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     

Effects of copolymer microstructure on the properties of electrospun poly(l‐lactide‐co‐ε‐caprolactone) absorbable nerve guide tubes

The main objective of this work has been to study the effects of copolymer microstructure, both chemical and physical, on the microporosity, in vitro hydrolytic degradability and biocompatibility of electrospun poly(l ‐lactide‐co‐ε‐caprolactone), PLC, copolymer tubes for potential use as absorbable nerve guides. PLC copolymers with L : C compositions of 50 : 50 and 67 : 33 mol % were synthesized via the ring‐opening copolymerization of l ‐lactide (L) and ε‐caprolactone (C) at 120°C for 72 h using stannous octoate (tin(II) 2‐ethylhexanoate) and n‐hexanol as the initiating system. Electrospinning was carried out from solution in a dichloromethane/dimethylformamide (7 : 3 v/v) mixed solvent at room temperature. The in vitro hydrolytic degradation of the electrospun PLC tubes was studied in phosphate buffer saline over a period of 36 weeks. The microporous tubes were found to be gradually degradable by a simple hydrolysis mechanism leading to random chain scission. At the end of the degradation period, the % weight retentions of the PLC 50 : 50 and 67 : 33 tubes were 15.6% and 70.2%, respectively. Pore stability during storage as well as cell attachment and proliferation of mouse fibroblast cells (L929) showed the greater potential of the PLC 67 : 33 tubes for use as temporary scaffolds in reconstructive nerve surgery. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4357–4366, 2013     

Characterization and cell response of electrospun Rana chensinensis skin collagen/poly(l‐lactide) scaffolds with different fiber orientations

Collagen was extracted from Rana chensinensis skin supplied from byproducts via an acid enzymatic extraction method. The R. chensinensis skin collagen (RCSC) and poly(l ‐lactide) (PLLA) were blended at a 3:7 ratio in 1,1,1,3,3,3‐hexafluoroisopropanol (HFIP) at a concentration of 10% (g/mL) and electrospun to produce nanofibers in an aligned and random orientation. For comparison, pure PLLA nanofibrous membranes with aligned and random nanofiber orientations were also produced. The secondary structure of the RCSC nanofibers was investigated by circular dichroism to confirm that the extracted substance was collagen. The presence of collagen in the blend nanofiber was verified by LSCM. The blended nanofibers showed uniform, smooth, and bead‐free morphologies and presented a smaller fiber diameter (278 and and 259 nm) than the pure the ones of PLLA (559 and and 439 nm) nanofibers. It was found that the addition of RCSC and the modification of the nanofiber's orientation affected the fiber's diameter and the crystallization of PLLA. The cell viability studies with human fibroblast cells demonstrated that the RCSC/PLLA nanofibrous membranes formed by electrospinning exhibited good biocompatibility and that the aligned scaffolds could regulate the cell morphology by inducing cell orientation. The empirical results in this study indicated that the aligned RCSC/PLLA nanofibrous membrane is a potential wound dressing candidate for skin regeneration. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45109.     

Preparation and characterization of nanohydroxyapatite strengthening nanofibrous poly(L‐lactide) scaffold for bone tissue engineering

