Immunomodulatory biomaterials against bacterial infections:Progress,challenges,and future perspectives

Bacterial infectious diseases are one of the leading causes of death worldwide.Even with the use of multiple antibiotic treatment strategies,4.95 million people died from drug-resistant bacterial infections in 2019.By 2050,the number of deaths will reach 10 milion annually.The increasing mortality may be partly due to bacterial heterogeneity in the infection microenvironment,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants.In addition,the complexity of the immune microenvironment at different stages of infection makes biomaterials with direct antimicrobial activity unsatisfactory for the longterm treatment of chronic bacterial infections.The increasing mortality may be partly attributed to the biomaterials failing to modulate the active antimicrobial action of immune cells.Therefore,there is an urgent need for effective alternatives to treat bacterial infections.Accordingly,the development of immunomodulatory antimicrobial biomaterials has recently received considerable interest;however,a comprehensive review of their research progress is lacking.In this review,we focus mainly on the research progress and future perspectives of immunomodulatory antimicrobial biomaterials used at different stages of infection.First,we describe the characteristics of the immune microenvironment in the acute and chronic phases of bacterial infections.Then,we highlight the immunomodulatory strategies for antimicrobial biomaterials at different stages of infection and their corresponding advantages and disadvantages.Moreover,we discuss biomaterial-mediated bacterial vaccines'potential applications and challenges for activating innate and adaptive immune memory.This review will serve as a reference for future studies to develop next-generation immunomodulatory biomaterials and accelerate their translation into clinical practice.

疏水基取代的分枝状聚乙酰亚胺衍生物:促进原发性血管细胞中的转染（英文）

针对血管细胞的基因治疗代表了一种有望用于预防和治疗内膜增生、血管支架狭窄和血管成形术后狭窄等病理状态的方法.聚合物非病毒载体的基因传递系统可以安全替代病毒载体,但是为了提高临床效果,它们的治疗效率及细胞相容性还需要进一步改善.本文合成了一系列24种被疏水基团修饰的分枝状聚乙酰亚胺衍生物(bPEI),并进行了表征及在体外原发性血管细胞内的测试,旨在筛选出具有优异的转染效率和低细胞毒性的传递剂.低分子量的聚乙酰亚胺(0.6,1.2 and 2 kDa)以不同取代程度接枝上了不同饱和度的长(C18)和短(C3)的不饱和脂肪链.丙酰取代衍生物(PEI2-PrA1,C3:0)在血管平滑肌细胞和内皮细胞转染中是最有效的,与著名的黄金标准25 kDa bPEI相比,具有更优异、更持久的基因表达,且毒性更低.此外,亚油酰基取代衍生物(PEI1.2-LA6,C18:2)由于在血管平滑肌细胞转染过程中效率高,而在内皮细胞中相对无效,且其具有可容忍的细胞毒性,可作为特定靶向于血管平滑肌细胞的载体.

Improving the radiopacity of Fe-Mn biodegradable metals by magnetron-sputtered W-Fe-Mn-C coatings:Application for thinner stents

In this exploratory work,micrometric radiopaque W-Fe-Mn-C coatings were produced by magnetron sputtering plasma deposition,for the first time,with the aim to make very thin Fe-Mn stents trackable by fluoroscopy.The power of Fe-13Mn-1.2C target was kept constant at 400 W while that of W target varied from 100 to 400 W producing three different coatings referred to as P100,P200,P400.The effect of the increased W power on coatings thickness,roughness,structure,corrosion behavior and radiopacity was investigated.The coatings showed a power-dependent thickness and W concentration,different roughness values while a similar and uniform columnar structure.An amorphous phase was detected for both P100 and P200 coatings while γ-Fe,bcc-W and W_(3)C phases found for P400.Moreover,P200 and P400 showed a significantly higher corrosion rate(CR)compared to P100.The presence of W,W_(3)C as well as the Fe amount variation determined two different micro-galvanic corrosion mechanisms significantly changing the CR of coatings,0.26±0.02,59.68±1.21 and 59.06±1.16μm/year for P100,P200 and P400,respectively.Sample P200 with its most uniform morphology,lowest roughness(RMS=3.9±0.4 nm)and good radiopacity(~6%)appeared the most suitable radiopaque biodegradable coating investigated in this study.

