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Biomimetic Biphasic Electrospun Scaffold for Anterior Cruciate Ligament Tissue Engineering
Tang Ya,Tian Jialiang,Li Long,Huang Lin,Shen Quan,Guo Shanzhu,Jiang Yue 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.5
Background: Replacing damaged anterior cruciate ligaments (ACLs) with tissue-engineered artificial ligaments is challenging because ligament scaffolds must have a multiregional structure that can guide stem cell differentiation. Here, we designed a biphasic scaffold and evaluated its effect on human marrow mesenchymal stem cells (MSCs) under dynamic culture conditions as well as rat ACL reconstruction model in vivo. Methods: We designed a novel dual-phase electrospinning strategy wherein the scaffolds comprised randomly arranged phases at the two ends and an aligned phase in the middle. The morphological, mechanical properties and scaffold degradation were investigated. MSCs proliferation, adhesion, morphology and fibroblast markers were evaluated under dynamic culturing. This scaffold were tested if they could induce ligament formation using a rodent model in vivo. Results: Compared with other materials, poly(D,L-lactide-co-glycolide)/poly(ε-caprolactone) (PLGA/PCL) with mass ratio of 1:5 showed appropriate mechanical properties and biodegradability that matched ACLs. After 28 days of dynamic culturing, MSCs were fusiform oriented in the aligned phase and randomly arranged in a paving-stone-like morphology in the random phase. The increased expression of fibroblastic markers demonstrated that only the alignment of nanofibers worked with mechanical stimulation to promote effective fibroblast differentiation. This scaffold was a dense collagenous structure, and there was minimal difference in collagen direction in the orientation phase. Conclusion: Dual-phase electrospun scaffolds had mechanical properties and degradability similar to those of ACLs. They promoted differences in the morphology of MSCs and induced fibroblast differentiation under dynamic culture conditions. Animal experiments showed that ligamentous tissue regenerated well and supported joint stability. Background: Replacing damaged anterior cruciate ligaments (ACLs) with tissue-engineered artificial ligaments is challenging because ligament scaffolds must have a multiregional structure that can guide stem cell differentiation. Here, we designed a biphasic scaffold and evaluated its effect on human marrow mesenchymal stem cells (MSCs) under dynamic culture conditions as well as rat ACL reconstruction model in vivo. Methods: We designed a novel dual-phase electrospinning strategy wherein the scaffolds comprised randomly arranged phases at the two ends and an aligned phase in the middle. The morphological, mechanical properties and scaffold degradation were investigated. MSCs proliferation, adhesion, morphology and fibroblast markers were evaluated under dynamic culturing. This scaffold were tested if they could induce ligament formation using a rodent model in vivo. Results: Compared with other materials, poly(D,L-lactide-co-glycolide)/poly(ε-caprolactone) (PLGA/PCL) with mass ratio of 1:5 showed appropriate mechanical properties and biodegradability that matched ACLs. After 28 days of dynamic culturing, MSCs were fusiform oriented in the aligned phase and randomly arranged in a paving-stone-like morphology in the random phase. The increased expression of fibroblastic markers demonstrated that only the alignment of nanofibers worked with mechanical stimulation to promote effective fibroblast differentiation. This scaffold was a dense collagenous structure, and there was minimal difference in collagen direction in the orientation phase. Conclusion: Dual-phase electrospun scaffolds had mechanical properties and degradability similar to those of ACLs. They promoted differences in the morphology of MSCs and induced fibroblast differentiation under dynamic culture conditions. Animal experiments showed that ligamentous tissue regenerated well and supported joint stability.
Thermo-/pH-dual responsive properties of hyperbranched polyethylenimine grafted by phenylalanine
Jie Chen,Jialiang Xia,Huayu Tian,Zhaohui Tang,Chaoliang He,Xuesi Chen 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.1
Novel thermo- and pH-dual responsiveamphiphilic copolymers were synthesized based on hyperbranchedpolyethylenimine (PEI) by grafting L-phenylalanine. The phenylalanine-modified PEI exhibited lowercytotoxicity than commercial PEI. These copolymersshowed the phenomena of phase transitions in response topH and temperature. The dilute copolymer solution atlower pH displayed the higher LCST. Furthermore, LCSTincreased with the increasing of phenylalanine graftingdensity. LCST of these copolymers were tunable from 7.2to 59.6 C by the degree of amidation and pH of solution. DLS and TEM experiments certified that the copolymerchains aggregated to form small size particles as increasingthe temperature above LCST. For these reasons, theobtained smart copolymers were considered to be potentialgene/drug carriers in biomedical field.
Thermo-/pH-dual responsive properties of hyperbranched polyethylenimine grafted by phenylalanine
Chen, Jie,Xia, Jialiang,Tian, Huayu,Tang, Zhaohui,He, Chaoliang,Chen, Xuesi 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.1
Novel thermo- and pH-dual responsive amphiphilic copolymers were synthesized based on hyperbranched polyethylenimine (PEI) by grafting $\small{L}$-phenylalanine. The phenylalanine-modified PEI exhibited lower cytotoxicity than commercial PEI. These copolymers showed the phenomena of phase transitions in response to pH and temperature. The dilute copolymer solution at lower pH displayed the higher LCST. Furthermore, LCST increased with the increasing of phenylalanine grafting density. LCST of these copolymers were tunable from 7.2 to $59.6^{\circ}C$ by the degree of amidation and pH of solution. DLS and TEM experiments certified that the copolymer chains aggregated to form small size particles as increasing the temperature above LCST. For these reasons, the obtained smart copolymers were considered to be potential gene/drug carriers in biomedical field.