Research and development of the ideal artificial bone-substitute materials to replace autologous and allogeneic bones for repairing bone defects is still a challenge in clinical orthopedics.Recently,poly(lactic-co-gly...Research and development of the ideal artificial bone-substitute materials to replace autologous and allogeneic bones for repairing bone defects is still a challenge in clinical orthopedics.Recently,poly(lactic-co-glycolic acid)(PLGA)-based artificial bone-substitute materials are attracting increasing attention as the benefit of their suitable biocompatibility,degradability,mechanical properties,and capabilities to promote bone regeneration.In this article,we comprehensively review the artificial bone-substitute materials made from PLGA or the composites of PLGA and other organic and inorganic substances,elaborate on their applications for bone regeneration with or without bioactive factors,and prospect the challenges and opportunities in clinical bone regeneration.展开更多
Non-small cell lung cancer(NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic-co-glyco...Non-small cell lung cancer(NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic-co-glycolic)acid(PLGA) large porous microparticle(LPMP) for in situ treatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of 10 mm, the aerodynamic diameter of the spheres was only 2.72 mm, leading to highly efficient lung deposition. In vitro studies showed that most of oridonin was released after 1 h, whereas the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPs via airway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGALPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations for in situ treatment of lung cancer.展开更多
Biodegradable polymer poly（lactic-co-glycolic acid）（PLGA） was used to encapsulate the pharmacological activity metabolite of tolterodine by means of O/W emulsion solvent evaporation method via homogenization in th...Biodegradable polymer poly（lactic-co-glycolic acid）（PLGA） was used to encapsulate the pharmacological activity metabolite of tolterodine by means of O/W emulsion solvent evaporation method via homogenization in the emulsification process. The influences of preparation parameters were investigated. The results indicate that increa- sing PLGA concentration from 15% to 40% made the encapsulation efficiency of 5-hydroxymethyl derivative of tol- terodine（5-HMT） increased from 55.39% to 76.32%, and the particle size increased from 34.33 μm to 70,78 lain. In addition, when homogenization speed increased from 850 r/min to 2300 r/min, both particle size and encapsulation efficiency of microspheres decreased. An increase in the volume of aqueous phase led to higher encapsulation efficiency and bigger particle size. Increasing temperature made encapsulation efficiency and particle size change significantly. While reaction temperature increased from 20 ℃ to 50 ℃, the encapsulation efficiency decreased from 70.44% to 24.07%, and particle size increased from 38.66 μm to 69.38 μm. High reaction temperature（over 40 ℃） may lead to porous surface of microspheres. Porous surface, encapsulation efficiency and particle size influenced on the in vitro release of 5-HMT together.展开更多
The use of periosteum-derived progenitor cells （PCs） combined with bioresorbable materials is an attractive approach for tissue engineering. The aim of this study was to characterize the osteogenic differentiation o...The use of periosteum-derived progenitor cells （PCs） combined with bioresorbable materials is an attractive approach for tissue engineering. The aim of this study was to characterize the osteogenic differentiation of PC in 3-dimensional （3D） poly-lactic-co-glycolic acid （PLGA） fleeces cultured in medium containing allogeneic human serum. PCs were isolated and expanded in monolayer culture. Expanded cells of passage 3 were seeded into PLGA constructs and cultured in osteogenic medium for a maximum period of 28 d. Morphological, histological and cell viability analyses of three-dimensionally cultured PCs were performed to elucidate osseous synthesis and deposition of a calcified matrix. Furthermore, the mRNA expression of type Ⅰ collagen, osteocalcin and osteonectin was semi-quantitively evaluated by real-time reverse transcriptase-polymerase chain reaction （RT-PCR）. The fibrin gel immobilization technique provided homogeneous PCs distribution in 3D PLGA constructs. Live-dead staining indicated a high viability rate of PCs inside the PLGA scaffolds. Secreted nodules ofneo-bone tissue formation and the presence of matrix mineralization were confirmed by positive yon Kossa staining. The osteogenic differentiation of PCs was further demonstrated by the detection of type I collagen, osteocalcin and osteonectin gene expression. The results of this study support the concept that this tissue engineering method presents a promising method for creation of new bone in vivo.展开更多
We have designed a novel nerve guidance conduit（NGC） made from silk fibroin and poly（lactic-co-glycolic acid） through electrospinning and weaving（ESP-NGCs）. Several physical and biological properties of the ESP-...We have designed a novel nerve guidance conduit（NGC） made from silk fibroin and poly（lactic-co-glycolic acid） through electrospinning and weaving（ESP-NGCs）. Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application.展开更多
