Description
Abstract

HAI (Healthcare-associated infection) are infections that acquired by patients during their stay in hospital or other healthcare scenario. The increasing incidence of healthcare-associated infections has posed a major threat to modern healthcare, especially in surgical and implant-related procedures. These infections not only prolong hospital stays and increase treatment costs but also contribute to the growing problem of antibiotic resistance [7]. However, the traditional surface coatings of implants are made of alloys and polyethylene. These surfaces are treated through micro-processing or sandblasting to increase their surface area and improve their wettability [8]. However, this traditional coating technology has inherent drawbacks, such as a tendency to adhere to microorganisms and other cells, thereby causing secondary pollution.

Our project aims to reduce device-associated infections by leveraging the power of synthetic biology. Responding to the global demand for safer healthcare environments, we are developing a new class of bioengineered antibacterial coatings using mussel foot proteins (Mfps). Our goal is to create safe, adhesion-strengthening, antibacterial, and antifouling performance coatings that can significantly minimize bacterial colonization on medical devices, especially in high-risk clinical settings.

Issue

According to the World Health Organization (WHO), the impact of healthcare-associated infections (HAI) implies prolonged hospital stay, long-term disability, increased resistance of microorganisms to antimicrobials. HAI is the most common adverse effect caused by medical procedures. The main sources of infection include drug-resistant microorganisms, infected patients, visitors, and healthcare workers[9].

HAI induces a massive additional financial burden for health systems, high costs for patients and their families, and excess deaths, which contribute to substantial patient suffering, families burden, and resources stress.

In terms of economy, in Europe, 16 million extra hospital days, 37,000 attributable deaths, and up to €7 billion in annual direct costs. Also, in the USA, 99,000 deaths were attributed to HCAIs in 2002, with an estimated economic impact of US$6.5 billion in 2004.

文本

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Fig.1: World Health Organization, 2010

In 2022, a survey study conducted by the cancer center in large regional hospitals in southern China showed that cancer patients with HAI have higher medical expenses, averaging around $16,927, and a hospital stay of 22 days. Compared to non-HAI patients, the costs and time increased by $4,919 and 9 days, respectively. Meanwhile, individual non-medical losses can reach between $478 and $835 [10]. These data demonstrate the importance of implementing effective infection prevention measures to reduce the economic losses for each hospital patient.

In terms of population infection, in low- and middle-income countries (LMICs), the burden of healthcare-associated infections (HAIs) is particularly severe. ICU-acquired infection rates have been reported at 42.7 episodes per 1000 patient-days, which is more than 2.5 times higher than rates observed in high-income countries. Infections associated with invasive medical devices—such as catheter-related bloodstream infections (CR-BSI), catheter-associated urinary tract infections (CR-UTI), and ventilator-associated pneumonia (VAP)—occur up to 13 times more frequently in LMICs. Furthermore, HAIs significantly prolong hospital stays by 5 to 29.5 days, leading to increased medical complications, higher treatment costs, and greater strain on limited health care resources. Despite these alarming statistics, 66% of developing countries lack national-level surveillance data on HCAI, severely limiting their capacity for effective policymaking and resource planning.

Fig. 2: Number of studies reporting health care-associated infection in low- and middle-income countries, 1995-2010 (World Health Organization, 2010)

According to the 2024 Global report on infection prevention and control from WHO, among countries with different income levels, there is a higher proportion of emergency patients in middle and low-income countries who experience at least one HAI, reaching 15%, which is about twice that of high-income countries and EU countries [9].

Fig. 3: The proportion of patients with at least one HAI-related case in hospital emergency departments across different countries and regions in 2022-2023.

At the same time, the proportion of HAI reported by different countries and regions worldwide also indicates that low-income countries face a more severe HAI situation. In particular, the proportion of HAI in the African region is as high as 27%.

Fig. 4: The frequency of HAI reported by each WHO region (2023)

In terms of personal influence, there was a case of a 13-year-old girl who developed post-operative osteomyelitis, resulting in permanent loss of arm function. Her family bore the entire cost of treatment, visiting multiple hospitals without institutional support. Such cases exemplify how HCAIs can devastate families emotionally and financially, especially where healthcare infrastructure and accountability are lacking.

