Objective This study aimed to evaluate the potential of a collagen-coated,3D-printed tracheal scaffold(3D-TechTra)integrated with human umbilical cord mesenchymal stem cells(hUC-MSCs)for tracheal tissue regeneration.M...Objective This study aimed to evaluate the potential of a collagen-coated,3D-printed tracheal scaffold(3D-TechTra)integrated with human umbilical cord mesenchymal stem cells(hUC-MSCs)for tracheal tissue regeneration.Methods The thermoplastic polyurethane/polylactic acid(TPU/PLA)scaffold was engineered to optimize mechanical properties and biocompatibility,with the goal of mimicking the structural and tensile characteristics of native tracheal tissue.Subsequently,preclinical experiments were conducted using rabbit models:the performance of the collagen-coated TPU/PLA scaffold with hUC-MSCs was compared with that of uncoated scaffolds and collagen-only scaffolds.In vitro tests were also performed to assess the adhesion,proliferation,and differentiation of hUC-MSCs on the scaffold.For in vivo evaluation,multiple analytical methods were employed,including immunohistological analysis(to detect glycosaminoglycan deposition and extracellular matrix remodeling),radiographic and endoscopic evaluations(to assess tracheal contour and airway obstruction),and survival analysis(to monitor animal outcomes and systemic toxicity).Results In vitro,hUC-MSCs successfully adhered to and proliferated on the TPU/PLA scaffold,and differentiated into adipogenic,osteogenic,and chondrogenic lineages,which supported the potential for tissue-specific regeneration;in vivo,compared with uncoated or collagen-only scaffolds,the collagen-coated TPU/PLA scaffold integrated with hUC-MSCs exhibited enhanced integration with host tissues,superior biocompatibility,and reduced tracheal stenosis,while also preserving airway patency,alleviating inflammation,and facilitating epithelial regeneration,smooth muscle formation,and vascularization.Immunohistological analysis further revealed significant glycosaminoglycan deposition and extracellular matrix remodeling in the hUC-MSC-treated group,and radiographic and endoscopic evaluations confirmed preserved tracheal contour and reduced airway obstruction;additionally,survival analysis showed significantly improved outcomes in animals treated with the collagen-coated TPU/PLA scaffold containing hUC-MSCs,with no systemic toxicity observed.Conclusions This study demonstrated the synergistic potential of TPU/PLA scaffolds,collagen coatings,and hUC-MSCs,providing valuable evidence for advancing the application of these components in tracheal tissue engineering.展开更多
背景:骨代谢紊乱会引起骨相关疾病的发生,而叉头框转录因子O3可以通过调节氧化应激、自噬水平等来影响骨组织细胞增殖、分化与凋亡,调控骨代谢过程。目的:系统性分析叉头框转录因子O3调控骨代谢及其在骨科疾病中作用机制的相关研究文献...背景:骨代谢紊乱会引起骨相关疾病的发生,而叉头框转录因子O3可以通过调节氧化应激、自噬水平等来影响骨组织细胞增殖、分化与凋亡,调控骨代谢过程。目的:系统性分析叉头框转录因子O3调控骨代谢及其在骨科疾病中作用机制的相关研究文献,为后续以叉头框转录因子O3为靶点治疗骨疾病的研究提供参考。方法:以“(SU=FoxO3a OR SU=Foxo3 OR SU=Forkhead box O3 OR SU=叉头框转录因子O3)AND SU=骨”为检索句在中国知网进行检索,以“主题:(“FoxO3a”)OR主题:(“Foxo3”)OR主题:(“Forkhead box O3”)OR主题:(“叉头框转录因子O3”)AND主题:(“骨”)”为检索句在万方医学数据库进行检索;以“((FoxO3a)OR(Foxo3)OR(Forkhead box O3))AND((bone)OR(Skeleton))”为检索句在PubMed数据库进行检索,排除陈旧、重复、质量较差以及不相关的文献,最终纳入56篇文献进行综述分析。结果与结论:①叉头框转录因子O3与骨髓间充质干细胞:叉头框转录因子O3能够促进成骨谱系的形成,还可通过激活自噬促进早期成骨分化。同时,叉头框转录因子O3在骨髓间充质干细胞中体现抗氧化特性,保护细胞免受氧化应激诱导的衰老。②叉头框转录因子O3与成骨细胞:叉头框转录因子O3在成骨细胞中能通过干扰Wnt/β-连环蛋白通路抑制成骨,同时能激活抗氧化酶保护成熟成骨细胞。叉头框转录因子O3能促进成骨祖细胞的增殖,并通过激活自噬促进成骨分化。③叉头框转录因子O3与破骨细胞:叉头框转录因子O3表达可抵抗氧化应激和激活自噬抑制破骨细胞生成。④叉头框转录因子O3与骨细胞:叉头框转录因子O3可通过抗氧化作用保护骨细胞,还可通过抑制p16和p53信号通路和抑制衰老相关分泌表型来减少骨流失。⑤叉头框转录因子O3与软骨细胞:叉头框转录因子O3在骨关节炎中对软骨细胞起到保护作用,抑制软骨细胞分解或凋亡,促进软骨细胞外基质合成,可抑制软骨细胞肥大;然而,叉头框转录因子O3与Runt相关转录因子1在软骨细胞中高度共表达却会促进软骨祖细胞的早期软骨形成和终末肥大。⑥叉头框转录因子O3通过参与氧化应激抵抗与调控自噬等过程影响骨代谢,参与多类骨相关疾病的病理进程。展开更多
基金funded by the Ministry of Higher Education Malaysia for the Prototype Research Grant Scheme(PRGS)with Project Code PRGS/1/2021/SKK07/USM/02/1.