In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-...In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.展开更多
Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody dru...Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody drug conjugate(ADC)of MMAE is currently used in clinical practice.However,the safety issues of MMAE-based ADC,such as high drug toxicity and poor bioavailability,still exist when using it for anticancer therapy.A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects.Herein,PLGA-b-PEG 2000 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy.The sustained release effect and the immunogenic cell death(ICD)effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments.The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention(EPR)effect,inducing cell apoptosis and causing a certain degree of immune response.The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC.Overall,this study provides a safe and effective chemotherapeutic approach,as well as a simple and effective synthetic process for MMAE-based nanoparticles,improving their therapeutic efficacy and safety.展开更多
In our study, the mechanical properties and degradability of vascular grafts made from poly(ε-caprolactone)(PCL) and poly(lactic-co-glycolic acid)(PLGA) at different ratios were investigated. The results showed that ...In our study, the mechanical properties and degradability of vascular grafts made from poly(ε-caprolactone)(PCL) and poly(lactic-co-glycolic acid)(PLGA) at different ratios were investigated. The results showed that the electrospun PCL/PLGA grafts possess good mechanical properties and biodegradability. The tensile and burst strength of the scaffolds met the demands of vascular grafts. In vitro degradation tests indicated that the degradation rate of the materials increased with the percentage of PLGA, and in vivo tests showed that increasing the amount of PLGA is an effective way to promote cell infiltration. Particularly, the electrospun PCL/PLGA blended scaffold with 10% PLGA exhibited a balance of mechanical and degradation properties, making it a promising tissue engineering material for vascular grafts.展开更多
Poly(lactic-co-glycolic acid)(PLGA)is one of the most representative degradable copolymers and promising drug carriers.In the current paper,the PLGAs with a lactic acid/glycolic acid(LA/GA)molar ratio of 52/48 and var...Poly(lactic-co-glycolic acid)(PLGA)is one of the most representative degradable copolymers and promising drug carriers.In the current paper,the PLGAs with a lactic acid/glycolic acid(LA/GA)molar ratio of 52/48 and various molecular weights were prepared by a melting method.The molecular weight,molecular weight distribution,and thermal stability were determined by 1H NMR and thermogravimetric analysis methods.The results demonstrated that PLGAs with the fixed LA/GA molar ratio(52/48),different molecular weights,and narrow molecular weight distribution could be obtained by solely altering the reaction time.The PLGA films were prepared,and their properties including micro-structure,mechanical property,in-vitro cytotoxicity,and biodegradability were characterized.In combination with the homogeneous microstructures and mechanical properties,the drug-loading and releasing properties of PLGA3.2 films were investigated.The results show that PLGA3.2 film with an LA/GA molar ratio of 52/48 is a promising curcumin carrier.展开更多
Anisotropic surface topography is known to induce the contact guidance of cells, and facile and biocompatible approaches of the physical modification of the pertinent matrix surfaces are thus meaningful for biomateria...Anisotropic surface topography is known to induce the contact guidance of cells, and facile and biocompatible approaches of the physical modification of the pertinent matrix surfaces are thus meaningful for biomaterials. Herein, we put forward a sugar-fiber imprinting technique to generate microgrooves on hydrophobic polymers demonstrated by the poly（lactic-eo-glycolic acid） （PLGA） films. Microgrooves were conveniently generated after removing sugar fibers simply by water. The resulting locally anisotropic microgrooves were confirmed to elongate the cells cultured on the surface.展开更多
Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and puriifcation of Schwann cells are compl...Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and puriifcation of Schwann cells are complicated by contamination with ifbroblasts. Current reported measures are mainly limited by either high cost or complicated procedures with low cell yields or purity. In this study, we collected dorsal root ganglia from neonatal rats from which we obtained highly puriifed Schwann cells using serum-free melanocyte culture medium. The purity of Schwann cells （〉95%） using our method was higher than that using standard medium containing fetal bovine serum. The obtained Schwann cells were implanted into poly（lactic-co-glycolic acid）/chi-tosan conduits to repair 10-mm sciatic nerve defects in rats. Results showed that axonal diameter and area were signiifcantly increased and motor functions were obviously improved in the rat sciatic nerve tissue. Experimental ifndings suggest that serum-free melanocyte culture medium is conducive to purify Schwann cells and poly（lactic-co-glycolic acid）/chitosan nerve conduits combined with Schwann cells contribute to restore sciatic nerve defects.展开更多