Importance--- Global Need and Human Benefit

Every year, over several million people die from medical device-related infections. The fight against bacteria has entered a new battlefield: the surface of the tools that save lives. Our project offers a bio-inspired, low-cost, and effective solution to this growing challenge.

Who We Are Helping

We aim to help not only these patients but also frontline clinicians seeking safer tools, and healthcare systems, particularly in low- and middle-income countries that face economic constraints. Moreover, our synthetic biology platform provides a modular protein design system that can be readily adopted by biomedical researchers and startups seeking new-generation coatings based on our project.

Why This Problem Needs Solving

Traditional antibacterial coatings often suffer from high toxicity, short duration of effectiveness, or manufacturing challenges. Mussel foot proteins (Mfps), often referred to as "ocean’s soft gold," offer a natural alternative with strong underwater adhesion and excellent biocompatibility. However, native extraction is inefficient and costly. Our project addresses this by synthesizing Mfps in E. coli and combining them with antimicrobial and zwitterionic peptides to create a robust, multifunctional, and scalable coating.

How We Are Helping Humanity

Our work helps reduce infection rates, especially in under-resourced healthcare systems, and lessens the global reliance on antibiotics—thereby slowing the spread of antimicrobial resistance. The use of genetically engineered E. coli for protein production ensures scalability and environmental sustainability. In the long term, our project contributes to safer surgeries, more affordable healthcare, and the advancement of bio-inspired medical technologies that benefit patients worldwide.

Current & Our Solutions

According to the World Health Organization (WHO), approximately 15 percent of all waste generated by healthcare activities is classified as hazardous, potentially infectious, toxic, carcinogenic, flammable, corrosive, reactive, or radioactive [1]. Therefore, if medical devices are not thoroughly sterilized, they can readily precipitate infectious events—for example, prosthetic valve endocarditis (PVE) following heart valve implantation. PVE carries a high mortality rate of approximately 20 – 40 percent [2], posing a severe threat to patient safety.

Infection control strategies for medical devices are diverse, encompassing traditional methods such as pressurized steam sterilization, ethylene oxide gas sterilization, and UV-C/ozone disinfection. These approaches offer proven sterilization efficacy and well-established protocols, but they are unsuitable for heat-sensitive materials, may leave toxic residues, and require specialized operation [3]. Clinical aseptic practices—such as hand hygiene, sterile barriers, and environmental controls (e.g., copper alloy surfaces, personal protective equipment)—are cost-effective and provide direct protection, yet they depend heavily on practitioner compliance and are vulnerable to human error, creating potential infection gaps.

By contrast, antimicrobial and anti‑adhesive coatings employ contact killing, sustained release, or fouling-resistant mechanisms to actively and persistently block bacterial attachment, while synergizing with other infection‑control measures—demonstrating considerable promise. However, these coatings must overcome challenges such as delamination and aging, biocompatibility risks, potential induction of antimicrobial resistance, and substantial regulatory approval and cost barriers. Therefore, positioning medical‑device coatings as the core infection‑prevention strategy, integrated with appropriate sterilization protocols and aseptic practices, establishes a multilayered defense that leverages coating’s proactive protection and customization capabilities while compensating for the limitations of traditional methods—representing the most feasible and effective comprehensive solution currently available.

What is a medical device coating? It refers to one or more layers of material intentionally applied to the surface of surgical tools, catheters, implants, or other medical devices via techniques such as dip-coating, spray/coatings, chemical vapor deposition (CVD), physical vapor deposition (PVD), plasma treatment, or other solution-based processes. These coatings are typically only a few micrometers thick—thin enough to leave device dimensions and mechanical performance essentially unchanged—while enabling targeted modifications to surface properties such as friction, wear resistance, wettability, biocompatibility, thrombogenicity, and antimicrobial activity.

Current medical-device coating technologies include silver nanoparticles, copper alloys, antimicrobial peptides, PEG/zwitterionic anti-fouling layers, antibiotic drug-eluting coatings, and hard-wear-resistant coatings. However, these approaches face significant limitations: metal-based coatings may release ions uncontrollably and induce cytotoxicity; anti-fouling layers can delaminate after mechanical wear or sterilization; antibiotic coatings have limited lifespan and may promote resistance.

