic symptoms of BD patients in between-group and within-group analysis.

A Microarray Screening Platform with an Experimental Conditions Gradient Generator for the High-Throughput Synthesis of Micro/Nanosized Calcium Phosphates.

Calcium phosphates (CaP) represent an impressive kind of biomedical material due to their excellent biocompatibility, bioactivity, and biodegradability. Their morphology and structure highly influence their properties and applications. Whilst great progress has been made in research on biomedical materials, there is still a need to develop a method that can rapidly synthesize and screen micro/nanosized biomedical materials. Here, we utilized a microarray screening platform that could provide the high-throughput synthesis of biomedical materials and screen the vital reaction conditions. With this screening platform, 9 × 9 sets of parallel experiments could be conducted simultaneously with one- or two-dimensions of key reaction condition gradients. We used this platform to establish a one-dimensional gradient of the pH and citrate concentration and a two-dimensional gradient of both the Ca/P ratio and pH to synthesize CaP particles with various morphologies. This screening platform also shows the potential to be extended to other reaction systems for rapid high-throughput screening.

Calcium alendronate-coated composite scaffolds promote osteogenesis of ADSCs via integrin and FAK/ERK signalling pathways.

Bioceramic-biopolymer composites have been used extensively as bone tissue engineering scaffolds due to their bioactive properties. However, composite scaffolds are insufficient in inducing osteogenic differentiation of stem cells. In this study, a strategy for the local delivery of bioactive factors by coating calcium alendronate (ALC) on the surface of composite scaffolds was systematically evaluated for the first time. The coated ALC not only displayed excellent cytocompatibility and cell adhesion properties but also resulted in the significant upregulation of osteogenic related gene expression, osteogenic related protein levels, alkaline phosphatase (ALP) activity and calcium deposition of ADSCs. Furthermore, our results suggested that the molecular mechanism of ADSC osteogenic differentiation induced by the constructed ALC may be related to the integrin binding and the activation of FAK/ERK signalling pathways. These findings suggested that ALC-coated composite scaffolds can serve as bone tissue engineering scaffolds, providing a simple and universal method to improve the osteogenic differentiation of ADSCs by calcium phosphate-containing composite materials.

Therapeutic potential of enhancer of zeste homolog 2 in autoimmune diseases.

Introduction: Autoimmune diseases (ADs) are idiopathic and heterogeneous disorders with contentious pathophysiology. Great strides have been made in epigenetics and its involvement in ADs. Zeste homolog 2 (EZH2) has sparked extensive interest because of its pleiotropic roles in distinct pathologic contexts.Areas covered: This review summarizes the epigenetic functions and the biological significance of EZH2 in the etiology of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), inflammatory bowel disease (IBD), multiple sclerosis (MS), and systemic sclerosis (SSc). A brief recapitulation of the therapeutic potential of EZH2 targeting is provided.Expert opinion: There are questions marks and controversies surrounding the feasibility and safety of EZH2 targeting; it is recommended in RA and SLE, but queried in T1D, IBD, MS, and SSc. Future work should focus on contrast studies, systematic analyses and preclinical studies with optimizing methodologies. Selective research studies conducted in a stage-dependent manner are necessary because of the relapsing-remitting clinical paradigms.

Assembling of electrospun meshes into three-dimensional porous scaffolds for bone repair.

Technical limitations of traditional electrospinning make it hard to produce three-dimensional (3D) scaffolds with hierarchical pore structures. Here, porous polycaprolactone (PCL) nanofiber meshes with different nano-hydroxyapatite (nHA) concentrations were prepared by electrospinning with stainless steel mesh as the collector, and 3D porous nanofiber scaffolds were fabricated via layer-by-layer assembly with a special binder (18% PCL/DCM solution). The single layer nanofiber mesh possessed very regular morphology with a hollow structure, and the nHA was not only embedded in the nanofiber but also exposed on the surfaces of the fiber, resulting in the improved surface chemical properties. The incorporation of nHA also had a significant effect on cell behaviours and functions. The 3D nanofiber scaffolds possessed hierarchical structures with interconnected micro and macro pores, which allowed cells to migrate between the adjacent layers, even throughout the scaffold. Cells filled the scaffold space and integrated with the nanofiber materials, forming scaffold/cells complexes in vitro. In addition, alendronate was successfully carried on the 3D composite scaffolds because of the high affinity of P-C-P backbone to calcium ions. The composite scaffolds treated with alendronate significantly promote the osteogenesis-related gene expression of human foetal osteoblasts. All these results suggest that 3D functional nanofiber scaffolds would be potentially useful for bone repair.

Periosteum tissue engineering-a review.

As always, the clinical therapy of critical size bone defects caused by trauma, tumor removal surgery or congenital malformation is facing great challenges. Currently, various approaches including autograft, allograft and cell-biomaterial composite based tissue-engineering strategies have been implemented to reconstruct injured bone. However, due to damage during the transplantation processes or design negligence of the bionic scaffolds, these methods expose vulnerabilities without the assistance of periosteum, a bilayer membrane on the outer surface of the bone. Periosteum plays a significant role in bone formation and regeneration as a store for progenitor cells, a source of local growth factors and a scaffold to recruit cells and growth factors, and more and more researchers have recognized its great value in tissue engineering application. Besides direct transplantation, periosteum-derived cells can be cultured on various scaffolds for osteogenesis or chondrogenesis application due to their availability. Research studies also provide a biomimetic methodology to synthesize artificial periosteum which mimic native periosteum in structure or function. According to the studies, these tissue-engineered periostea did obviously enhance the therapeutic effects of bone graft and scaffold engineering while they could be directly used as substitutes of native periosteum. Periosteum tissue engineering, whose related research studies have provided new opportunities for the development of bone tissue engineering and therapy, has gradually become a hot spot and there are still lots to consummate. In this review, tissue-engineered periostea were classified into four kinds and discussed, which might help subsequent researchers get a more systematic view of pseudo-periosteum.

The construction of three-dimensional composite fibrous macrostructures with nanotextures for biomedical applications.

The development of modern biomedical nanotechnology requires three-dimensional macrostructures with nanotextures to meet the requirements for practical applications in intricate biological systems. Additionally, the restoration and regeneration of some specific body tissues and organs rely on the function of conductive polymers, which can provide electrical cues for cells. In this study, we fabricated three-dimensional composite nanofibre macrostructures of polycaprolactone (PCL) with different concentrations of polyaniline (PANi) by employing an improved electrospinning technology with a specially designed collector. The 3D structures possessed cap-like macrostructures with centimetre-scale thickness and interconnected pore nanotextures with nanometre-scale nanofibres. To estimate the biocompatibility of the 3D PCL/PANi composite nanofibre macrostructures, mouse myoblasts (C2C12 cells) were cultured as model cells. The initial responses of C2C12 cells to the 3D PCL/PANi composite macrostructures were significantly superior to those to pure PCL, that is, the cells exhibited typical myoblast-like morphologies with obvious pseudopodia and the moderate incorporation (less than 2.0 wt%) of conductive PANi facilitated cell proliferation, which indicated that PANi has appreciable cell affinity. Moreover, the addition of conductive PANi to the 3D composite nanofibre macrostructures considerably enhanced myoblast differentiation and myotube maturation. These results suggest that electrospun 3D PCL/PANi composite nanofibre macrostructures would have promising applications in tissue engineering.