The lattice of active metal borides shows a rich bond mode, which can hydrolyze to produce intermediate boron-hydrogen nanosheets and release ions, which gives boride materials versatility.

In addition, the proposed new strategy of "boron capture" reveals that active metal borides can destroy bacterial structure by binding to key polysaccharide components of bacterial cell walls (lipopolysaccharide/peptidoglycan), thus achieving sterilization.

The results of a series of comparative experiments showed that the bactericidal activity of the strategy was comparable to that of classical antibiotics such as amikacin, gentamicin and ciprofloxacin, and even the antibacterial effect was much better than that of amtronam, ampicillin and sulbactam.

It is worth mentioning that active metal borides can reduce bacterial resistance by destroying the bactericidal mechanism of bacterial structure, and it is expected to achieve a more long-term bactericidal effect.

Therefore, as a highly effective antibacterial component, the material can be added to textiles to inhibit bacterial growth and prevent odor; It can also be made into an antibacterial coating, which can be applied to the surface of metal implants or medical devices to achieve efficient sterilization.

In addition, it is reported that active metal borides not only have antibacterial function, but also can use the "boron capture" function, combined with free lipopolysaccharide/peptidoglycan released by dead bacteria, effectively inhibit the excessive inflammatory response induced by dead bacteria.

Therefore, the material can also be used for a series of bacterial infection-related diseases such as skin infection, wound infection and gastrointestinal ulcer, solving the clinical problem that traditional antimicrobials are limited to killing live bacteria and cannot inhibit the excessive inflammation caused by dead bacteria in the host.

The team further found that the "boron-trapping" properties of active metal borides can affect the function of sugars by complexing key sites of sugars, thus playing an important role in the treatment of diabetes complications and other carbohydrate-metabolic types of diseases.

They predict that the controlled ion release properties of such materials also have the potential to regulate ion current, which is expected to play a potentially important role in fields related to neurological diseases.

                                               To achieve effective treatment of infected wounds

Bacterial infection is an important cause of chronic wound failure, which can lead to sepsis, multiple organ failure and even death in severe cases.

At present, the main clinical use of antibiotics and antibacterial nanomedical treatment of wound infection. Although these drugs can effectively inhibit bacterial growth, dead bacteria will release a large amount of free lipopolysaccharide or peptidoglycan, which will activate host immune cells and cause excessive inflammatory response, resulting in long-term wound healing, which greatly limits the therapeutic effect of these drugs.

Therefore, how to make drugs both inhibit the growth of live bacteria and induce excessive inflammation by dead bacteria is a scientific problem that needs to be solved.

                                      Diagram of live and dead bacteria hindering wound healing

It has been shown that some key components of pathogens play a key role in their structure and function. For example, lipopolysaccharides/peptidoglycans are key components of Gram-negative and Gram-positive bacteria, respectively.

On the one hand, lipopolysaccharide/peptidoglycan is a key structural component of bacterial cell wall, which plays a role in maintaining the integrity of bacterial structure and protecting bacteria from antibacterial agents.

On the other hand, lipopolysaccharide/peptidoglycan is also a major functional component of bacterial toxins, which can be released from the outer membrane of dead bacteria, and is highly immunogenic, inducing excessive inflammation in the host and damaging the host tissue.

It is worth noting that the polysaccharide components contained in lipopolysaccharides/peptidoglycans all contain typical 1,2- or 1, 3-o-dihydroxyl groups, which are the important structural basis for the corresponding functions of lipopolysaccharides/peptidoglycans.

Therefore, the team speculated that if the key groups of lipopolysaccharide/peptidoglycan are captured by chemical means, it can not only inhibit the survival ability of live bacteria structurally, but also inhibit the excessive inflammation induced by dead bacteria functionally, so as to achieve the purpose of promoting efficient wound healing.

Therefore, how to design new functional materials from the perspective of materials science, by capturing lipopolysaccharide/peptidoglycan, a key component of bacteria, so that the material can both inhibit the growth of live bacteria and inhibit excessive inflammation induced by dead bacteria, is the key to achieve efficient treatment of infected wounds.

Based on this, the team first thought of borate materials, which are rich in boron dihydroxyl and can esterify with the o-dihydroxyl of sugar to generate dynamic borate ester bonds. This dynamic covalent bond has been widely used to identify substances such as blood support, glucose, and adenosine triphosphate.

Unfortunately, the borate bond dissociates very easily under acidic and inflammatory conditions, and it is possible that borate materials are not suitable for such disease models.

To this end, the team further wondered whether the material could be designed to improve the stability of the borate bond in the pathological microenvironment.

After investigating the classic reaction "borate-sugar complexation", they found that the stability of borate ester bond is closely related to the configuration of boron element.