文摘Objective This study aimed to evaluate the potential of a collagen-coated,3D-printed tracheal scaffold(3D-TechTra)integrated with human umbilical cord mesenchymal stem cells(hUC-MSCs)for tracheal tissue regeneration.Methods The thermoplastic polyurethane/polylactic acid(TPU/PLA)scaffold was engineered to optimize mechanical properties and biocompatibility,with the goal of mimicking the structural and tensile characteristics of native tracheal tissue.Subsequently,preclinical experiments were conducted using rabbit models:the performance of the collagen-coated TPU/PLA scaffold with hUC-MSCs was compared with that of uncoated scaffolds and collagen-only scaffolds.In vitro tests were also performed to assess the adhesion,proliferation,and differentiation of hUC-MSCs on the scaffold.For in vivo evaluation,multiple analytical methods were employed,including immunohistological analysis(to detect glycosaminoglycan deposition and extracellular matrix remodeling),radiographic and endoscopic evaluations(to assess tracheal contour and airway obstruction),and survival analysis(to monitor animal outcomes and systemic toxicity).Results In vitro,hUC-MSCs successfully adhered to and proliferated on the TPU/PLA scaffold,and differentiated into adipogenic,osteogenic,and chondrogenic lineages,which supported the potential for tissue-specific regeneration;in vivo,compared with uncoated or collagen-only scaffolds,the collagen-coated TPU/PLA scaffold integrated with hUC-MSCs exhibited enhanced integration with host tissues,superior biocompatibility,and reduced tracheal stenosis,while also preserving airway patency,alleviating inflammation,and facilitating epithelial regeneration,smooth muscle formation,and vascularization.Immunohistological analysis further revealed significant glycosaminoglycan deposition and extracellular matrix remodeling in the hUC-MSC-treated group,and radiographic and endoscopic evaluations confirmed preserved tracheal contour and reduced airway obstruction;additionally,survival analysis showed significantly improved outcomes in animals treated with the collagen-coated TPU/PLA scaffold containing hUC-MSCs,with no systemic toxicity observed.Conclusions This study demonstrated the synergistic potential of TPU/PLA scaffolds,collagen coatings,and hUC-MSCs,providing valuable evidence for advancing the application of these components in tracheal tissue engineering.
文摘背景:骨代谢紊乱会引起骨相关疾病的发生,而叉头框转录因子O3可以通过调节氧化应激、自噬水平等来影响骨组织细胞增殖、分化与凋亡,调控骨代谢过程。目的:系统性分析叉头框转录因子O3调控骨代谢及其在骨科疾病中作用机制的相关研究文献,为后续以叉头框转录因子O3为靶点治疗骨疾病的研究提供参考。方法:以“(SU=FoxO3a OR SU=Foxo3 OR SU=Forkhead box O3 OR SU=叉头框转录因子O3)AND SU=骨”为检索句在中国知网进行检索,以“主题:(“FoxO3a”)OR主题:(“Foxo3”)OR主题:(“Forkhead box O3”)OR主题:(“叉头框转录因子O3”)AND主题:(“骨”)”为检索句在万方医学数据库进行检索;以“((FoxO3a)OR(Foxo3)OR(Forkhead box O3))AND((bone)OR(Skeleton))”为检索句在PubMed数据库进行检索,排除陈旧、重复、质量较差以及不相关的文献,最终纳入56篇文献进行综述分析。结果与结论:①叉头框转录因子O3与骨髓间充质干细胞:叉头框转录因子O3能够促进成骨谱系的形成,还可通过激活自噬促进早期成骨分化。同时,叉头框转录因子O3在骨髓间充质干细胞中体现抗氧化特性,保护细胞免受氧化应激诱导的衰老。②叉头框转录因子O3与成骨细胞:叉头框转录因子O3在成骨细胞中能通过干扰Wnt/β-连环蛋白通路抑制成骨,同时能激活抗氧化酶保护成熟成骨细胞。叉头框转录因子O3能促进成骨祖细胞的增殖,并通过激活自噬促进成骨分化。③叉头框转录因子O3与破骨细胞:叉头框转录因子O3表达可抵抗氧化应激和激活自噬抑制破骨细胞生成。④叉头框转录因子O3与骨细胞:叉头框转录因子O3可通过抗氧化作用保护骨细胞,还可通过抑制p16和p53信号通路和抑制衰老相关分泌表型来减少骨流失。⑤叉头框转录因子O3与软骨细胞:叉头框转录因子O3在骨关节炎中对软骨细胞起到保护作用,抑制软骨细胞分解或凋亡,促进软骨细胞外基质合成,可抑制软骨细胞肥大;然而,叉头框转录因子O3与Runt相关转录因子1在软骨细胞中高度共表达却会促进软骨祖细胞的早期软骨形成和终末肥大。⑥叉头框转录因子O3通过参与氧化应激抵抗与调控自噬等过程影响骨代谢,参与多类骨相关疾病的病理进程。
