Diethylamine, di-n-hexylamine, dicyclohexylamine and triethylamine have been used as initiators for the ring-opening polymerization of γ-benzyl-L-glutamate N-carboxyanhydride (BLG NCA) to synthesize poly(γ-benzyl-L-glutamate) (PBLG). The relationship between the molecular weight of PBLG and the molar ratio of monomer and initiator was studied. With dicy- clohexylamine as initiator, the influence of monomer concentration, and reaction temperature and time on the polymerization of BLG NCA was examined. Three reagents were used for the deprotection of benzyl groups in PBLG, including hydrobromic acid/acetic acid (33 wt.%), NaOH aqueous solution and trimethylsilyl iodide (TMSI). Through examining the molecular weight of PLGA obtained using different deprotection methods, it was revealed that TMSI could minimize chain cleavage in the process of deprotection and retain the degree of polymerization. The biocompatibilities of PBLG obtained using different initiators were evaluated by a live/dead assay against L929 fibroblast cells. The in vitro cytotoxicities of PLGA obtained using different deprotecting agents were evaluated by a methyl thiazolyl tetrazolium assay. The results revealed that both PBLG and PLGA exhibited good biocompatibilities.
HAN JinDongDING JianXunWANG ZhiChunYAN ShiFengZHUANG XiuLiCHEN XueSiYIN JingBo
Poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide)(PLGA-PEG-PLGA) triblock copolymer was synthesized through the ring-opening polymerization of LA and GA with PEG as macroinitiator and stannous octoate as catalyst. The amphiphilic copolymer self-assembled into micelles in aqueous solutions, and formed hydrogels as the increase of temperature at relatively high concentrations(〉 15 wt%). The favorable degradability of the hydrogel was confirmed by in vitro and in vivo degradation experiments. The good cellular and tissular compatibilities of the thermogel were demonstrated. The excellent adhesion and proliferation of bone marrow mesenchymal stem cells endowed PLGA-PEGPLGA thermogelling hydrogel with fascinating prospect for cartilage tissue engineering.
The osteochondral defects caused by vigorous trauma or physical disease are difficult to be managed.Tissue engineering provides a possible option to regenerate the damaged osteochondral tissues.For osteochondral reconstruction,one intact scaffold should be considered to support the regeneration of both cartilage and subchondral bone.Therefore,the biphasic scaffolds with the mimic structures of osteochondral tissues have been developed to close this chasm.A variety of biomimetic bilayer scaffolds fabricated from natural or synthetic polymers,or the ones loading with growth factors,cells,or both of them make great progresses in osteochondral defect repair.In this review,the preparation and in vitro and/or in vivo verification of bioinspired biphasic scaffolds are summarized and discussed,as well as the prospect is predicted.
A series of well-defined amphiphilic linear-dendritic block copolymers (telodendrimers, MPEG-b-PAMAM-cholesterol) with 1,2,4 or 8 cholesteryl groups (named as P1, P2, P4, P8, respectively) were synthesized. Their chemical structures were char- acterized with IH NMR and mass spectrum (MALDI-TOF MS). The telodendrimers could self-assemble into micelles in aqueous solution, and encapsulate chemotherapeutic drug doxorubicin (DOX) and paclitaxel (PTX) for combination therapy. All the telodendrimers could encapsulate DOX with similar capability. However, their drug-loading capability of PTX is in- creased with the increasing number of cholesteryl groups. P8 exhibited much higher PTX loading efficiency than its counter- parts. Thus, P8 was selected for further application of drug delivery in the paper. The drug-loading micellar nanoparticles (NPs) of P8 were spherical in shape and their diameters were less than 150 nm which were determined by dynamic light scattering measurements (DLS) and transmission electron microscope (TEM). In vitro drug release experiment demonstrated that P8 ex- hibited a controlled release manner for both DOX and PTX, and the two drugs were released simultaneously. In vitro cytotoxi- city experiment further demonstrated that the co-delivery of DOX and PTX in P8 exhibited better anti-cancer efficiency than the delivery systems encapsulated with single drug (DOX or PTX). This indicates a synergistic effect. The co-delivery system showed potential in future anti-cancer treatment.
Complications arising from tendon injury include tendon sheath infection and peritendinous adhesion, in which tendon adhesion often leads to serious motor dysfunction. In this work, the electrospun membranes of poly(L-lactide)(PLA) and poly(ε-caprolactone)(PCL) with different degradation kinetics were used to investigate their efficacy for anti-adhesion toward Achilles tendon repair. Compared with the PCL membrane, the PLA sample showed a faster rate of degradation in 42 d, and all the degradation media(i.e., phosphate-buffered saline) maintained at a constant p H of around 7.4. Meanwhile, the superior biocompatibility of both the PLA and PCL membranes were proved by the in vitro cellular adhesion tests and in vivo histopathological assays. Simultaneously, the PLA membrane was more effective than the PCL sample in decreasing adhesion and promoting functional recovery. Furthermore, the experiment result was further confirmed by hematoxylin-eosin and Masson's trichrome staining, and type I collagen immunohistochemical analysis. All results revealed that the model treated with the electrospun PLA membrane was obviously better with regard to both anti-adhesion and tendon repair than that in the PCL membrane group. Considering the results of degradation and adhesion prevention efficacy, the electrospun polyester membranes, especially the PLA one, would be applied with fascinating potential in clinical prevention of postoperative tendon adhesion.
An electrospun poly(lactide-co-glycolide) (PLGA) membrane was prepared and used to perform the anti-adhesion of Achilles tendon. Throughout the experiments, the membrane showed an appropriate degradation rate, and the pH values of degradation media were maintained at around 7.4. Simultaneously, the excellent biocompatibility of the membrane in vitro and in vivo was confirmed by live/dead and histopathological analyses. Meanwhile, the membrane can reduce tendon adhesion significantly and promote functional recovery effectively. The encouraging results were further demonstrated by hematoxylin and eosin (H&E), and Masson's trichrome stainings, and type I collagen immunohistochemical analysis. It was concluded that the model treated with the electrospun PLGA membrane was significantly better with respect to the adhesion prevention and tissue repair than that without treatment. Considering the results of degradation and adhesion prevention efficacy, the electrospun PLGA membrane would be a great candidate for the prevention of postoperative tendon adhesion.