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1.
The biodegradation rate and biocompatibility of poly(d, / -lactide) (PDLLA) in vivo were evaluated. The aim of this study was to establish a nerve guide constructed by the PDLLA with 3-D microenvironment and to repair a 10 mm of sciatic nerve gap in rats. The process of the nerve regeneration was investigated by histological assessment, electrophysiological examination, and determination of wet weight recovery rate of the gastrocnemius muscle. After 3 weeks, the nerve guide had changed from a transparent to an opaque status. The conduit was degraded and absorbed partly and had lost their strength with breakage at the 9th week of postoperation. At the conclusion of 12 weeks, proximal and distal end of nerves were anastomosed by nerve regeneration and the conduit vanished completely. The results suggest that PDLLA conduits may serve for peripheral nerve regeneration and PDLLA is a sort of hopeful candidate for tissue engineering.  相似文献   

2.
The biodegradation rate and biocompatibility of poly(d, l -lactide) (PDLLA) in vivo were evaluated. The aim of this study was to establish a nerve guide constructed by the PDLLA with 3-D microenvironment and to repair a 10 mm of sciatic nerve gap in rats. The process of the nerve regeneration was investigated by histological assessment, electrophysiological examination, and determination of wet weight recovery rate of the gastrocnemius muscle. After 3 weeks, the nerve guide had changed from a transparent to an opaque status. The conduit was degraded and absorbed partly and had lost their strength with breakage at the 9th week of postoperation. At the conclusion of 12 weeks, proximal and distal end of nerves were anastomosed by nerve regeneration and the conduit vanished completely. The results suggest that PDLLA conduits may serve for peripheral nerve regeneration and PDLLA is a sort of hopeful candidate for tissue engineering.  相似文献   

3.
Peripheral nerve regeneration has been evaluated using a biodegradable nerve conduit, which is made of a 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)/N-hydroxysuccinimide (NHS) cross-linked gelatin. The EDC/NHS crosslinked gelatin (ENG) conduit is brownish in appearance, and is concentric and round with a smooth outer surface and inner lumen. After subcutaneous implantation on the dorsal side of a rat, the degraded ENG conduit only evoked a mild tissue response, with the formation of a thin tissue capsule surrounding the conduit. Biodegradability of the ENG conduit and its effectiveness as a guidance channel has been examined by its use to repair a 10 mm gap in the rat sciatic nerve. As a result, the tubes degraded throughout the implantation period, but still remained circular with a thin round lumen until they were completely integrated with the enclosed nerves. Successful regeneration through the gap occurred in all the conduits over the three experimental periods of 4, 8, and 12 weeks. Histological observation showed that numerous myelinated axons had crossed through the gap region even at the shortest implantation period of 4 weeks. Peak amplitude, area under the muscle action potential curve, and nerve conductive velocity all showed an increase as a function of the recovery period, which indicates that the nerve had undergone adequate regeneration. These results indicate the superiority of the ENG materials and suggest that the novel ENG conduits provide a promising tool for neuro-regeneration.  相似文献   

4.
Chitosan (CTS) has been used as a nerve guidance conduit (NGC) material for bridging peripheral nerve defects due to its biocompatible, biodegradable, and non-toxic properties. However, the nerve regeneration effect of chitosan alone is restricted due to its inadequate biological activity. Herein, a composite, bioactive chitosan based nerve conduit, consisting of outer warp-knitted tube scaffold made from medical-grade chitosan fiber, and inner porous cross linked carboxymethyl chitosan (C-CM-CTS) sponge with radial texture was developed. The inner wall of the scaffold was coated with C-CM-CTS solution. CM-CTS provided favorable bioactivities in the composite chitosan-based nerve conduit. An in vitro study of CM-CTS revealed its satisfying biocompatibility with fibroblast and its inhibition of oxidative damage to Schwann cells. As the internal filler of the NGC, the lyophilized sponge of C-CM-CTS showed a longitudinal guidance effect for nerve reconstruction. After 10 mm defect in rat sciatic nerve was bridged with the composite bioactive chitosan-based nerve conduit, the nerve conduit was able to effectively promote axonal regeneration and played a positive role in inducing nerve regeneration and functional recovery. In addition to the functional advantages, which are equal to those of an autograft; the technology for the preparation of this conduit can be put into mass production.  相似文献   

