Speaker: David Grainger, University of Utah
Infection-Resisting Biomaterials: Surveying The State of the Field and Directions for the Future
Despite many materials designs, innovations and antimicrobial approaches continuing to address infection prophylaxis and infection treatments, few concepts ever make it beyond preclinical testing to clinical use. Fewer still are commercialized for global use. This is because very few strategies actually exhibit convincing efficacy in vivo in human infections despite promising in vitro antimicrobial efficacy and even some translation to animal implant models. Lack of agreement or standardization of experimental protocols, a general lack of correlation between in vitro and in vivo preclinical results and lack of validation between in vivo preclinical implant infection models and clinical (human) results are well-recognized.1,2 The translational impasse for antimicrobial devices is complex, confounded by problems in fundamental research models, biomaterials needs, efficacy claims, commercial manufacturing, regulatory reviews, and industrial risk-benefit assessments required for new clinical trials.
These disparities might be better understood by renewed focus on:
- Impact of the host implant foreign body response on local host immune competence.3
- Exploiting antimicrobial peptides (AMPs) that interact uniquely with microbial membranes, resulting in pathogen death, but can be expensive, immunogenic and unstable. Few were designed to act in implant formats. Common AMP tethering reduces antimicrobial activity
- Local drug delivery to achieve local concentrations exceeding those possible systemically, requiring reduced total drug amounts and improving delivery control. This equates to reduced risk of systemic toxicity but limited duration. Local application of antibiotics has been shown in some preclinical in vivo studies to be active against antibiotic-resistant bacteria. Guidelines for local delivery (antibiotic agent selection specific to species, tissue and resistance status), clarification of pharmacodynamic principles applicable to local antimicrobial delivery, design of local delivery strategies to achieve these pharmacodynamic profiles in vivo remain as unaddressed issues.
- Standards for preclinical research:4,5 Both in vitro and in vivo research conduct and performance standards for antimicrobial materials research must be recognized for consistency and reliability to the many antimicrobial claims published for new biomaterials.
- Regulatory agencies must recognize that translating these new antimicrobial technologies to humans is both high risk and cost-prohibitive currently.1,2 Types of data and antimicrobial validation for clinical trials must be clear.
- A holistic antimicrobial approach that encompasses clinical practices, patient health status, implant type and design, pathogen profiles for that implant, and standards of care.
David Grainger is a University Distinguished Professor and Department Chair of Biomedical Engineering, and Distinguished Professor of Pharmaceutics and Pharmaceutical Chemistry at the University of Utah, USA. Grainger’s research focuses on improving drug delivery methods, implanted medical device and clinical diagnostics performance, and nanomaterials toxicity. Grainger has published >220 research papers and >30 book chapters on biomaterials innovation in medicine and biotechnology, and novel surface and diagnostics chemistry. His research awards include a 2016 Fulbright Scholar Award (New Zealand), the 2013 Excellence in Surface Science Award (Surfaces in Biomaterials Foundation), the 2007 Clemson Award for Basic Research (Society for Biomaterials), and the 2005 American Pharmaceutical Research and Manufacturer’s Association’s award for “Excellence in Pharmaceutics."
Grainger also has received several prominent university teaching and mentoring recognitions, as well as the 2019 Daniels Fund Award for Education in Research Ethics and 2020 International Award from the European Society for Biomaterials. He has served as Chair of several prominent USA research review panels and on the National Institutes of Health NIBIB Council. He serves on editorial boards for 6 major journals, past handling editor for the journal, Biomaterials, for over two decades, and a special topics editor for Advanced Drug Delivery Reviews. He has co-organized 33 major international symposia.
Grainger is recognized with numerous prominent university teaching awards and has provided nearly 400 invited lectures and outreach workshops globally. He provides leadership in official Scientific Advisory Board roles on several international medical technology research consortia and global research foundations. He consults widely for the biomedical device and pharmaceutical industry and has been a principal in 6 biotech start-ups, with successful commercialization efforts and marketed FDA-approved medtech products. Grainger continues to emphasize translational approaches to clinical biomaterials, and validation of clinical effectiveness in implants and drug delivery systems for value-based medicine.