Biotechnology Journal最新文献

{"title":"Overexpression of Geranylgeranyl Diphosphate Synthase and Cyclase Enhances Pleuromutilin Production in Clitopilus Passeckerianus T6","authors":"Bochun Wen,&nbsp;Huiwen Huang,&nbsp;Li Lu,&nbsp;Tiangang Liu,&nbsp;Ran Liu","doi":"10.1002/biot.202500004","DOIUrl":"https://doi.org/10.1002/biot.202500004","url":null,"abstract":"<div>\u0000 \u0000 <p>Pleuromutilin, a tricyclic diterpene compound with significant inhibitory activity against gram-positive bacteria and mycoplasmas, serves as a precursor for various veterinary and human medicines. Previous efforts have primarily focused on strain screening and fermentation process optimization to enhance pleuromutilin production in native pleuromutilin-producing strains, with the absence of genetic engineering strategies. In this study, we performed whole-genome sequencing of the pleuromutilin-producing strain <i>Clitopilus passeckerianus</i> T6 to identify the biosynthetic genes related to pleuromutilin production. Transcriptomic and metabolomic data were collected during the fermentation of <i>C. passeckerianus</i> T6, and gene transcription and metabolite accumulation in the pleuromutilin biosynthetic pathway were analyzed to identify the rate-limiting steps in pleuromutilin biosynthesis. Overexpression of the key genes <i>ple-ggpps</i> and <i>ple-cyc</i> increased pleuromutilin production by 50%, achieving a titer of 6.9 g/L. This study is the first to employ metabolic engineering to enhance pleuromutilin production in a native strain, providing a strategy for efficient pleuromutilin production.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"20 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzymatically Crafted Bacterial Cellulose Nanoparticles Functionalized With Antimicrobial Peptides: Toward Sustainable Antimicrobial Formulations","authors":"Martina Schibeci,&nbsp;Rosa Gaglione,&nbsp;Noemi Russo,&nbsp;Raffaele Velotta,&nbsp;Bartolomeo Della Ventura,&nbsp;Angela Arciello","doi":"10.1002/biot.202400573","DOIUrl":"https://doi.org/10.1002/biot.202400573","url":null,"abstract":"<p>Although natural antimicrobial peptides (AMPs) are endowed with excellent antimicrobial properties, only a few of them have been successfully translated to the market so far. This is mainly due to their short half-life, to their high susceptibility to protease degradation, and to the lack of appropriate strategies for their efficient targeted delivery. Hence, the development of an effective system to deliver AMPs to the site of infection is urgent. The system here selected is represented by bacterial cellulose nanoparticles (BCNPs). Nanocellulose has recently emerged as one of the most promising “green” materials, attracting great attention due to its unique features, including biodegradability, sustainability, biocompatibility, and special physicochemical properties. To produce BCNPs, <i>Komagataeibacter xylinus</i> has been selected as host producing strain. Once obtained BC macrofibers, the production of BCNPs was set up by enzymatic hydrolysis using a commercial mixture of cellulases from <i>Trichoderma reesei</i> to develop a sustainable green biotechnological process. The storage stability of produced BCNPs has been also evaluated. Obtained BCNPs have been functionalized through non-covalent bindings with an antimicrobial peptide previously identified in human apolipoprotein B and found to be endowed with strong antimicrobial properties in in vitro analyses and with good biocompatibility profiles when analyzed on human skin cells. This opens interesting perspectives to the applicability of the developed system in several biotechnological fields.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"20 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biot.202400573","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chicken-Derived Single-Chain Variable Fragments Targeting Monkeypox Virus A29L Protein","authors":"Chi-Hsin Lee,&nbsp;Chao-Jung Wu,&nbsp;Jia-Yun Chiang,&nbsp;Fang-Yi Yen,&nbsp;Ting-Jing Shen,&nbsp;Sy-Jye Leu,&nbsp;Bor-Yu Tsai,&nbsp;Yan-Chiao Mao,&nbsp;Valencia Andriani,&nbsp;Wei-Chu Wang,&nbsp;Priskila Cherisca Thenaka,&nbsp;Yu-Pin Chao,&nbsp;Yi-Yuan Yang","doi":"10.1002/biot.202400634","DOIUrl":"https://doi.org/10.1002/biot.202400634","url":null,"abstract":"<div>\u0000 \u0000 <p>Monkeypox (mpox), a zoonotic disease, has rapidly spread globally, prompting the WHO to declare it a public health emergency. The long incubation period, early symptoms resembling respiratory infections, and diagnostic challenges hinder timely epidemic control and accurate clinical diagnosis. The monkeypox virus (MPXV) encodes the A29L protein, which binds to cellular heparan sulfate to facilitate infection and serves as a target for treatment and diagnostics. Thus, developing effective