The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly（lactic-co-glycolic acid）（PLGA） nanoparticles（TPNs） was studied. Stabilizer-free nanoprecipitation met...The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly（lactic-co-glycolic acid）（PLGA） nanoparticles（TPNs） was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles＇ surface with use of poly（styrene sulfonate） sodium salt（PSS） as anionic layer and poly（allylamine hydrochloride）（PAH） as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs（4 layers） exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of –57.8 m V. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles＇ surface could dramatically influence the drug release profile of TPNs（4 layers vs. 3 layers）. In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles＇ surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.展开更多
Doxorubicin（DOX） loaded poly（lactic-co-glycolic acid）（PLGA） microparticles with internal pores（MP-D） were developed for long-acting release in pulmonary inhalation treatment. The PLGA microparticles exhibited ...Doxorubicin（DOX） loaded poly（lactic-co-glycolic acid）（PLGA） microparticles with internal pores（MP-D） were developed for long-acting release in pulmonary inhalation treatment. The PLGA microparticles exhibited favorable aerodynamic properties for pulmonary delivery. In vitro drug release profile suggested that MP-D have the advantage of long-term maintenance of drug concentrations. MTT assay demonstrated the in vitro anti-tumor efficiency of the DOX loaded PLGA microparticles. Furthermore, melanoma lung metastasis model was established to determine the in vivo antitumor efficiency. The mice treated with MP-D showed significantly fewer lesions than the untreated ones. The survival analysis indicated that MP-D prolonged the survival time of tumor-bearing mice. These results suggested that DOX loaded PLGA microparticles with internal pores have the potential to be used as long-acting release carriers in clinical lung cancer treatment.展开更多
A degradable poly（lactic-co-glycolic acid, LA：GA=80：20）（PLGA） urethral tubular scaffold was fabricated by electrospinning. In order to enhance the mechanical properties, the scaffold was crosslinked with glutara...A degradable poly（lactic-co-glycolic acid, LA：GA=80：20）（PLGA） urethral tubular scaffold was fabricated by electrospinning. In order to enhance the mechanical properties, the scaffold was crosslinked with glutaraldehyde. The structure and properties of the crosslinked scaffolds were investigated by the mechanical property testing, scanning electron microscopy（SEM）, degradability test in vitro and 3-（4,5）-dimethylthiahiazo（-z-yl）-3,5-diphenytetrazo- liumromide（MTT）. The results show that the scaffold has the nano-structure. The pore size and the porosity are suitable for cell seeding, growth and extracellular matrix production. Although influenced by the crosslinking slightly, the pore size and the porosity could still support cell proliferation and tissuse formation. The mechanical properties are remarkably increased by the crosslinking of glutaraldehyde, and it could meet the demands of a urethral stent. The scaffold could completely collapse within 70 d. The results of the biocompatibility test show that the PLGA scaffold had no cytotoxicity.展开更多
In this paper, we fabricated three kinds of 3D microgrooves with different depth on biocompatible poly（lactic-co-glycolic acid） （PLGA） substrate via combination of soft-lithography and melt-casting methods, and in...In this paper, we fabricated three kinds of 3D microgrooves with different depth on biocompatible poly（lactic-co-glycolic acid） （PLGA） substrate via combination of soft-lithography and melt-casting methods, and investigated in detail their influence on C2C12 cell behaviors. It is found that cell proliferation, migration, alignment, spatial distribution, F-actin protein expression and gene expression are all remarkably distinct on these microgrooved samples and the smooth control PLGA substrate. The associated underlying mechanisms were further analyzed and discussed using real-time living cell monitoring, confocal laser scanning microscopy and gene microarray. Our preliminary results suggested that 3D microstruc- ture could affect cell behaviors in a much more extensive manner than what we had understood before.展开更多