5.
The feasible fabrication of nerve guidance conduits (NGCs) with good biological performance is important for translation in clinics. In this study, poly(d ,l ‐lactide‐co‐caprolactone) (PLCL) films loaded with various amounts (wt; 5%, 15%, 25%) of methylcobalamin (MeCbl) are prepared, and are further rolled and sutured to obtain MeCbl‐loaded NGCs. The MeCbl can be released in a sustainable manner up to 21 days. The proliferation and elongation of Schwann cells, and the proliferation of Neuro2a cells are enhanced on these MeCbl‐loaded films. The MeCbl‐loaded NGCs are implanted into rats to induce the regeneration of 10 mm amputated sciatic nerve defects, showing the ability to facilitate the recovery of motor and sensory function, and to promote myelination in peripheral nerve regeneration. In particular, the 15% MeCbl‐loaded PLCL conduit exhibits the most satisfactory recovery of sciatic nerves in rats with the largest diameter and thickest myelinated fibers.  相似文献   

6.
In this work amorphous poly(L-lactide-co-D,L-lactide) (PLLA/PDLLA) was blended with four different commercial adipates to obtain films with enhanced mechanical and thermal properties. Efficiency of plasticizers was evaluated by studying their compatibility with the polymer and their effect on its glass transition temperature. All plasticizers were compatible with the matrix up to a critical composition depending on its molar mass. The addition of plasticizers caused a decrease in elastic modulus and tensile stress, meanwhile elongation at break had a maximum increase for polyadipates with the lower molar mass. Monomeric adipate showed some migration at concentration higher than 10 mass%, while the addition of the higher molar mass plasticizer lead to eventual phase separation. Polyadipates with low molar mass showed a promising behaviour to overcome the brittleness in PLLA/PDLLA films.  相似文献   

7.
Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and poly(dl-lactide) (PDLLA) were blended at different ratios in an attempt to form a biomaterial with suitable properties for nerve regeneration. FT-IR and X-ray analysis showed that the blending of the PDLLA component did not alter the helical structure of PHBHHx, but did lead to a reduction of crystallinity. Differential scanning calorimetry (DSC) analysis indicated that the two polymers were immiscible in the melted state. The mechanical properties of certain composite films were more desirable than those of unblended PDLLA films. Blends consisting of PDLLA and PHBHHx at ratios of 2:1 and 1:2 exhibited a lower elastic modulus and a higher elongation at break compared to unblended PDLLA. ELISA results indicated that the amount of fibronectin adsorbed on composite films was much higher than the amount adsorbed on PDLLA film. The results of this study demonstrate the feasibility of using PDLLA/PHBHHx blended materials for biomedical applications.  相似文献   

8.
Graft copolymers of poly(tulipalin A) (PT) and poly(DL‐lactide) (PDLLA) (PT‐g‐PDLLA) having various graft lengths and ratios were synthesized by free‐radical copolymerization of α‐methylene‐γ‐butyrolactone (MBL) and PDLLA macromonomers (HEMA‐PDLLA) terminated by 2‐hydroxyethyl methacrylate (HEMA)‐terminated. HEMA‐PDLLA were synthesized by ring opening polymerization (ROP) of DL‐lactide in the presence of HEMA. Both HEMA‐PDLLA and the copolymers were characterized by NMR spectroscopy and gel permeation chromatography (GPC). The thermal properties of the graft copolymers were found to depend on the graft length and the ratio. The copolymers consisting of PDLLA side chains of Mn = 500 Da showed a single Tg between Tgs of the two component polymers, suggesting a miscible state of PT and PDLLA. In contrast, the copolymers consisting of PDLLA side chains of Mn = 1100, 2000, and 7000 Da showed two isolated Tg, suggesting two segregated domains. The AFM phase images of the copolymers supported the single and phase‐separated morphologies for the former and latter systems, respectively. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012  相似文献   

9.
Using differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and Fourier transformed infrared spectroscopy (FTIR), upper critical solution temperature (UCST) phase behavior with immiscibility–miscibility transformation in blends of poly(ethylene succinate) (PESu) with poly(lactic acid)s (PLAs), such as poly(D ,L ‐lactic acid) (PDLLA), poly(L ‐lactic acid) (PLLA), poly(D ‐lactic acid) (PDLA), differing in D/L configurations and molecular weights were investigated. All three binary blends of PDLLA/PESu, PLLA/PESu, and PESu/PDLA exhibit UCST behavior, which means they are immiscible at ambient temperature but can become miscible upon heating to higher temperatures at 240–268 °C depending on molecular weights. The PLLAs/PESu blends at UCST could be reverted back to the original phase‐separated morphology, as proven by solvent redissolution. The blends upon quenching from above UCST could be frozen into a quasi‐miscible state, where the Flory‐Huggins interaction parameter (χ12) was determined to be a negative value (by melting point depression technique). The interaction between PDLLA and PESu in blend resulted in significant reduction in spherulite growth rate of PESu. Furthermore, blends of PESu with lower molecular weight PLLA or PDLA (Mw of PLLA and PDLA are 152,000 and 124,000 g/mol, respectively), instead of the higher Mw of PDLLA (Mw of PDLLA = 157,000 g/mol), are immiscible with UCST phase behavior, which are affected by molecular weights rather than the ratio of L/D monomer in the chemical structure of PLAs. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1135–1147, 2010  相似文献   

