Study Of Novel Poly (Urethane Urea) For Bone Repair And Preventing Non-union

Bone is one of the most complicated composite in the nature. Bone, not only provides mechanical support but also elegantly serves as a reservoir for minerals, particularly calcium and phosphate. It is a good example of a dynamic tissue, since it has a unique capability of self-regenerating or self-remodeling to a certain extent throughout the life. However, many circumstances call for bone grafting owing to bone defects either from traumatic or from non-traumatic destruction. In the case of severe defects and loss of volume, bone can't heal by itself and grafting is required to restore function without damaging living tissues. In the repair, non-union is one of the hot problems. The one most reason of non-union is that the common bone repair materials result in gap between body and graft, or the irregular interfaces in the irregular defect, which will result in the energy barrier, and non-union. In my study, SMPUU is used in the bone repair for its shape memory property.Shape memory polyurethane is a novel intelligent material that is able to response to external temperature change and exhibit shape memory property. It has received wide attentions in biomedical fields, especially in minimally invasive surgery because of its shape memory property.In this paper, several kinds of biodegradable poly (urethane urea) (SMPUU) based on HO-P(LA-co-PDO)-OH is synthesized. The mechanical property, shape memory property, degradation, compatibility, biological safety and medical application in jaw bone of the rabbit were investigated. The main works and conclusions are included as follows:1. HO-P(LA-co-PDO)-OH was synthesized by melt ring-opening polymerization of D, L-lactide and PDO using Sn(Oct)2 as initiator and EG as coinitiator. Then, an extensive investigation effort was expended in understanding the effects of ratio of D, L-lactide to PDO, dosage of coinitiator on the molecular weight, preparation methods on the Mw and thermal properties were characterized. Otherwise, the reaction mechanism of D, L-lactide and PDO was studied furtherly.①FTIR, NMR showed that SMPUU prepolymer was successfully prepared by one-step method and two-step method. Hydroxyl value, GPC-MALLS analysis indicated that SMPUU prepolymer with different molecular could synthesized by varying the dosage of coinitiator, ratio of D, L-lactide to PDO, and preparation method; ②The results of DSC indicated that the glass transition temperature (Tg) molecular weight of SMPUU prepolymer are affected by the ratio of D, L-lactide to PDO; random copolymer and block copolymer were prepared by one-step method and two-step method, respectively.2. SMPUU was synthesized by polymerizing of SMPUU prepolymer, hexamethylene diisocyanate (HDI) and butanediamine (BDA). The effects of solvent kinds, content of catalyst and the reactive temperature, ratio of hard segment/soft segment on the reactive activity of SMPUU prepolymer and HDI were discussed, and the structure and thermal properties of SMPUU were characterized.①FTIR, 1HNMR exhibited that the SMPUU can be successfully synthesized; By varying the molecular weight of soft segment and the ratio of soft segment/hard segment, the SMPUU with different physicochemical properties could be synthesized.②The result of physical property of SMPUU indificated that the chemical structure of SMPUU from the hydrophilic solvent or hydrophobic solvent are similar, however, the shape memory property, mechanical property are different. The SMPUU with suitable properties can be synthesized in the toluene-IPA solvent.③The results of thermal analysis showed that Tg, thermoplasticity were affected by the structure, Mw of SMPUU, and can be regulated by the ratio of hard segment/soft segment, structure of soft segment, Mw of soft segment and SMPUU.3. The mechanical and shape memory properties of SMPUU were characterized by mechanical tensile tests, compression test and bending test. The paper primarily investigated the influences of molecular weight of soft segment, the ratio of soft segment/hard segment, shape deformation and temperature on the shape memory fixation and recovery ratio.①The results indicated that SMPUU have nice mechanical properties. The modulus and maximum stress increased with the increasing of the hard segment content, while the elongation at break had the opposite trend.②SMPUU had good shape memory properties. Shape recovery ratio and fixation ratio were more than 95%. Meanwhile, the shape memory properties were affected by the components and the hard segment content. The fixation ratio of SMPPU showed slightly downward trend with the increasing of the molecular weight of soft segment; the shape recovery ratio decreased with the increasing of the hard segment content, however, the shape fixation ratio increased.③The deformation strain, deformation/recovery temperature had important effects on the shape memory properties. With the deformation strain increasing, the shape recovery ratio decreased. When the deformation range was from 50 to 200%, the shape memory properties are nice, however, when the deformation increased to 400%, the shape recovery ratio decreased to 85%; SMPUU showed good shape memory behavior when the deformation temperature was Tg+15℃, while the shape recovery ratio had apparent decrease, when the deformation temperature was above Tg+25℃; Shape recovery time shortened with the increasing of the recovery temperature.4. The surface wettability and biodegradation of SMPUU were investigated. Moreover, the degradation positions were confirmed by 1H NMR in my study.①The wettability of SMPUU was smaller than PDLLA controls. Meanwhile, the wettability had a uptrend with the increasing of hard segment content.②Comparing with the PDLLA, the weight loss ratio, Mw, and pH value changes of SMPUU decreased fast at prophase, and then, the changes ratio of SMPUU decreased, which can be attributed to the alkaline substance during the degradation of SMPUU could eliminate or weaken the acid induced auto-catalysis.③During the degradation, the SEM showed that the surface of SMPUU appeared the pores after 8 weeks. The amount of pores decreased with the increasing of content of hard segment, which can generate the alkaline group.④The results of 1H NMR indicated that, the degradation of SMPUU started from the hard segment, or in the hard segment and soft segment simultaneously, however, the degradation rate in soft segment was lower than in the hard segment, so the -NH2 in degradation product can release the acidity during degradation.5. In addition, the cytocompatibility of SMPUU was studied by employing primary SD rat osteoblasts as the model cells and poly (DL-lactic acid) (PDLLA) as the control. The growth behavior and function behavior were detected to indicate the cytocompatibility of SMPUU. Furthermore, the effects of stretching-shape recovering process of SMPUU on ostoblasts behaviors were also examined.①Initial morphology, adhesion, spreading and proliferation of osteoblasts on all SMPUU films is no better than those on PDLLA film. Despite this, the cell doubling rate and migration rate on SMPUU elevated with the increasing culture time. Furthermore, with the increased amount of hard segments in SMPUU, both cell doubling rate and migration rate correspondingly increased, which is mostly possibly attributed to the improved hydrophilicity.②Osteoblast on different SMPUU films all exhibited lower physiological functions compared to those on PDLLA films within the first 10 days after seeding. Thereafter, however, the osteoblasts on SMPUU demonstrated better differentiation and mineralization than those on PDLLA films, and SMPUU3 > SMPUU2 > SMPUU1.③The AFM results showed that there were obvious and regular phase separation resulted from soft segments and hard segments in SMPUU, and some groove-ridge architectures within a scale of micrometers were produced by the stretching-shape recovering process. These special micropatterned structures promoted osteoblasts adhesion and proliferation, and also resulted in partially oriented cell growth along the grooves. Stretching-shape recovering process could change the surface morphology of SMPUU films and contribute to enhanced cell adhesion and proliferation, and even produce oriented arrangement of osteoblasts.6. The safety of SMPUU in vivo was evaluated by sensitization test, acute toxicity tests; the biocompatibility in vivo was evaluated by the implantation experiment in muscle; at last, the bone repair function for preventing non-union was confirmed by implanting in the jaw bone of rabbit.