Esophageal Neoplasms

The lack of physiologically relevant human esophageal cancer models has as a result that many esophageal cancer studies are encountering major bottleneck challenges in achieving breakthrough progress. To address the issue, here a 3D esophageal tumor tissue model was engineered using a biomimetic decellularized esophageal matrix in a customized bioreactor. To obtain a biomimetic esophageal matrix, a detergent-free, rapid decellularization method was developed to decellularize porcine esophagus. The decellularized esophageal matrix (DEM) was characterized and the DEM was utilized for the growth of esophageal cancer cell KYSE30 in well plates and the bioreactor. Then the expression of cancerrelated markers of KYSE30 cells was analyzed and compared with formalin-fixed, paraffin-embedded (FFPE) esophageal squamous cell carcinoma (ESCC) tissue biospecimens. Results show that the detergent-free decellularization method preserved the esophageal matrix components and effectively removed cell nucleus. KYSE30 cancer cells proliferated well on and inside the DEM. KYSE30 cells cultured on the DEM in the dynamic bioreactor show different cancer marker expressions than those in the static well plate, and also share some similarities to the FFPE-ESCC biospecimens.

Palliation therapy for dysphagia using esophageal stents is the current treatment of choice for those patients with inoperable esophageal malignancies. However, the stents currently used in the clinical setting, regardless of the type of metal mesh or plastic mesh stents (covered/uncovered), may cause complications, such as tumor ingrowth and stent migration into the stomach. Furthermore, metal mesh stents have limited capacities for loading anti-cancer drugs. To effectively reduce/overcome those complications and enhance the efficacy of drug release, we designed and 3D-printed a tubular, flexible polymer stent with spirals, and then load anti-cancer drug, paclitaxel, on the stent for drug release. Non- spiral 3D-printed tubular and mesh polymer stents served as controls. The self-expansion and anti migration properties, cytotoxicity, drug release profile, and cancer cell inhibition of the 3D-printed stent were fully characterized. Results showed the self-expansion force of the 3D-printed polymer stent with spirals was slightly higher than the stent without spirals. The anti-migration force of the 3D-printed stent with spirals was significantly higher than the anti-migration force of a non-spiral stent. Furthermore, the stent with spirals significantly decreased the migration distance compared to the migration distance of the non-spiral 3D-printed polymer stent. The in vitro cytotoxicity of the new stent was examined through the viability test of human esophagus epithelial cells, and results indicated that the polymer stent does not have any cytotoxicity. The results of in vitro cell viability of esophageal cancer cells further indicated that the paclitaxel in the spiral stent treated esophageal cancer cells much more efficiently than that in the mesh stent. Furthermore, the results of the in vitro drug release profile and drug permeation showed that the dense tubular drug-loaded stent could efficiently be delivered more paclitaxel through the esophageal mucosa/submucosa layers in a unidirectional way than mesh stent that delivered less paclitaxel to the esophageal mucosa/submucosa but more to the lumen. In summary, these results showed that the 3D-printed dense polymer stent with spirals has promising potential to treat esophageal malignancies.