摘要：合成生物学是借助基因工具改造活细胞和生物体的学科,其经历了蓬勃发展阶段,在生物医学领域得到广泛应用,包括新型生物传感器和生物材料设计,以及最新临床治疗药物和疫苗的开发.纳米材料具有独特的物理、化学和生物特性,在拓展合成生物学的生物医学应用场景上具有巨大的潜力,可以提高治疗剂的生产效率,并增强改造生物体的功能.在此,我们简要概述了纳米材料应用于合成生物学领域的最新进展,主要涵盖纳米材料作为递送载体、信号转导器和功能增强剂的角色及其制备过程和性能特点.本综述首先强调了纳米材料作为基因载体的最新成果,包括有机、无机和仿生递送系统;其次,回顾了纳米材料介导的刺激响应型基因表达调控的研究;第三,总结了在可编程的杂化生物活性材料方面的开创性工作,包括纳米材料/细菌杂合系统和纳米材料/哺乳动物细胞杂合系统;最后,讨论了该领域当前面临的挑战,并从个人观点展望了未来的发展前景.

摘要：Introduction The climax of the industrial revolution was marked by the rapid growth of industry,and advancement in technologies have further fueled this industrial expansion,leading to a surge in economic *** technologies have also increased the degree of destructive human inter-ference with the biosphere.

摘要：In this study,boron-doped hydroxyapatite(BHT)-loaded alginate/gelatin-based(A/G)hydrogel coating on Ti was fabricated to support bone integration through triggering osteoinduction,vascularization and ***,highly reproducible,cheap and time-effective BHT was produced,which significantly promoted higher osteogenic and angiogenic maturation,while a mild innate immune response was *** immense potential of BHT was evidenced by the production of a gap-filling A/G/BHT interphase on Ti implants to mimic the osseous extracellular matrix to achieve functional bridging and exert control over the course of innate immune *** initially aminosilanized the implant surface using 3-aminopropyl triethoxysilane,and then coated it with 0.25%w/v alginate with 20 mM 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide to allowthe A/G/BHT pre-gel to disperse evenly and covalently attach on the *** pre-gel was added with 0.2 M NaCl to homogeneously blend BHT in the structure without inducing ionic ***,the coated implants were freeze-dried and *** coated layer demonstrated high cohesive and adhesive strength,and 8-month-long shelf-life at room temperature and normal *** A/G/BHT was able to coat an irregularly shaped Ti *** and endothelial cells thrived on the A/G/BHT,and it demonstrated greatly improved osteogenic and angiogenic ***,A/G/BHT maintained macrophage viability and generated an acute increase in immune response that could be resolved ***,A/G/BHT was shown to induce the robust integration of implant in a rabbit femur osteochondral model within ***,we concluded that A/G/BHT coatings could serve as amultifunctional reservoir,promoting the strong and rapid osseointegration of metallic implants.

摘要：Specific and dynamic biological interactions pave the blueprint of signal networks in cell. For example, a great variety of specific protein-ligand interactions define how intracellular signals flow. Taking advantage of the specificity of these interactions, we postulate an "affinity-guided covalent conjugation" strategy to lock binding ligands through covalent reactions between the ligand and the receptor protein. The presence of a nucleophile close to the ligand binding site of a protein is sine qua none of this reaction. Specific noncovalent interaction of a ligand derivative(which contains an electrophile at a designed position) to the ligand binding site of the protein brings the electrophile to the close proximity of the nucleophile. Subsequently, a conjugation reaction spontaneously takes place between the nucleophile and the electrophile, and leads to an intermolecular covalent linkage. This strategy was first showcased in coiled coil peptides which include a cysteine mutation at a selected position. The short peptide sequence was used for covalent labeling of cell surface receptors. The same strategy was then used to guide the design of a set of protein Lego bricks for covalent assembly of protein complexes of unnatural geometry. We finally made "reactive peptides" for natural adaptor proteins that play significant roles in signal transduction. The peptides were designed to react with a single domain of the multidomain adaptor protein, delivered into the cytosol of neurons, and re-directed the intracellular signal of neuronal migration. The trilogy of protein labeling, assembly, and inhibition of intracellular signals, all through a specific covalent bond, fully demonstrated the generality and versatility of "affinity-guided covalent conjugation" in various applications.

摘要：At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal *** method has great trauma to patients,poor plasticity and inaccurate ***-dimensional(3D)printing technology has made a great breakthrough in the clinical application of orthopedic *** study explored the combination of 3D printing and tissue engineering to precisely reconstruct the ***,a polylactic acid(PLA)polymer scaffold with a precisely customized patient appearance was fabricated,and then auricle cartilage fragments were loaded into the 3D-printed porous PLA scaffold to promote auricle *** vitro,gelatin methacrylamide(GelMA)hydrogels loaded with different sizes of rabbit ear cartilage fragments were studied to assess the regenerative activity of various autologous cartilage *** vivo,rat ear cartilage fragments were placed in an accurately designed porous PLA polymer ear scaffold to promote auricle *** results indicated that the chondrocytes in the cartilage fragments could maintain the morphological phenotype in *** three months of implantation observation,it was conducive to promoting the subsequent regeneration of cartilage in *** autologous cartilage fragments combined with 3D printing technology show promising potential in auricle reconstruction.

