Study On Fallopian Tubes Contraceptive Device Based On Shape-memory Polymers

It is important for human reproductive health and population control to develop secure, effective, microinvasive, convinient and even reversable contraceptive devices. Although many kinds of contraceptive agents and devices have been adapted in clinic, they are not widely accepted yet due to more or less complications. Development of pro vagina contraceptive device was limited due to inconvenience and lack of reliability. Intrauterine device is effective, however, it is still accompanied with distinct extent of side effects such as increased menstrual blood volume, abnormal menstrual cycle, high probability in pelvic infection and ectopic pregnancy, defluxion of contraceptive device and pregnancy with band. Recently, more attentions have been paid to intrauterin contraceptive system with progestogen application in the clinic, but it is not optimistic due to spotting vagnal bleeding after placement, adaptation time elongation and high price. Oral contraceptives and subcutaneous implants often interfers with woman endocrine so that they are limited for wide and long-term usage. Lately, contraceptive interventions targeted to fallopian tube is noticed by its superiorities in noninterference woman endocrine, no uterus endomembrane disturbation, low probility in pelvic infection and reliable contraception.In this study, ideal fallopian tube contraceptive materials were designed and synthesized based on the knowledge of fallopian tube structures and functions and on the principles of mordern bioengineering and chemical engineering. The obtained materials were employed to fabricate fallopian tube conceptive devices, which would hopefully overcom those limitations as mentioned above. Ideal fallopian tube contraceptive materials should be nontoxic and have favourable biocompatibility and histocompatibility, without damage to local uterine tubal epithelium and easy to be placed in and block fallopian tubes. It is best to satify controllable degradation rate and thus controllable contraception. According to the above-mentioned features, we designed and synthesized temperature-sensitive polylactic acid based shape-memory polymers. The shape memory temperature and the degradation rate of the polymers could be tuned to near body-temperature by modulating the ratio of soft segment to hard segment and the molecular weight of soft segment and hard segment. The obtained shape memory polymers were employed to prepare fallopian tubes contraceptive devices, whose permanent shape was formed with a customered fallopian tubes mold. The permanent shape has a dameter larger than the fallopian tubes diameter. Before placement into the tube, the fallopian tubes contraceptive device was heated and stretched so that its diameter was much smaller than the fallopian tube, and then cooled so that the tempory shape was fixed. Once the fallopian tubes contraceptive device was placed in the fallopian tube, it would recover to the permanent shape, thereby blocking the fallopian tube completely due to the close contact between the contraceptive device and the fallopian tube. The obtained results and conclusions are listed as follows:The whole experiments were dived into four sections1. The synthesis and characterization of the fallopian tubes contraceptive materials, i.e. polylactic acid based polymers. Firstly, D,L-lactide and butylene glycol were used to form macrodiols through melting polymerization; and then the obtained macrodiols.were used to reacted with diisocyanate and butanediamine, producing the desired fallopian tubes contraceptive materials. The chemical and physical properties of the obtained polymers were characterized.2. Biological safety evaluation of the polylactic acid based polymers. Biological safety evaluation of the polylactic acid based polymers were carried out according to national relavent standards, including endotoxin assay, cell toxicity test, sensitization test, acute toxicity tests, micronucleus tests, cell chromosomal aberration test and ames test.3. In vivo experiments of the shape-memory fallopian tubes contraceptive device by implantation into rabbit fallopian tubes. Female New-Zealand rabbits were used in this study. After the fallopian tubes contraceptive device maded from the polylactic acid based polymers was implanted into rabbit fallopian tubes, the pathological changes in tunica mucosa tubae uterinae were observed at different post-implantation time points. And the histocompatibility and the effects of the materials on uterine tubal epithelium were evaluated. 4. Shape design and manufacture of clinic shape-memory fallopian tubes contraceptive device. According to the anatomic structure of human fallopian tubes and the shape memory characteristics of the polylactic acid based polymers, we screened and got an optimal proposal to design and manufacture fallopian tubes contraceptive device and placer. Furthermore, the fallopian tubes contraceptive device with shape-memory was prelimilarily evaluated through in vitro placement experiment.The main results and conclusions are listed as follows:1. The obtained polylactic acid based polymers had a glass transition temperature of 37.68℃, fixation ratio of nearly 100% and shape recoverty of 97%. Moreover, the hydrophilicty increased with increasing hard segment contents.2. Biosafety evaluation of polylactic acid shap-memory polymers showed that the endotoxin content complied with the standard, showing no obvious toxity to in vitro trichoblast and animals. The sensitivity response was negnative. Ames test, CHL chromosomal aberration test and multi-philiation erythrocytes micronucleus tests of mouse bone marrow suggested that the materials had no significant genotoxicity. The above results comfirm that the polylactic acid based shape-memory fallopian tubes contraceptive materials have no bacterial contamination and breeding and their biological safety is sound.3. The implantation of the shape-memory fallopian tubes contraceptive device induced inflammatory stimulation to fallopian tubal epithelium for short time, however, the inflammatory reaction decreased with extending implantation time. The villus in the tubal wall might be repaired, which provided a histological basis for reversible implantation of the shape-memory fallopian tubes contraceptive device. In vivo tests demonstrated that the materials have good histocompatibility. Further experiments for degradation of contraceptive device materials, contraception effectiveness, and preganancy after unloading the contraceptive device are under work.4. The clinic shape-memory fallopian tubes contraceptive devices have designed and fabricated.