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，研究人员描述了该材料制造的植入物如何成功地消除了动物模型中两种假体感染。
Currently, most infections involving total joint replacement prostheses require a two-stage surgery, in which the patient's daily activities are largely compromised for 4-6 months. Delivering antibiotics to an infected prosthetic joint is challenging because of the limited supply of blood to the area. The standard treatment for prosthetic joint infection in the U.S. involves removal of the implant and adjacent infected tissues and placement of a temporary spacer made from antibiotic-releasing bone cement that remains within the joint space for at least six weeks and sometimes for as long as six months. During that time, the patient's movement may be significantly restricted, depending on the involved joint. In a second surgery, a new prosthesis is implanted, using antibiotic-releasing bone cement. But patients still can be at risk for recurrent infection, which may lead to the need for permanent joint fusion or amputation and has a 10-15% mortality rate. Antibiotic-releasing bone cement has several limitations. Its ability to release an effective antibiotic dose may be brief, lasting little more than a week, and increasing the antibiotic content reduces the material's durability. In addition, some antibiotics with desirable qualities cannot be incorporated into a bone cement. 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 in自然微生物学describing a promising alternative technology to combat multidrug-resistant bacteria. Instead of designing a traditional chemical drug treatment, the team developed what they callstructurally nano engineered antimicrobial peptide polymers (SNAPPs).研究人员的灵感来自天然抗菌肽，这些蛋白质是在许多生物体的免疫系统中起重要作用的小蛋白质。科学家精心设计的聚合物，直至单个构建块 - 氨基酸的水平，这将构成肽。
在他们可用的许多氨基酸中，科学家选择了赖氨酸和缬氨酸。赖氨酸是一种带正电的阳离子，因此选择是因为已知阳离子肽表现出抗菌活性。另一方面，缬氨酸是未充电的，因此是疏水性的，这意味着它与水或其他极性分子的相互作用并不相互作用。由于疏水材料与其他疏水材料相互作用，因此瓦琳的疏水性使Snapps能够渗入细胞膜，这也主要是疏水。研究人员不仅会创建长长的氨基酸链或使聚合物自组装，还将16或32个链的组附加到多功能核心上，这有助于促进水溶性并创建特征性的星形形状。他们假设恒星形状优化了功能，因为它促进了肽聚集和局部电荷浓度，从而导致与细菌膜更有效的离子相互作用。
研究人员评估了SNAPP对不同种类细菌的活性。SNAPP对所有细菌物种都具有活性E. coli. Gram-negative bacteria are characterized by an outer membrane that normally acts as a highly impermeable barrier, but the researchers discovered that the SNAPPs could penetrate this membrane since they have a high affinity for specific molecules found on it. The treatment was equally effective against antibiotic-resistant and susceptible strains of bacteria. The effectiveness of SNAPPs against Gram-negative bacteria is especially important because no antibiotic drugs currently under development are effective against Gram-negative infections.
The SNAPPs have multiple mechanisms of killing cells, making it more difficult for bacteria to develop resistance against them. The polymers’ partially hydrophobic composition allows them to infiltrate the membrane, but once they have done so, the positively charged amino acids disrupt membrane integrity and prevent regulation of ion flow. The star-shaped polymers can even aggregate and rip apart the membrane. The SNAPPs may also trigger the cellular processes that induce apoptosis, or cell suicide. All these mechanisms of antibiotic action are impressive individually, but when combined in a single molecule they are incredibly powerful and difficult for bacteria to fight. Even after exposing 600 generations of bacteria to low concentrations of SNAPPs, the researchers could not detect bacterial resistance to the treatment. These results show great promise for SNAPPs as a long-term solution to the rise of superbugs.
To bring treatments like SNAPPs into regular use, more research, development, and eventually clinical trials are needed.