In vitro methodologies to evaluate biocompatibility: Status quo and perspective

C. James Kirkpatrick, Kirsten Peters, M. Iris Hermanns, F. Bittinger, Vera Krump-Konvalinkova, Sabine Fuchs, Ronald E. Unger

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

The increasing use of biomaterials in clinical medicine to augment or replace failing organ function has heightened the need to apply relevant test systems to study the safety and efficacy of new medical devices. This becomes all the more important as the field of "tissue engineering" develops, in which the aim is to reconstruct tissue and organ function, for example, by using the patient's own cells seeded on to a three-dimensional (3-D) scaffold structure. In the biomaterial research field, there has been a necessary expansion of the concept of biocompatibility to address not only the biosafety issue, that is, the exclusion of cytotoxic and other deleterious effects of biomaterials, but also the biofunctionality component, which concerns the fulfilment of the intended function of the applied biomaterial. Careful scrutiny of this concept leads to the conclusion that relevant test systems for biofunctionality must centre on human cells, studied under conditions relevant to the situation in the living organism for which the medical device has been constructed. Thus, progress in biocompatibility and tissue engineering would today be inconceivable without the aid of in vitro techniques. In designing such biofunctionality assays, there are certain fundamental principles which must be adhered to. A constant difficulty is the availability of sterile human tissue for such test systems. Also of paramount importance is proving the maintenance of the cell phenotype in vitro. Loss of essential characteristic functions of the cultivated cells makes extrapolatory interpretations meaningless for the clinical situation. This paper gives an overview of the basic design principles for suitable assays, and various examples covering a spectrum of applications. Relevant functional parameters will be emphasised, as well as the use of modern methods of cell and molecular biology, with measurement of these parameters at both the gene product and transcription levels. These parameters include the expression of cytokines, growth factors and cell adhesion molecules. In addition, assays can be constructed to study inflammation and the wound healing response, which includes the angiogenic reaction. Tissue remodelling around biomaterials can be studied in vitro by using cells such as fibroblasts, endothelial cells and various inflammatory cells, important parameters reflecting control of this remodelling being the matrix metalloproteinases and their inhibitors. The need for more co-culture and 3-D models is stressed and data from the authors' own laboratory are presented to illustrate these principles. Finally, the importance of signal transduction within those cells in contact with, or in the vicinity of, biomaterials is emphasised, as this knowledge offers the scientific basis for rational therapeutic intervention to suppress negative effects and enhance positive biological responses (use of drug delivery systems). In understanding these processes modern technologies using nucleic acid micro-arrays coupled with methods of bioinformatics will hopefully identify key genes which can be targeted. Well-designed in vitro assays have a central role to play in this endeavour.

Original languageEnglish
Pages (from-to)192-199
Number of pages8
JournalITBM-RBM
Volume26
Issue number3
DOIs
StatePublished - Jun 2005
Externally publishedYes

Bibliographical note

Funding Information:
The author wishes to gratefully acknowledge the support of the European Commission over the past 10 years from various grants within the scope of its biomaterial programmes, the German Research Foundation (DFG; Priority Programme Biosystem 322 1100) and support from the state government of Rhineland-Palatinate, Germany.

Keywords

  • Cell adhesion
  • Cell function
  • Cell migration
  • Cell proliferation
  • Cell spreading

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