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The present study describes a local drug delivery system with two functions, which can suppress tumor growth and accelerate wound healing. Thе system consists of a two-layer multicomponent fibrin-based gel (MCPFTG). The internal layer of MCPFTG, which is in direct contact with the wound surface, contains cisplatin placed on a CultiSpher-S collagen microcarrier. The external layer of MCPFTG consists of a CultiSpher-S microcarrier with lyophilized bone marrow stem cells (BMSCs). The efficacy of MCPFTG was evaluated in a rat model of squamous cell carcinoma of the tongue created with 4-nitroquinoline 1-oxide. The results of the study showed that, within 20–25 days, a non-healing wound of the tongue was formed in animals that underwent only 85% resection of squamous cell carcinoma, while rapid progression of the residual tumor was concomitantly observed. Immunohistochemical methods revealed high expression of cyclin D1 and low expression of E-cadherin in these animals. Additionally, high expression of p63 and Ki-67 was noted. In 80% of animals with squamous cell carcinoma of the tongue that were treated with MCPFTG after 85% tumor resection, a noticeable suppression of tumor growth was evident throughout 150 days, and tumor recurrence was not detected. Immunohistochemistry revealed low or moderate expression of cyclin D1, and high expression of E-cadherin throughout the whole observation period. The MCPFTG-based local drug delivery system was shown to be effective in suppressing tumor growth and preventing recurrence. MCPFTG decreased the toxicity of cisplatin and enhanced its antitumor activity. In addition, lyophilized paracrine BMSC factors present in MCPFTG accelerated wound healing after tumor removal. Thus, the present study suggests novel opportunities for the development of a multifunctional drug delivery system for the treatment of squamous cell carcinoma.

The gold standard following segmental mandibulectomy is vascularized autologous bone graft in the form of the fibula flap. However, in bone reconstruction the use of autogenous bone does not always guarantee a successful outcome. The aim of the present investigation was to develop a novel biologically active bone (BAB) graft, and to use it for the reconstruction of large size defects of the mandible bone following tumor resection. In the first part of the present study, biologically active bone graft was developed by using human freeze-dried bone marrow stem cells (BMSCs) paracrine factors and three-dimensional bone scaffold derived from cancellous bovine bone following decellularization. In the second part of the research, one male and three female patients with primary tumors of the mandible underwent hemimandibulectomy. The mandibular bone defects following tumor resection were reconstructed with autogenous rib grafts in three patients and BAB graft was used in one patient. The graft-host interfaces were covered with decellularized human amnion/chorion membrane graft. All patients were followed-up every five months following the reconstruction of the mandible, with no complications observed. Preliminary clinical investigations demonstrated that a BAB graft containing freeze-dried BMSC paracrine factors may be used for the reconstruction of large mandibular bone defects following tumor resection.

Background and Objectives Squamous cell carcinoma is the most common pathological type among the cancers of the larynx. Standard treatment for squamous cell carcinoma of the larynx is the combination of chemotherapy, radiotherapy, and laryngectomy. Pharyngocutaneous fistula is a common complication of laryngectomy. We hypothesized that decellularized and lyophilized human amnion/chorion membrane can be an effective, non-invasive method of treating pharyngocutaneous fistula. Methods A total of 67 patients with laryngeal squamous cell carcinoma were retrospectively analyzed after treatment in a prospective trial. After preoperative chemotherapy, radiotherapy, and total or extended laryngectomy, primary wound healing occurred in 42 (62.7%) patients. Pharyngocutaneous fistula developed in 8 (11.9%) patients. Decellularized and lyophilized human amnion/chorion membrane grafts were used to reconstruct the fistulas. Results The average time for the full healing of the wound in all patients after transplantation of these grafts was 18 days. Conclusion The advantages of using these grafts over other existing methods of pharyngocutaneous fistula treatment are that they are non-invasive, prevent donor morbidity, and enable management of the wound without using classical wound gauze. J. Surg. Oncol. 2016;113:538–543. © 2016 Wiley Periodicals, Inc.

Transplantation of mature islets into portal vein has been most effective thus far, although attrition of transplanted islets constitutes a major limitation, and alternative approaches are required. We analyzed the mechanisms by which islets engrafted, vascularized and functioned over the long term in the small intestinal submucosa. To determine engraftment, survival and function, 350 syngenic islets were transplanted into either intestinal segments or portal vein of diabetic rats. Islet reorganization, vascularization and function were analyzed by histological analysis, RT-PCR analysis as well as glycemic control over up to 1 year. Transplantation of syngeneic islets in marginal numbers successfully restored normoglycemia in diabetic rats. Transplantation of semi-pure islet preparation did not impair their engraftment, vascularization and function. Islets were morphologically intact and expressed insulin as well as glucagon over the year. Expression of angiogenic genes permitted revascularization of transplanted islets. We identified the expression of transcription factors required for maintenance of beta cells. These studies demonstrated that marginal mass of transplanted islets was sufficient to restore euglycemia in streptozotocin-treated rats. These superior results were obtained despite use of an impure preparation of islets in animals with small intestinal segment. Our findings will help advance new horizons for cell therapy in patients with diabetes.