A biomimetic nanofibrous poly(L ‐lactide) scaffold strengthened by nanohydroxyapatite particles was fabricated via a thermally induced phase separation technique. Scanning electron microscopy results showed that nanohydroxyapatite particles uniformly dispersed in the nanofibrous poly(L ‐lactide) scaffold (50–500 nm in fiber diameter) with slight aggregation at a high nHA content, but showed no influence on the interconnected macroporous and nanofibrous structure of the scaffold. The nanofibrous poly(L ‐lactide) scaffold presented a specific surface area of 34.06 m² g^?1, which was much higher than that of 2.79 m² g^?1 for the poly(L ‐lactide) scaffold with platelet structure. Moreover, the specific surface area of the nanofibrous scaffold was further enhanced by incorporating nanohydroxyapatite particles. With increasing the nanohydroxyapatite content, the compressive modulus and amount of bovine serum albumin adsorbed on the surface of the nanofibrous composite scaffold were markedly improved, as opposed to the decreased crystallinity. In comparison to poly(L ‐lactide) scaffold, both the nanofibrous poly(L ‐lactide) and poly(L ‐lactide)/nanohydroxyapatite scaffolds exhibited a faster degradation rate for their much larger specific surface area. The culture of bone mesenchymal stem cell indicated that the composite nanofibrous poly(L ‐lactide) scaffold with 50 wt % nanohydroxyapatite showed the highest cells viability among various poly(L ‐lactide)‐based scaffolds. The strengthened biomimetic nanofibrous poly(L ‐lactide)/nanohydroxyapatite composite scaffold will be a potential candidate for bone tissue engineering. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

AB‐ and ABC‐type di‐ and triblock copolymers of poly[styrene‐block‐(ε‐caprolactone)] and poly[styrene‐block‐(ε‐caprolactone)‐block‐lactide]: synthesis,characterization and thermal studies

Polystyrene terminated with benzyl alcohol units was employed as a macroinitiator for ring‐opening polymerization of ε‐caprolactone and L ‐lactide to yield AB‐ and ABC‐type block copolymers. Even though there are many reports on the diblock copolymers of poly(styrene‐block‐lactide) and poly(styrene‐block‐lactone), this is the first report on the poly(styrene‐block‐lactone‐block‐lactide) triblock copolymer consisting of two semicrystalline and degradable segments. The triblock copolymers exhibited twin melting behavior in differential scanning calorimetry (DSC) analysis with thermal transitions corresponding to each of the lactone and lactide blocks. The block derived from ε‐caprolactone also showed crystallization transitions upon cooling from the melt. In the DSC analysis, one of the triblock copolymers showed an exothermic transition well above the melting temperature upon cooling. Thermogravimetric analysis of these block copolymers showed a two‐step degradation curve for the diblock copolymer and a three‐step degradation for the triblock copolymer with each of the degradation steps associated with each segment of the block copolymers. The present study shows that it is possible to make pure triblock copolymers with two semicrystalline segments which also consist of degradable blocks. Copyright © 2009 Society of Chemical Industry     

Ring‐opening copolymerization of L‐lactide with ε‐caprolactone initiated by diphenylzinc

Copolymerization of mixtures of L ‐lactide and ε‐caprolactone has been initiated by diphenylzinc. The reaction conditions were investigated, to discover the effects on yield, molecular weight and microstructure of copolymers obtained. The temperature used varied between 50 and 120 °C, the molar ratio of monomer to initiator ranged between 90 and 1440 mol/mol, and the molar ratio of ε‐caprolactone to L ‐lactide employed was between 100/0 and 0/100 mol/mol. Copolymers were characterized by ¹H‐NMR, ¹³C‐NMR, DSC and gel permeation chromatography. The results indicate that incorporation of L ‐lactide to the growing chain is preferred and ε‐caprolactone is copolymerized after most of the L ‐lactide has been depleted. The microstructure of obtained copolyesters was affected considerably by transesterification reactions. It was observed that increasing reaction temperature, reaction time and concentration initiator was advantageous to the transesterification. The crystallinity of copolyester obtained was determined by differential scanning calorimetry. The results are in good agreement with both molar composition and sequence distribution of copolyesters. Copyright © 2006 Society of Chemical Industry     

Electrospun poly(L‐lactide)/poly(ε‐caprolactone) blend fibers and their cellular response to adipose‐derived stem cells

