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Man, Biomaterials and Microbes

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The main focus of this programme is on the prevention of biofilm formation on all biomaterials implants and devices. The aims are formulated with respect to the infection prevention of temporarily and permanent implants and devices.​

Programme Leaders   Mission  

Healthy ageing with a high quality of life is a general desire. Ageing starts with birth and no matter how well we adapt our lifestyles to age in a healthy way, sooner or later the human body will become beyond natural repair. Sometimes, severe trauma causes the human body to become damaged beyond natural repair. Often, oncological removal surgery creates irreparable damage by natural processes. Eventually as the body ages, the natural repair capabilities will not be able to keep up with the everyday wear and tear on the body, requiring intervention.

Nowadays irreparable damage to the human body needs not necessarily be associated with loss of function and quality of life. Numerous permanent biomaterials implants or temporary devices are available for the restoration or temporary support of function. Whereas the implants and devices may differ widely (e.g., artificial hearts, prosthetic joints, vascular prostheses, dental implants, surgical meshes, breast implants, sutures, urinary and intravascular catheters, voice prostheses, contact lenses), all biomaterials implants and devices will attract microorganisms that interfere with their intended function, limit their lifespan or cause sepsis which can even be life threatening. Biomaterials implants for permanent applications share the same two barriers with respect to their extended use: “the possibility of biomaterials-associated-infection and the lack of tissue integration”.

In MBM, we fight the biofilm from lab to bed, while designing biomaterial implants and devices that promote tissue integration. This leads to the three aims of the program:

1.To study the physico-chemical and biological mechanisms for the (simultaneous) interaction of microorganisms, mammalian cells and immune system components with biomaterials surfaces.

  1. Communication
  2. Target finding
  3. Promoting tissue integration over biofilm formation.

2.To design new multi-functional biomaterials that can be applied to discourage microbial adhesion and growth and at the same time stimulate mammalian cell adhesion and growth on totally internal, permanent biomaterials implants.

  1. Coatings
  2. Surface modifications

3. To translate promising results to clinical applications using newly developed in vitro and in vivo evaluation methods and to substantiate biomaterials-related claims with respect to reduced infection risks of different implants and devices currently used in modern medicine. Having access to the clinic allows for direct translation of successful developments to patient-related applications.

Description of the Programme  

Biomaterials implant surfaces in the human body are prone to infection. These can develop through three distinctly different infection routes, each with its own unique cell/material/infection interface. Since a biomaterial-associated infection (BAI) is difficult to treat with antibiotics due to the protection offered by the biofilm mode of growth and intra-cellular sheltering of microorganisms, the fate of an infected implant often is removal, at great discomfort to the patient and costs to the healthcare system.

Frequently even, the condition of a patient does not allow replacement surgery or removal of the implant or device. BAI can even be lethal when bacterial spreading throughout the body occurs (sepsis). Whereas the infection rate of primary implants may be considered low (4-6% on average, depending on the implant type), infection rates in revision surgery are much higher (~15%) with huge discomfort to the patients and much higher costs than of primary placement.  Furthermore, many implants are used in society translating the ‘low’ BAI percentages into large absolute numbers of patients worldwide. Treatment involves the use of antimicrobials, but antimicrobial resistance is developing faster than new antimicrobials are developed, and the number of effective antimicrobials may reach a critical mass within this century.

The Man, Biomaterials and Microbes (MBM) programme merges the fundamental research on biofilm, the development of biomaterial coatings, infection and antimicrobial resistance, while being closely linked to the clinic for translation of promising materials. The programme works closely with NANOBIOMAT (another programme of the KOLFF Institute) and the Zernike Institute for Advanced Materials, along with other industrial and academic partners.

Although mechanisms of bacterial and mammalian cell adhesion have been studied for decades, no ubiquitously accepted mechanism has been forwarded, and research is ongoing. An important general conclusion is, however, that bacteria often use the same adhesive sites in adsorbed protein layers on biomaterials implants and devices, as do mammalian cells. In order to put mammalian cells at an advantage we need a shift in biomaterial coatings from mono-functional (only non-adhesive to bacteria OR only adhesive to cells) to multi-functional (non-adhesive to bacteria AND adhesive to mammalian cells) ones.

New insights in mechanisms of microbial and mammalian cell adhesion will be applied to develop multi-functional biomaterials coatings. Promising coatings can be translated to clinically-relevant experiments en route to clinical translation.  Additionally, the mechanisms of transition of adhered bacteria to the biofilm state, and the development of antimicrobial resistance will translate into new (antibiotic-less) treatments that are less prone to resistance development.

Importantly, methods to evaluate biomaterials coatings are being developed to accommodate multi-functional coatings that require methods by which mammalian cell interaction on a biomaterial can be evaluated simultaneously with biofilm formation and preferably also with the reaction of immune components.

Such studies not only attempt to find solutions for the current problem of BAI, but also prepare for the future problem of infections related to porous, biodegradable scaffold materials as used in tissue engineering.

Relevance to Healthy Ageing  

Modern health care is greatly dependent on the use of biomaterial implants and devices for the restoration of function after trauma, (oncological) intervention surgery, or simply wear due to old age. This means that sooner or later, everybody in an ageing society will have to rely on biomaterials implants or devices, either temporary or permanent. Therefore, biomaterials are indispensable for healthy ageing, as recognized by the UMCG in defining the field of Technology for Ageing People within the Healthy Ageing programme.

Total joint arthroplasties and dental implants form the majority of all implants clinically applied, requiring tissue integration over biofilm formation. In dental implants, tissue integration is stimulated by creating a tight fit between the bone and the implant surface, but reportedly up to 15% of all implants fail due to peri-implantitis. In orthopedics, joint arthroplasties were usually fixed with antibiotic-releasing bone cements, but there is a strong preference developing in the field for uncemented prostheses that have better bone integration. Thus, the protection offered by antibiotic-releasing cements disappears and the clinical situation becomes very similar with dental implants. Infections are not limited to orthopedics and dentistry and invade all kinds of permanent implants.  

The programme focuses on the study of biofilms and the design of multifunctional coatings that can be applied for clinical applications as described above, requiring tissue integration. However, the programme is not limited to this application as the design phase will also yield opportunities to prepare non-adhesive, contact-killing and antimicrobial-releasing coatings that can be applied on temporary implants and devices like dental abutments, contact lenses, voice prostheses and intravascular or urinary catheters, as used extensively (but not exclusively) in the elderly.

Principal Investigators