Review Article Engineered biomaterial and biophysical stimulation as combinatorial strategies to address prosthetic infection by pathogenic bacteria Sunil Kumar Boda, 1 Bikramjit Basu 1,2 1 Laboratory for Biomaterials, Materials Research Centre, Indian Institute of Science, Bangalore 560012, India 2 Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India Received 29 February 2016; revised 8 June 2016; accepted 20 June 2016 Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.33740 Abstract: A plethora of antimicrobial strategies are being developed to address prosthetic infection. The currently avail- able methods for implant infection treatment include the use of antibiotics and revision surgery. Among the bacterial strains, Staphylococcus species pose significant challenges particularly, with regard to hospital acquired infections. In order to combat such life threatening infectious diseases, researchers have developed implantable biomaterials incor- porating nanoparticles, antimicrobial reinforcements, surface coatings, slippery/non-adhesive and contact killing surfaces. This review discusses a few of the biomaterial and biophysi- cal antimicrobial strategies, which are in the developmental stage and actively being pursued by several research groups. The clinical efficacy of biophysical stimulation methods such as ultrasound, electric and magnetic field treatments against prosthetic infection depends critically on the stimulation pro- tocol and parameters of the treatment modality. A common thread among the three biophysical stimulation methods is the mechanism of bactericidal action, which is centered on biophysical rupture of bacterial membranes, the generation of reactive oxygen species (ROS) and bacterial membrane depolarization evoked by the interference of essential ion- transport. Although the extent of antimicrobial effect, normal- ly achieved through biophysical stimulation protocol is insuf- ficient to warrant therapeutic application, a combination of antibiotic/ROS inducing agents and biophysical stimulation methods can elicit a clinically relevant reduction in viable bacterial numbers. In this review, we present a detailed account of both the biomaterial and biophysical approaches for achieving maximum bacterial inactivation. Summarizing, the biophysical stimulation methods in a combinatorial man- ner with material based strategies can be a more potent solu- tion to control bacterial infections. V C 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000–000, 2016. Key Words: prosthetic infection, biophysical methods, ultra- sound, magnetic and electric field, antimicrobial How to cite this article: Boda, SK, Basu, B 2016. Engineered biomaterial and biophysical stimulation as combinatorial strategies to address prosthetic infection by pathogenic bacteria. J Biomed Mater Res Part B 2016:00B:000–000. INTRODUCTION The perennial issue of prosthetic infection is among the leading causes for implant failure. 1 The number of patients requiring artificial implants/prostheses is on the rise and so is the risk of prosthetic infection during pre-/peri-/post- operative surgical procedures. For example, aging related degenerative joint disease like osteoarthritis and osteoporo- sis, bacterial infections like osteomyelitis and accidents lead- ing to major fractures comprise the commonly occurring bone disorders. Such afflictions of the bone necessitate the use of orthopedic implants in very large numbers. It is esti- mated that >2,000,000 hip replacement surgeries are per- formed annually in the United States of America (USA) and around 50,000 per year are done in the United Kingdom (UK). Around 1–2% of the orthopaedic implants are reported to fail due to prosthetic infection. 2 The failure arises from prosthetic contamination by microbial patho- gens, leading to the formation of biofilms on the material surface. Traditional treatment of such biomaterial associated infections (BAI) by b-lactam antibiotics like penicillin, meth- icillin and cephalosporins has led to the emergence of drug resistant bacterial strains, for example, methicillin resistant Staphylococcus aureus (MRSA), the most common human pathogen implicated in prosthetic infection. 3 In acute cases, the only solution to these hospital acquired infections is the removal of the implant, followed by revision surgery. Often, recurrent prosthetic infections occur due to persisting pathogens after the revision surgery. A third of the total knee joint arthroplasties were reported to cause peri- prosthetic joint infections by MRSA following revision Correspondence to: B. Basu; e-mail: bikram@mrc.iisc.ernet.in V C 2016 WILEY PERIODICALS, INC. 1