10.
Successful bench‐to‐bedside translation of nanomedicine relies heavily on the development of nanocarriers with superior therapeutic efficacy and high biocompatibility. However, the optimal strategy for improving one aspect often conflicts with the other. Herein, we report a tactic of designing tumor‐pH‐labile linkage‐bridged copolymers of clinically validated poly(d,l ‐lactide) and poly(ethylene glycol) (PEG‐Dlinkm‐PDLLA) for safe and effective drug delivery. Upon arriving at the tumor site, PEG‐Dlinkm‐PDLLA nanoparticles will lose the PEG layer and increase zeta potential by responding to tumor acidity, which significantly enhances cellular uptake and improves the in vivo tumor inhibition rate to 78.1 % in comparison to 47.8 % of the non‐responsive control. Furthermore, PEG‐Dlinkm‐PDLLA nanoparticles show comparable biocompatibility with the clinically used PEG‐b‐PDLLA micelle. The improved therapeutic efficacy and safety demonstrate great promise for our strategy in future translational studies.  相似文献   

11.
Novel butanediamine-grafted poly(dl-lactic acid) polymers (BDPLAs) were synthesized via a series of chemical bulk modifications in this study. Briefly, maleic anhydride (MAH) was first grafted onto the side chain of poly(dl-lactic acid) (PDLLA) molecules via melt free radical copolymerization using benzoyl peroxide (BPO) as initiator to get maleic anhydride-grafted PDLLA polymers (MPLAs); thereafter butanediamine (BDA) was immobilized onto grafted anhydride groups in MPLAs via N-acylation reaction to obtain the desired BDPLAs. Gel permeation chromatography with multi-angle laser light scattering (GPC-MALLS), FT-IR, 13C NMR and XPS were employed to qualitatively characterize these synthesized polymers. Rhodamine-carboxyl interaction method and ninhydrin reaction were further used to quantitatively determine the graft ratio of MAH (MAH%) in MPLAs and the graft ratio of BDA (BDA%) in BDPLAs, respectively. The degradations of BDPLAs, PDLLA and MPLAs were investigated by observation of the changes of the pH value of incubation medium, molecular weight and weight loss ratio for a time interval of 12 weeks in vitro, respectively. The results revealed that grafting butanediamine onto PDLLA has weakened or neutralized the acidity of PDLLA degradation products. A uniform degradation of BDPLAs was observed in comparison with an acidity-induced auto-accelerating degradation featured by PDLLA and MPLAs. The biodegradation behaviors of BDPLAs are tunable by controlling the content of BDA. BDPLAs might be a new derivative of PDLLA-based biodegradable materials for medical applications without acidity-caused irritations and acidity-induced auto-accelerating degradation behavior as that of PDLLA.  相似文献   

12.
Monodisperse poly(D ,L ‐lactide) (PDLLA) microspheres were prepared by dispersion polymerization of D ,L ‐lactide in xylene/heptane (1/2, v/v) with poly[(dodecyl methacrylate)‐co‐(2‐hydroxyethyl methacrylate)] (P(DMA‐co‐HEMA)) as a dispersion stabilizer. P(DMA‐co‐HEMA) contains hydroxy groups, which act as an initiation group for pseudoanionic dispersion polymerization. The best coefficient of variation (CV) values concerning particle diameter distribution and the particle diameter of obtained PDLLA microspheres were 3.7% and 5.3 μm, respectively. The particle diameter decreased with increasing concentration of P(DMA‐co‐HEMA) and HEMA maintained low CV (<10%) values. As a result, monodisperse PDLLA microspheres ranging from 1.3 to 5.3 μm were obtained. In addition, it was found that monodisperse PDLLA microspheres were obtained by sufficient capture of growing polymers and monomers in the particle growth stage. Therefore, the HEMA concentration in P(DMA‐co‐HEMA) strongly affecting the capturing capability is the most important factor. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5230–5240, 2009  相似文献   

