Costa Bruna, Martínez-de-Tejada Guillermo, Gomes Paula A C, L Martins M Cristina, Costa Fabíola
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
Pharmaceutics. 2021 Nov 12;13(11):1918. doi: 10.3390/pharmaceutics13111918.
Prevention of orthopedic implant-related infections is a major medical challenge, particularly due to the involvement of biofilm-encased and multidrug-resistant bacteria. Current therapies, based on antibiotic administration, have proven to be insufficient, and infection prevalence may rise due to the dissemination of antibiotic resistance. Antimicrobial peptides (AMPs) have attracted attention as promising substitutes of conventional antibiotics, owing to their broad-spectrum of activity, high efficacy at very low concentrations, and, importantly, low propensity for inducing resistance. The aim of this review is to offer an updated perspective of the development of AMPs-based preventive strategies for orthopedic and dental implant-related infections. In this regard, two major research strategies are herein addressed, namely (i) AMP-releasing systems from titanium-modified surfaces and from bone cements or beads; and (ii) AMP immobilization strategies used to graft AMPs onto titanium or other model surfaces with potential translation as coatings. In overview, releasing strategies have evolved to guarantee higher loadings, prolonged and targeted delivery periods upon infection. In addition, avant-garde self-assembling strategies or polymer brushes allowed higher immobilized peptide surface densities, overcoming bioavailability issues. Future research efforts should focus on the regulatory demands for pre-clinical and clinical validation towards clinical translation.
预防骨科植入物相关感染是一项重大医学挑战,尤其是因为生物膜包裹的多重耐药细菌的存在。目前基于抗生素给药的治疗方法已被证明并不充分,而且由于抗生素耐药性的传播,感染患病率可能会上升。抗菌肽(AMPs)因其具有广谱活性、在极低浓度下具有高效性,以及重要的是诱导耐药性的倾向较低,而作为传统抗生素的有前景替代品受到关注。本综述的目的是提供基于抗菌肽的预防骨科和牙科植入物相关感染策略发展的最新观点。在这方面,本文讨论了两种主要研究策略,即(i)从钛改性表面以及骨水泥或珠子中释放抗菌肽的系统;以及(ii)用于将抗菌肽接枝到钛或其他具有潜在转化为涂层可能性的模型表面上的抗菌肽固定策略。总体而言,释放策略已经发展到能够保证更高的负载量、在感染时延长且有针对性的递送时间。此外,前沿的自组装策略或聚合物刷能够实现更高的固定化肽表面密度,克服生物利用度问题。未来的研究工作应集中在临床转化的临床前和临床验证的监管要求上。