3D cryo-printed hierarchical porous scaffolds provide immobilization of surface-functionalized sleep-inspired small extracellular vesicles: synergistic therapeutic strategies for vascularized bone regeneration based on macrophage phenotype modulation and angiogenesis-osteogenesis coupling

被引：3

作者：

Li, Xu-Ran ^{[1
,2
,3
]}

Deng, Qing-Song ^{[1
,2
,3
]}

He, Shu-Hang ^{[1
,2
,3
]}

Liu, Po-Lin ^{[1
,2
,3
]}

Gao, Yuan ^{[1
,2
,3
]}

Wei, Zhan-Ying ^{[4
]}

Zhang, Chang-Ru ^{[5
,6
]}

Wang, Fei ^{[7
]}

Zhu, Tong-He ^{[8
]}

Dawes, Helen ^{[9
,10
,11
]}

Rui, Bi-Yu ^{[1
,2
]}

Tao, Shi-Cong ^{[1
,2
]}

Guo, Shang-Chun ^{[1
,2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Dept Orthoped Surg, Shanghai Peoples Hosp 6, Sch Med, 600 Yishan Rd, Shanghai 200233, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, 227 South Chongqing Rd, Shanghai 200025, Peoples R China

[3] Shanghai Jiao Tong Univ, Shanghai Sixth Peoples Hosp, Shanghai Peoples Hosp 6, Sch Med, Yishan Rd 600, Shanghai 200233, Peoples R China

[4] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 6, Shanghai Clin Res Ctr Bone Dis, Sch Med,Dept Osteoporosis & Bone Dis, Shanghai 200233, Peoples R China

[5] Shanghai Jiao Tong Univ, Shanghai Key Lab Orthoped Implants, Dept Orthoped Surg, Shanghai Peoples Hosp 9,Sch Med, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China

[6] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Med 3D Printing Innovat Res Ctr, Clin & Translat Res Ctr 3D Printing Technol,Sch Me, Shanghai 200125, Peoples R China

[7] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Traumatol & Orthopaed, Shanghai Key Lab Prevent & Treatment Bone & Joint, 197 Ruijin Second Rd, Shanghai 200025, Peoples R China

[8] Shanghai Univ Engn Sci, Shanghai Engn Res Ctr Pharmaceut Intelligent Equip, Shanghai Frontiers Sci Res Ctr Druggabil Cardiovas, Sch Chem & Chem Engn,Inst Frontier Med Technol, Shanghai, Peoples R China

[9] Oxford Brookes Univ, Fac Hlth & Life Sci, Headington Rd, Oxford OX3 0BP, England

[10] NIHR Oxford Hlth Biomed Res Ctr, Oxford OX3 7JX, England

[11] Univ Exeter, Coll Med & Hlth, St Lukes Campus,Heavitree Rd, Exeter EX1 2LU, England

来源：

JOURNAL OF NANOBIOTECHNOLOGY | 2024年 / 22卷 / 01期

基金：

中国国家自然科学基金;

关键词：

3D printing; Extracellular vesicles; Vascularized bone regeneration; Surface functionalization; Macrophage polarization; ULTRALONG HYDROXYAPATITE NANOWIRES; MESENCHYMAL STEM-CELLS; IN-VITRO; DIFFERENTIATION; NANOCOMPOSITE; POLARIZATION; FABRICATION; HYDROGEL; EXOSOMES; FOXC2;

D O I：

10.1186/s12951-024-02977-5

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Bone defect healing is a multi-factorial process involving the inflammatory microenvironment, bone regeneration and the formation of blood vessels, and remains a great challenge in clinical practice. Combined use of three-dimensional (3D)-printed scaffolds and bioactive factors is an emerging strategy for the treatment of bone defects. Scaffolds can be printed using 3D cryogenic printing technology to create a microarchitecture similar to trabecular bone. Melatonin (MT) has attracted attention in recent years as an excellent factor for promoting cell viability and tissue repair. In this study, porous scaffolds were prepared by cryogenic printing with poly(lactic-co-glycolic acid) and ultralong hydroxyapatite nanowires. The hierarchical pore size distribution of the scaffolds was evaluated by scanning electron microscopy (SEM) and micro-computed tomography (micro-CT). Sleep-inspired small extracellular vesicles (MT-sEVs) were then obtained from MT-stimulated cells and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-inorganic pyrophosphate (DSPE-PEG-PPi) was used to modify the membrane of MT-sEVs to obtain PPi-MT-sEVs. RNA sequencing was performed to explore the potential mechanisms. The results demonstrated that PPi-MT-sEVs not only enhanced cell proliferation, migration and angiogenesis, but also regulated the osteogenic/adipogenic fate determination and M1/M2 macrophage polarization switch in vitro. PPi-MT-sEVs were used to coat scaffolds, enabled by the capacity of PPi to bind to hydroxyapatite, and computational simulations were used to analyze the interfacial bonding of PPi and hydroxyapatite. The macrophage phenotype-modulating and osteogenesis-angiogenesis coupling effects were evaluated in vivo. In summary, this study suggests that the combination of hierarchical porous scaffolds and PPi-MT-sEVs could be a promising candidate for the clinical treatment of bone defects.

引用

页数：20

共 92 条

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