title: Critical factors in the translation of improved antimicrobial strategies for medical implants and devices.
abstract: Biomaterials-associated infection incidence represents an increasing clinical challenge as more people gain access to medical device technologies worldwide and microbial resistance to current approaches mounts. Few reported antimicrobial approaches to implanted biomaterials ever get commercialized for physician use and patient benefit. This is not for lack of ideas since many thousands of claims to new approaches to antimicrobial efficacy are reported. Lack of translation of reported ideas into medical products approved for use, results from conflicting goals and purposes between the various participants involved in conception, validation, development, commercialization, safety and regulatory oversight, insurance reimbursement, and legal aspects of medical device innovation. The scientific causes, problems and impressive costs of the limiting clinical options for combating biomaterials-associated infection are well recognized. Demands for improved antimicrobial technologies constantly appear. Yet, the actual human, ethical and social costs and consequences of their occurrence are less articulated. Here, we describe several clinical cases of biomaterials-associated infections to illustrate the often-missing human elements of these infections. We identify the current societal forces at play in translating antimicrobial research concepts into clinical implant use and their often-orthogonal constituencies, missions and policies. We assert that in the current complex environment between researchers, funding agencies, physicians, patients, providers, producers, payers, regulatory agencies and litigators, opportunities for translatable successes are minimized under the various risks assumed in the translation process. This argues for an alternative approach to more effectively introduce new biomaterials and device technologies that can address the clinical issues by providing patients and medical practitioners new options for desperate clinical conditions ineffectively addressed by biomedical innovation.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, Salt Lake City, UT 84112-5820, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT 84112-5820, USA. Electronic address: david.grainger@utah.edu.
authors.forename: David W
authors.initials: DW
authors.lastname: Grainger
authors.forename: Henny C
authors.initials: HC
authors.lastname: van der Mei
authors.forename: Paul C
authors.initials: PC
authors.lastname: Jutte
authors.forename: Jan J A M
authors.initials: JJ
authors.lastname: van den Dungen
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: Bernard F A M
authors.initials: BF
authors.lastname: van der Laan
authors.forename: Sebastian A J
authors.initials: SA
authors.lastname: Zaat
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Busscher
mesh_terms: D000293:Adolescent; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001019:Aortic Rupture / Q000150:complications / Q000601:surgery; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D001672:Biocompatible Materials / Q000009:adverse effects*; D001807:Blood Vessel Prosthesis / Q000009:adverse effects / Q000382:microbiology; D001858:Bone Nails / Q000382:microbiology; D004696:Endocarditis / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology; D005260:Female; D050723:Fractures, Bone / Q000150:complications / Q000382:microbiology; D006350:Heart Valve Prosthesis / Q000009:adverse effects / Q000382:microbiology; D006622:Hip Prosthesis / Q000009:adverse effects / Q000382:microbiology; D006801:Humans; D007831:Larynx, Artificial / Q000009:adverse effects / Q000382:microbiology; D007869:Leg Injuries / Q000150:complications / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D019736:Prostheses and Implants / Q000009:adverse effects* / Q000382:microbiology; D016459:Prosthesis-Related Infections / Q000188:drug therapy* / Q000209:etiology* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials
keywords: Biomaterial-associated infection; Clinical translation; Clinical trials; Hospital hygiene; Implant infection; Stakeholders