Soft hydrogels are excellent candidate materials for repairing various tissue defects,yet the mechanical strength,anti-swelling properties,and biocompatibility of many soft hydrogels need to be improved.Herein,inspire...Soft hydrogels are excellent candidate materials for repairing various tissue defects,yet the mechanical strength,anti-swelling properties,and biocompatibility of many soft hydrogels need to be improved.Herein,inspired by the nanostructure of collagen fibrils,we developed a strategy toward achieving a soft but tough,anti-swelling nanofibrillar hydrogel by combining the self-assembly and chemical crosslinking of nanoparticles.Specifically,the collagen fibril-like injectable hydrogel was subtly designed and fabricated by self-assembling methylacrylyl hydroxypropyl chitosan(HM)with laponite(LAP)to form nanoparticles,followed by the inter-nanoparticle bonding through photo-crosslinking.The assembly mechanism of nanoparticles was elucidated by both experimental and simulation techniques.Due to the unique structure of the crosslinked nanoparticles,the nanocomposite hydrogels exhibited low stiffness(G’<2 kPa),high compressive strength(709 kPa),and anti-swelling(swelling ratio of 1.07 in PBS)properties.Additionally,by harnessing the photo-crosslinking ability of the nanoparticles,the nanocomposite hydrogels were processed as microgels,which can be three-dimensionally(3D)printed into complex shapes.Furthermore,we demonstrated that these nanocomposite hydrogels are highly biocompatible,biodegradability,and can effectively promote fibroblast migration and accelerate blood vessel formation during wound healing.This work presents a promising approach to develop biomimetic,nanofibrillar soft hydrogels for regenerative medicine applications.展开更多
目的探讨Toll样受体2(TLR2)、基质金属蛋白酶9(MMP-9)、低氧诱导因子1α(HIF-1α)作为免疫炎症因子与心房颤动(房颤)发生和维持的关系。方法入选125例房颤患者,其中阵发性房颤34例,持续性房颤49例,永久性房颤42例,选择窦性心律者38例作...目的探讨Toll样受体2(TLR2)、基质金属蛋白酶9(MMP-9)、低氧诱导因子1α(HIF-1α)作为免疫炎症因子与心房颤动(房颤)发生和维持的关系。方法入选125例房颤患者,其中阵发性房颤34例,持续性房颤49例,永久性房颤42例,选择窦性心律者38例作为对照组。比较各组患者血清中TLR2、MMP-9、HIF-1α的表达水平,同时测量左心房内径及射血分数。结果 TLR2表达水平在永久房颤组和持续房颤组明显高于对照组847.3(1 047.7)ng/L、757.2(1 032.5)ng/L vs 744.8(652.3)ng/L(P<0.05);永久房颤组TLR2高于阵发房颤组847.3(1 047.7)ng/L vs 796.6(849.1)ng/L(P<0.05)。MMP-9表达水平在永久房颤组明显高于对照组447.1(491.9)ng/L vs 308.9(200.7)ng/L(P<0.05);永久性房颤组和持续房颤组MMP-9高于阵发房颤组447.1(491.9)ng/L、307.7(678.0)ng/L vs 264.2(303.3)ng/L(P<0.05)。HIF-1α表达水平在永久房颤组和持续房颤组高于对照组57.2(48.8)ng/L、61.4(46.3)ng/L vs 46.7(29.6)ng/L(P<0.05);永久性房颤组和持续房颤组HIF-1α高于阵发房颤组57.2(48.8)ng/L、61.4(46.3)ng/L vs 52.5(42.8)ng/L(P<0.05)。永久房颤组和持续房颤组左心房内径较对照组和阵发性房颤组增加(45.70±6.71)mm、(42.67±6.83)mm vs(38.55±4.51)mm、(40.82±5.45)mm(P<0.05)。而持续房颤组左心室射血分数较对照组和阵发性房颤组明显降低(49.47±7.14)%vs(54.89±6.25)%、(53.90±8.02)%(P<0.05);永久性房颤组左心室射血分数较持续性房颤组明显降低(45.60±8.02)%vs(49.47±7.14)%(P<0.05)。结论 TLR2、HIF-1α、MMP-9作为免疫炎症因子水平的升高可能与房颤的发生及维持有关,提示炎症参与了房颤的发生与维持。展开更多
Toll-like receptor 2 （TLR2） has recently been shown to be up-regulated in patients with non-valvular atrial fi-brillation （AF）. The present study was aimed to determine whether the pathogenesis and development of ...Toll-like receptor 2 （TLR2） has recently been shown to be up-regulated in patients with non-valvular atrial fi-brillation （AF）. The present study was aimed to determine whether the pathogenesis and development of AF is associated with the up-regulation of TLR2. Clinical data and right atrial appendage （RAA） specimens were col-lected from 20 patients with persisten AF （PeAF）, 15 patients with paroxysmal AF （PaAF） and 13 patients with no history of AF undergoing valvular replacement. The results showed that gene expression and protein content of TLR2 were increased in both the AF subgroups, compared with the sinus rhythm （SR） group. Between the two AF subgroups, PaAF had a higher TLR2 level than PeAF. However, no difference in interluekin （IL）-6 content was found among the three groups, and no correlation was found between TLR2 and IL-6 in PeAF patients （r = 0.090, P = 0.706）, PaAF patients （r = 0.408, P = 0.131） and AF patients （r = -0.301, P = 0.079）. Immunohistochemical analysis revealed that TLR2 was distributed in RAAs of AF patients and confirmed the immunoblotting results. In conclusion, we demonstrated that TLR2 was elevated in AF （especially PaAF） patients with valvular heart disease, further implicating inflammation involved in the pathogenesis and development of AF.展开更多
基金financially supported in part by the Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515120038 and 2021A1515012154)the Fundamental Research Funds for the Central Universities(No.2022ZYGXZR105)+3 种基金the National Natural Science Foundation of China(Nos.82072470 and 81871809)the State Key Laboratory of Pulp and Paper Engineering(No.2022C02)supported by the High-performance Computing Platform of Guangxi Universitysupport from the Vice-Chancellor Early Career Professorship Scheme of The Chinese University of Hong Kong.
