Totally bioresorbable composites prepared from poly(l‐lactide)‐co‐(trimethylene carbonate) copolymers and poly(l‐lactide)‐co‐(glycolide) fibers as cardiovascular stent material

This paper aims to evaluate the potential of totally bioresorbable composites as cardiovascular stent material. Copolymers were synthesized by ring‐opening polymerization of L ‐lactide (LLA) and 1,3‐trimethylene carbonate (TMC) with LLA‐TMC ratios of 3/1, 4/1, and 5/1 and characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). Wt. 5% of poly(L ‐lactide)‐co‐(glycolide) (PLGA) fibers are used to reinforce PTMC‐LLA copolymer matrices to prepare totally bioresorbable composites. Heat treatment under vacuum and oxygen plasma treatment are applied to improve the mechanical performance of the composites in terms of eliminating the imperfections inside, enhancing interfacial affinity, surface roughness, and enriching surface oxidative chemical bonds. After plasma treatment, the viscosity and tensile strength of the fibers decrease, but the surface chemical bonds are enriched and surface roughness is increased. The composites with 15‐min plasma‐treated fibers and 2 h heat treatment exhibit the highest tensile strength of 46 MPa, i.e., very close to that of PLLA (48 MPa), which is usually used as biodegradable stent material. Moreover, the tensile modulus of the above composite is 1711 MPa, which is only 34% of PLLA's modulus (4985 MPa). Therefore, novel composites with sufficient tensile strength and better flexibility are obtained as promising cardiovascular stent material. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers     

In vitro Degradation of Poly[(L‐lactide)‐co‐(trimethylene carbonate)] Copolymers and a Composite with Poly[(L‐lactide)‐co‐glycolide] Fibers as Cardiovascular Stent Material

TMC/LLA copolymers with several TMC/LLA ratios are synthesized and a composite is obtained by reinforcing with short PLGA fibers. In vitro degradation is studied at 37 °C in pH = 7.4 buffer and compared with a PLLA homopolymer. The degradation of the copolymers appears slower than that of PLLA, showing that TMC units are more resistant to hydrolysis than LLA. Compositional changes indicate a preferential degradation of LLA units as compared to TMC ones. Morphological changes with crystallization of degradation by‐products are observed. The composite degrades much faster than the neat copolymer and PLLA because the faster degradation of PLGA fibers speeds up the degradation of the matrix. The composite appears promising for the fabrication of totally bioresorbable stents.

     

Plasticization of Poly‐L‐lactide with L‐lactide,D‐lactide,and D,L‐lactide monomers

Poly‐L ‐lactide (PLLA) is being widely considered for repair of damaged tissues, for controlled antibiotic release, and also as scaffolds for cultured cells. PLLA was blended with the lactide monomer in its two enantiomeric forms: D ‐lactide (D ‐la) and L ‐lactide (L ‐la) and with the cyclic dimmer D ,L ‐la, in order to enhance its flexibility and thereby overcome its inherent problem of brittleness. In this work, the crystallization, phase structure, and tensile properties of PLLA and PLLA plasticized with 5, 10, 15, and 20 wt% of D ‐la, L ‐la, and D ,L ‐la are explored. The three plasticizers used were effective in lowering the glass transition temperature (T_g) and the melting temperature (T_m) of PLLA, around 20°C for a plasticizer content of 20 wt%. The tensile strength and modulus of the blends decreased following the increasing content of plasticizers from approximately 58 MPa to values below 20 MPa, and from 1667 to 200 MPa, respectively. Aging the blends at storage ambient temperature revealed that the enhanced flexibility as well as the morphological stability was lost over time due to the migration of the plasticizer to the surface, this being less marked in the case of D ‐la as a result of interactions between the polymer and its enantiomeric monomer of complementary configuration. POLYM. ENG. SCI., 53:2073–2080, 2013. © 2013 Society of Plastics Engineers     

Synthesis and characterization of novel ABA triblock copolymers from L‐lactide,glycolide, and PEG

A series of novel triblock copolymers, consisting of a poly(ethylene glycol) center block joined by two blocks of random L ‐lactide/glycolide copolymers, are synthesized and their characteristics (spectral, thermal, and mechanical) determined. Polymer compositions and structures are assessed via ¹H‐NMR and ¹³C‐NMR spectroscopies. DSC and stress–strain behavior studies demonstrate that these copolymers are generally more amorphous, more elastic, and tougher than are poly(L ‐lactides). © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 2004–2009, 1999     