In recent years,much research has been suggested and examined for the development of tissue engineering scaffolds to promote cellular behaviors.In our study,RGD peptide and graphene oxide(GO)co-functionalized poly(lac...In recent years,much research has been suggested and examined for the development of tissue engineering scaffolds to promote cellular behaviors.In our study,RGD peptide and graphene oxide(GO)co-functionalized poly(lactide-co-glycolide,PLGA)(RGD-GO-PLGA)nanofiber mats were fabricated via electrospinning,and their physicochemical and thermal properties were characterized to explore their potential as biofunctional scaffolds for vascular tissue engineering.Scanning electron microscopy images revealed that the RGD-GO-PLGA nanofiber mats were readily fabricated and composed of randomoriented electrospun nanofibers with average diameter of 558nm.The successful co-functionalization of RGD peptide and GO into the PLGA nanofibers was confirmed by Fourier-transform infrared spectroscopic analysis.Moreover,the surface hydrophilicity of the nanofiber mats was markedly increased by co-functionalizing with RGD peptide and GO.It was found that the mats were thermally stable under the cell culture condition.Furthermore,the initial attachment and proliferation of primarily cultured vascular smoothmuscle cells(VSMCs)on the RGD-GO-PLGA nanofibermats were evaluated.It was revealed that the RGD-GO-PLGA nanofibermats can effectively promote the growth of VSMCs.In conclusion,our findings suggest that the RGD-GO-PLGA nanofiber mats can be promising candidates for tissue engineering scaffolds effective for the regeneration of vascular smooth muscle.展开更多
The goal of the present study is to utilize cis-diamminedichloroplatinum (cisplatin) loaded polymer nanoparticles (NPs) to give a controlled, extended, and local drug therapy for the treatment of cancer. We have used ...The goal of the present study is to utilize cis-diamminedichloroplatinum (cisplatin) loaded polymer nanoparticles (NPs) to give a controlled, extended, and local drug therapy for the treatment of cancer. We have used biodegradable and biocompatible poly(lactic-co-glycolic acid) (PLGA) to prepare the NPs by adjusting the double emulsion technique using poly(vinylalcohol) as a surface active agent. The PLGA NPs were characterized for particle size and shape, controlled release of cisplatin, and degradation. Cisplatin solubility in deionized water was increased up to 4 mg/mL by simply changing the solution parameters. Cisplatin encapsulated NPs were incubated in phosphate buffered saline (PBS) at 37?C to study the release kinetics of cisplatin. Cisplatin was released in a sustained manner with less than 20% release during a 3-day period followed by 50% release during a 21-day period. A degradation study of PLGA NPs demonstrated the loss of spherical shape during a 21-day period. We also examined the cisplatin sensitive A2780 cell apoptosis when cells were incubated with cisplatin encapsulated PLGA NPs. A large number of cell apoptosis occurred as a result of cisplatin release from the PLGA NPs. These results suggest that cisplatin encapsulated PLGA NPs can be used to treat the cancer cells by injecting them into a localized site minimizing the side effects.展开更多
A novel unsaturated polyphosphoester(UPPE) was devised in our previous research,which is a kind of promising scaffold for improving bone regeneration.However,the polymerization process of UPPE scaffolds was unfavorabl...A novel unsaturated polyphosphoester(UPPE) was devised in our previous research,which is a kind of promising scaffold for improving bone regeneration.However,the polymerization process of UPPE scaffolds was unfavorable,which may adversely affect the bioactivity of osteoinductive molecules added if necessary,such as recombinant human bone morphogenetic protein-2(rhBMP2).The purpose of this study was to build a kind of optimal scaffold named UPPE-PLGA-rhBMP2(UPB) and to investigate the bioactivity of rhBMP2 in this scaffold.Furthermore,the cytotoxicity and biocompatibility of UPB scaffold was assessed in vitro.A W1/O/W2 method was used to fabricate PLGA-rhBMP2 microspheres,and then the microspheres were added to UPPE for synthesizing UPB scaffold.The morphological characters of PLGA-rhBMP2 microspheres and UPB scaffolds were observed under the scanning electron microscopy and laser scanning confocal microscopy.The cumulative release of UPB scaffolds was detected by using ELISA.The cytotoxicity and biocompatibility of UPB scaffolds were evaluated through examining the adsorption and apoptosis of bone marrow stromal cells(bMSCs) seeded on the surface of UPB scaffolds.The bioactivity of rhBMP2 in UPB scaffolds was assessed through measuring the alkaline phosphates(ALP) activity in bMSCs seeded.The results showed that UPB scaffolds sequentially exhibited burst and sustained release of rhBMP2.The cytotoxicity was greatly reduced when the scaffolds were immersed in buffer solution for 2 h.bMSCs attached and grew on the surface of soaked UPB scaffolds,exerting well biocompatibility.The ALP activity of bMSCs seeded was significantly enhanced,indicating that the bioactivity of rhBMP2 remained and still took effect after the unfavorable polymerization process of scaffolds.It was concluded that UPB scaffolds have low cytotoxicity,good biocompatibility and preserve bioactivity of rhBMP2.UPB scaffolds are promising in improving bone regeneration.展开更多
基金This study was financially supported by the National Natural Science Foundation of China(Grant Nos.51973216,51873207,51803006,and 51833010)the Science and Technology Development Program of Jilin Province(Grant No.20200404182YY)+1 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Grant No.2019005)the State Key Laboratory of Advanced Technology for Materials Synthesis and Processing(Wuhan University of Technology)(Grant No.2020-KF-5).
