Dataset Information

Exosomal mRNAs for Angiogenic-Osteogenic Coupled Bone Repair.

ABSTRACT: Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone regeneration in rats with challenging femur critical-size defects are introduced. Abundant t-sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track-etched membrane (TM-nanoEP) to deliver plasmid DNAs to human adipose-derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t-sEVs for enhanced angiogenic-osteogenic regeneration. Localized and controlled release of t-sEVs within the PEGS-A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs.

SUBMITTER: Ma Y

PROVIDER: S-EPMC10667797 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Exosomal mRNAs for Angiogenic-Osteogenic Coupled Bone Repair.

Ma Yifan Y Sun Lili L Zhang Jingjing J Chiang Chi-Ling CL Pan Junjie J Wang Xinyu X Kwak Kwang Joo KJ Li Hong H Zhao Renliang R Rima Xilal Y XY Zhang Chi C Zhang Anan A Liu Yutong Y He Zirui Z Hansford Derek D Reategui Eduardo E Liu Changsheng C Lee Andrew S AS Yuan Yuan Y Lee Ly James LJ

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20231017 33

Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone rege ...[more]

PMID: 37847907

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Project description:BackgroundThe bone regeneration of artificial bone grafts is still in need of a breakthrough to improve the processes of bone defect repair. Artificial bone grafts should be modified to enable angiogenesis and thus improve osteogenesis. We have previously revealed that crystalline Ca10Li(PO4)7 (CLP) possesses higher compressive strength and better biocompatibility than that of pure beta-tricalcium phosphate (β-TCP). In this work, we explored the possibility of cobalt (Co), known for mimicking hypoxia, doped into CLP to promote osteogenesis and angiogenesis.MethodsWe designed and manufactured porous scaffolds by doping CLP with various concentrations of Co (0, 0.1, 0.25, 0.5, and 1 mol%) and using 3D printing techniques. The crystal phase, surface morphology, compressive strength, in vitro degradation, and mineralization properties of Co-doped and -undoped CLP scaffolds were investigated. Next, we investigated the biocompatibility and effects of Co-doped and -undoped samples on osteogenic and angiogenic properties in vitro and on bone regeneration in rat cranium defects.ResultsWith increasing Co-doping level, the compressive strength of Co-doped CLP scaffolds decreased in comparison with that of undoped CLP scaffolds, especially when the Co-doping concentration increased to 1 mol%. Co-doped CLP scaffolds possessed excellent degradation properties compared with those of undoped CLP scaffolds. The (0.1, 0.25, 0.5 mol%) Co-doped CLP scaffolds had mineralization properties similar to those of undoped CLP scaffolds, whereas the 1 mol% Co-doped CLP scaffolds shown no mineralization changes. Furthermore, compared with undoped scaffolds, Co-doped CLP scaffolds possessed excellent biocompatibility and prominent osteogenic and angiogenic properties in vitro, notably when the doping concentration was 0.25 mol%. After 8 weeks of implantation, 0.25 mol% Co-doped scaffolds had markedly enhanced bone regeneration at the defect site compared with that of the undoped scaffold.ConclusionIn summary, CLP doped with 0.25 mol% Co2+ ions is a prospective method to enhance osteogenic and angiogenic properties, thus promoting bone regeneration in bone defect repair.

Project description:ObjectiveBone regeneration involves a coordinated cascade of events that are regulated by several cytokines and growth factors, among which bone morphogenic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) play important roles. In this study, we investigated the effects of dual release of the three growth factors on bone regeneration in femur defects.MethodsA composite consisting of Gelatin microparticles loaded with VEGF/FGF-2 and poly(lactic-co-glycolic acid)-poly(ethylene glycol)-carboxyl (PLGA-PEG-COOH) microparticles loaded with BMP-2 encapsulated in a nano hydroxyapatite-poly actic-co-glycolic acid (nHA-PLGA) scaffold was prepared for the dual release of the growth factors.ResultsOn the 14th day, decreased release rate of BMP-2 compared with FGF-2 and VEGF was observed. However, after 14 days, compared to FGF-2 and VEGF, BMP-2 showed an increased release rate. Controlled dual release of BMP-2 and VEGF, FGF-2 resulted in a significant osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Moreover, effects of the composite scaffold on functional connection of osteoblast-vascular cells during bone development were evaluated. The synergistic effects of dual delivery of growth factors were shown to promote the expression of VEGF in BMSCs. Increased secretion of VEGF from BMSCs promoted the proliferation and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) in the co-culture system. At 12 weeks after implantation, blood vessel and bone formation were analyzed by micro-CT and histology. The composite scaffold significantly promoted the formation of blood vessels and new bone in femur defects.ConclusionsThese findings demonstrate that dual delivery of angiogenic factors and osteogenic factors from Gelatin and PLGA-PEG-COOH microparticles-based composite scaffolds exerted an osteogenic-angiogenic coupling effect on bone regeneration. This approach will inform on the development of appropriate designs of high-performance bioscaffolds for bone tissue engineering.

Dataset Information

Exosomal mRNAs for Angiogenic-Osteogenic Coupled Bone Repair.

Publications

Exosomal mRNAs for Angiogenic-Osteogenic Coupled Bone Repair.

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