diagnostic tools and treatments is critically important. In this study, we expressed and purified <i>Escherichia coli</i>-derived A29L protein, which was used for chicken immunization to generate specific polyclonal IgY antibodies. The results demonstrated a successful elicitation of a humoral immune response. Subsequently, two single-chain variable fragments (scFv) antibody libraries were constructed using phage display technology, comprising 2.6 × 10⁸ and 3.8 × 10⁸ transformants. After bio-panning, phage-based ELISA indicated the enrichment of specific clones. Three scFv-expressing clones, including cA29LS1, cA29LS5, and cA29LS13, were selected from 13 randomly chosen clones and classified based on nucleotide sequence analysis. Their binding activities were evaluated through ELISA and Western blot, followed by purification for affinity determination via competitive ELISA. Among the selected clones, cA29LS5 demonstrated the highest binding affinity (1.3 × 10⁻⁶ M), followed by cA29LS1 (5.3 × 10⁻⁶ M). Additionally, both IgY and all three clones demonstrated binding activity to cell-derived and commercially purchased A29L proteins, as confirmed by Western blot and ELISA. Overall, these findings suggested that the IgY and scFv antibodies developed hold promise as potential diagnostic and therapeutic agents against MPXV infections.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"20 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mRNA Vaccines: Design Principles, Mechanisms, and Manufacturing—Insights From COVID-19 as a Model for Combating Infectious Diseases","authors":"Saeideh Khorshid Sokhangouy,&nbsp;Matine Behzadi,&nbsp;Shokuh Rezaei,&nbsp;Mahsa Farjami,&nbsp;Maryam Haghshenas,&nbsp;Yahya Sefidbakht,&nbsp;Sina Mozaffari-Jovin","doi":"10.1002/biot.202400596","DOIUrl":"https://doi.org/10.1002/biot.202400596","url":null,"abstract":"<div>\u0000 \u0000 <p>The full approval of two SARS-CoV-2 mRNA vaccines, Comirnaty and Spikevax, has greatly accelerated the development of numerous mRNA vaccine candidates targeting infectious diseases and cancer. mRNA vaccines provide a rapid, safe, and versatile manufacturing process while eliciting strong humoral and cellular immune responses, making them particularly beneficial for addressing emerging pandemics. Recent advancements in modified nucleotides and lipid nanoparticle delivery systems have further emphasized the potential of this vaccine platform. Despite these transformative opportunities, significant improvements are needed to enhance vaccine efficacy, stability, and immunogenicity.</p>\u0000 <p>This review outlines the fundamentals of mRNA vaccine design, the manufacturing process, and administration strategies, along with various optimization approaches. It also offers a comprehensive overview of the mRNA vaccine candidates developed since the onset of the COVID-19 pandemic, the challenges posed by emerging SARS-CoV-2 variants, and current strategies to address these variants. Finally, we discuss the potential of broad-spectrum and combined mRNA vaccines and examine the challenges and future prospects of the mRNA vaccine platform.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"20 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methionine Restriction Exerts Anti-Tumor Immunity via Joint Intervention of T-Bet Palmitoylation in Gastric Cancer","authors":"Lin Xin,&nbsp;He-Song Xu,&nbsp;Luo-Jun Fan,&nbsp;Chuan Liu,&nbsp;Yong-Hui Zou,&nbsp;Qi Zhou,&nbsp;Zhen-Qi Yue,&nbsp;Jin-Heng Gan,&nbsp;Jiang Liu","doi":"10.1002/biot.202400574","DOIUrl":"https://doi.org/10.1002/biot.202400574","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Methionine restriction (MR) exerts an anti-tumor immunomodulatory role. Th1 cells facilitate CD8⁺ cytotoxic T cell activation and targeted tumor cell killing. Our previous work shows that MR enhances the immunotherapy effect of PD-L1/PD-1 blockade on gastric cancer, MR can simultaneously inhibit Th1 cell differentiation, which may affect their synergistic therapeutic outcome. We aim to elucidate the molecular mechanism of MR regulating Th1 cell activation in gastric cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Murine Foregastric Carcinoma (MFC) cells were injected into 615 mice to establish transplanted tumor models, which were then treated with an MR diet or combined with 2-bromopalmitate (2-BP). CD4⁺T cells were cultured with deficient methionine. The acyl-biotinyl exchange (ABE) method was to detect T-bet palmitoylation and cycloheximide experiments to detect protein stability. GPS-Palm tool was employed to screen palmitoyltransferases. The impact of T-bet palmitoylation on the pro-tumor-killing effect of Th1 cells was examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MR enhanced anti-PD-1's inhibition of tumor growth, while concurrently suppressing