文摘Research and development of the ideal artificial bone-substitute materials to replace autologous and allogeneic bones for repairing bone defects is still a challenge in clinical orthopedics.Recently,poly(lactic-co-glycolic acid)(PLGA)-based artificial bone-substitute materials are attracting increasing attention as the benefit of their suitable biocompatibility,degradability,mechanical properties,and capabilities to promote bone regeneration.In this article,we comprehensively review the artificial bone-substitute materials made from PLGA or the composites of PLGA and other organic and inorganic substances,elaborate on their applications for bone regeneration with or without bioactive factors,and prospect the challenges and opportunities in clinical bone regeneration.
基金supported in part by grants from the National Key Technologies R&D Program for New Drugs of China (No. 2012ZX09301003-001-009)the Beijing Natural Science Foundation of China (No.7154230)
文摘Non-small cell lung cancer(NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic-co-glycolic)acid(PLGA) large porous microparticle(LPMP) for in situ treatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of 10 mm, the aerodynamic diameter of the spheres was only 2.72 mm, leading to highly efficient lung deposition. In vitro studies showed that most of oridonin was released after 1 h, whereas the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPs via airway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGALPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations for in situ treatment of lung cancer.
基金Supported by Key Projects in the National Science & Technology Pillar Program During the Eleventh Five-Year Plan Period 2009,China(No.ZX9103-122)
文摘Biodegradable polymer poly（lactic-co-glycolic acid）（PLGA） was used to encapsulate the pharmacological activity metabolite of tolterodine by means of O/W emulsion solvent evaporation method via homogenization in the emulsification process. The influences of preparation parameters were investigated. The results indicate that increa- sing PLGA concentration from 15% to 40% made the encapsulation efficiency of 5-hydroxymethyl derivative of tol- terodine（5-HMT） increased from 55.39% to 76.32%, and the particle size increased from 34.33 μm to 70,78 lain. In addition, when homogenization speed increased from 850 r/min to 2300 r/min, both particle size and encapsulation efficiency of microspheres decreased. An increase in the volume of aqueous phase led to higher encapsulation efficiency and bigger particle size. Increasing temperature made encapsulation efficiency and particle size change significantly. While reaction temperature increased from 20 ℃ to 50 ℃, the encapsulation efficiency decreased from 70.44% to 24.07%, and particle size increased from 38.66 μm to 69.38 μm. High reaction temperature（over 40 ℃） may lead to porous surface of microspheres. Porous surface, encapsulation efficiency and particle size influenced on the in vitro release of 5-HMT together.
基金Project supported by the Investitionsbank Berlin (IBB), Germany (No. 10020666) and the Science and Technology Bureau of ZhejiangProvince, China (No. 991110052)
文摘The use of periosteum-derived progenitor cells （PCs） combined with bioresorbable materials is an attractive approach for tissue engineering. The aim of this study was to characterize the osteogenic differentiation of PC in 3-dimensional （3D） poly-lactic-co-glycolic acid （PLGA） fleeces cultured in medium containing allogeneic human serum. PCs were isolated and expanded in monolayer culture. Expanded cells of passage 3 were seeded into PLGA constructs and cultured in osteogenic medium for a maximum period of 28 d. Morphological, histological and cell viability analyses of three-dimensionally cultured PCs were performed to elucidate osseous synthesis and deposition of a calcified matrix. Furthermore, the mRNA expression of type Ⅰ collagen, osteocalcin and osteonectin was semi-quantitively evaluated by real-time reverse transcriptase-polymerase chain reaction （RT-PCR）. The fibrin gel immobilization technique provided homogeneous PCs distribution in 3D PLGA constructs. Live-dead staining indicated a high viability rate of PCs inside the PLGA scaffolds. Secreted nodules ofneo-bone tissue formation and the presence of matrix mineralization were confirmed by positive yon Kossa staining. The osteogenic differentiation of PCs was further demonstrated by the detection of type I collagen, osteocalcin and osteonectin gene expression. The results of this study support the concept that this tissue engineering method presents a promising method for creation of new bone in vivo.
基金supported by the National Natural Science Foundation of China,No.81371687,81171457
文摘We have designed a novel nerve guidance conduit（NGC） made from silk fibroin and poly（lactic-co-glycolic acid） through electrospinning and weaving（ESP-NGCs）. Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application.
