Daping Quan

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (29)76.46 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Nerve conduits (NCs) with multiple longitudinally aligned channels, being mimicking the natural nerves anatomic structure, have been attracted more and more attentions. However, some specific structural parameters of a conduit that would be beneficial for further improvement of neural tissue regeneration were not comprehensively considered. Using a systematized device and combining low-pressure injection molding and thermal induced phase separation (TIPS), we fabricated 33-channel NCs (outer diameter 3.5 mm, channel diameter 200 μm) with different well-defined microscopic features, including a nanofibrous microstructure (NNC), a spherical porous microstructure (MNC) and a ladder-like microstructure (LNC). The porosities of these NCs were approximately 90% and were independent of the fine microstructures, while the pore size distributions were clearly distinct. The adsorption of bovine serum albumin (BSA) for the NNC was a result of having the highest specific surface area, which was 3.5 times that of the LNC. But the mechanical strength of NNC was lower than that of two groups, because of a relative high crystallinity and brittle characteristics. In vitro nerve stem cells (NSCs) incubation revealed that 14 days after seeding the NSCs, 31.32% cells were Map2 positive in the NNC group, as opposed to 15.76% in the LNC and 23.29% in the MNC groups. Addition NGF into the culture medium, being distinctive specific surface area and a high adsorption of proteon for NNC, 81.11% of neurons derived from the differentiation of the seeded NSCs was obtained. As a result of imitating the physical structure of the basement membrane of the neural matrix, the nano-fibrous structure of the NCs has facilitated the differentiation of NSCs into neurons.
    Tissue Engineering Part A 10/2013; · 4.64 Impact Factor
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    ABSTRACT: Introducing concentration gradients of nerve growth factor (NGF) into conduits for repairing of peripheral nerve injury is crucial for nerve regeneration and guidance. Herein, combining differential adsorption of NGF/silk fibroin (SF) coating, the gradient of NGF-immobilized membranes (G-Ms) and nanofibrous nerve conduits (G-nNCs) were successfully fabricated. The efficacy of NGF gradients was confirmed by a quantitative comparison of dorsal root ganglia (DRG) neurite outgrowth on the G-Ms or uniform NGF-immobilized membranes (U-Ms). Significantly, the neurite turning ratio was 0.48 ± 0.11 for G-M group, but it was close to zero for U-M group. The neurite length of DRGs in the middle of the G-Ms was significantly longer than that of U-M group, even though the average NGF concentration was approximated. Furthermore, 12 weeks after implantation in rats with a 14 mm gap of sciatic nerve injury, G-nNCs achieved satisfying outcomes of nerve regeneration associated with morphological and functional improvements, which was superior to that of the uniform NGF-immobilized nNCs (U-nNCs). Sciatic function index (SFI), compound muscle action potentials (CMAPs), total number of myelinated nerve fibers, thickness of myelin sheath were similar for the G-nNCs and autografts, with the G-nNCs having a higher density of axons than the autografts. Our results demonstrated the significant role of introducing NGF gradients into scaffolds in promoting nerve regeneration.
    Biomaterials 06/2013; · 7.60 Impact Factor
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    ABSTRACT: Nano-fibrous scaffolds modified with biological peptides, which can mimic the physical and chemical characteristics of an extracellular matrix (ECM), have been considered good candidate matrices for cell culture in tissue engineering application. In this study, a series of semicrystalline block copolymers, specifically pendent carboxyl-containing poly(ε-caprolactone-co-β-malic acid)-block-poly(l-lactide), were synthesized to fabricate nano-fibrous scaffolds via thermal induced liquid–liquid phase separation process. Random prepolymers P(CL-co-BMD) were first synthesized through ring-opening copolymerization of ε-CL and 3(S)-[(benzyloxycarbony)methyl]-1,4-dioxane-2,5-dione (BMD) in the presence of dodecanol as initiator and stannous octoate(Sn(Oct)2) as catalyst. The terminal hydroxyl of P(CL-co-BMD)-OH was subsequently added to initiate the ring-opening of l-LA catalyzed by Sn(Oct)2. After deprotection, a series of block copolymers, poly(ε-caprolactone-co-β-malic acid)-block-poly(l-lactide)(PCM-b-PLLA), were obtained and fabricated into nanofibrous scaffolds through thermally induced phase separation (TIPS) technique using tetrahydrofuran (THF) as solvent at a gelation temperature of −40 °C. The structure of the copolymers was characterized Nuclear Magnetic Resonance (1H NMR, 13C NMR), Gel Permeation Chromatography (GPC), and Differential Scanning Calorimetry (DSC). The crystallinity of the PCL segment generally decreased when the amount of BMD segment in P(CL-co-BMD) was increased. However, for PCM-b-PLLA, aside from the crystal melting peak of PLLA at 170 °C–180 °C, no indication of PCL section crystallization occurred because the crystallization of the PCL segment was interrupted by PLLA segment. The nanofiber size of the matrices was in the range of 180 nm–650 nm, similar to the architecture of ECM at the nanometer scale. These nanofibrous matrices have design potential to conjugate covalently to bioactive molecules for tissue engineering.
