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
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
Extrusion bioprinting is a popular method for fabricating tissue engineering scaffolds because of its potential to rapidly produce complex,bioactive or cell-laden scaffolds.However,due to the relatively high viscosity...Extrusion bioprinting is a popular method for fabricating tissue engineering scaffolds because of its potential to rapidly produce complex,bioactive or cell-laden scaffolds.However,due to the relatively high viscosity required to maintain shape fidelity during printing,many extrusion-based inks lack the ability to achieve precise structures at scales lower than hundreds of micrometers.In this work,we present a novel poly(N-isopropylacrylamide)(PNIPAAm)-based ink and poloxamer support bath system that produces precise,multi-layered structures on the tens of micrometers scale.The support bath maintains the structure of the ink in a hydrated,heated environment ideal for cell culture,while the ink undergoes rapid thermogelation followed by a spontaneous covalent crosslinking reaction.Through the combination of the PNIPAAm-based ink and poloxamer bath,this system was able to produce hydrogel scaffolds with uniform fibers possessing diameters tunable from 80 to 200μm.A framework of relationships between several important printing factors involved in maintaining support and thermogelation was also elucidated.As a whole,this work demonstrates the ability to produce precise,acellular and cell-laden PNIPAAm-based scaffolds at high-resolution and contributes to the growing body of research surrounding the printability of extrusion-based bioinks with support baths.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.
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.
基金the National Institutes of Health(P41 EB023833)the National Science Foundation Graduate Research Fellowship Program(A.M.N.)for financial supportsupported by a Rubicon postdoctoral fellowship from the Dutch Research Council(NWO,Project No.019.182 EN.004).
文摘Extrusion bioprinting is a popular method for fabricating tissue engineering scaffolds because of its potential to rapidly produce complex,bioactive or cell-laden scaffolds.However,due to the relatively high viscosity required to maintain shape fidelity during printing,many extrusion-based inks lack the ability to achieve precise structures at scales lower than hundreds of micrometers.In this work,we present a novel poly(N-isopropylacrylamide)(PNIPAAm)-based ink and poloxamer support bath system that produces precise,multi-layered structures on the tens of micrometers scale.The support bath maintains the structure of the ink in a hydrated,heated environment ideal for cell culture,while the ink undergoes rapid thermogelation followed by a spontaneous covalent crosslinking reaction.Through the combination of the PNIPAAm-based ink and poloxamer bath,this system was able to produce hydrogel scaffolds with uniform fibers possessing diameters tunable from 80 to 200μm.A framework of relationships between several important printing factors involved in maintaining support and thermogelation was also elucidated.As a whole,this work demonstrates the ability to produce precise,acellular and cell-laden PNIPAAm-based scaffolds at high-resolution and contributes to the growing body of research surrounding the printability of extrusion-based bioinks with support baths.