Polymer blending is one of the most effective methods for providing new, desirable biocomposites for tissue‐engineering applications. In this study, electrospun poly(L ‐lactide)/poly(ε‐caprolactone) (PLLA/PCL) blend fibrous membranes with defect‐free morphology and uniform diameter were optimally prepared by a 1 : 1 ratio of PLLA/PCL blend under a solution concentration of 10 wt %, an applied voltage of 20 kV, and a tip‐to‐collector distance of 15 cm. The fibrous membranes also showed a porous structure and high ductility. Because of the rapid solidification of polymer solution during electrospinning, the crystallinity of electrospun PLLA/PCL blend fibers was much lower than that of the PLLA/PCL blend cast film. To obtain an initial understanding of biocompatibility, adipose‐derived stem cells (ADSCs) were used as seed cells to assess the cellular response, including morphology, proliferation, viability, attachment, and multilineage differentiation on the PLLA/PCL blend fibrous scaffold. Because of the good biocompatibility and nontoxic effect on ADSCs, the PLLA/PCL blend electrospun fibrous membrane provided a high‐performance scaffold for feasible application in tissue engineering using ADSCs. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Optimization and investigation of the governing parameters in electrospinning the home‐made poly(l‐lactide‐co‐ε‐caprolactone‐diOH)

Poly(l ‐lactide‐co‐ε‐caprolactone‐diOH) (PCLA) with (ABA)_n type is synthesized using poly(lactic acid) (PLA) and poly(ε‐caprolactone) di‐OH (PCL‐diOH) via chain extending method. FT‐IR, ¹H‐NMR, and GPC data demonstrate that PLA and PCL‐diOH have reacted completely. The product is electrospun into ultrafine fibers subsequently. The optimum electrospinning parameters obtain from an orthogonal experiment are a solvent ratio (DMF/DCM) of 5/5, a polymer concentration of 28 wt %, a collector distance of 20 cm and a voltage of 18 kV. As a result, the average diameter of fibers is 0.77 µm and the uniformity is above 80%. Via range analysis, it is found that the order of the influence on diameter is solvent ratio, applied voltage, collector distance, and polymer concentration, successively. Single effect of the four governing factors on diameter and morphology is also experimentally investigated. This may provide clues for obtaining fibers with various structures by controlling the parameters. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 3600–3610, 2013     

Synthesis,characterization and biocompatibility of novel biodegradable poly[((R)‐3‐hydroxybutyrate)‐block‐(D,L‐lactide)‐block‐(ε‐caprolactone)] triblock copolymers

BACKGROUND: Biodegradable block copolymers have attracted particular attention in both fundamental and applied research because of their unique chain architecture, biodegradability and biocompatibility. Hence, biodegradable poly[((R )‐3 ‐hydroxybutyrate)‐block‐(D ,L ‐lactide)‐block‐(ε‐caprolactone)] (PHB‐PLA‐PCL) triblock copolymers were synthesized, characterized and evaluated for their biocompatibility. RESULTS: The results from nuclear magnetic resonance spectroscopy, gel permeation chromatography and thermogravimetric analysis showed that the novel triblock copolymers were successfully synthesized. Differential scanning calorimetry and wide‐angle X‐ray diffraction showed that the crystallinity of PHB in the copolymers decreased compared with methyl‐PHB (LMPHB) oligomer precursor. Blood compatibility experiments showed that the blood coagulation time became longer accompanied by a reduced number of platelets adhering to films of the copolymers with decreasing PHB content in the triblocks. Murine osteoblast MC3T3‐E1 cells cultured on the triblock copolymer films spread and proliferated significantly better compared with their growth on homopolymers of PHB, PLA and PCL, respectively. CONCLUSION: For the first time, PHB‐PLA‐PCL triblock copolymers were synthesized using low molecular weight LMPHB oligomer as the macroinitiator through ring‐opening polymerization with D ,L ‐lactide and ε‐caprolactone. The triblock copolymers exhibited flexible properties with good biocompatibility; they could be developed into promising biomedical materials for in vivo applications. Copyright © 2008 Society of Chemical Industry     

Thermally exfoliated graphene oxide reinforced fluorinated pentablock poly(l‐lactide‐co‐ε‐caprolactone) electrospun scaffolds: Insight into antimicrobial activity and biodegradation

