The Blood Compatibility Challenge

Despite >50 years of study, there are no materials that are considered truly nonthrombogenic. Some materials minimize protein adsorption or cell adhesion while others actively inhibit thrombin generation through heparinization. Nonetheless the problem of biomaterial associated thrombogenicity remains. While once an active area of research, the problem has not only not been solved, it has also been largely abandoned. It is considered too hard or efforts attack only one particular aspect of the problem or more broadly new ideas and approaches have not been brought to bear. This frustration has led to a series of review papers where we summarize the features of broad agreement and provide commentary on those aspects of the problem that were subject to dispute. These are (see also Figure 1): 1. Blood-contacting medical devices: The scope of the problem; 2. Protein adsorption phenomena governing blood reactivity; 3. Material associated activation of blood cascades and cells; 4. Surface modification for hemocompatible materials: passive and active approaches to guide blood-material interactions. We were inspired by the structure of the >1500 year old book of Jewish laws, called the Talmud, in which commentaries are layered on commentaries to interpret and reinterpret a biblical law. It takes the form of a record of discussions pertaining to Jewish law, ethics, philosophy, customs and history. Here we began with what we believed to be a generally accepted truth regarding thrombogenicity and then added our thoughts and commentaries regarding with respect to aspects that were not as scientifically firm as the opening "truth." We hope that future investigators will update these reviews as new scholarship resolves the uncertainties of today.