13.
Tissue engineering approach aims to overcome the transplant drawbacks and facilitate tissue repair and regeneration. Here, a new conductive, highly porous, and flexible polycaprolactone/gelatin/polypyrrole/graphene 3D scaffolds for nerve tissue repair is presented. A simple and efficient porogen leaching fabrication method is applied to create a 3D network with a pore radius of 3.8 ± 0.7 to 4.2 ± 0.8 μm with an exceptional uniform circular porous structure. The conductivity of the polymeric scaffold without graphene, in wet conditions, was found to be 0.78 ± 0.1 S.m−1 and it increased to 3.3 ± 0.2 S.m−1 for the optimized sample containing 3wt% graphene (G3). Tensile strength was measured at 163 KPa for the base sample (without graphene) and improved to 526 KPa for G3 sample. Following 42 days of incubation in PBS, 32.5% degradation for the base sample (without graphene) was observed. The cell study demonstrated a non-cytotoxic nature of all scaffolds tested and the cells had mostly stretched and covered the surface. Overall, the sum of results presented in this study demonstrate a simple fabrication platform with extraordinary aspects that can be utilized to mimic the native conductive tissue properties, and also because of its flexibility it can easily be rolled into a nerve conduit to fill gaps in nerve tissue regeneration.  相似文献   

14.
Poly(D,L-lactide) (PDLLA) microspheres with narrow diameter distribution were prepared by dispersion polymerization of D,L-lactide in xylene/heptane (1:2, v/v) using poly(dodecyl methacrylate)-g-poly(D,L-lactide) (PDMA-g-PDLLA) as a dispersion stabilizer. The particle diameters of PDLLA microspheres were controlled from 200 nm to 5 μm by altering the concentration and the graft chain number of PDMA-g-PDLLA. The effect of the copolymer composition on the particle diameter was investigated to clarify an important factor of the copolymer structure for the control of the particle diameter. As a result, it was necessary for anchor block in diblock copolymer as a dispersion stabilizer to have low solubility in the solution rather than the compatibility with particles. Moreover, we confirmed by dynamic light scattering measurement that PDMA-g-PDLLA formed micelles in the solution. In conclusion, it was clarified that PDLLA microspheres with a wide range of particle diameter were prepared due to the different kinetic stability of micelles.  相似文献   

15.
A family of azo and stilbene derivatives ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ) are synthesized, and their chromo‐fluorogenic behavior in the presence of nerve‐agent simulants, diethylchlorophosphate (DCP), diisopropylfluorophosphate (DFP), and diethylcyanophosphate (DCNP) in acetonitrile and mixed solution of water/acetonitrile (3:1 v/v) buffered at pH 5.6 with MES, is investigated. The prepared compounds contain 2‐(2‐N,N‐dimethylaminophenyl)ethanol or 2‐[(2‐N,N‐dimethylamino)phenoxy]ethanol reactive groups, which are part of the conjugated π‐system of the dyes and are able to give acylation reactions with phosphonate substrates followed by a rapid intramolecular N‐alkylation. The nerve‐agent mimic‐triggered cyclization reaction transforms a dimethylamino group into a quaternary ammonium, inducing a change of the electronic properties of the delocalized systems that results in a hypsochromic shift of the absorption band of the dyes. Similar reactivity studies are also carried out with other “non‐toxic” organophosphorus compounds, but no changes in the UV/Vis spectra were observed. The emission behaviour of the reagents in acetonitrile and water–acetonitrile 3:1 v/v mixtures is also studied in the presence of nerve‐agent simulants and other organophosphorous derivatives. The reactivity between 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 and DCP, DCNP, or DFP in buffered water–acetonitrile 3:1 v/v solutions under pseudo first‐order kinetic conditions, using an excess of the corresponding simulant, are studied in order to determine the rate constants (k) and the half‐life times (t1/2=ln2/k) for the reaction. The detection limits in water/acetonitrile 3:1 v/v are also determined for 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 and DCP, DCNP, and DFP. Finally, the chromogenic detection of nerve agent simulants both in solution and in gas phase are tested using silica gel containing adsorbed compounds 1 , 2 , 3 , 4 , or 5 with fine results.  相似文献   