Synthesis and characterization of a random terpolymer of L‐lactide, ϵ‐caprolactone and glycolide

A random terpolymer of L ‐lactide (LL), ?‐caprolactone (CL) and glycolide (G) has been synthesized in bulk at 130 °C using stannous octoate as the coordination–insertion initiator. The terpolymer, poly(LL‐ran‐CL‐ran‐G), has been characterized by a combination of analytical techniques: GPC, ¹H NMR, ¹³C NMR, DSC and TG. Molecular weight characterization by GPC shows a unimodal molecular weight distribution with values of M _n = 1.01 × 10⁵ g mol^?1 and M _w / M _n = 2.17. Compositional and microstructural analysis by ¹H NMR and ¹³C NMR, respectively, reveal a terpolymer composition of LL:CL:G = 74:15:11 (mol%) with a chain microstructure consistent with random monomer sequencing. This latter view is supported by the terpolymer temperature transitions (T_g and T_m) from DSC and the thermal decomposition profile from TG. The results and, in particular, the conclusion that it is a random rather than a statistical terpolymer are discussed in the light of current theories regarding the mechanism of this type of polymerization. © 2001 Society of Chemical Industry     

Surfactant‐free nanoparticles of poly(DL‐lactide‐co‐glycolide) prepared with poly(L‐lactide)/ poly(ethylene glycol)

Surfactant‐free nanoparticles of poly(DL ‐lactide‐co‐glycolide) (PLGA) nanoparticles were prepared with or without poly(L ‐lactide)‐poly(ethylene oxide) (LE) diblock copolymer (abbreviated as PLGA/LE and PLGA nanoparticles) by dialysis method. LE diblock copolymer was used to make PLGA nanoparticles to alternate conventional surfactant. The size of PLGA and PLGA/LE nanoparticles was 295.3 ± 171.3 and 307.6 ± 27.2 nm, respectively, suggesting LE diblock copolymer might be coated onto the surface of nanoparticles. Observation of scanning electron microscope (SEM) showed that PLGA/LE nanoparticles have spherical shapes ranging ～ 200–500 nm. In ¹H‐NMR study, characteristic peaks of the methyl protons of PLGA disappeared in D₂O, whereas characteristic peaks of the methyl proton of both PEG and PLGA were shown in both CDCl₃ and D₂O, indicating that LE diblock copolymer coated on the surface of the PLGA nanoparticles. The higher the initial content of drug, the higher the drug contents and the lower the loading efficiency. PLGA/LE nanoparticles at higher drug contents resulted in slower adriamycin·HCl (ADR) release rate than that of lower drug contents. Also, slower release rate of ADR was achieved by entrapped into the PLGA/LE nanoparticles, whereas LE polymeric micelles showed rapid ADR release. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1116–1123, 2003     

Microstructure and mechanism study of polylactide obtained by the copolymerization of L‐lactide and D,L‐lactide

The stereosequence of polylactide has been analyzed with ¹³C‐NMR spectroscopy, according to which syndiotactic addition is preferred. According to Markovian statistics, the reactivity ratio, which determines the extent of the syndiotactic stereosequence in the polymer chain, can be calculated by an analysis of the carbonyl and methine regions in the spectra. Moreover, the average lengths of segments SS and RR can be proposed and calculated with the distributing function of the sequence. On this basis, we have investigated the formation mechanism with respect to the preference for the syndiotactic addition of polylactide chains. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Comparative study of the hydrolytic degradation of glycolide/L‐lactide/ε‐caprolactone terpolymers initiated by zirconium(IV) acetylacetonate or stannous octoate

A series of copolymers have been synthesized by the ring‐opening polymerization of glycolide, L ‐lactide, and ?‐caprolactone with zirconium(IV) acetylacetonate [Zr(Acac)₄] or stannous octoate [Sn(Oct)₂] as the catalyst. The resulting terpolymers have been characterized by analytical techniques such as proton nuclear magnetic resonance, size exclusion chromatography, and differential scanning calorimetry. Data have confirmed that Sn(Oct)₂ leads to less transesterification of polymer chains than Zr(Acac)₄ under similar conditions. The various copolymers have been compression‐molded and allowed to degrade in a pH 7.4 phosphate buffer at 37°C. The results show that the degradation rate depends not only on the copolymer composition but also on the chain microstructure, the Sn(Oct)₂‐initiated copolymers degrading less rapidly than Zr(Acac)₄‐initiated ones with more random chain structures. The caproyl component appears the most resistant to degradation as its content increases in almost all cases. Moreover, caproyl units exhibit a protecting effect on neighboring lactyl or glycolyl units. The glycolyl content exhibits different features: it decreases because of faster degradation of glycolyl units, which are more hydrophilic than caproyl and lactyl ones, remains stable in the case of abundant C? G? C sequences, which are very resistant to degradation, or even increases because of the formation of polyglycolide crystallites. Terpolymers can crystallize during degradation if the block length of one of the components is sufficiently long, even though they are amorphous initially. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Mechanical properties and thermal stability of poly(L‐lactide)/calcium carbonate composites

