Bacterial infection is a very troublesome issue in wound treatment, which stimulates exudate formation and severely delays the healing process. Herein, a thermogelling dressing system composed of two triblock copolyme...Bacterial infection is a very troublesome issue in wound treatment, which stimulates exudate formation and severely delays the healing process. Herein, a thermogelling dressing system composed of two triblock copolymers of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid)(PLGA-PEG-PLGA) with different block lengths was developed to deliver teicoplanin(TPN), a glycopeptide antibiotic, for cutaneous wound repair. The TPN-loaded thermogel was a free-flowing sol at room temperature and formed a semi-solid gel at physiological temperature. In vitro studies demonstrated that the TPN-loaded thermogel system exhibited desired tissue adhesiveness and realized the sustained release of TPN in a fast-followed-slow manner for over three weeks. Furthermore, a full-thickness excision wound model in Sprague-Dawley(SD) rats was constructed to assess the efficacy of TPNloaded thermogel formulation. Gross and histopathologic observations implied that treatment with the thermogel formulation reduced inflammation response, promoted disposition of collagen, enhanced angiogenesis, and accelerated wound closure and maturity of SD rats.The combination of the bioactivity of TPN and the acidic nature of the thermogel matrix was responsible for such an enhanced wound healing process. Consequently, the TPN-loaded PLGA-PEG-PLGA thermogel is a good candidate of wound dressing for full-thickness excision wound healing.展开更多
目的:合成不同的PLGA-PEG-PLGA温敏水凝胶,并研究水凝胶相变温度及流变学与原料比例的关系。方法:以混旋丙交酯(DLlactide)、乙交酯(Glycolide)和PEG为原料,异辛酸亚锡为催化剂,采用开环聚合法,通过改变投料配比和PEG的分子量,制备PLGA-...目的:合成不同的PLGA-PEG-PLGA温敏水凝胶,并研究水凝胶相变温度及流变学与原料比例的关系。方法:以混旋丙交酯(DLlactide)、乙交酯(Glycolide)和PEG为原料,异辛酸亚锡为催化剂,采用开环聚合法,通过改变投料配比和PEG的分子量,制备PLGA-PEGPLGA嵌段共聚物。倒转试管法测定共聚物水溶液的相变温度和沉淀温度;同时用Anton Paar MCR301对水凝胶流变学进行研究。结果:原料比例不同,合成的水凝胶流变学参数和相变温度也不同。结论:改变聚乙二醇的分子量和丙交酯与乙交酯的比例来控制合成共聚物的流变学参数以及相变温度,也可以通过改变共聚物的浓度来小范围地调节其流变学参数和相变温度。展开更多
Both growth hormone-releasing peptide 6 （GHRP-6） and growth hormone-releasing hormone （GHRH） have potent GH-releasing activity in animals. We have previously demonstrated that the administration of a plasmid encod...Both growth hormone-releasing peptide 6 （GHRP-6） and growth hormone-releasing hormone （GHRH） have potent GH-releasing activity in animals. We have previously demonstrated that the administration of a plasmid encoding the GHRH gene to pregnant mice and pig augmented long-term growth in first generation progeny,and that the administration of GHRP-6 results in growth augmentation in mice and rabbits. However,it has not yet been reported if GHRP-6 induces intergenerational growth effects in pigs. Ploy lactic-co-glycolic acid （PLGA） microsphere adsorption of treatment proteins enhances gene expression,genetic immunization and the ability to protect plasmid DNA and peptides from degradation. The cur-rent study was conducted to determine the growth performance of piglets born to gilts treated with GHRP-6 incorporated into thermosensitive PLGA-PEG-PLGA triblock copolymers. Gilts were injected intra-muscularly once at day 85 of gestation with 30 mg of GHRP6-loaded thermosensitive PLGA-PEG-PLGA triblock copolymers. Piglets were weighed periodically between birth and 28 days. Mean body weights of piglets born to GHRP-6-treated gilts were 6. 58% to 18. 89% （P 〈 0. 05 ） greater than those of piglets born to control gilts. This study confirms that enhanced maternal GHRP-6 mediated by thermosensitive PLGA-PEG-PLGA can augment growth of piglets.展开更多