    Polymer. 10/2012; 53(22):4993–5001.
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    ABSTRACT: Acellular porcine corneal stroma (APCS) has been proven to maintain the matrix microenvironment and is therefore an ideal biomaterial for the repair and reconstruction of corneal stroma. This study aims to develop a method to prepare cosmetic corneal lens implants for leukoma using genipin-crosslinked APCS (Gc-APCS). The Gc-APCS was prepared from APCS immersed in 1.0% genipin aqueous solution (pH 5.5) for 4 h at 37 °C, followed by lyophilization at -10 °C. The color of the Gc-APCS gradually deepened to dark-blue. The degree of crosslinking was 45.7 ± 4.6%, measured by the decrease of basic and hydroxy amino acids. The porous structure and ultrastructure of collagenous lamellae were maintained, and the porosity and BET SSA were 72.7 ± 4.6% and 23.01 ± 3.45 m(2)/g, respectively. The Gc-APCS rehydrated to the physiological water content within 5 min and was highly resistant to collagenase digestion. There were no significant differences in the areal modulus and curvature variation between Gc-APCS and nature porcine cornea. The dark-blue pigments were stable to pH, light and implantation in vivo. Gc-APCS extracts had no inhibitory effects on the proliferation of keratocytes. Corneal neovascularization, graft degradation and corneal rejection were not observed within 6 months.
    Biomaterials 07/2012; 33(30):7336-46. · 7.60 Impact Factor
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    ABSTRACT: Four kinds of chitosan conduits with longitudinal multi-channels and controlled internal microstructures were prepared using a special mold and a freeze-drying method. One of the conduits was fabricated from a chitosan solution (ab NC), while the other three groups were made from a pre-gelled chitosan solution using genipin as a chemical cross-linker (ab gNC), dibasic sodium phosphate as a physical cross-linker (ab pNC) or a combined ionic and covalent co-cross-linker (ab gpNC), respectively. The porosity of the chitosan conduits ranged from 88 to 90%. The gpNC showed highly interconnected and uniformly distributed pores compared to NC, the gNC and pNC. In contrast, the gNC and gpNC showed about 10% of the volume swelling ratio in 37°C PBS solution, although the gpNC scaffold's water uptake was the highest, at more than 17 times its original mass. Compressive tests showed that gpNC had significant elasticity and maintained its physical integrity even after compressing them down to 20% of their original height. The elastic modulus of gpNC reached 80 kPa, which was more than twice that of the other groups. Adhesion and proliferation of PC12 cells on chitosan gpNC scaffolds showed excellent properties by MTT and SEM observation, which indicated the potential of gpNC scaffolds for nerve tissue engineering applications.
