Development of medical devices for diagnosing cartilage injury and metastatic cancers

Abstract

My research focused on applying biomedical engineering techniques to diagnose different diseases and conditions. The results of these work led to one published paper and two submitted manuscripts which are summarized in Chapters 2, 3 &4. Briefly, in Chapter 2, my work laid emphasis on developing a method for early detection of cartilage injury. An apoptotic cell-detecting probe was fabricated by the conjugation of the apoptotic cell-binding peptide (CQRPPR) and a sulfo-cyanine7 N-hydroxysuccinimide ester (Cy7 dye). Both in vitro and ex vivo examination showed an excellent relationship between the number of apoptotic chondrocytes and probe binding affinity. Finally, using a xiphoid injury model was created using mechanical pressure, we found that the apoptosis probes may serve as a powerful tool to monitor the extent of mechanical force-induced cartilage injury in vivo. In Chapter 3, my work was centered on the creation and optimization of a new device, “cancer trap”, for capturing migrating prostate cancer (PCa) cells. The cancer trap is composed of hyaluronic acid microparticles that have good cell and tissue compatibility and can extend the release of chemokines to 4 days in vitro. After testing various chemokines, Erythropoietin (EPO) and stromal-derived factor-1α (SDF1α) are the best chemokines for chemokine-releasing cancer traps in vitro. Finally, using an intravenous PCa transplantation model, we found that subcutaneously implanted and EPO- releasing cancer trap attracted many circulating PCa and significantly reduced cancer spreading in the lung. These results support that cancer traps may serve as a unique device to sequester circulating PCa cells and subsequently reduce distant metastasis. In Chapter 4, we expanded the use of cancer capturing devices from cancer trapping devices to cancer diagnosis devices. For that, our study focused on metastatic esophageal cancer (EC). EC lymph node (LN) metastasis is one of the most important prognostic factors and the inability to diagnose EC earlier is believed to be responsible for the poor prognosis. To overcome such a challenge, my study was aimed at engineering an implantable device, a “diagnostic trap, ”, capable of intercepting migrating ECs prior to LN metastasis for early EC diagnosis. A diagnosis cancer trap was composed of a biocompatible Gelfoam and EPO. The results of our orthotopic EC animal study demonstrated that diagnostic trap recruited 40,300 migrating cancer cells. The diagnostic trap not only recruited EGFR+ cancer cells but also decreased LN metastasis. Histological analysis proved that the porous structure increased the capacity of the cancer trap to allow more cancer cell infiltration compared to the previous design. The overall results support that trap implants can be used for diagnosing EC metastasis and, potentially, for reducing LN metastasis.