Use of a Novel Polymer in an Animal Model of Head and Neck Squamous Cell Carcinoma.

Objective To evaluate the adverse effects and therapeutic efficacy of our biocompatible polymer platform delivering targeted local therapy of cytokine CCL21 and cisplatin in a partially resected xenograft animal model of head and neck squamous cell carcinoma. In addition, to evaluate the efficacy of cotreatment with radiotherapy and assess the biocompatibility of the cisplatin-eluting polymer in the murine neck. Study Design Experimental animal study. Setting Academic research laboratory. Subjects and Methods SCCVII/SF cell injection established head and neck squamous cell carcinoma tumors in C3H/HeJ mice. Subjects underwent surgery, and a chemokine-eluting polymer was implanted into the resected site. Subjects treated with cisplatin received radiation or no radiation, and tissue was harvested after 8 weeks to assess polymer biocompatibility. Results Our results with the polymer platform significantly ( P < .05) reduced SCCVII/SF tumor size in C3H/HeJ mice with cisplatin (49% ± 8.7%, Δ3.4 ± 0.6 cm3 [95% CI]), CCL21 (42% ± 4.8%, Δ3.5 ± 0.4 cm3), and cisplatin/CCL21 dual-agent polymer (82% ± 4.4%, Δ8.0 ± 0.4 cm3) as compared with controls. Cisplatin polymer with high-dose (16 Gy) and low-dose (4 Gy) radiation reduced tumor mass (respectively, 92% ± 7.2%, Δ6.1 ± 0.5 cm3; 85% ± 7.4%, Δ5.7 ± 0.5 cm3) as compared with the reduction from high-dose radiotherapy alone (70% ± 7.9%, Δ4.7 ± 0.5 cm3). No significant toxicity or inflammation was noted on histopathology after radiotherapy and cisplatin-eluting polymer treatment. Conclusion Cisplatin, CCL21, and cisplatin/CCL21 dual-agent polymer all exhibit significant antitumor effects and decrease tumor burden. Moreover, combination cisplatin polymer with radiotherapy may permit a decrease in intensity of radiation therapy in patients having received the cisplatin polymer. Histopathologic analysis suggests that the polymer is free from significant adverse effects in this model and warrants clinical trial.

A novel biodegradable device for intestinal lengthening.

PURPOSE: Previous studies demonstrated successful mechanical lengthening of rat jejunum using an encapsulated Nitinol spring device over a stabilizing guidewire. We sought to improve the applicability of intestinal lengthening by creating a biodegradable device. METHODS: Using properties of the Nitinol spring device, polycaprolactone (PCL) springs with similar outer diameter and spring constant were created. After in vitro testing in dry and hydrated environments, they were used to lengthen 1-cm isolated segments of rat jejunum in vivo. Retrieved segments were analyzed histologically. RESULTS: Optimal PCL spring devices had an average spring constant 1.8 ± 0.4 N/m, pitch 1.55 ± 0.85 mm, and band width 0.825 ± 0.016 mm. In vitro testing demonstrated stable spring constants. Jejunal segments were lengthened from 1.0 cm to 2.7 ± 0.4 cm without needing a stabilizing guidewire. Histology demonstrated increased smooth muscle thickness and fewer ganglia compared to controls. Lengthened jejunum was successfully restored into intestinal continuity and demonstrated peristalsis under fluoroscopy. CONCLUSIONS: A novel biodegradable spring device was successfully created and used to mechanically lengthen intestinal segments. Use of a biodegradable device may obviate the need for retrieval after lengthening. This improves device applicability and may be useful for the treatment of short bowel syndrome.