JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE PERSPECTIVE J Tissue Eng Regen Med 2007; 1: 110–119. Published online in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/term.4 A new and evolving paradigm for biocompatibility J¨ ons Hilborn 1 and Lars M. Bjursten 2 * 1 Department of Materials Chemistry, Uppsala University, Uppsala, Sweden 2 Department of Clinical Sciences, Lund University, Malm¨o, Sweden Abstract We propose that the mechanical property of the interface between an implant and its surrounding tissues is critical for the host response and the performance of the device. The interfacial mechanics depends on several different factors related to the physical shape of the device and its surface as well as properties of the host tissue and the loading conditions of the device and surrounding tissue. It seems plausible that the growth of the fibrotic tissue to support mechanical loads is governed by the same priniciples as depicted by Wolfs’ Law for bone. Of course, biocompatibility will have different implications depending on which vantage point we look at the host–material interface. Another implication is that only limited aspects of biocompatibility is measurable with current in vitro tests and that the elicited host response in vivo models remains crucial for evaluation of medical devices and tissue engineering constructs. Copyright  2007 John Wiley & Sons, Ltd. Received 19 January 2007; Accepted 30 January 2007 Keywords biocompatibility; mechanical stress; interfacial mechanics; macrophage; Young’s modulus; surface texture 1. Introduction The successful clinical outcome of the implantation of biomaterials is strongly dependent on their material properties, which holds especially true for approaches where the material used should trigger or assist the regeneration of missing tissue. Therefore, the design criteria of the material have become among the most discussed issues in biomaterials research. The tissue surrounding the implanted biomaterial is characterized by an inner layer, consisting primarily of macrophages and/or foreign body giant cells, and a surrounding zone of fibroblasts and connective tissue (Figure 1). A foreign body reaction typically occurs for implants, exemplified by stents, catheters and breast implants, and often necessitates repeated surgery and the subsequent removal of the implant, with resulting morbidity. The inflammatory reaction results in capsule formation and is the most serious impediment to the use of biomaterials, often resulting in an unwanted growth of fibrotic tissue around the implant, loss of function and pain to the patient. For tissue engineering the result is formation of *Correspondence to: Lars M. Bjursten, Department of Clinical Sciences, Lund University, Malm¨o, Sweden. E-mail: lars magnus.bjursten@med.lu.se scar instead of functional tissue. Basic understanding of the mechanisms eliciting this response is limited but is beginning to evolve. Many studies of the mechanisms by which biomaterials trigger capsule formation have been focused on the fundamental interactions between the outermost surface layer of the material and various biomolecules, with perceived importance for the overall biological response to the implanted material. These reports have in general pointed to large differences in the interactions, depending on the model surfaces investigated and the biomolecules studied. In many cases these differences have also been demonstrated to carry over to in vitro cell culture experiments, e.g. surfaces with low protein adsorption indeed show diminished thrombus formation when in contact with blood (Brash, 2000). Along these lines, one strategy has been to minimize the host response by producing surfaces that are chemically inert. Such biomaterials are selected based on their minimal in vitro cytotoxicity to cell lines as well as minimal activation of soluble mediators of inflammation. Such mediator systems are the complement and the coagulation systems. An example of this biomaterial selection is the choice of silicon elastomer for breast implants, which exhibits minimal cell toxicity in vitro but elicits a strong foreign body reaction in vivo. Copyright  2007 John Wiley & Sons, Ltd.