Effect of silver in thermal treatments of Fe-Mn-C degradable metals:Implications for stent processing

Twinning-induced plasticity(TWIP)steels are considered excellent materials for manufacturing products requiring extremely high mechanical properties for various applications including thin medical devices,such as biodegradable intravascular stents.It is also proven that the addition of Ag can guarantee an appropriate degradation while implanted in human body without affecting its bioactive properties.In order to develop an optimized manufacturing process for thin stents,the effect of Ag on the recrystallization behavior of TWIP steels needs to be elucidated.This is of major importance since manufacturing stents involves several intermediate recrystallization annealing treatments.In this work,the recrystallization mechanism of two Fe-Mn-C steels with and without Ag was thoroughly investigated by microstructural and mechanical analyses.It was observed that Ag promoted a finer microstructure with a different texture evolution,while the recrystallization kinetics resulted unaffected.The presence of Ag also reduced the effectiveness of the recrystallization treatment.This behavior was attributed to the presence of Ag-rich second phase particles,precipitation of carbides and to the preferential development of grains possessing a{111}orientation upon thermal treatment.The prominence of{111}grains can also give rise to premature twinning,explaining the role of Ag in reducing the ductility of TWIP steels already observed in other works.Furthermore,in vitro biological performances were unaffected by Ag.These findings could allow the design of efficient treatments for supporting the transformation of Fe-Mn-C steels alloyed with Ag into commercial products.

Surface processing for iron-based degradable alloys:A preliminary study on the importance of acid pickling

The formation of a heterogeneous oxidized layer,also called scale,on metallic surfaces is widely recognized as a rapid manufacturing event for metals and their alloys.Partial or total removal of the scale represents a mandatory integrated step for the industrial fabrication processes of medical devices.For biodegradable metals,acid pickling has already been reported as a preliminary surface preparation given further processes,such as electropolishing.Unfortunately,biodegradable medical prototypes presented discrepancies concerning acid pickling studies based on samples with less complex geometry(e.g.,non-uniform scale removal and rougher surface).Indeed,this translational knowledge lacks a detailed investigation on this process,deep characterization of treated surfaces properties,as well as a comprehensive discussion of the involved mechanisms.In this study,the effects of different acidic media(HCl,HNO_(3),H_(3)PO_(4),CH_(3)COOH,H_(2)SO_(4) and HF),maintained at different temperatures(21 and 60℃)for various exposition time(15-240 s),on the chemical composition and surface properties of a Fe-13Mn-1.2C biodegradable alloy were investigated.Changes in mass loss,morphology and wettability evidenced the combined effect of temperature and time for all conditions.Pickling in HCl and HF solutions favor mass loss(0.03-0.1 g/cm^(2))and effectively remove the initial scale.

Proteomics as a tool to gain next level insights into photo-crosslinkable biopolymer modifications

The distribution of photo-crosslinkable moieties onto a protein backbone can affect a biomaterial’s crosslinking behavior, and therefore also its mechanical and biological properties. A profound insight in this respect is essential for biomaterials exploited in tissue engineering and regenerative medicine. In the present work, photo-crosslinkable moieties have been introduced on the primary amine groups of: (i) a recombinant collagen peptide (RCPhC1) with a known amino acid (AA) sequence, and (ii) bovine skin collagen (COL BS) with an unknown AA sequence. The degree of substitution (DS) was quantified with two conventional techniques: an ortho-phthalic dialdehyde (OPA) assay and ^(1)H NMR spectroscopy. However, neither of both provides information on the exact type and location of the modified AAs. Therefore, for the first time, proteomic analysis was evaluated herein as a tool to identify functionalized AAs as well as the exact position of photo-crosslinkable moieties along the AA sequence, thereby enabling an in-depth, unprecedented characterization of functionalized photo-crosslinkable biopolymers. Moreover, our strategy enabled to visualize the spatial distribution of the modifications within the overall structure of the protein. Proteomics has proven to provide unprecedented insight in the distribution of photo-crosslinkable moieties along the protein backbone, undoubtedly contributing to superior functional biomaterial design to serve regenerative medicine.

A microfluidic approach for development of hybrid collagen-chitosan extracellular matrix-like membranes for on-chip cell cultures

To advance organ-on-a-chip development and other areas befitting from physiologically-relevant biomembranes,a microfluidic platform is presented for synthesis of biomembranes during gelation and investigation into their role as extracellular matrix supports.In this work,high-throughput studies of collagen,chitosan,and collagen-chitosan hybrid biomembranes were carried out to characterize and compare key properties as a function of the applied hydrodynamic conditions during gelation.Specifically,depending on the biopolymer material used,varying flow conditions during biomembrane gelation caused width,uniformity,and swelling ratio to be differently affected and controllable.Finally,cell viability studies of seeded fibroblasts were conducted,thus showing the potential for biological applications.