Poly（lactide-co-glycolide）-poly（ethylene glycol）-poly（lactide-co-glycolide）（PLGA-PEG-PLGA） triblock copolymer was synthesized through the ring-opening polymerization of LA and GA with PEG as macroinitiator and...Poly（lactide-co-glycolide）-poly（ethylene glycol）-poly（lactide-co-glycolide）（PLGA-PEG-PLGA） triblock copolymer was synthesized through the ring-opening polymerization of LA and GA with PEG as macroinitiator and stannous octoate as catalyst. The amphiphilic copolymer self-assembled into micelles in aqueous solutions, and formed hydrogels as the increase of temperature at relatively high concentrations（〉 15 wt%）. The favorable degradability of the hydrogel was confirmed by in vitro and in vivo degradation experiments. The good cellular and tissular compatibilities of the thermogel were demonstrated. The excellent adhesion and proliferation of bone marrow mesenchymal stem cells endowed PLGA-PEGPLGA thermogelling hydrogel with fascinating prospect for cartilage tissue engineering.展开更多
Thermogelling hydrogels,such as poly(N-isopropylacrylamide)[P(NiPAAm)],provide tunable constructs leveraged in many regenerative biomaterial applications.Recently,our lab developed the crosslinker poly(glycolic acid)-...Thermogelling hydrogels,such as poly(N-isopropylacrylamide)[P(NiPAAm)],provide tunable constructs leveraged in many regenerative biomaterial applications.Recently,our lab developed the crosslinker poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol),which crosslinks P(NiPAAm-co-glycidyl methacrylate)via thiol-epoxy reaction and can be functionalized with azide-terminated peptides via alkyne-azide click chemistry.This study’s aim was to evaluate the impact of peptides on the physicochemical properties of the hydrogels.The physicochemical properties of the hydrogels including the lower critical solution temperature,crosslinking times,swelling,degradation,peptide release and cytocompatibility were evaluated.The gels bearing peptides increased equilibrium swelling indicating hydrophilicity of the hydrogel components.Comparable sol fractions were found for all groups,indicating that inclusion of peptides does not impact crosslinking.Moreover,the inclusion of a matrix metalloproteinase-sensitive peptide allowed elucidation of whether release of peptides from the network was driven by hydrolysis or enzymatic cleavage.The hydrophilicity of the network determined by the swelling behavior was demonstrated to be the most important factor in dictating hydrogel behavior over time.This study demonstrates the importance of characterizing the impact of additives on the physicochemical properties of hydrogels.These characteristics are key in determining design considerations for future in vitro and in vivo studies for tissue regeneration.展开更多
基金financially supported by the National Natural Science Foundation of China (Nos. 51773043, 81772363, and 21474019)National Key R&D Program of China (No. 2016YFC1100300)China Postdoctoral Science Foundation (No. 2018M632020)
文摘Bacterial infection is a very troublesome issue in wound treatment, which stimulates exudate formation and severely delays the healing process. Herein, a thermogelling dressing system composed of two triblock copolymers of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid)(PLGA-PEG-PLGA) with different block lengths was developed to deliver teicoplanin(TPN), a glycopeptide antibiotic, for cutaneous wound repair. The TPN-loaded thermogel was a free-flowing sol at room temperature and formed a semi-solid gel at physiological temperature. In vitro studies demonstrated that the TPN-loaded thermogel system exhibited desired tissue adhesiveness and realized the sustained release of TPN in a fast-followed-slow manner for over three weeks. Furthermore, a full-thickness excision wound model in Sprague-Dawley(SD) rats was constructed to assess the efficacy of TPNloaded thermogel formulation. Gross and histopathologic observations implied that treatment with the thermogel formulation reduced inflammation response, promoted disposition of collagen, enhanced angiogenesis, and accelerated wound closure and maturity of SD rats.The combination of the bioactivity of TPN and the acidic nature of the thermogel matrix was responsible for such an enhanced wound healing process. Consequently, the TPN-loaded PLGA-PEG-PLGA thermogel is a good candidate of wound dressing for full-thickness excision wound healing.