In contrast, our solution draws inspiration from the “marine soft gold”—mussel foot proteins (MFPs)—particularly recombinant fusion coatings based on Mfp5, which is rich in the catechol-bearing amino acid DOPA and amines. Such coatings not only exhibit robust wet adhesion, chemical stability, and thermal resistance [4] [5], but the catechol groups (DOPA) undergo auto-oxidation to generate hydrogen peroxide, imparting intrinsic antimicrobial activity [6]. The MFP is highly biocompatible and stable, thereby significantly extending infection resistance on device surfaces. At the same time, we combined antimicrobial peptides, anti-fouling dual ionic peptides, and mussel foot protein to create the final fusion protein zwi-Mfp-D51, which is then used to produce coating proteins for different materials.

By leveraging this nature-inspired, smart, multifunctional composite coating—integrating wet adhesion, chemical robustness, and self-generated antimicrobial defense—our approach overcomes traditional durability and safety constraints, while remaining compatible with existing sterilization protocols and clinical practices, positioning it as an optimal integrated strategy for preventing device-associated infections.

Reference

[1]https://www.medprodisposal.com/world-health-organization-information-on-biohazardous-waste/

[2] Grambow-Velilla J, Mahida B, Benali K, Deconinck L, Chong-Nguyen C, Cimadevilla C, Duval X, Iung B, Rouzet F, Hyafil F. Prognosis and follow-up of patients with prosthetic valve endocarditis treated conservatively in relation to WBC-SPECT imaging. J Nucl Cardiol. 2023 Dec;30(6):2633-2643. doi: 10.1007/s12350-023-03335-y. Epub 2023 Jul 10. PMID: 37430176.

[3] Rutala WA, Weber DJ. Disinfection and Sterilization in Health Care Facilities: An Overview and Current Issues. Infect Dis Clin North Am. 2016 Sep;30(3):609-37. doi: 10.1016/j.idc.2016.04.002. PMID: 27515140; PMCID: PMC7134755.

[4] Pandey N , Soto-Garcia LF , Liao J , Philippe Zimmern , Nguyen KT , Hong Y . Mussel-inspired bioadhesives in healthcare: design parameters, current trends, and future perspectives. Biomater Sci. 2020 Mar 7;8(5):1240-1255. doi: 10.1039/c9bm01848d. Epub 2020 Jan 27. PMID: 31984389; PMCID: PMC7056592.

[5] Taghizadeh A, Taghizadeh M, Yazdi MK, Zarrintaj P, Ramsey JD, Seidi F, Stadler FJ, Lee H, Saeb MR, Mozafari M. Mussel-inspired biomaterials: From chemistry to clinic. Bioeng Transl Med. 2022 Aug 11;7(3):e10385. doi: 10.1002/btm2.10385. PMID: 36176595; PMCID: PMC9472010.

[6] Fichman G, Andrews C, Patel NL, Schneider JP. Antibacterial Gel Coatings Inspired by the Cryptic Function of a Mussel Byssal Peptide. Adv Mater. 2021 Oct;33(40):e2103677. doi: 10.1002/adma.202103677. Epub 2021 Aug 22. PMID: 34423482; PMCID: PMC8492546.

[7] World Health Organization. (2010, April 29). The burden of health care-associated infection worldwide. www.who.int. https://www.who.int/news-room/feature-stories/detail/the-burden-of-health-care-associated-infection-worldwide

[8] Jim C.E. Odekerken, Tim J.M. Welting, Jacobus J.C. Arts, Geert H.I.M.Walenkamp, & Emans, P. J. (2013). Modern Orthopaedic Implant Coatings — Their Pro’s, Con’s and Evaluation Methods. InTech EBooks. https://doi.org/10.5772/55976

[9] World Health Organization. (Global report on infection prevention and control 2024) https://www.who.int/publications/i/item/9789240103986

[10] Huang L, Ning H, Liu XC, Wang Y, Deng C, Li H. Economic burden attributable to hospital-acquired infections among tumor patients from a large regional cancer center in Southern China. Am J Infect Control. 2024 Aug;52(8):934-940. doi: 10.1016/j.ajic.2024.03.002. Epub 2024 Mar 7. PMID: 38460730