    International journal of biological macromolecules 04/2012; 51(1-2):105-12. · 2.37 Impact Factor
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    ABSTRACT: A novel anti-proliferative macromolecular conjugate, CS-g-MMCs, was synthesized in order to decrease the cytotoxicity of Mitomycin C (MMC) which was a traditional anti-proliferative agent of fibroblast in trabeculectomy. The structure of CS-g-MMCs was characterized by (1)H NMR, FT-IR spectroscopy and GPC analysis. The grafting degree (dg) of MMC onto chitosan (CS) was determined to be in the range of 2.8-11.3%, which could be controlled by variation of the molar ratios of MMC to oxidized chitosan (CS-CHO). In the drug release profiles of CS-g-MMCs in vitro, an initial burst followed by slow leakage was observed, and addition of acid or lysozyme obviously accelerated the MMC release. The MTS assay indicated that CS-CHO of 8 mg/ml has no cytotoxicity against human Tenon's capsule fibroblasts (HTCFs). The inhibition of HTCFs proliferation by CS-g-MMCs increased along with increasing the dg of conjugate. The CS-g-MMCs also caused the apoptosis of HTCFs and interfered in the active DNA synthesis in HTCFs. Furthermore, the expression of a-SMA at gene and protein levels were obviously lower when HTCFs were treated with CS-g-MMCs, as compared to MMC or blend of MMC/CS-CHO (p<0.05). Our results primarily demonstrated that the CS-g-MMCs conjugates have low cytotoxicity and have the effect to inhibit fibroblast proliferation.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 03/2012; 46(5):357-66. · 2.61 Impact Factor
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    ABSTRACT: Bone morphogenetic protein 2 (BMP-2) is the most powerful osteogenic factor; its effectiveness in enhancing osteoblastic activation has been confirmed both in vitro and in vivo. We developed a novel peptide (designated P24) derived from the 'knuckle' epitope of BMP-2 and found it also had osteogenic bioactivity to some extent. The main objective of this study was to develop a controlled release system based on poly(trimethylene carbonate)-F127-poly(trimethylene carbonate) (PTMC(11)-F127-PTMC(11)) hydrogels for the P24 peptide, to promote bone formation. By varying the copolymer concentrations, we demonstrated that P24/PTMC(11)-F127-PTMC(11) hydrogels were an efficient system for the sustained release of P24 over 21-35 days. The P24-loaded hydrogels elevated alkaline phosphatase activity and promoted the expression of osteocalcin mRNA in bone marrow stromal cells (BMSCs) in vitro. Radiographic and histological examination showed that P24-loaded hydrogels could induce more effective ectopic bone formation in vivo than P24-free hydrogels. These results indicate that the PTMC(11)-F127-PTMC(11) hydrogel is a suitable carrier for the controlled release of P24, and is a promising injectable biomaterial for the induction of bone regeneration.
    Biomedical Materials 01/2012; 7(1):015008. · 2.17 Impact Factor
  • Journal of Controlled Release 11/2011; 152 Suppl 1:e234-6. · 7.63 Impact Factor
  • Journal of Controlled Release 11/2011; 152 Suppl 1:e18-20. · 7.63 Impact Factor
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    ABSTRACT: Mitomycin C is an anti-proliferative agent which is usually adopted to prevent fibroblast proliferation in trabeculectomy. However, the shorter half-life of Mitomycin C limits its use. In this paper, a novel anti-proliferative conjugate was synthesized by Schiff base reaction. The cytotoxicity of periodate-oxidized chitosan and drug efficiency were also performed by cell proliferation assay, flow cytometry. The results clearly suggested that the conjugate: periodate-oxidized chitosan-g-mitomycin C could be a suitable polymeric system for controlling the release of mitomycin C.
    4th International Conference on Biomedical Engineering and Informatics, BMEI 2011, Shanghai, China, October 15-17, 2011; 01/2011
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    ABSTRACT: Topographical features, including fiber dimensions and pattern, are important aspects in developing fibrous scaffolds for tissue engineering. In this study aligned poly(l-lactide) (PLLA) fibers with diameters of 307+/-47, 500+/-53, 679+/-72 and 917+/-84 nm and random fibers with diameters of 327+/-40, 545+/-54, 746+/-82 and 1150+/-109 nm were obtained by optimizing the electrospinning parameters. We cultured neonatal mouse cerebellum C17.2 cells on the PLLA fibers. These neural stem cells (NSCs) exhibited significantly different growth and differentiation depending upon fiber dimension and pattern. On aligned fibers cell viability and proliferation was best on 500 nm fibers, and reduced on smaller or larger fibers. However, on random fibers cell viability and proliferation was best with the smallest (350 nm) and largest (1150 nm) diameter fibers. Polarized and elongated cells were orientated along the fiber direction on the aligned fibers, with focal contacts bridging the cell body and aligned fibers. Cells of spindle and polygonal morphologies were randomly distributed on the random fibers, with no focal contacts observed. Moreover, longer neurites were obtained on the aligned fibers than random fibers within the same diameter range. Thus, the surface topographic morphologies of fibrous scaffolds, including fiber pattern, dimensions and mesh size, play roles in regulating the viability, proliferation and neurite outgrowth of NSCs. Nevertheless, our results indicated that aligned 500 nm fiber are most promising for fine tuning the design of a nerve scaffold.
