关键词: Angiogenesis Immunomodulation Osteogenic differentiation Piezoelectric hydrogel Tissue engineering scaffold

Mesh : Rats Humans Animals Osteogenesis Tissue Engineering Hydrogels / chemistry pharmacology Phosphatidylinositol 3-Kinases / pharmacology Military Medicine Biocompatible Materials / chemistry pharmacology Chitosan / pharmacology Human Umbilical Vein Endothelial Cells Hydroxyapatites / pharmacology

来  源:   DOI:10.1186/s40779-023-00469-5   PDF(Pubmed)

Abstract:
Most bone-related injuries to grassroots troops are caused by training or accidental injuries. To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops, it is imperative to develop new strategies and scaffolds to promote bone regeneration.
In this study, a porous piezoelectric hydrogel bone scaffold was fabricated by incorporating polydopamine (PDA)-modified ceramic hydroxyapatite (PDA-hydroxyapatite, PHA) and PDA-modified barium titanate (PDA-BaTiO3, PBT) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physical and chemical properties of the Cs/Gel/PHA scaffold with 0-10 wt% PBT were analyzed. Cell and animal experiments were performed to characterize the immunomodulatory, angiogenic, and osteogenic capabilities of the piezoelectric hydrogel scaffold in vitro and in vivo.
The incorporation of BaTiO3 into the scaffold improved its mechanical properties and increased self-generated electricity. Due to their endogenous piezoelectric stimulation and bioactive constituents, the as-prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory, angiogenic, and osteogenic capabilities; they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration, tube formation, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) and facilitated the migration, osteo-differentiation, and extracellular matrix (ECM) mineralization of MC3T3-E1 cells. The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model. The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis, and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.
The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation, angiogenesis, and osteogenesis functions may be used as a substitute in periosteum injuries, thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat effectiveness in grassroots troops.
摘要:
基层部队大多数与骨骼有关的伤害是由训练或意外伤害引起的。建立预防措施,减少各种创伤,提高基层部队的战斗力,必须开发新的策略和支架来促进骨再生。
在这项研究中,通过掺入聚多巴胺(PDA)改性的陶瓷羟基磷灰石(PDA-羟基磷灰石,PHA)和PDA修饰的钛酸钡(PDA-BaTiO3,PBT)纳米颗粒进入壳聚糖/明胶(Cs/Gel)基质中。分析了具有0-10wt%PBT的Cs/Gel/PHA支架的物理和化学性质。进行细胞和动物实验以表征免疫调节,血管生成,压电水凝胶支架的体外和体内成骨能力。
将BaTiO3掺入支架中改善了其机械性能并增加了自生电。由于它们的内源性压电刺激和生物活性成分,制备的Cs/Gel/PHA/PBT水凝胶具有细胞相容性和免疫调节作用,血管生成,和成骨能力;它们不仅有效地诱导巨噬细胞极化为M2表型,管形成,和血管生成分化的人脐静脉内皮细胞(HUVECs)和促进迁移,骨分化,MC3T3-E1细胞的细胞外基质(ECM)矿化。体内评估表明,这些具有多功能功能的压电水凝胶显着促进了大鼠大型颅脑损伤模型中的新骨形成。潜在的分子机制可以部分归因于通过转录组测序分析显示的Cs/Gel/PHA/PBT水凝胶的免疫调节。PI3K/Akt信号轴在调节巨噬细胞M2极化中起重要作用。
此处开发的压电Cs/Gel/PHA/PBT水凝胶具有良好的免疫调节作用,血管生成,成骨功能可以作为骨膜损伤的替代品,从而提供了在骨组织工程中应用压电刺激的新策略,以提高基层部队的战斗力。
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