the increased Th1 cells. Combined with 2-BP further inhibited tumor and increased Th1 cells. Suppressing Th1 activity attenuated 2-BP's synergistic therapeutic effect and reduced CD8⁺ GZMB⁺ T cells. MR inhibited Th1 differentiation by reducing T-bet expression, 2-BP treatment restored, while T-bet interference reversed 2-BP's effect. MR increased palmitoylation and T-bet underwent palmitoylation modification. ZDHHC23 mediated T-bet palmitoylation and promoted T-bet degradation. MR promoted T-bet degradation, thereby decreasing T-bet content, inhibiting Th1 cell polarization and CD8⁺ T cell killing effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MR combined with T-bet palmitoylation intervention promotes Th1 polarization and CD8⁺ T cell toxicity, thereby enhancing anti-tumor immunity in gastric cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"20 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient Conversion of Nicotinamide Mononucleotide Based on Elucidation of the Limitations in Multienzyme Cascade Reactions","authors":"Fengrui Yu,&nbsp;Hongwen Li,&nbsp;Xianglong Li,&nbsp;Jianping Shi,&nbsp;Yanbin Feng,&nbsp;Song Xue","doi":"10.1002/biot.202400707","DOIUrl":"https://doi.org/10.1002/biot.202400707","url":null,"abstract":"<div>\u0000 \u0000 <p>Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD), provides a direct method for maintaining NAD levels, which may alleviate aging and metabolic disorders. However, the enzymatic conversion of NMN in cascade reactions is limited by intermediate product inhibition, and quantitative insights into these limitations remain scarce. Here, an efficient multienzyme cascade system was developed by quantifying intermediate inhibition, which synthesizes NMN from D-ribose in three tandem reactions with an Adenosine Triphosphate (ATP) regeneration system and pyrophosphatase (PPase). A critical Adenosine Diphosphate (ADP) concentration of 0.5 mM was determined, which inhibits phosphoribosyl pyrophosphate synthetase (Prs) at 0.08 µM. The incorporation of an ATP regeneration system and PPase markedly increased the NMN yield to 81.3%. The intermediate phosphoribosyl pyrophosphate (PRPP) hydrolysis rate was measured at 3 µM/min. The highly active nicotinamide phosphoribosyltransferase (Nampt) could compete with PRPP hydrolysis, thereby increasing the yield of NMN. This research facilitates large-scale, efficient NMN manufacturing.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"20 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A precise targeting of Staphylococcus aureus with phage RBP-decorated antibiotic-loaded nanoparticles","authors":"Senanur Dokuz,&nbsp;Irem Coksu,&nbsp;Serap Acar,&nbsp;Tulin Ozbek","doi":"10.1002/biot.202300520","DOIUrl":"https://doi.org/10.1002/biot.202300520","url":null,"abstract":"<p>Resistant strains of <i>Staphylococcus aureus</i>, which have emerged due to the excessive and indiscriminate use of antibiotics, have become one of the most significant causes of hospital-acquired infections, highlighting the necessity for specific and effective alternative methods in combating them. Leveraging the therapeutic potential of bacteriophage receptor binding protein (RBP), which occurs unique and irreversible binding of its host, in recognizing bacteria renders them valuable components in the development of targeted nanoparticle-based drug delivery systems, and offers promising approach to combat antibiotic resistance. In this study, synthesis and characterization of rifampicin-loaded PLGA nanoparticle (RIF-NP) were conducted and for selective targeting of <i>S. aureus</i>, rGp144, the RBP derived from Bacteriophage K, was conjugated onto the surface of the synthesized RIF-NP (RIF144-NP). While RIF-NP initially exhibited approximately a zeta potential of −26 mV and a size of 250 nm, after the conjugation with rGp144 led to an increase in zeta potential to −11 mV and a size to 300 nm. FT-IR analysis after conjugation confirmed the presence of primary amide bands in the regions of 1650 cm⁻¹ and 1550 cm⁻¹. Furthermore, the nanoparticles exhibited an encapsulation efficiency of 35.26% and a drug loading capacity of 26.64%. When the antimicrobial activities were evaluated, it was observed that compared to free RIF, the nano systems reduced the MIC value by twofold for all <i>S. aureus</i> strains. Incorporating a targeting strategy based on phage RBP in decoration to the surface of nanoparticular drug carriers represents a noteworthy and innovative treatment when combating bacterial infections.