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Bioadhesion, biocompatibility and infection (BIOBI)

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The main focus of the programme Bioadhesion, Biocompatibility and Infection is on prevention of biofilm formation on all biomaterials 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 life styles in an attempt 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 while not seldom the results of wear cannot be repaired by natural processes.
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. 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”.
Although the programme focusses on the prevention of biofilm formation on all biomaterials implants and devices, its aims are formulated with respect to the infection prevention of permanent implants and devices:

  1. To determine physico-chemical and biological mechanisms for the (simultaneous) interaction of microorganisms, mammalian cells and immune system components with biomaterials surfaces yielding tissue integration over biofilm formation to protect an implant.
  2. To design new multi-functional coatings 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.
  3. To develop new in vitro and in vivo evaluations methods to substantiate biomaterials-related claims with respect to reduced infection risks of different implants and devices currently used in modern medicine.
Description of the Programme  

Biomaterials implant surfaces in the human body are prone to infection. These can develop through three distinctly different routes. Peri-operative contamination is the best documented route and usually causes early implant-related infection. Also immediate post-operative contamination can be a cause of early failure of a biomaterials implant. Late post-operative infections by spreading of organisms from infections elsewhere in the body, have been described as well to be a cause for implant-related infections and failure of the implant. 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 or 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. 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 and around 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.

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 in their attempts to integrate a biomaterials surface in the body versus microbial biofilm formation, we need a shift in paradigm for the development of biomaterials 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 in combination with the Zernike Institute for Advanced Materials, Groningen, The Netherlands and Stevens Institute of Technology (Hoboken, USA) and other industrial and academic partners. Importantly, methods to evaluate biomaterials coatings, have only focussed on measuring one aspect of the coating performance at a time, while the shift in paradigm toward multi-functional coatings requires 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 biomaterials 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. Therewith, biomaterials are indispensable for healthy ageing, as recognized by the UMCG in defining the field of Technology for Ageing People within the Healthy Ageing program.
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 orthopaedics, joint arthroplasties are fixed with antibiotic-releasing bone cements, but there is a strong preference developing in the field for uncemented prostheses. Therewith the protection offered by antibiotic-releasing cements disappears and the clinical situation becomes very similar with dental implants.
The program focusses on the design of multifunctional coatings that can be applied for clinical applications as described above, requiring tissue integration. However, the program is not limited to these 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