摘要：Currently,cell culture models play a key role in determining cell behavior under various ***,the accurate simulation of cellular behavior that imitates the body’s conditions remains a ***,to overcome this obstacle,three-dimensional cell culture models have been *** tissues/organs-on-chips(TOOCs)are new devices that have provided the opportunity to culture cells in a medium that is almost similar to the physiological conditions of the *** can be designed in simple or complex models,which are mostly fabricated by soft *** novel structures have been developed to mimic the conditions of various tissues and organs;however,microfluidic models for oral and dental tissues have not yet been widely *** application of TOOCs for oral tissues/organs can provide the opportunity to study cell interactions with biomaterials used in ***,TOOCs can provide the opportunity to study the cellular interactions and developmental stages of oral tissues/organs more *** review of the current advances in the field of TOOC development for oral tissues provides a comprehensive understanding of this burgeoning concept,shows the progress and applications of these novel models in the imitation of oral tissues/organs thus far,and reveals the limitations that TOOCs ***,it suggests further perspectives for future applications.

摘要：Vinblastine has been used clinically as one of the most potent therapeutics for the treatment of several types of ***,the traditional plant extraction method suffers from unreliable supply,low abundance,and extremely high ***,we use synthetic biology approach to engineer Saccharomyces cerevisiae for de novo biosynthesis of vindoline and catharanthine,which can be coupled chemically or biologically to *** the basis of a platform strain with sufficient supply of precursors and cofactors for biosynthesis,we reconstituted,debottlenecked,and optimized the biosynthetic pathways for the production of vindoline and *** vindoline biosynthetic pathway represents one of the most complicated pathways ever reconstituted in microbial cell *** shake flask fermentation,our engineered yeast strains were able to produce catharanthine and vindoline at a titer of 527.1 and 305.1μg·liter^(−1),respectively,without accumulating detectable amount of pathway *** study establishes a representative example for the production of valuable plant natural products in yeast.

摘要：Organ-on-a-chip systems have been increasingly recognized as attractive platforms to assess toxicity and to develop new therapeutic ***,current organ-on-a-chip platforms are limited by a“single pot”design,which inevitably requires holistic analysis and limits parallel ***,we developed a digital organ-on-a-chip by combining a microwell array with cellular microspheres,which significantly increased the parallelism over traditional organ-on-a-chip for drug *** to 127 uniform liver cancer microspheres in this digital organ-on-a-chip format served as individual analytical units,allowing for analysis with high consistency and quick *** platform displayed evident anti-cancer efficacy at a concentration of 10μM for sorafenib,and had greater alignment than the“single pot”organ-on-a-chip with a previous in vivo *** addition,this digital organ-on-a-chip demonstrated the treatment efficacy of natural killer cell-derived extracellular vesicles for liver cancer at 50μg/*** successful development of this digital organ-on-a-chip platform provides high-parallelism and a low-variability analytical tool for toxicity assessment and the exploration of new anticancer modalities,thereby accelerating the joint endeavor to combat cancer.

摘要：近年来,活细胞内原位聚合由于具有高细胞内化效率和延长药物滞留时间的特性而备受关注.然而,对原位聚合过程的可视化追踪仍缺失,聚合过程对细胞功能的影响机制尚不明确,极大地限制了其在生物医学领域的应用.在本文中,我们设计了一种带正电荷的Y型二乙炔脂肽(Y-DLPA1),系统研究了其在细胞内微环境中活性氧引发的原位聚合行为.作为对照组,具有类似分子拓扑结构的两性离子型二乙炔脂肽Y-DLPA2和负电荷型二乙炔脂肽Y-DLPA3在水溶液中能够发生紫外光辐照聚合,而在细胞内微环境中无法聚合.尤为重要的是,聚合后的Y-DLPA1具有红色荧光,实现了原位可视化追踪细胞内聚合过程.此外,二乙炔脂肽原位聚合反应能够诱导肿瘤细胞凋亡,增加细胞黏度,降低细胞运动能力,为抑制肿瘤转移提供了一种潜在的策略.

摘要：Introduction and research overview Recently,increasing need for organ transplantation and lack of donated organs have led to the rapid development of new technologies for artificial organ *** the era of burgeoning breakthroughs around 3D bioprinting technologies,the personalization of organs and medicine is an ongoing nice vision[1–5].As one of the leading laboratories in the interdisciplinary field of materials,manufacturing and bioengineering,the Biofabrication(3D Bioprinting)Research Laboratory at Sichuan University has been engaging in the research on customized regenerativemedicine since 2012.