基金supported by a grant from the National Key Basic Research Program of China,No.2014CB542202 and 2014CB542205the National Natural Science Foundation of China,No.30973095&81371354+2 种基金a grant from Science and Technology Project of Guangzhou,in China,No.12C32121609the Natural Science Foundation of Guangdong Province of China,No.S2013010014697 to Guo JSHong Kong SCI Fund to Wu WT
文摘In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.
基金funded by the Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(No.820LH027)the Hainan Provincial Natural Science Foundation of China(No.823RC472)+1 种基金the Open Project Program of Wuhan National Laboratory for Optoelectronics(No.2021WNLOKF008)the Hainan University Scientific Research Foundation(KYQD(ZR)19107).
文摘Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody drug conjugate(ADC)of MMAE is currently used in clinical practice.However,the safety issues of MMAE-based ADC,such as high drug toxicity and poor bioavailability,still exist when using it for anticancer therapy.A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects.Herein,PLGA-b-PEG 2000 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy.The sustained release effect and the immunogenic cell death(ICD)effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments.The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention(EPR)effect,inducing cell apoptosis and causing a certain degree of immune response.The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC.Overall,this study provides a safe and effective chemotherapeutic approach,as well as a simple and effective synthetic process for MMAE-based nanoparticles,improving their therapeutic efficacy and safety.
基金supported by National Key Research and Development Program of China(No.2017YFC1103500)National Natural Science Foundation of China(No.81671842)Natural Science Foundation of Tianjin,China(No.16JCZDJC37600)
文摘In our study, the mechanical properties and degradability of vascular grafts made from poly(ε-caprolactone)(PCL) and poly(lactic-co-glycolic acid)(PLGA) at different ratios were investigated. The results showed that the electrospun PCL/PLGA grafts possess good mechanical properties and biodegradability. The tensile and burst strength of the scaffolds met the demands of vascular grafts. In vitro degradation tests indicated that the degradation rate of the materials increased with the percentage of PLGA, and in vivo tests showed that increasing the amount of PLGA is an effective way to promote cell infiltration. Particularly, the electrospun PCL/PLGA blended scaffold with 10% PLGA exhibited a balance of mechanical and degradation properties, making it a promising tissue engineering material for vascular grafts.
基金Major Research and Development Project of Shandong Province,China(No.2019JZZY011118)Program for Scientific Research Innovation Team in Colleges and Universities of Shandong Province,China and the Project of the Jinan Science and Technology Bureau,China(No.2019GXRC021).
文摘Poly(lactic-co-glycolic acid)(PLGA)is one of the most representative degradable copolymers and promising drug carriers.In the current paper,the PLGAs with a lactic acid/glycolic acid(LA/GA)molar ratio of 52/48 and various molecular weights were prepared by a melting method.The molecular weight,molecular weight distribution,and thermal stability were determined by 1H NMR and thermogravimetric analysis methods.The results demonstrated that PLGAs with the fixed LA/GA molar ratio(52/48),different molecular weights,and narrow molecular weight distribution could be obtained by solely altering the reaction time.The PLGA films were prepared,and their properties including micro-structure,mechanical property,in-vitro cytotoxicity,and biodegradability were characterized.In combination with the homogeneous microstructures and mechanical properties,the drug-loading and releasing properties of PLGA3.2 films were investigated.The results show that PLGA3.2 film with an LA/GA molar ratio of 52/48 is a promising curcumin carrier.
文摘Anisotropic surface topography is known to induce the contact guidance of cells, and facile and biocompatible approaches of the physical modification of the pertinent matrix surfaces are thus meaningful for biomaterials. Herein, we put forward a sugar-fiber imprinting technique to generate microgrooves on hydrophobic polymers demonstrated by the poly（lactic-eo-glycolic acid） （PLGA） films. Microgrooves were conveniently generated after removing sugar fibers simply by water. The resulting locally anisotropic microgrooves were confirmed to elongate the cells cultured on the surface.
基金supported by the National Natural Science Foundation of China,No.30973060
文摘Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and puriifcation of Schwann cells are complicated by contamination with ifbroblasts. Current reported measures are mainly limited by either high cost or complicated procedures with low cell yields or purity. In this study, we collected dorsal root ganglia from neonatal rats from which we obtained highly puriifed Schwann cells using serum-free melanocyte culture medium. The purity of Schwann cells （〉95%） using our method was higher than that using standard medium containing fetal bovine serum. The obtained Schwann cells were implanted into poly（lactic-co-glycolic acid）/chi-tosan conduits to repair 10-mm sciatic nerve defects in rats. Results showed that axonal diameter and area were signiifcantly increased and motor functions were obviously improved in the rat sciatic nerve tissue. Experimental ifndings suggest that serum-free melanocyte culture medium is conducive to purify Schwann cells and poly（lactic-co-glycolic acid）/chitosan nerve conduits combined with Schwann cells contribute to restore sciatic nerve defects.