    Acta biomaterialia 02/2010; 6(8):2960-9. · 5.09 Impact Factor
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    ABSTRACT: In order to improve the surface properties of PLGA polymer for a better material/cell interface to modulate the cells behaviors, we prepared a novel three-block copolymer, PLGA-[ASP-PEG], and immobilized an RGD-containing peptide, Gly-Arg-Gly-Asp-Ser-Pro-Cys (GRGDSPC) on the surface of it. Transforming growth factor-beta1 (TGF-beta1) was transfected into bone marrow stromal cells (MSCs) employed as seeded cells. Cell adhesion, spreading, proliferation and differentiation on this material were investigated. The results showed that the cell adhesive ratio on RGD-modified materials was higher than on un-modified materials (P<0.05). The extent of cell spreading was also wider on RGD-modified materials than on un-modified materials. Cell proliferation indices of transfected MSCs were increased as compared with the un-transfected MSCs (P<0.05). The ALP activities in the MSCs cultured with RGD-modified materials were higher than on un-modified materials after 14 days (P<0.05), and those in transfected MSCs were higher than in un-transfected MSCs (P<0.05). It was suggested that the combined use of RGD-modification and TGF-beta gene transfection could improve the interaction of biomaterial and cells.
    Journal of Huazhong University of Science and Technology 10/2009; 29(5):592-8. · 0.58 Impact Factor
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    ABSTRACT: To explore the differences of three-dimensional porous blended silk scaffolds with different sericin ratios in terms of molecular structure, mechanical properties, and biological characteristics. Fibroin/sericin blended aqueous solution [concentration 8% (W/V)] with various sericin ratios 0%, 2%, 4%, 6%, 8%, 10%, 12% and NaCl as a porogen with different particle sizes (125-200, 200-300, 300-450, 450-600, 600-900, 900-1100 microm) were used to fabricate the three-dimensional porous blended silk scaffolds. Gross observation of the formation of three-dimensional porous blended silk scaffolds of different sericin ratios and pore sizes was performed. Scanning electron microscope (SEM) was used to detect the distribution and diameter of the pore sizes. Its porosity was calculated by liquids replacement method. X-ray diffractometer (XRD) and fourier transform infrared (FTIR) were used to detect its internal molecular structure. Its mechanical properties, enzyme degration rate in vitro and experiment on SD rats in vivo, and histology observation after coculturing homogeneous scaffold (sericin ratio 0-12%, NaCl particle size 600-900 microm) with adipose tissue-derived mesenchymal stem cells (ADSCs) were detected. Gross observation showed that the higher of the ratio of sericin protein, the greater of the porogen sizes scope which used to form homogeneous silk scaffolds. The result of SEM showed that the pores of the three-dimensional porous blended silk scaffolds had uniform distribution and was connected with each other. Its pore sizes was in the scope of the porogen sizes, and its porosity all above 90%. The angel corresponding to the characteristic peak of the sericin/fibroin blended scaffolds were 20.6 degrees and 24.6 degrees (XRD), and the wavelength corresponding to the characteristic peak of the sericin/fibroin blended scaffolds were 3 296, 2 933 and 1629 cm(-1) (FTIR) which was the same as the angel and wavelength corresponding to the characteristic peak of the natural silk. The mechanical properties of the sericin/fibroin blended scaffolds was improved with the increase of sericin ratios, and the compressional resilience reached 100% when the ratio > or = 6%. The different ratios of sericin and the different particle size of porogen had no significant effect on the enzyme degradation rate in vitro. The histological observation 14 days after ADSCs-scaffold co-culture indicated that the scaffolds had slow degradation rate, and slight inflammatory response in vivo. ADSCs were well attached to the sericin/fibroin blended scaffolds of different sericin ratios, with varied morphology, rich cytoplasm, and nuclear enrichment, the light staining ECM was observed surrounding the cells. The mechanical property of the three-dimensional porous blended silk scaffolds is improved by silk sericins with ratio > or = 6% obviously, which will lay the groudwork for further research and making of strengthen silk scaffolds.
    Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery 10/2009; 23(10):1264-70.
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    ABSTRACT: By the method of injection molding combined with thermally induced phase separation (TIPS), a novel nerve conduit with a plurality of channels and macro-/microporous architecture was fabricated using poly (lactide-co-glycolide) (PLGA, 75:25; Mn=1.22x10(5)). The diameter of the conduits and the number of channels could be regulated by changing the parameters of the mold, and the porosity of the conduit was as high as 95.4%. Meanwhile, the hierarchical pore architecture of the walls could be controlled through varying the solution concentration and the contents of porogen. The degradation study in vitro showed that 7-channel conduit could hold its apparent geometry for about 12 weeks in phosphate buffer solution (PBS) at 37degreesC, and the pH values of the degradation solution were detected in the range 4.1-4.5. The influences of the conduit architecture on the cell attachment, spreading, and proliferation were evaluated by culturing rat mesenchymal stem cells alone or together with Schwann cells in vitro. The implantation of the PLGA conduit in the spinal cord showed that it had good biocompatibility, and no obvious inflammatory response was detected. Therefore, the results implied that these PLGA multiple-channel nerve conduits have the potential use for spinal cord injury.
    Tissue Engineering Part C Methods 02/2009; 15(2):243-55. · 4.64 Impact Factor
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    ABSTRACT: Chemical guiding cues are being exploited to stimulate neuron adhesion and neurite outgrowth. In this study, an amino-functioned PLLA, lysine-capped PLLA [K-(CH2)n-PLLA (n = 2, 5, 8)], was synthesized with different length of linking spaces between lysine molecule and PLLA backbone. Drop-cast films were fabricated from K-(CH2)n-PLLA/PLLA blends (10/90, w/w) and amino groups were detected on the surfaces of the resultant films. More amine groups were detected on the surface and the hydrophilicity of the films was obviously improved by annealing the films in water. The representative atomic force microscopy (AFM) images indicated that incorporation of lysine-capped PLLA into PLLA matrix increased the roughness of the films and resulted in a phase separation with distinct two nano-domains which may correspond to the hydrophilic and hydrophobic domains. Furthermore, the laminin-derived peptides, CYIGSR (Cys-Tyr-Ile-Gly-Ser-Arg) and CSIKVAV (Cys-Ser-Ile-Lys-Val-Ala-Val), were jointly tethered to the amine groups of lysine-capped PLLA by a linking reagent sulfo-succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC). The neonatal mouse cerebellum C17.2 stem cells were seeded on the peptides-grafted K-(CH2)n-PLLA/PLLA (n = 2, 5, 8) films and pure PLLA films were used as controls. Improved viability and longer neurites were obtained on the peptide-grafted films than PLLA film over the cultivation period, especially for K-(CH2)5-PLLA/PLLA, which had the highest peptide density of 0.28 ± 0.03 μg/cm2. This study highlights the potential of using the lysine-cappeded PLLA with laminin-derived peptides for promoting nerve regeneration.