Three‐dimensional fluorinated pentablock poly(l ‐lactide‐co‐ε‐caprolactone)‐based scaffolds were successfully produced by the incorporation of thermally exfoliated graphene oxide (TEGO) as an antimicrobial agent with an electrospinning technique. In a ring‐opening polymerization, the fluorinated groups in the middle of polymer backbone were attached with a perfluorinated reactive stabilizer having oxygen‐carrying ability. The fiber diameter and its morphologies were optimized through changes in TEGO amount, voltage, polymer concentration, and solvent type to obtain an ideal scaffold structure. Instead of the widely used graphene oxide synthesized by Hummer's method, TEGO sheets having a low amount of oxygen produced by thermal expansion were integrated into the fiber structure to investigate the effect of the oxygen functional groups of TEGO sheets on the degradation and antimicrobial activity of the scaffolds. There was no antimicrobial activity in TEGO‐reinforced scaffolds in the in vitro tests in contrast to the literature. This study confirmed that a low number of oxygen functional groups on the surface of TEGO restricted the antimicrobial activity of the fabricated composite scaffolds. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43490.     

Part 7. Effects of poly(L‐lactide‐co‐ϵ‐caprolactone) on morphology,structure, crystallization,and physical properties of blends of poly(L‐lactide) and poly(ϵ‐caprolactone)

Blended films of poly(L ‐lactide) [ie poly(L ‐lactic acid)] (PLLA) and poly(?‐caprolactone) (PCL) without or mixed with 10 wt% poly(L ‐lactide‐co‐?‐caprolactone) (PLLA‐CL) were prepared by solution‐casting. The effects of PLLA‐CL on the morphology, phase structure, crystallization, and mechanical properties of films have been investigated using polarization optical microscopy, scanning electron microscopy, differential scanning calorimetry and tensile testing. Addition of PLLA‐CL decreased number densities of spherulites in PLLA and PCL films, and improved the observability of spherulites and the smoothness of cross‐section of the PLLA/PCL blend film. The melting temperatures (T_m) of PLLA and PCL in the films remained unchanged upon addition of PLLA‐CL, while the crystallinities of PLLA and PCL increased at PLLA contents [X_PLLA = weight of PLLA/(weight of PLLA and PCL)] of 0.4–0.7 and at most of the X_PLLA values, respectively. The addition of PLLA‐CL improved the tensile strength and the Young modulus of the films at X_PLLA of 0.5–0.8 and of 0–0.1 and 0.5–0.8, respectively, and the elongation at break of the films at all the X_PLLA values. These findings strongly suggest that PLLA‐CL was miscible with PLLA and PCL, and that the dissolved PLLA‐CL in PLLA‐rich and PCL‐rich phases increased the compatibility between these two phases. © 2003 Society of Chemical Industry     

Synthesis and characterization of poly(L‐lactide‐co‐ϵ‐caprolactone)‐b‐poly(L‐lactide) biodegradable diblock copolyesters: Effect of the block lengths on their thermal properties