文摘目的:合成不同的PLGA-PEG-PLGA温敏水凝胶,并研究水凝胶相变温度及流变学与原料比例的关系。方法:以混旋丙交酯(DLlactide)、乙交酯(Glycolide)和PEG为原料,异辛酸亚锡为催化剂,采用开环聚合法,通过改变投料配比和PEG的分子量,制备PLGA-PEGPLGA嵌段共聚物。倒转试管法测定共聚物水溶液的相变温度和沉淀温度;同时用Anton Paar MCR301对水凝胶流变学进行研究。结果:原料比例不同,合成的水凝胶流变学参数和相变温度也不同。结论:改变聚乙二醇的分子量和丙交酯与乙交酯的比例来控制合成共聚物的流变学参数以及相变温度,也可以通过改变共聚物的浓度来小范围地调节其流变学参数和相变温度。
基金supported by grants from the National Natural Science Foundation of China (u0731004, 30771572 )the National Basic Research Program of China (2009CB941601)the Hebei Province Nature Science Foundation (0722553)
文摘Both growth hormone-releasing peptide 6 （GHRP-6） and growth hormone-releasing hormone （GHRH） have potent GH-releasing activity in animals. We have previously demonstrated that the administration of a plasmid encoding the GHRH gene to pregnant mice and pig augmented long-term growth in first generation progeny,and that the administration of GHRP-6 results in growth augmentation in mice and rabbits. However,it has not yet been reported if GHRP-6 induces intergenerational growth effects in pigs. Ploy lactic-co-glycolic acid （PLGA） microsphere adsorption of treatment proteins enhances gene expression,genetic immunization and the ability to protect plasmid DNA and peptides from degradation. The cur-rent study was conducted to determine the growth performance of piglets born to gilts treated with GHRP-6 incorporated into thermosensitive PLGA-PEG-PLGA triblock copolymers. Gilts were injected intra-muscularly once at day 85 of gestation with 30 mg of GHRP6-loaded thermosensitive PLGA-PEG-PLGA triblock copolymers. Piglets were weighed periodically between birth and 28 days. Mean body weights of piglets born to GHRP-6-treated gilts were 6. 58% to 18. 89% （P 〈 0. 05 ） greater than those of piglets born to control gilts. This study confirms that enhanced maternal GHRP-6 mediated by thermosensitive PLGA-PEG-PLGA can augment growth of piglets.
基金financially supported by the National Natural Science Foundation of China(Nos.81171681,51233004,51273196,51203153 and 51303174)the Scientific Development Program of Jilin Province(No.20140520050JH)
文摘Poly（lactide-co-glycolide）-poly（ethylene glycol）-poly（lactide-co-glycolide）（PLGA-PEG-PLGA） triblock copolymer was synthesized through the ring-opening polymerization of LA and GA with PEG as macroinitiator and stannous octoate as catalyst. The amphiphilic copolymer self-assembled into micelles in aqueous solutions, and formed hydrogels as the increase of temperature at relatively high concentrations（〉 15 wt%）. The favorable degradability of the hydrogel was confirmed by in vitro and in vivo degradation experiments. The good cellular and tissular compatibilities of the thermogel were demonstrated. The excellent adhesion and proliferation of bone marrow mesenchymal stem cells endowed PLGA-PEGPLGA thermogelling hydrogel with fascinating prospect for cartilage tissue engineering.
基金supported by the National Institutes of Health(R01 AR068073 and P41 EB023833).
文摘Thermogelling hydrogels,such as poly(N-isopropylacrylamide)[P(NiPAAm)],provide tunable constructs leveraged in many regenerative biomaterial applications.Recently,our lab developed the crosslinker poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol),which crosslinks P(NiPAAm-co-glycidyl methacrylate)via thiol-epoxy reaction and can be functionalized with azide-terminated peptides via alkyne-azide click chemistry.This study’s aim was to evaluate the impact of peptides on the physicochemical properties of the hydrogels.The physicochemical properties of the hydrogels including the lower critical solution temperature,crosslinking times,swelling,degradation,peptide release and cytocompatibility were evaluated.The gels bearing peptides increased equilibrium swelling indicating hydrophilicity of the hydrogel components.Comparable sol fractions were found for all groups,indicating that inclusion of peptides does not impact crosslinking.Moreover,the inclusion of a matrix metalloproteinase-sensitive peptide allowed elucidation of whether release of peptides from the network was driven by hydrolysis or enzymatic cleavage.The hydrophilicity of the network determined by the swelling behavior was demonstrated to be the most important factor in dictating hydrogel behavior over time.This study demonstrates the importance of characterizing the impact of additives on the physicochemical properties of hydrogels.These characteristics are key in determining design considerations for future in vitro and in vivo studies for tissue regeneration.
