¹ i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal

² INEB—Instituto de Engenharia Biomédica, R. Alfredo Allen 208, 4200-135 Porto, Portugal

³ FMUP—Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

⁴ ISEP - Instituto Superior de Engenharia do Porto, IPP-Instituto Politécnico do Porto, R. Dr. António Bernardino de Almeida 431, 4200-072 Porto, Portugal 

⁵ EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas 135, 4050-600 Porto, Portugal

⁶ Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

⁷ ITR-Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional, Rua das Taipas 135, 4050-600 Porto, Portugal

⁸ FEUP—Faculdade de Engenharia, Universidade do Porto, R. Dr. Roberto Frias, 4200-465 Porto, Portugal

⁹ CHUSJ—Centro Hospitalar Universitário S. João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

* Correspondence: nuno.alegrete@ineb.up.pt
 

Abstract: Aims: the focus of this study is to evaluate if the combination of an antibiotic with a ceramic biomaterial is effective in treating osteomyelitis in an infected animal model and to define which model and protocol are best suited for in vivo experiments of local bone infection treatment. Methods:a systematic review was carried out based on PRISMA statement guidelines. A PubMed search was conducted to find original papers on animal models of bone infections using local antibiotic delivery systems with the characteristics of bone substitutes. Articles without a control group, differing from the experimental group only by the addition of antibiotics to the bone substitute, were excluded. Results: a total of 1185 records were retrieved, and after a three-step selection, 34 papers were included. Six manuscripts studied the effect of antibiotic-loaded biomaterials on bone infection prevention. Five articles studied infection in the presence of foreign bodies. In all but one, the combination of an antibiotic with bioceramic bone substitutes tended to prevent or cure bone infection while promoting biomaterial osteointegration. Conclusions: this systematic review shows that the combination of antibiotics with bioceramic bone substitutes may be appropriate to treat bone infection when applied locally. The variability of the animal models, time to develop an infection, antibiotic used, way of carrying and releasing antibiotics, type of ceramic material, and endpoints limits the conclusions on the ideal therapy, enhancing the need for consistent models and guidelines to develop an adequate combination of material and antimicrobial agent leading to an effective human application.

Keywords: ceramic-based biomaterials; scaffolds; bone regeneration; bone-graft substitutes; bone infection; antibacterial materials