Poly(L ‐lactide‐co‐ε‐caprolactone)‐b‐poly(L ‐lactide) [P(LL‐co‐CL)‐b‐PLL] diblock copolyesters were synthesized in a two‐step process with 1‐dodecanol (DDC) and stannous octoate as the initiating system. In the first‐step reaction, a 50:50 mol % amorphous poly(L ‐lactide‐co‐ε‐caprolactone) [P(LL‐co‐CL)] copolyester was synthesized via the bulk copolymerization of L ‐lactide and ε‐caprolactone, which was followed by the polymerization of the PLL crystalline block at the end chain in the second‐step reaction. The yielded copolyesters were characterized with dilute‐solution viscometry, gel permeation chromatography, ¹H‐ and ¹³C‐NMR, and differential scanning calorimetry methods. The molecular weights of the P(LL‐co‐CL) copolyesters from the first‐step reaction were controlled by the DDC concentrations, whereas in the second‐step reaction, the molecular weights of the P(LL‐co‐CL)‐b‐PLL diblock copolyesters depended on the starting P(LL‐co‐CL) copolyester molecular weights and L ‐lactide/prepolymer molar ratios. The starting P(LL‐co‐CL) copolyester molecular weights and PLL block lengths seemed to be the main factors affecting specific thermal properties, including the melting temperature (T_m), heat of melting (ΔH_m), crystallizing temperature (T_c), and heat of crystallizing (ΔH_c), of the final P(LL‐co‐CL)‐b‐PLL diblock copolyester products. T_m, ΔH_m, T_c, and ΔH_c increased when the PLL block lengths increased. However, these thermal properties of the diblock copolyesters also decreased when the P(LL‐co‐CL) block lengths increased. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Properties and degradation behavior of surface functionalized MWCNT/poly(L‐lactide‐co‐ε‐caprolactone) biodegradable nanocomposites

In this research, poly(L ‐lactide‐co‐ε‐caprolactone) (PLACL) reinforced with well‐dispersed multiwalled carbon nanotubes (MWCNTs) nanocomposites were prepared by oxidization and functionalization of the MWCNT surfaces using oligomeric L ‐lactide (LA) and ε‐caprolactone (CL). It is found that the surface functionalization can effectively improve the dispersion and adhesion of MWCNTs in PLACL. The surface functionalization will have a significant effect on the physical, thermomechanical, and degradation properties of MWCNT/PLACL composites. The tensile modulus, yield stress, tensile strength, and elongation at break of composite increased 49%, 60%, 70%, and 94%, respectively, when the concentration of functionalized MWCNTs in composite is 2 wt %. The in vitro degradation rate of nanocomposites in phosphate buffer solution increased about 100%. The glass transition temperature (T_g) of composites was decreased when the concentration of functionalized MWCNTs is 0.5 wt %. With further increasing the concentration of functionalized MWCNTs, the T_g was increased. The degradation kinetics of nanocomposites can be engineered and functionalized by varying the contents of pristine or functionalized MWCNTs. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Influence of microstructure of lactone‐based triblock copolymers on drug release behavior of their microspheres

The current work focuses on the influence of microstructure of different lactone‐based triblock copolymers on drug delivery, where the middle segment was δ‐valerolactone or ?‐caprolactone and the terminal segment was d ,l ‐lactide or cis ‐lactide. Microspheres were fabricated from the triblocks using salicylic acid as the model drug. The microsphere formation and drug release were investigated by scanning electron microscopy, ultraviolet–visible spectroscopy, X‐ray diffraction, and thermogravimetry. The size of the microspheres ranged from 2 to 20 µm in diameter. The diffusion coefficient values showed that replacement of the middle segment, δ‐valerolactone with ?‐caprolactone, retarded the diffusion of the drug molecules. The diffusion coefficient was lowered when d ,l ‐lactide content was decreased in the triblock. Mathematical models were used to predict the drug release from the microspheres of different triblocks. The modeling study on drug release profiles revealed that the biodegradable nature of the triblock played a crucial role in determining the drug release kinetics. The diffusion and degradation reaction justified the drug release from microsphere. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 45284.     

Heat‐Induced Dry Tailoring of Porosity in Polymer Scaffolds

The present study evaluates the effect of heat treatment on electrospun poly(lactide‐co‐glycolide) fibrous membranes. Both a temperature (75–150 °C) and a treatment time range (5–40 min) are tested. The effect on the fibrous structure is investigated in terms of morphology, showing that with increasing temperature or longer treatment time the fusion of fibres progresses continuously. Additionally, the tensile properties of the various scaffolds deliver results on the effect of increasing fibre‐to‐fibre linkages. Both modulus and yield increase within the heat treatment procedures. The elevated stiffness of the membranes accompanies a loss in porosity. These findings deliver insights into the tailoring of membranes that might be used in the fabrication of customised scaffolds intended for cell culture in tissue engineering.