基金supported by grants from the National Natural Science Foundation of China(No.81101690)Natural Science Foundation of Hubei Province(No.2014CFB403)Applied Basic Research Foundation of Wuhan Science and Technology Committee(No.2014060101010034)
文摘The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly（lactic-co-glycolic acid）（PLGA） nanoparticles（TPNs） was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles＇ surface with use of poly（styrene sulfonate） sodium salt（PSS） as anionic layer and poly（allylamine hydrochloride）（PAH） as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs（4 layers） exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of –57.8 m V. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles＇ surface could dramatically influence the drug release profile of TPNs（4 layers vs. 3 layers）. In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles＇ surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.
基金financially supported by the National Natural Science Foundation of China(Nos.51222307,51303173,51390480,21474104 and 51403205)the Ministry of Science and Technology of China(International cooperation and communication program 2011DFR51090)Jilin Province Science and Technology Development Program(Nos.20120306,20130521011JH)
文摘Doxorubicin（DOX） loaded poly（lactic-co-glycolic acid）（PLGA） microparticles with internal pores（MP-D） were developed for long-acting release in pulmonary inhalation treatment. The PLGA microparticles exhibited favorable aerodynamic properties for pulmonary delivery. In vitro drug release profile suggested that MP-D have the advantage of long-term maintenance of drug concentrations. MTT assay demonstrated the in vitro anti-tumor efficiency of the DOX loaded PLGA microparticles. Furthermore, melanoma lung metastasis model was established to determine the in vivo antitumor efficiency. The mice treated with MP-D showed significantly fewer lesions than the untreated ones. The survival analysis indicated that MP-D prolonged the survival time of tumor-bearing mice. These results suggested that DOX loaded PLGA microparticles with internal pores have the potential to be used as long-acting release carriers in clinical lung cancer treatment.
基金Supported by the National Natural Science Foundation of China(No. 50973043)
文摘A degradable poly（lactic-co-glycolic acid, LA：GA=80：20）（PLGA） urethral tubular scaffold was fabricated by electrospinning. In order to enhance the mechanical properties, the scaffold was crosslinked with glutaraldehyde. The structure and properties of the crosslinked scaffolds were investigated by the mechanical property testing, scanning electron microscopy（SEM）, degradability test in vitro and 3-（4,5）-dimethylthiahiazo（-z-yl）-3,5-diphenytetrazo- liumromide（MTT）. The results show that the scaffold has the nano-structure. The pore size and the porosity are suitable for cell seeding, growth and extracellular matrix production. Although influenced by the crosslinking slightly, the pore size and the porosity could still support cell proliferation and tissuse formation. The mechanical properties are remarkably increased by the crosslinking of glutaraldehyde, and it could meet the demands of a urethral stent. The scaffold could completely collapse within 70 d. The results of the biocompatibility test show that the PLGA scaffold had no cytotoxicity.
基金supported by the National Basic Research Program of China(Nos.2012CB619100 and 2011CB606204)the National Natural Science Foundation of China(Nos.51373056,51232002 and 51372085)+1 种基金the“111 Project”(No.B13039)the Fundamental Research Funds for the Central Universities
文摘In this paper, we fabricated three kinds of 3D microgrooves with different depth on biocompatible poly（lactic-co-glycolic acid） （PLGA） substrate via combination of soft-lithography and melt-casting methods, and investigated in detail their influence on C2C12 cell behaviors. It is found that cell proliferation, migration, alignment, spatial distribution, F-actin protein expression and gene expression are all remarkably distinct on these microgrooved samples and the smooth control PLGA substrate. The associated underlying mechanisms were further analyzed and discussed using real-time living cell monitoring, confocal laser scanning microscopy and gene microarray. Our preliminary results suggested that 3D microstruc- ture could affect cell behaviors in a much more extensive manner than what we had understood before.
基金This study was supported by the Bio&Medical Technology Development Program of the National Research Foundation(NRF)funded by the Korean government(MEST)(No.2015M3A9E2028643)Basic Science Research Program through the NRF of Korea funded by the Ministry of Education(No.2016R1D1A1B03931076).