Poly(L ‐lactide) (PLA) was melt‐mixed with micrometer‐sized and nanosized calcium carbonate (CaCO₃) particles before and after modification with calcium stearate. Adhesion between the CaCO₃ particles and the PLA matrix was assessed qualitatively by scanning electron microscopy observation of the fractured surface morphology of the composites. The effect of the incorporation of the CaCO₃ particles on the thermal stability of the PLA‐based composites was quantified by the temperatures corresponding to 5 and 50% of weight loss and the activation energy determined through thermogravimetric analyses of the composites. The tensile strength and modulus values of the composite were improved greatly without a significant loss in the elongation at break when the nanosized CaCO₃ was incorporated up to 30 wt %. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Effects of plasma treatment on biocompatibility of poly[(L‐lactide)‐co‐(ϵ‐caprolactone)] and poly[(L‐lactide)‐co‐glycolide] electrospun nanofibrous membranes

Poly[(l ‐lactide)‐co ‐(? ‐caprolactone)] (PLCL) and poly[(l ‐lactide)‐co ‐glycolide] (PLGA) copolymers are widely used in neural guide tissue regeneration. In this research, the surface modification of their hydrophilicity was achieved using plasma treatment. Attachment and proliferation of olfactory ensheathing cells on treated electrospun membranes increased by 26 and 32%, respectively, compared to the untreated PLCL and PLGA counterparts. Cells cultivated on both the PLCL and PLGA membranes showed high viability (>95%) and healthy morphologies with no evidence of cytotoxic effects. Cells grown on treated electrospun fibres displayed significant increases in mitochondrial activity and reductions in membrane leakage when compared to untreated samples. The results suggested that plasma treatment of the surface of the polymers enhanced both cell viability and growth without incurring any cytotoxic effects. © 2017 Society of Chemical Industry     

More on the poly(L‐lactide) prepared using ferrous acetate as catalyst

Polylactides were prepared by ring‐opening polymerization (ROP) in bulk using as catalyst either stannous 2‐ethylhexanoate at a monomer to catalyst ratio of 2000, or ferrous acetate (Fe(OAc)₂) at monomer to catalyst ratios of 500, 1000, 2000 and 3000. The crystallization behaviour was studied for the prepared polymers as well as the degradation behaviour both in laboratory and natural compost environments by using differential scanning calorimetry, size exclusion chromatography, X‐ray diffractiometry and microscopy. No differences were apparent due to the choice or amount of catalyst used, except for those which could be related to the increased racemization when the Fe(OAc)₂ was used. Copyright © 2004 Society of Chemical Industry     

Photocurable biodegradable polyesters from poly(L‐lactide) diols

α,ω‐Dihydoxy‐terminated poly(L ‐lactide)s (PLLA diols) with various molecular weights (1000, 2000 and 3000 g mol^?1) were prepared by the ring‐opening polymerization of L ‐lactide using 1,6‐hexanediol as an initiator. These were subsequently chain‐extended with the diacyl chloride of 4,4′‐(adipoyldioxy)dicinnamic acid (CAC) to obtain high‐molecular‐weight photocurable polyesters (CAC/PLLAs). The resulting polyesters were characterized by gel permeation chromatography, Fourier‐transform infrared, ultraviolet–visible and proton nuclear magnetic resonance spectroscopies, differential scanning calorimetry and thermogravimetry. These photoreactive polyesters were irradiated with a high‐pressure mercury lamp (λ > 280 nm) for 30–180 min to produce the crosslinked polyesters. The gel fraction yield increased with photocuring time, and exceeded 80 % after 180 min. The photocuring process disturbed the crystallization of the CAC/PLLA films, while it enhanced their thermal stabilities. With increasing photocuring time, both the tensile strength and modulus increased markedly. The best mechanical properties (tensile strength = 41 MPa; tensile modulus = 1550 MPa) were obtained for a CAC/PLLA‐3000 film photocured for 180 min. The tensile modulus of this photocured film was larger than that of pure PLLA. The hydrolytic degradation rates of the CAC/PLLA films in a phosphate buffer solution (pH, 7.2) of proteinaze‐k at 37 °C were much slower than those of pure PLLA films. Copyright © 2004 Society of Chemical Industry     

