An antibiotic-releasing polymer that may greatly simplify the treatment of prosthetic joint infection has been developed by a team of Massachusetts General Hospital (MGH) investigators. In their report published inNature Biomedical Engineering, the researchers describe how implants made from this material successfully eliminated two types of prosthetic infection in animal models.
目前，大多数涉及全关节置换假体的感染需要进行两阶段的手术​​，其中患者的日常活动在很大程度上被损害了4万博平台盘口-6个月。由于对该地区的血液供应有限，将抗生素送给感染的假肢关节很具有挑战性。美国假体关节感染的标准处理涉及去除植入物和相邻感染组织以及放置由抗生素释放骨水泥制成的临时间隔，该间隔在关节空间内保持至少六周，有时长达六个星期万博平台盘口月份。在此期间，根据所涉及的关节，患者的运动可能受到显着限制。在第二次手术中，使用抗生素释放骨水泥植入了新的假体。但是患者仍然可能有复发感染的风险，这可能导致需要永久关节融合或截肢，并且死亡率为10-15％。抗生素释放骨水泥有多个局限性。它释放有效抗生素剂量的能力可能是短暂的，持续不到一周，并且增加抗生素含量会降低材料的耐用性。此外，某些具有理想品质的抗生素不能掺入骨水泥中。 For the current study, the research team - including lead author Jeremy Vincentius Suhardi, a Harvard/MIT MD/PhD student, and senior author Ebru Oral, PhD, both of the Harris Lab - designed and developed an antibiotic-releasing polymer that could be incorporated into the implant itself.
Based on mathematical and statistical models, the material they developed contained antibiotic clusters which were irregularly shaped, making them able to release effective drug doses over extended periods of time without compromising the strength of the material. Implants made from this polymer were tested in animal models of prosthetic joint infection produced either by injecting a Staph. aureus-containing solution into the prosthesis or implanting a titanium rod covered with a Staph. Aureus biofilm, a coating of bacteria that is particularly difficult to treat. In both situations, the antibiotic-releasing polymer successfully eliminated the infection, while implantation of a drug-release bone cement spacer was not effective. "We used two separate infection models because, when patients present with prosthetic joint infection symptoms, it is not clear what proportion of bacteria may be in a biofilm and what are free floating in solution," says Muratoglu. "The ability of our devices to eradicate all bacteria in the joints in both models strongly suggests they would be successful against both types of periprosthetic infection." A professor of Orthopedic Surgery at Harvard Medical School, Muratoglu notes that, in addition to speeding the recovery of patients and reducing the chance of complications, the elimination of a second surgical procedure should reduce overall costs. The team is now working with the Food and Drug Administration and other regulatory agencies to pursue necessary approvals and develop this material into clinical products.

Antibiotic-resistant ‘superbugs’ could soon be a thing of the past after a team of Australian scientists discovered a protein that literally rips them apart. The team including Qiao, Eric Reynolds, and PhD candidate Shu Lam- published a paper inNature Microbiologydescribing a promising alternative technology to combat multidrug-resistant bacteria. Instead of designing a traditional chemical drug treatment, the team developed what they call结构上纳米工程的抗菌肽聚合物（SNAPPS）。The researchers were inspired by natural antimicrobial peptides, which are small proteins that play important roles in the immune systems of many organisms. The scientists meticulously designed the polymers, down to the level of the individual building blocks- amino acid, that would make up the peptides.
的许多可用的氨基酸,scientists chose lysine and valine. Lysine is a positively charged cation, and was selected because cationic peptides were already known to exhibit antimicrobial activity. Valine, on the other hand, is uncharged and therefore hydrophobic, meaning it does not interact favorably with water or other polar molecules. Since hydrophobic materials interact favorably with other hydrophobic materials, valine’s hydrophobicity enables the SNAPPs to infiltrate the cell membrane, which is also mostly hydrophobic. Instead of just creating long chains of amino acids or allowing the polymers to self-assemble, the researchers attached groups of 16 or 32 chains to a multifunctional core, which served to promote water solubility and create the characteristic star shape. They hypothesize that the star shape optimizes functionality because it promotes peptide aggregation and localized charge concentration, which leads to more effective ionic interactions with bacterial membranes.
The researchers assessed the activity of the SNAPPs against different species of bacteria. The SNAPPs were active against all bacterial species but were especially effective against Gram-negative bacteria likeE. coli。革兰氏阴性细菌的特征是通常充当高度不可渗透的屏障的外膜，但是研究人员发现，snapps可以穿透该膜，因为它们对在其上发现的特定分子具有很高的亲和力。该治疗对抗生素耐药性和易感细菌菌株同样有效。SNAPP对革兰氏阴性细菌的有效性尤其重要，因为目前正在开发的抗生素药物均有效地抗革兰氏阴性感染。
SNAPP具有多种杀死细胞的机制，使细菌更难对它们产生抗性。聚合物的部分疏水组成使它们能够渗入膜，但是一旦这样做，带正电荷的氨基酸氨基酸破坏了膜完整性并防止离子流动的调节。星形聚合物甚至可以聚集并撕裂膜。SNAPP还可能触发诱导凋亡或细胞自杀的细胞过程。所有这些抗生素作用的机制都是令人印象深刻的，但是当将单个分子组合在一起时，它们非常强大，并且很难对细菌进行战斗。即使将600代细菌暴露于低浓度的SNAPP之后，研究人员也无法检测到对治疗的细菌耐药性。这些结果显示了Snapps作为超级细菌兴起的长期解决方案的巨大希望。
To bring treatments like SNAPPs into regular use, more research, development, and eventually clinical trials are needed.