文摘In recent years,much research has been suggested and examined for the development of tissue engineering scaffolds to promote cellular behaviors.In our study,RGD peptide and graphene oxide(GO)co-functionalized poly(lactide-co-glycolide,PLGA)(RGD-GO-PLGA)nanofiber mats were fabricated via electrospinning,and their physicochemical and thermal properties were characterized to explore their potential as biofunctional scaffolds for vascular tissue engineering.Scanning electron microscopy images revealed that the RGD-GO-PLGA nanofiber mats were readily fabricated and composed of randomoriented electrospun nanofibers with average diameter of 558nm.The successful co-functionalization of RGD peptide and GO into the PLGA nanofibers was confirmed by Fourier-transform infrared spectroscopic analysis.Moreover,the surface hydrophilicity of the nanofiber mats was markedly increased by co-functionalizing with RGD peptide and GO.It was found that the mats were thermally stable under the cell culture condition.Furthermore,the initial attachment and proliferation of primarily cultured vascular smoothmuscle cells(VSMCs)on the RGD-GO-PLGA nanofibermats were evaluated.It was revealed that the RGD-GO-PLGA nanofibermats can effectively promote the growth of VSMCs.In conclusion,our findings suggest that the RGD-GO-PLGA nanofiber mats can be promising candidates for tissue engineering scaffolds effective for the regeneration of vascular smooth muscle.
文摘The goal of the present study is to utilize cis-diamminedichloroplatinum (cisplatin) loaded polymer nanoparticles (NPs) to give a controlled, extended, and local drug therapy for the treatment of cancer. We have used biodegradable and biocompatible poly(lactic-co-glycolic acid) (PLGA) to prepare the NPs by adjusting the double emulsion technique using poly(vinylalcohol) as a surface active agent. The PLGA NPs were characterized for particle size and shape, controlled release of cisplatin, and degradation. Cisplatin solubility in deionized water was increased up to 4 mg/mL by simply changing the solution parameters. Cisplatin encapsulated NPs were incubated in phosphate buffered saline (PBS) at 37?C to study the release kinetics of cisplatin. Cisplatin was released in a sustained manner with less than 20% release during a 3-day period followed by 50% release during a 21-day period. A degradation study of PLGA NPs demonstrated the loss of spherical shape during a 21-day period. We also examined the cisplatin sensitive A2780 cell apoptosis when cells were incubated with cisplatin encapsulated PLGA NPs. A large number of cell apoptosis occurred as a result of cisplatin release from the PLGA NPs. These results suggest that cisplatin encapsulated PLGA NPs can be used to treat the cancer cells by injecting them into a localized site minimizing the side effects.
基金supported by a grant from the Scientific and Technological Project of Wuhan,China (No. 200960223069)
文摘A novel unsaturated polyphosphoester(UPPE) was devised in our previous research,which is a kind of promising scaffold for improving bone regeneration.However,the polymerization process of UPPE scaffolds was unfavorable,which may adversely affect the bioactivity of osteoinductive molecules added if necessary,such as recombinant human bone morphogenetic protein-2(rhBMP2).The purpose of this study was to build a kind of optimal scaffold named UPPE-PLGA-rhBMP2(UPB) and to investigate the bioactivity of rhBMP2 in this scaffold.Furthermore,the cytotoxicity and biocompatibility of UPB scaffold was assessed in vitro.A W1/O/W2 method was used to fabricate PLGA-rhBMP2 microspheres,and then the microspheres were added to UPPE for synthesizing UPB scaffold.The morphological characters of PLGA-rhBMP2 microspheres and UPB scaffolds were observed under the scanning electron microscopy and laser scanning confocal microscopy.The cumulative release of UPB scaffolds was detected by using ELISA.The cytotoxicity and biocompatibility of UPB scaffolds were evaluated through examining the adsorption and apoptosis of bone marrow stromal cells(bMSCs) seeded on the surface of UPB scaffolds.The bioactivity of rhBMP2 in UPB scaffolds was assessed through measuring the alkaline phosphates(ALP) activity in bMSCs seeded.The results showed that UPB scaffolds sequentially exhibited burst and sustained release of rhBMP2.The cytotoxicity was greatly reduced when the scaffolds were immersed in buffer solution for 2 h.bMSCs attached and grew on the surface of soaked UPB scaffolds,exerting well biocompatibility.The ALP activity of bMSCs seeded was significantly enhanced,indicating that the bioactivity of rhBMP2 remained and still took effect after the unfavorable polymerization process of scaffolds.It was concluded that UPB scaffolds have low cytotoxicity,good biocompatibility and preserve bioactivity of rhBMP2.UPB scaffolds are promising in improving bone regeneration.