以三亚甲基碳酸酯和丙交酯为单体的三嵌段共聚物的合成和表征

以1,6-己二醇为引发剂,辛酸亚锡为催化剂,通过开环聚合制备了PLLA-b-PTMC-b-PLLA和PDLA-b-PTMC-b-PDLA两种三嵌段共聚物,采用核磁共振和红外光谱谱图对产物进行了验证表征,并使用DSC和TGA对共聚物的热力学性能进行了测试。结果表明,通过控制单体与引发剂的比例可以分别获得不同分子量和分子量分布的三嵌段聚合物。在DSC曲线上,PLA-b-PTMC-b-PLA三嵌段共聚物表现出两个玻璃化温度,熔融峰的高度与PLA部分的含量呈正相关,而当PTMC含量占绝大部分时,该熔融峰变得不明显。     

Novel bioresorbable hydrogels prepared from chitosan‐graft‐polylactide copolymers

A series of biodegradable chitosan‐graft‐polylactide (CS‐g‐PLA) copolymers were prepared by grafting of poly(L ‐lactide) (PLLA) or poly(D ‐lactide) (PDLA) precursor to the backbone of chitosan using N,N′‐carbonyldiimidazole as coupling agent. The composition of the copolymers was varied by adjusting the chain length of PLA as well as the ratio of chitosan to PLA. The copolymers synthesized via this ‘graft‐onto’ method present interesting properties as shown by NMR and infrared spectroscopy, gel permeation chromatography and solubility tests. Hydrogels were prepared by mixing water‐soluble CS‐g‐PLLA and CS‐g‐PDLA solutions. Gelation was assigned to stereocomplexation between PLLA and PDLA blocks as evidenced by differential scanning calorimetry and wide‐angle X‐ray diffraction measurements. Thymopentin (TP5) was taken as a model drug to evaluate the potential of these CS‐g‐PLA hydrogels as drug carriers. An initial burst and a final release up to 82% of TP5 were observed from high‐performance liquid chromatography analysis. Copyright © 2011 Society of Chemical Industry     

Plasticization of poly‐L‐lactide for tissue engineering

Plasticization of medical grade poly‐L ‐lactide (PLLA) by addition of polyethylene glycol (PEG) with various molar masses has been evaluated as means of producing low stiffness matrices for bioresorbable scaffolds for soft‐tissue engineering applications. As reported previously, the T_g of injection molded specimens of the PLLA/PEG blends decreased strongly with PEG content, so that at PEG contents of 15 and 25 wt % it became significantly lower than normal human body temperature, implying an essentially rubber‐like mechanical response in vivo. The degree of crystallinity of the moldings also increased strongly with PEG content, reaching a maximum of about 60 wt % at 25 wt % PEG. Moreover, after the immersion in phosphate‐buffered saline for 5 days in 37°C to simulate conditions in vivo, the moldings with the highest PEG contents showed increased water uptake and, for relatively low molar mass PEG, significant mass loss, associated with phase separation and leaching of the PEG. Blends with relatively low PEG contents also showed large increases in their degree of crystallinity. The implications of these changes for the in vivo performance of the blends and their potential for development as matrices for bioresorbable scaffolds are discussed in the light of results from a series of PLLA/PEG copolymers. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Synthesis and properties of polycarbonate copolymers of trimethylene carbonate and 2‐phenyl‐5,5‐bis(hydroxymethyl) trimethylene carbonate

The polycarbonate copolymers poly[trimethylene carbonate‐co‐2‐phenyl‐5,5‐bis(hydroxymethyl) trimethylene carbonate] [P(TMC‐co‐PTC)] were synthesized by the ring‐opening polymerization of trimethylene carbonate (TMC) and 2‐phenyl‐5,5‐bis(hydroxymethyl) trimethylene carbonate (PTC) with tin(II) 2‐ethylhexanoate and aluminum isopropoxide as the catalysts. These copolymers were further reduced by a palladium/carbonate (Pd/C; 10%) catalyst to produce partly deprotected copolymers. These two types of copolymers were characterized by ¹H‐NMR, Fourier transform infrared spectroscopy, UV spectroscopy, gel permeation chromatography, differential scanning calorimetry, and an automatic contact angle meter. The influences of the feed molar ratio of the monomers, the catalyst concentration, the reaction time, and the reaction temperature on the copolymerization process were also studied. The copolymerization of the TMC and PTC monomers was a nonideal copolymerization, and the copolymerization reactivity ratio of TMC was higher than that of PTC. In vitro degradation tests indicated that the partly deprotected copolymers possessed faster degradation rates and more hydrophilicity than the corresponding unreduced copolymers. Moreover, the degradation of these two type copolymers increased when the pH value of the buffer solutions decreased. In vitro drug‐release experiments showed that these two types of copolymers had steady drug‐release rates and good controlled release properties. Moreover, the partly deprotected copolymers had faster drug‐release rates than the corresponding unreduced copolymers. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Preparation of porous poly(D,L‐lactide) and poly(D,L‐lactide‐co‐glycolide) membranes by a phase inversion process and investigation of their morphological changes as cell culture scaffolds

