ABSTRACT
Background: Natural orifice transluminal endoscopic surgery (NOTES) is a minimal invasive treatment. However, tissue dissection under endoscopy is still challenging due to the flexibility of endoscopy body and there is still no effective method for establishing a tunnel towards the targeted area. We previously showed that a new kind of thermogel could be submucosallly injected and served as a cushion for endoscopic dissection. Thus, in this study we investigated the feasibility and safety of tunnel creation using poly (lactic acid-co-glycolic acid)-poly (ethylene glycol)-poly (lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) thermogel for NOTES in a porcine model. Methods: We prepared an injectable thermogel composed of PLGA-PEG-PLGA triblock copolymers which exhibited a low-viscous sol at room temperature and spontaneously transformed into a no-flowing gel at body temperature. This thermogel was used in NOTES in pigs. The success rate and adverse events were observed. Results: The PLGA-PEG-PLGA thermogels were successfully injected to the targeted areas under the guide of endoscopic ultrasonography and the tunnels were created by sucking the gel during NOTES as the endoscopy went forwards in all the three animals. The necropsy of the pigs showed no evidence of iatrogenic injury. No serious bleeding and perforation was observed. The results demonstrated that thermogel injection and tunnel creation by suction during NOTES were feasible, which simplified the procedure of tissue dissection and developed a new method of identifying the targeted area for surgical interventions without causing severe tissue damage. Conclusion: The application of thermogel for tunnel creation in NOTES could optimize current procedures and may have a promising prospect in clinical application
ABSTRACT
BACKGROUND: Thermogel is an aqueous solution that exhibits a sol-to-gel transition as the temperature increases. Stem cells, growth factors, and differentiating factors can be incorporated in situ in the matrix during the sol-to-gel transition, leading to the formation of a three-dimensional (3D) cell-culture scaffold. METHODS: The uses of thermogelling polypeptides, such as collagen, Matrigel™, elastin-like polypeptides, and synthetic polypeptides, as 3D scaffolds of cells, are summarized in this paper. RESULTS: The timely supply of growth factors to the cells, cell survival, and metabolite removal is to be insured in the cell culture matrix. Various growth factors were incorporated in the matrix during the sol-to-gel transition of the thermogelling polypeptide aqueous solutions, and preferential differentiation of the incorporated stem cells into specific target cells were investigated. In addition, modulus of the matrix was controlled by post-crosslinking reactions of thermogels or employing composite systems. Chemical functional groups as well as biological factors were selected appropriately for targeted differentiation of the incorporated stem cells. CONCLUSION: In addition to all the advantages of thermogels including mild conditions for cell-incorporation and controlled supplies of the growth factors, polypeptide thermogels provide neutral pH environments to the cells during the degradation of the gel. Polypeptide thermogels as an injectable scaffold can be a promising system for their eventual in vivo applications in stem cell therapy.
Subject(s)
Biological Factors , Cell Culture Techniques , Cell Survival , Collagen , Equipment and Supplies , Hydrogen-Ion Concentration , Intercellular Signaling Peptides and Proteins , Peptides , Stem CellsABSTRACT
@#To prepare a budesonide rectal thermogel. The gel solution was prepared by cold method, and the gelation temperature of the gel solution was determined by reverse tube method. The amount of poloxamer 407(P407), poloxamer 188(P188)and hydroxy propyl methyl cellulose(HPMC)was optimized by central composite design/response surface method. The in vivo gelation character was investigated after rectal administration of the budesonide thermogel into the rat, and the in vitro drug release from the gel was examined by the Franz diffusion cell method. Finally, the optimal formulation includes 0. 002% budesonide, 0. 93% HPMC, 2. 00% P188, and 18. 31% P407. It is preferable to obtain the appropriate formulation for budesonide rectal in situ thermogel, which can achieve wide distribution and adhesion to the rectum, as well as long-term drug release.