(4bc) Methods for Assessing Biocompatibility and the Foreign Body Response of Polymers and Drug Delivery Systems

In vivo fluorescence imaging of cathepsin and macrophage activity and genomic profiling have been developed as powerful tools for understanding biocompatibility. Traditionally, biocompatibility of materials has been determined via histology which has the severe limitation in that only one time point can be examined, making kinetic observations of the interaction between the immune system and the implant improbable. Genomic and molecular level understanding of what influences the foreign body response has remained largely unknown. Fluorescence imaging circumvents this issue by allowing observations of immune system responses in vivo in conjunction with genomic profiling to identify potential cytokines influential in eliciting the foreign body response. In vivo imaging holds the advantage that multiple time points can be analyzed while genomic profiling can lead to mechanistic understanding of the foreign body response process. Together, we are able to have a more detailed understanding of the biocompatibility of a certain material. These techniques have been used to study the biocompatibility of polymers subcutaneously injected in an array format in mice. Validation via histology through the use of positive and negative controls established these methods as a means of observing immunological responses to biomaterials. Through surface functionalization, the phagocytitic response to different chemical groups can be ranked. A library of chemically modified alginates were synthesized and assayed for biocompatibility through this technique which allowed for rapid and complete analysis of the library. Drug delivery systems were also interrogated for their ability to curtail foreign body responses.