     

Preparation,characterization, and drug release behaviors of drug‐loaded ε‐caprolactone/L‐lactide copolymer nanoparticles

Copolymers of ε‐caprolactone and L ‐lactide (PCLLA) with different monomer ratio were synthesized by ring opening polymerization, and drug‐loaded nanoparticles of poly‐ε‐caprolactone (PCL), poly‐L ‐lactide (PLLA), and their copolymers were prepared by precipitation method, respectively. The results of differential scanning calorimetry and X‐ray diffraction indicated that the copolymerization of PCLLA decreased the crystallinity of the polymers, and the results of transmission electron micrograph and laser light scattering (LLS) revealed that the prepared nanoparticles had a spherical shape, and the size of PCLLA nanoparticles (∼ 85 nm) was smaller than that of the PCL and PLLA nanoparticles. The experiment of in vitro drug release showed that the drug release rate from PCLLA nanoparticles was slower than that from PCL and PLLA nanoparticles, and the release profile of PCL6/LA4 nanoparticles appeared to follow zero order kinetics. These results suggested that the polymer composition made a great influence on the nanoparticle size and drug release behavior. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 874–882, 2000     

Enhanced crystallization of poly(L‐lactide‐co‐ε‐caprolactone) during storage at room temperature

Copolymer of L ‐lactide and ε‐caprolactone [P(LLA‐CL)] (50/50) was synthesized using stannous octoate and was stored at room temperature. The change in physical properties occurring during this storage at room temperature was investigated by differential scanning calorimetry (DSC), X‐ray diffractometry, polarizing optical microscopy, tensile and bending tests, and light absorbance measurements. It was concluded that the increase in mechanical properties and light absorbance during storage can be ascribed to gradual selective crystallization of the L ‐lactide sequence in P(LLA‐CL) at room temperature. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 947–953, 2000     

Shape‐memory behaviors of biodegradable poly(L‐lactide‐co‐ϵ‐caprolactone) copolymers

A series of biodegradable poly(L ‐lactide‐co‐?‐caprolactone) (PCLA) copolymers with different chemical compositions are synthesized and characterized. The mechanical properties and shape‐memory behaviors of PCLA copolymers are studied. The mechanical properties are significantly affected by the copolymer compositions. With the ?‐caprolactone (?‐CL) content increasing, the tensile strength of copolymers decreases linearly and the elongation at break increases gradually. By means of adjusting the compositions, the copolymers exhibit excellent shape‐memory effects with shape‐recovery and shape‐retention rate exceeding 95%. The effects of composition, deformation strain, and the stretching conditions on the recovery stress are also investigated systematically. A maximum recovery stress around 6.2 MPa can be obtained at stretching at T_g ? 15°C to 200% deformation strain for the PCLA70 copolymer. The degradation results show that the copolymers with higher ?‐CL content have faster degradation rates and shape‐recovery rates, meanwhile, the recovery stress can maintain a relative high value after 30 days in vitro degradation. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

α‐Amino acids as initiators of ε‐caprolactone and L,L‐lactide polymerization

Biodegradable polymers/oligomers were successfully synthesized through a ring‐opening polymerization of ε‐caprolactone and L ,L ‐lactide, initiated by L ‐arginine and L ‐citrulline. The α‐amino acid initiators are natural, operationally simple, inexpensive, environmentally friendly and safe for human health. The polymerizations were performed with no solvents and without introducing any metal impurities. The chemical structures of the polymers obtained were elucidated using ¹H NMR, ¹³C NMR and Fourier transform infrared spectroscopies. In addition, incorporation of α‐amino acid molecules into the polymer chain was confirmed using matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry. Due to the significant biological activity of L ‐arginine and L ‐citrulline, these α‐amino acid initiators may open a new route for the synthesis of functional polymers especially for pharmaceutical applications. Copyright © 2011 Society of Chemical Industry