    Biomaterials. 01/2009;
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    ABSTRACT: Nano-fibrous scaffolds which could potentially mimic the architecture of extracellular matrix (ECM) have been considered a good candidate matrix for cell delivery in tissue engineering applications. In the present study, a semicrystalline diblock copolymer, poly(epsilon-caprolactone)-block-poly(L-lactide) (PCL-b-PLLA), was synthesized and utilized to fabricate nano-fibrous scaffolds via a thermally induced phase separation process. Uniform nano-fibrous networks were created by quenching a PCL-b-PLLA/THF homogenous solution to -20 degrees C or below, followed by further gelation for 2 hours due to the presence of PLLA and PCL microcrystals. However, knot-like structures as well as continuously smooth pellicles appeared among the nano-fibrous network with increasing gelation temperature. DSC analysis indicated that the crystallization of PCL segments was interrupted by rigid PLLA segments, resulting in an amorphous phase at high gelation temperatures. Combining TIPS (thermally induced phase separation) with salt-leaching methods, nano-fibrous architecture and interconnected pore structures (144+/-36 mm in diameter) with a high porosity were created for in vitro culture of chondrocytes. Specific surface area and protein adsorption on the surface of the nano-fibrous scaffold were three times higher than on the surface of the solid-walled scaffold. Chondrocytes cultured on the nano-fibrous scaffold exhibited a spherical condrocyte-like phenotype and secreted more cartilage-like extracellular matrix (ECM) than those cultured on the solid-walled scaffold. Moreover, the protein and DNA contents of cells cultured on the nano-fibrous scaffold were 1.2-1.4 times higher than those on the solid-walled scaffold. Higher expression levels of collagen II and aggrecan mRNA were induced on the nano-fibrous scaffold compared to on the solid-walled scaffold. These findings demonstrated that scaffolds with a nano-fibrous architecture could serve as superior scaffolds for cartilage tissue engineering.
    European cells & materials 01/2009; 18:63-74. · 4.56 Impact Factor
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    ABSTRACT: To overcome multidrug resistance (MDR) existing in tumor chemotherapy, polymeric micelles encoded with folic acid on the micelle surface were prepared with the encapsulation of a potent MDR modulator, FG020326. The micelles were fabricated from diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable poly(epsilon-caprolactone) (PCL) with folate attached to the distal ends of PEG chains. The folate-conjugated copolymers, folate-PEG-PCL, were synthesized by multistep chemical reactions. First, allyl-terminated copolymer (allyl-PEG-PCL) was synthesized through a ring-opening polymerization of epsilon-caprolactone in bulk employing monoallyl-PEG as a macroinitiator. Second, the allyl terminal groups of copolymers were converted into primary amino groups by a radical addition reaction, followed by conjugation of the carboxylic group of folic acid. In vitro studies at 37 degrees C demonstrated that FG020326 release from micelles at pH 5.0 was faster than that at pH 7.4. Cytotoxicity studies with MTT assays indicated that folate-functionalized and FG020326-loaded micelles resensitized the cells approximately five times more than their folate-free counterparts (p < 0.01) in human KB(v200) cells treated with vincristine (VCR). The in vitro Rhodamine 123 efflux experiment using MDR KB(v200) cells revealed that when cells were pretreated with folate-attached and FG020326-loaded micelles, the P-glycoprotein (P-gp) drug efflux function was significantly inhibited.
    Journal of Biomedical Materials Research Part A 08/2008; 86(1):48-60. · 2.83 Impact Factor
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    ABSTRACT: To synthesize a ternary cationic copolymer called CS-g-(PEI-b-mPEG) and characterize its features as a non-viral siRNA carrier; in turn, to investigate the influence of small interfering RNA (siRNA) targeting IkappaB kinase subunit beta (IKKbeta) on the proliferation of human Tenon's capsule fibroblasts (HTFs) in vitro. First, a novel cationic copolymer composed of low molecular weight, linear poly(ethyleneimine) [PEI] blocked with polyethylene glycol (PEG) and grafted onto a chitosan (CS) molecule was synthesized. CS-g-(PEI-b-mPEG) was then compacted with 21nt siRNA at various copolymer/siRNA charge (N/P) ratios, and the resulting complexes were characterized by dynamic light scattering, gel electrophoresis, and serum incubation. Cell Titer 96 AQ(ueous) One Solution cell proliferation assay was used to investigate the cytotoxicity of this cationic copolymer. Second, siRNAs targeting IKKbeta (IKKBeta-siRNAs) were delivered into the HTFs using CS-g-(PEI-b-mPEG) as the vehicle. Real-time reverse transcription polymerase chain reaction (RT-PCR) subsequently assessed the mRNA level of IKKbeta, and western blot assay was used to determine protein expression. After IKKB-siRNA transfection, Cell Titer 96 AQ(ueous) One Solution cell proliferation assay was used to evaluate the proliferation of HTFs. The diameter of the CS-g-(PEI-b-mPEG)/siRNA complexes tended to decrease whereas their zeta potential tended to increase as the N/P ratio increased. The CS-g-(PEI-b-mPEG) copolymer showed good siRNA binding ability and high siRNA protection capacity. Furthermore, the copolymer presented remarkable transfection efficiency and showed much less cytotoxicity than 25 kDa PEI. IKKB-siRNAs were successfully delivered into HTFs using CS-g-(PEI-b-mPEG) as a vector. As a result, the expression of IKKbeta was downregulated at both the mRNA and protein levels, and the activation of nuclear factor-kappaB (NF-kappaB) in the HTFs was subsequently inhibited. Most impressively, the proliferation of HTFs was also effectively suppressed through the blocking of the NF-kappaB pathway. All the results demonstrate that CS-g-(PEI-b-mPEG) is a promising candidate for siRNA delivery, featuring excellent biocompatibility, biodegradability, and transfection efficiency. The RNA interference (RNAi) strategy using cationic copolymers as siRNA carriers will be a safe and efficient anti-scarring method following glaucoma filtration surgery.