Under alkaline conditions, the configuration of boron elements can be changed from sp2 to sp3, which can cause the change of bond Angle of boron dihydroxyl group, which can effectively release the bond tension of cyclic borate ester bond and improve the stability of borate ester bond.

Based on these principles, the team believes that designing materials that can form stable borate ester bonds will be the key to efficient

lipopolysaccharide/peptidoglycan capture.

Based on the above background, they designed and synthesized this type of active metal boride, which can hydrolyze to form boron dihydroxyl and hydroxide, and release metal cations.

Among them, the alkaline microenvironment created by hydroxide can make the configuration of boron atoms change from sp2 to sp3, thereby promoting the esterification of boron dihydroxyl group and sugar dihydroxyl group, thus forming a stable borate ester bond.

This also means that using this new "boron capture" mechanism, it is possible to capture lipopolysaccharide/peptidoglycan on the surface of bacteria: on the one hand, by destroying the structure of living bacteria for sterilization, on the other hand, by neutralizing the toxins released by dead bacteria for anti-inflammatory, and ultimately effectively promote the healing of infected wounds.

With this strategy, they solved the clinical bottleneck problem that traditional antimicrobials are limited to killing live bacteria and cannot inhibit excessive inflammation induced by dead bacteria.

           Schematic diagram of antibacterial and anti-inflammatory use of the "boron capture" mechanism

However, the question arises, how do active metal borides achieve antibacterial and anti-inflammatory effects after capturing lipopolysaccharide/peptidoglycan on the surface of bacteria

Molecular biological mechanism studies have shown that the combination of active metal borides with lipopolysaccharides/peptidoglycans on the surface of bacteria can significantly increase the concentration of local cations, such as Mg ions, on the surface of bacteria, thereby changing the membrane potential of the bacterial outer membrane, thereby destroying the membrane permeability, and finally activating the bacterial RNA degradation signal pathway, which plays an efficient bactericidal function.

On the other hand, after binding with free lipopolysaccharide/peptidoglycan released by dead bacteria, active metal borides can effectively inhibit the phosphorylation of free lipopolysaccharide/peptidoglycan induced MAPKs, including P38, Erk and JNK signaling pathways, thereby inhibiting the inflammatory response.

A series of experiments in vivo showed that active metal borides can significantly promote the healing of infected wounds in mice. It can be said that this study not only solves the key bottleneck problem that dead bacteria are easy to cause excessive inflammation, which has been neglected in previous studies, but also groundbreaking reveals the new mechanism of active metal borides in antibacterial and anti-inflammatory aspects, which is expected to provide new ideas for the development of new antibacterial and wound healing therapeutics and clinical treatment of infectious diseases.

In summary, Bu Wenbo's team summarized this kind of active metal boride material as "boron magnetic" material, proposed the strategy of "boron magnetic" to capture the key components of bacteria, and revealed its antibacterial and anti-inflammatory functional mechanism, which can realize the effective treatment of infected wounds.

                             Active metal borides and bacteria two "same and different"

Looking back, the topic comes from their discovery that the main reason why infected wounds are difficult to heal is because they cannot take into account killing live bacteria and inhibiting excessive inflammation induced by dead bacteria.

In order to solve this bottleneck problem, they focused on the key polysaccharide component (lipopolysaccharide/peptidoglycan) shared by living and dead bacteria, and learned from the classic esterification reaction that can occur between boron dihydroxyl group and adjacent dihydroxyl group, and ingenically used the boron dihydroxyl group produced by hydrolysis of boric acid materials to complex the lipopolysaccharide/peptidoglycan of bacteria, blocking the biological effect of bacteria.

At the same time, in order to overcome the bottleneck problem that borate ester bond is easily dissociated under acidic and inflammatory conditions, the team designed and synthesized a new type of active metal boride material system, and speculated that the hydroxide released by its hydrolysis can create an alkaline microenvironment and help to improve the stability of borate ester bond.

Next, the study enters the feasibility verification phase. Specifically, the team used an improved high-temperature self-propagating combustion method, where they prepared a series of active metal borides with particle sizes around 200nm.

Taking magnesium boride as an example, the research team first verified the material's ability to create an alkaline microenvironment by releasing hydroxide during hydrolysis.

During this time, they observed that active metal borides can be complexed with lipopolysaccharides/peptidoglycans to form borate ester bonds. In addition, the preliminary antibacterial experiment proves that magnesium boride has excellent antibacterial properties, and the feasibility of the project can be verified.