文摘Soft hydrogels are excellent candidate materials for repairing various tissue defects,yet the mechanical strength,anti-swelling properties,and biocompatibility of many soft hydrogels need to be improved.Herein,inspired by the nanostructure of collagen fibrils,we developed a strategy toward achieving a soft but tough,anti-swelling nanofibrillar hydrogel by combining the self-assembly and chemical crosslinking of nanoparticles.Specifically,the collagen fibril-like injectable hydrogel was subtly designed and fabricated by self-assembling methylacrylyl hydroxypropyl chitosan(HM)with laponite(LAP)to form nanoparticles,followed by the inter-nanoparticle bonding through photo-crosslinking.The assembly mechanism of nanoparticles was elucidated by both experimental and simulation techniques.Due to the unique structure of the crosslinked nanoparticles,the nanocomposite hydrogels exhibited low stiffness(G’<2 kPa),high compressive strength(709 kPa),and anti-swelling(swelling ratio of 1.07 in PBS)properties.Additionally,by harnessing the photo-crosslinking ability of the nanoparticles,the nanocomposite hydrogels were processed as microgels,which can be three-dimensionally(3D)printed into complex shapes.Furthermore,we demonstrated that these nanocomposite hydrogels are highly biocompatible,biodegradability,and can effectively promote fibroblast migration and accelerate blood vessel formation during wound healing.This work presents a promising approach to develop biomimetic,nanofibrillar soft hydrogels for regenerative medicine applications.
文摘目的探讨Toll样受体2(TLR2)、基质金属蛋白酶9(MMP-9)、低氧诱导因子1α(HIF-1α)作为免疫炎症因子与心房颤动(房颤)发生和维持的关系。方法入选125例房颤患者,其中阵发性房颤34例,持续性房颤49例,永久性房颤42例,选择窦性心律者38例作为对照组。比较各组患者血清中TLR2、MMP-9、HIF-1α的表达水平,同时测量左心房内径及射血分数。结果 TLR2表达水平在永久房颤组和持续房颤组明显高于对照组847.3(1 047.7)ng/L、757.2(1 032.5)ng/L vs 744.8(652.3)ng/L(P<0.05);永久房颤组TLR2高于阵发房颤组847.3(1 047.7)ng/L vs 796.6(849.1)ng/L(P<0.05)。MMP-9表达水平在永久房颤组明显高于对照组447.1(491.9)ng/L vs 308.9(200.7)ng/L(P<0.05);永久性房颤组和持续房颤组MMP-9高于阵发房颤组447.1(491.9)ng/L、307.7(678.0)ng/L vs 264.2(303.3)ng/L(P<0.05)。HIF-1α表达水平在永久房颤组和持续房颤组高于对照组57.2(48.8)ng/L、61.4(46.3)ng/L vs 46.7(29.6)ng/L(P<0.05);永久性房颤组和持续房颤组HIF-1α高于阵发房颤组57.2(48.8)ng/L、61.4(46.3)ng/L vs 52.5(42.8)ng/L(P<0.05)。永久房颤组和持续房颤组左心房内径较对照组和阵发性房颤组增加(45.70±6.71)mm、(42.67±6.83)mm vs(38.55±4.51)mm、(40.82±5.45)mm(P<0.05)。而持续房颤组左心室射血分数较对照组和阵发性房颤组明显降低(49.47±7.14)%vs(54.89±6.25)%、(53.90±8.02)%(P<0.05);永久性房颤组左心室射血分数较持续性房颤组明显降低(45.60±8.02)%vs(49.47±7.14)%(P<0.05)。结论 TLR2、HIF-1α、MMP-9作为免疫炎症因子水平的升高可能与房颤的发生及维持有关,提示炎症参与了房颤的发生与维持。
基金supported by a grant for the PhD candidates of Jiangsu Province (No. JX22013082)
文摘Toll-like receptor 2 （TLR2） has recently been shown to be up-regulated in patients with non-valvular atrial fi-brillation （AF）. The present study was aimed to determine whether the pathogenesis and development of AF is associated with the up-regulation of TLR2. Clinical data and right atrial appendage （RAA） specimens were col-lected from 20 patients with persisten AF （PeAF）, 15 patients with paroxysmal AF （PaAF） and 13 patients with no history of AF undergoing valvular replacement. The results showed that gene expression and protein content of TLR2 were increased in both the AF subgroups, compared with the sinus rhythm （SR） group. Between the two AF subgroups, PaAF had a higher TLR2 level than PeAF. However, no difference in interluekin （IL）-6 content was found among the three groups, and no correlation was found between TLR2 and IL-6 in PeAF patients （r = 0.090, P = 0.706）, PaAF patients （r = 0.408, P = 0.131） and AF patients （r = -0.301, P = 0.079）. Immunohistochemical analysis revealed that TLR2 was distributed in RAAs of AF patients and confirmed the immunoblotting results. In conclusion, we demonstrated that TLR2 was elevated in AF （especially PaAF） patients with valvular heart disease, further implicating inflammation involved in the pathogenesis and development of AF.