Porous membranes composed of the biodegradable polyesters poly(D,L ‐lactide) (PLA) and poly(D,L ‐lactide‐co‐glycolide) (PLGA) were prepared by a phase inversion process. The molecular weights of the polymers and the concentrations of the polymer solutions affected the pore size and structure of the PLA and PLGA membranes. The molecular weights and morphological changes of the membranes as a function of time were investigated under incubation at 37°C in a humidified 5% CO₂ atmosphere. The pores that formed in the membranes changed dramatically with increasing time under these conditions. From the thermal characterization of the polymers in their dry and wet states, we found that the glass‐transition temperatures of PLA and PLGA affected morphological structure changes in the porous membranes. We also prepared a collagen‐coated membrane to improve the interaction between the cell and the substrate, and we observed that the collagen coating enhanced the attachment and growth of Chinese hamster ovary cells on the substrate. Finally, we found that only PLA was a suitable material to prepare a porous membrane scaffold with the phase inversion process with PLA, and a collagen coating was necessary for cell culture on the membrane. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2082–2092, 2004     

Morphology and melt crystallization of poly(L‐lactide) obtained by ring opening polymerization of L‐lactide with zinc catalyst

The morphology and melt crystallization of zinc catalyzed poly(L ‐lactide) (PLLA) were investigated by using differential scanning calorimetry (DSC), polarized optical microscopy, and scanning electron microscopy. Isothermal melt crystallization performed at 95–135°C showed that the morphology depends on the degree of supercooling, as illustrated by crystallite perfection and lamellar thickening behaviors. Double melting peak was observed on DSC thermograms and attributed to the melt‐recrystallization mechanism, small and imperfect crystals becoming gradually more stable ones. Circumferential and hexagonal cracks were detected in PLLA spherulites, which were formed during melt‐crystallization at 135°C and quenching in liquid nitrogen. Rhythmic growth and thermal shrinkage are suggested to be the two main factors accounting for the formation of periodic cracks. Spherulite growth rates of PLLA were evaluated by using combined isothermal and nonisothermal procedures, and were analyzed by the secondary nucleation theory. The maximum growth rate reached 9.1 μm/min at 130°C. The temperature range investigated (120–155°C) belongs to the Regime II of crystallization. The value of U* was found to be 1890 cal/mol, instead of 1500 cal/mol commonly used in literature, and K_g and σ were estimated to be 3.03 × 10⁵ K² and 1.537 × 10^?4 J/m², respectively. As a result, no distinct difference between PLLA catalyzed by zinc metal and those prepared with stannous octoate catalyst exists in this work. POLYM. ENG. SCI., 46:1583–1589, 2006. © 2006 Society of Plastics Engineers.     

Microwave‐irradiated ring‐opening polymerization of D,L‐lactide under atmosphere

Poly(D ,L ‐lactide) (PDLLA) was synthesized by microwave‐irradiated ring‐opening polymerization catalyzed by stannous octoate (Sn(Oct)₂) under atmosphere. The effects of heating medium, monomer purity, catalyst concentration, microwave irradiation time, and vacuum level were discussed. Under the appropriate conditions such as carborundum (SiC) as heating‐medium, 0.15% catalyst, lactide with purity above 99.9%, 450 W microwave power, 30 min irradiation time, and atmosphere, PDLLA with a viscosity–average molecular weight (M_η) over 2.0 × 10⁵ and a yield over 85% was obtained. The dismission of vacuum to ring‐opening polymerization of D ,L ‐lactide (DLLA) under microwave irradiation simplified the process greatly. The temperature under microwave irradiation and conventional heating was compared. The largely enhanced ring‐opening polymerization rate of DLLA under microwave irradiation was the coeffect of thermal effects and microwave effects. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2244–2247, 2006