Subsequently, the research entered the phase of systematically testing the functional properties of the materials. The team analyzed the characteristics of the hydrolysis of a series of active metal borides to produce boron dihydroxyl, hydroxide and release metal ions, and used infrared spectroscopy and other testing techniques to prove that this series of active metal borides can react with lipopolysaccharide/peptidoglycan and bacteria to generate borate ester bonds.

Further, through theoretical calculation, they found that the borate bond formed by the complexation of active metal borides and lipopolysaccharides was stronger than the corresponding boric acid complexation. Through SEM-mapping, the team also observed that active metal borides bind to bacterial cell walls more easily than boric acid, a key experimental data, demonstrating that active metal borides can form stable borate bonds with lipopolysaccharides/peptidoglycans.

Next, the research entered the stage of revealing the antibacterial and anti-inflammatory function mechanism of active metal borides. During this period, the team evaluated the excellent antibacterial effect of active metal borides by using flow cytometry, biological electron microscopy, laser confocal and other testing methods, and observed that active metal borides could change the membrane potential of bacterial cell membranes, and the bacterial cell membranes were also ruptured.

Then, through transcriptome sequencing experiments, they found that the cause of bacterial death caused by active metal borides was closely related to the over-activated RNA degradation signaling pathway in bacteria.

Based on the above results, the team speculated that the combination of active metal borides with lipopolysaccharides/peptidoglycans on the bacterial surface can significantly increase the local concentration of metal cations on the bacterial surface, thereby changing the membrane potential of the bacterial outer membrane and destroying the membrane permeability, thereby activating the bacterial RNA degradation signaling pathway, and finally achieving efficient sterilization.

On the other hand, through immune cell activation experiments, the team also demonstrated that active metal borides can bind free lipopolysaccharide/peptidoglycan released by dead bacteria, and thus inhibit free lipopolysaccharide/peptidoglycan induced MAPKs, including phosphorylation of P38, Erk, and JNK signaling pathways, thereby providing a potent anti-inflammatory effect.

The final step is the functional verification of living mice. In a bacteria-infected mouse model, a mouse model of dead bacteria-induced inflammation, and an infected wound model, the team systematically verified the anti-infective, anti-inflammatory, and pro-infected wound functions of the material, as well as the antibacterial, anti-inflammatory, and pro-infected wound healing effects of active metal borides from pathological sections and immunofluorescence levels. At this point, finally for this topic to draw a successful end.

For the research process, Bu Wenbo also said such a tidbits: "In the early stage of the experiment, we tried to synthesize a series of active metal borides that can be decomposed in water phase, and verify whether the material has the assumed antibacterial function.

The preliminary experimental results gave us a great surprise - the active metal borides of this series have excellent antibacterial activity. It is worth mentioning that different types of active metal borides are not the same for the antibacterial activity of the same bacteria; The same type of active metal borides also exhibit different antimicrobial activity for different species of bacteria."

This shows that the antibacterial function of different active metal borides is different, and there is still a lot of room in the future to explore the characteristics of various materials, explore the new antibacterial mechanism of materials, and optimize the antibacterial function of materials.

                                                                    "His arsenic, his sweetness."

When designing the material, Bu Wenbo inadvertently communicated with a researcher in the field of superconductivity, through which he learned that magnesium diboride, a classic material in the field, has a unique phenomenon of tidal decomposition that affects the performance of subsequent experiments.

"In reverse thinking, we found the inherent weakness of poor stability when applied to superconductivity, but this can be exploited by the biomedical field, and then turned into a unique performance advantage." Bu Wenbo said.

At the same time, the achievement was jointly completed by materials workers from Fudan University and biomedical researchers from the 10th People's Hospital Affiliated to Tongji University, which fully reflects the importance of cross-disciplinary and close cooperation between different disciplines. This cooperation mode also gives play to the respective advantages of universities and hospitals.

Next, the team will delve deeper into the unique "boron capture" material science mechanism of active metal borides. As mentioned earlier, in this study, they clearly observed the difference in "boron capture" performance between active metal borides and ordinary boric acid components, so the future will be explored from the perspective of polycentric bonding characteristics of boron-containing components of borides.

Second, the team will also explore new antimicrobial mechanisms of active metal borides "boron capture." As mentioned above, the antibacterial effect of different active metal borides on the same bacteria is not the same; For different bacteria, even the same active metal boride will show different activity.

Therefore, they will explore the molecular biological mechanisms involved to help identify antimicrobials with optimal function and find the best way to manufacture antimicrobials.

Of course, the team will also strive to advance the clinical conversion of active metal borides. At present, the achievement has been declared the relevant patent. Next, they will systematically study the safety of active metal borides in and out of organisms and develop related products such as hydrogels, powders and patches in order to evaluate the bioactivity and stability of these products, and ultimately promote clinical conversion.