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 in自然生物医学工程，研究人员描述了从这种材料制成的植入物如何成功地消除了动物模型中两种假肢感染。
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.
基于数学和统计模型，它们所开发的材料包含不规则形状的抗生素簇，使它们能够长时间释放有效的药物剂量，而不会损害材料的强度。在通过注射葡萄球菌产生的假体关节感染动物模型中测试了由该聚合物制成的植入物。含金黄色葡萄球菌的溶液中的假体或植入带有葡萄球菌的钛杆。金黄色生物膜，一种特别难以治疗的细菌涂层。在这两种情况下，抗生素释放聚合物都成功地消除了感染，而植入药物释放骨水泥垫片则无效。Muratoglu说：“我们使用了两个独立的感染模型，因为当患者出现人义关节感染症状时，尚不清楚生物膜中可能是哪些细菌的比例，而溶液中的自由漂浮是什么。”“我们的设备在两种模型中消除关节中所有细菌的能力都强烈表明它们将在两种类型的周围感染中都取得成功。”穆拉托格鲁（Muratoglu）是哈佛医学院的骨科手术教授，他指出，除了加快患者的康复并减少并发症的机会外，消除第二次手术程序还应降低整体成本。该团队现在正在与食品药品监督管理局和其他监管机构合作，以寻求必要的批准，并将这些材料开发为临床产品。

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荷的阳离子，被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有利相互作用，因此Valine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恒星形状。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对不同种类的活性。SNAPP对所有细菌物种都具有活性，但特别有效地针对革兰氏阴性细菌大肠杆菌. 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.