16.
Peripheral nerve injury can considerably affect the daily life of affected people through reduced function and permanent deformation of the nerve. One of the conventional treatments used for the management of the disease is the application of autograft, which is recognized as a golden standard method; however, the process of gaining access to autograft has posed a significant challenge to its use. Nerve guidance channels (conduits), which are made in different methods, can act as an alternative therapy for patients that have undergone nerve injury; but, achieving these conduits has always been a major dilemma to be applied for patients with nerve injury. In this study, a novel conduit based on polymer blend nanocomposites of polyglycolic acid (PGA), collagen, and nanobioglass (NBG) were prepared by electrospinning technique and then compared with PGA/collagen and PGA conduits that were made in previous studies. Additionally, their various properties were characterized by scanning electron microscopy (SEM), X‐ray diffraction (XRD), contact angle, dynamic mechanical thermal analysis (DMTA), tensile strength, Fourier‐transform infrared (FTIR), and the porosity and degradation. The results showed that the mechanical, chemical, biocompatibility, and biodegradability properties of PGA/collagen/NBG conduits were more favorable in comparison with other materials. According to 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and 4′,6‐diamidino‐2‐phenylindole (DAPI) staining technique, nanofibrous electrospun PGA/collagen/NBG conduits are more suitable for cell adhesion and proliferation in comparison with either PGA or PGA/collagen conduits and can have potential for nerve regeneration.  相似文献   

17.
Monodisperse poly(D ,L ‐lactide) (PDLLA) microspheres have been prepared by dispersion polymerization of D ,L ‐lactide with a synthetic polymeric stabilizer. The polymerization is carried out in xylene/heptane (1:2, v/v) at 368 K for 3 h with poly[(dodecyl methacrylate)‐co‐(2‐hydroxyethyl methacrylate)] (P(DMA‐co‐HEMA)). P(DMA‐co‐HEMA) has hydroxy groups as an initiation group for pseudoanionic dispersion polymerization. The particle diameter and the coefficient of variation concerning the diameter distribution of the obtained PDLLA microspheres are 3.9 µm and 4.3%, respectively. In addition, from the results of dynamic light scattering measurements, it is found that P(DMA‐co‐HEMA) and the PDLLA‐grafted copolymer form a micellar structure in solution.

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18.
Chitosan has been widely used in a variety of biomedical applications including peripheral nerve repair because of its excellent mechanical properties and biocompatibility. However, chitosan itself has a very slow degradation rate, and its molecules degrade in an uncontrollable manner. We hypothesized that the cross-linking of carboxymethyl chitosan (CM-chitosan), which is soluble in water, would result in a higher degradation rate in lysozyme solutions, while retaining its excellent mechanical properties and nerve cell affinity. In this study, we characterized the constructed matrix formed using a combination of carboxymethylation of chitosan chains and thereafter 1-ethyl-3(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) cross-linking. Specifically, after EDC cross-linking, the hydrophilicity and elastic modulus of the CM-chitosan films decreased. These changes are beneficial in the application of chitosan derivatives for nerve repair. The porous conduits degraded to 30% in weight during eight weeks of incubation in lysozyme solution (pH 7.4, 37 °C). In addition, the cross-linked CM-chitosan films enhanced the spread of Neuro-2a cells and provided a good proliferation substratum for Neuro-2a cells, as compared to chitosan films. Therefore, cross-linking with EDC is a promising way to modify chitosan derivatives for peripheral nerve regeneration.  相似文献   

19.
Poly (d,l-lactic acid) (PDLLA) was combined with α-CD to form inclusion complexes (ICs) with distinct PDLLA fractions. The structural changes resulting from this coalescence process were analyzed by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), and X-ray diffraction (XRD). The presence of both components in the ICs was confirmed by FTIR. The encapsulated PDLLA fraction was quantified by 1H NMR. XRD data evidenced that it was possible to transform the amorphous PDLLA into a well-organized channel-type crystalline structure. DSC showed that the glass transition temperature of the PDLLA fraction in the ICs was higher than in the pure polymer, indicating that the ultra-confinement effect imposed by the ICs organization clearly limits PDLLA molecular dynamics. The confinement effect on the glass transition dynamics was investigated by unconventional dynamic mechanical analysis experiments, which confirmed that ICs segmental mobility is highly restricted when compared with the one of pure PDLLA. Bulk PDLLA presents a typical VFTH behavior while the ICs dynamics shows an Arrhenius trend.  相似文献   

20.
Degradable behaviors of polymer for implantation in body should be evaluated before clinical application. The effect of continuous mechanical load on the degradation progress of poly(d,l-lactic acid) (PDLLA) foam gasket was investigated in detail by specially designed load-providing devices. While PDLLA degraded in the PBS solution (pH, 7.4) at 37 °C for 3 months, the changes of surface morphology, molecular weight, elastic modulus, tensile strength and mass loss were recorded. The results revealed that the degradation rates of PDLLA under continuous loads were obviously quicker than those without load. Moreover, the influence of tensile plus compressive load was larger than that of tensile load. It was indicated that in vivo degradation of PDLLA would not only be influenced by the local solution, but also by the surrounding load. When regulating the degradation rate of bioabsorbable polymer, one should consider the indispensable effect of load where implanted.  相似文献   

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