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"20 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 3D Bioprinted Gelatine-Based Bilayer Hydrogel Dressing Loaded With Curcumin and Ciprofloxacin Hydrochloride With Antibacterial, Anti-Inflammatory and Antioxidative Properties","authors":"Zijiao Feng,&nbsp;Jiaqi Liu,&nbsp;Yueqi Lu,&nbsp;Hailin Ma,&nbsp;Yuen Yee Cheng,&nbsp;Jie Xu,&nbsp;Yanchun Guan,&nbsp;Bo Pan,&nbsp;Kedong Song","doi":"10.1002/biot.202400556","DOIUrl":"https://doi.org/10.1002/biot.202400556","url":null,"abstract":"<div>\u0000 \u0000 <p>Skin wound repair, a highly integrated and overlapping complex process, is susceptible to infection, excessive inflammation, high oxidative stress, which can prolong the wound healing time or even lead to chronic wound. Meanwhile, single-layer hydrogels are unavoidably dehydrated usually due to water evaporation, which is not conducive to wound healing. Therefore, a bilayer hydrogel dressing composed of gelatin (G) and sodium alginate (A) loaded with ciprofloxacin (C) and curcumin (Cur) was manufactured by extrusion 3D bioprinting technology in this study, which is denoted as GACCur. The experimental results showed that the bilayer hydrogel loaded with 50 µg/mL of Cur (GACCur50) had excellent antibacterial properties and high antioxidative activity with a 54.35 ± 0.48% DPPH scavenging ratio. In addition, this GACCur50 bilayer hydrogel exhibited the capacity to mitigate the polarization of inflammatory cells toward pro-inflammatory states, observably reducing the expression of pertinent pro-inflammatory cytokines. Furthermore, the bilayer hydrogel dressing also showed good biocompatibility as assessed by live-dead fluorescent staining, scanning electron microscopy (SEM), and CCK-8 test. Therefore, the GACCur50 bilayer hydrogel dressing is promising for wound healing.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"20 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Barriers Composed of tRNA Genes Can Complement the Benefits of a Ubiquitous Chromatin Opening Element to Enhance Transgene Expression","authors":"Rebecca E. Sizer,&nbsp;Richard M. Ingram,&nbsp;Robert J. White","doi":"10.1002/biot.202400455","DOIUrl":"https://doi.org/10.1002/biot.202400455","url":null,"abstract":"<p>Random integration of transgenes into host cell genomes often occurs in epigenetically unstable regions, leading to variable and unreliable transgene expression. To address this, biomanufacturing organizations frequently employ barrier elements, such as the widely-used ubiquitous chromatin opening element (UCOE). We have compared UCOE barrier activity against a barrier provided by tRNA genes. We demonstrate that the tRNA genes provide a more effective barrier than a UCOE in preventing transgene silencing in Chinese hamster ovary (CHO) cells. Nevertheless, the UCOE offers other benefits, increasing expression strongly, albeit transiently, and reducing production variability. Both the UCOE and tRNA genes counteract the repressive heterochromatin mark H3K9me3, but only the tRNA genes sustain euchromatic H3K27ac and recruitment of RNA polymerase II (Pol II) throughout long-term culture. A hybrid combining these distinct types of elements can provide benefits of both, enhancing expression in a more enduring manner. This synthetic hybrid offers potential for biomanufacturing applications.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"20 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biot.202400455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Experimental Study of Double-Layer Heterogeneous CA Scaffold in Promoting the Surface Shape Recovery and Internal Osteogenesis of Alveolar Bone","authors":"Songxia Ke,&nbsp;Xiaohui Sun,&nbsp;Jing Qian,&nbsp;Ziqing Zhou,&nbsp;Minhong Lin,&nbsp;Baoying He,&nbsp;Renze Shen,&nbsp;Zhanchao Ye","doi":"10.1002/biot.202400603","DOIUrl":"https://doi.org/10.1002/biot.202400603","url":null,"abstract":"<div>\u0000 \u0000 <p>In this work, double-layer heterogeneous CA scaffolds were designed for alveolar bone defects. The outer layer featured high hardness and slow degradation, and large pores and rapid degradation characterized the inner layer. The CA scaffold morphology was akin to bone defects, and its direct implantation reduced the operation time. A higher concentration of CA resulted in smaller pores and slower degradation. CA can promote the formation of mineralized nodules and the expression of genes related to mineralization without inducing cytotoxic effects. It also promoted the expression of cellular inflammatory factors, potentially through the TLR4 pathway. In vivo studies confirmed that CA did not promote the aggregation of inflammatory cells or the expression of inflammatory factors. In conclusion, the scaffold's characteristics of high surface hardness and slow degradation were beneficial for surface osteogenesis and maintaining the defect's shape and osteogenic space. Conversely, rapid internal degradation favors the formation of bone tissue.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"20 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}