    Molecular vision 02/2008; 14:2616-28. · 1.99 Impact Factor
  • Journal of Polymer Science Part A Polymer Chemistry 05/2007; 45(12):2556 - 2568. · 3.54 Impact Factor
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    ABSTRACT: Articular cartilage repair remains a clinical and scientific challenge with increasing interest focused on the combined techniques of gene transfer and tissue engineering. Transforming growth factor beta 1 (TGF-beta(1)) is a multifunctional molecule that plays a central role in promotion of cartilage repair, and inhibition of inflammatory and alloreactive immune response. Cell mediated gene therapy can allow a sustained expression of TGF-beta(1) that may circumvent difficulties associated with growth factor delivery. The objective of this study was to investigate whether TGF-beta(1) gene modified mesenchymal stem cells (MSCs) could enhance the repair of full-thickness articular cartilage defects in allogeneic rabbits. The pcDNA(3)-TGF-beta(1) gene transfected MSCs were seeded onto biodegradable poly-L-lysine coated polylactide (PLA) biomimetic scaffolds in vitro and allografted into full-thickness articular cartilage defects in 18 New Zealand rabbits. The pcDNA(3) gene transfected MSCs/biomimetic scaffold composites and the cell-free scaffolds were taken as control groups I and II, respectively. The follow-up times were 2, 4, 12 and 24 weeks. Macroscopical, histological and ultrastructural studies were performed. In vitro SEM studies found that abundant cartilaginous matrices were generated and completely covered the interconnected pores of the scaffolds two weeks post-seeding in the experimental groups. In vivo, the quality of regenerated tissue improved over time with hyaline cartilage filling the chondral region and a mixture of trabecular and compact bone filling the subchondral region at 24 weeks post-implantation. Joint repair in the experimental groups was better than that of either control group I or II, with respect to: (1) synthesis of hyaline cartilage specific extracellular matrix at the upper portion of the defect; (2) reconstitution of the subchondral bone at the lower portion of the defect and (3) inhibition of inflammatory and alloreactive immune responses. The transfected MSCs overexpressed their TGF-beta(1) gene products for at least 4 weeks in vivo. The control defects were filled with a mixture of fibrous and fibrocartilaginous tissue. The TGF-beta(1) gene transfected MSCs/poly-L-lysine coated PLA composite allografts used in this study are effective for articular cartilage repair. This novel TGF-beta(1) gene enhanced tissue engineering strategy may be of potential benefit to enhancing the repair of damaged articular cartilage, especially such damage caused by degenerative disease.
    Biomedical Materials 01/2007; 1(4):206-15. · 2.17 Impact Factor

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178 Citations
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Institutions

  • 2004–2013
    • Sun Yat-Sen University
      • • Department of Chemical Engineering
      • • Department of Orthopaedics
      Shengcheng, Guangdong, China
  • 2007
    • Huazhong University of Science and Technology
      • Department of Cancer
      Wu-han-shih, Hubei, China