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基于 MoTiC MXene 的水凝胶的导电性和增强的机械强度促进骨缺损修复中的神经发生和骨再生。

Conductive and Enhanced Mechanical Strength of MoTiC MXene-Based Hydrogel Promotes Neurogenesis and Bone Regeneration in Bone Defect Repair.

机构信息

The First Affiliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology, Shenzhen 518055, China.

Shenzhen Key Laboratory of Reconstruction of Structure and Function in Sports System, Shenzhen 518000, Guangdong Province, China.

出版信息

ACS Appl Mater Interfaces. 2024 Apr 10;16(14):17208-17218. doi: 10.1021/acsami.3c19410. Epub 2024 Mar 26.

DOI:10.1021/acsami.3c19410
PMID:38530974
Abstract

Bone defects are common with increasing high-energy fractures, tumor bone invasion, and implantation revision surgery. Bone is an electroactive tissue that has electromechanical interaction with collogen, osteoblasts, and osteoclasts. Hydrogel provides morphological plasticity and extracellular matrix (ECM) 3D structures for cell survival, and is widely used as a bone engineering material. However, the hydrogels have poor mechanical intensity and lack of cell adhesion, slow gelation time, and limited conductivity. MXenes are novel nanomaterials with hydrophilic groups that sense cell electrophysiology and improve hydrogel electric conductivity. Herein, gelatin had multiple active groups (NH2, OH, and COOH) and an accelerated gelation time. Acrylamide has Schiff base bonds to cross-link with gelatin and absorb metal ions. Deacetylated chitosan improved cell adhesion and active groups to connect MXene and acrylamide. We constructed MoTiC MXene hydrogel with improved elastic modulus and viscosity, chemical cross-linking structure, electric conductivity, and good compatibility. MoTiC MXene hydrogel exhibits outstanding osteogenesis in vitro. MoTiC MXene hydrogel promotes osteogenesis via alkaline phosphatase (ALP) and alizarin red S (ARS) staining, improving osteogenic marker genes and protein expressions in vitro. MoTiC MXene hydrogel aids new bone formation in the in vivo calvarial bone defect model via micro-CT and histology. MoTiC MXene hydrogel facilitates neurogenesis factors nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression, and aids newly born neuron marker Tuj-1 and sensory neuron marker serotonin (5-HT) and osteogenesis pathway proteins, runt-related transcription factor 2 (Runx2), osteocalcin (OCN), SMAD family member 4 (SMAD4), and bone morphogenetic protein-2 (BMP2) in the bone defect repair process. MoTiC MXene hydrogel promotes osteogenesis and neurogenesis, which extends its biomedical application in bone defect reconstruction.

摘要

骨缺损在高能骨折、肿瘤骨侵犯和植入物翻修手术中很常见。骨骼是一种电活性组织,与胶原蛋白、成骨细胞和破骨细胞具有机电相互作用。水凝胶为细胞存活提供形态可塑性和细胞外基质(ECM)3D 结构,被广泛用作骨工程材料。然而,水凝胶的机械强度差,缺乏细胞黏附性,凝胶化时间缓慢,导电性有限。MXenes 是一种具有感知细胞电生理学并提高水凝胶导电性的新型纳米材料。在此,明胶具有多个活性基团(NH2、OH 和 COOH)和加速的凝胶化时间。丙烯酰胺具有席夫碱键与明胶交联并吸收金属离子。脱乙酰壳聚糖提高了细胞黏附性和活性基团,将 MXene 和丙烯酰胺连接起来。我们构建了具有改进的弹性模量和粘度、化学交联结构、导电性和良好相容性的 MoTiC MXene 水凝胶。MoTiC MXene 水凝胶在体外表现出出色的成骨能力。MoTiC MXene 水凝胶通过碱性磷酸酶(ALP)和茜素红 S(ARS)染色促进成骨,体外提高成骨标志物基因和蛋白的表达。MoTiC MXene 水凝胶通过微 CT 和组织学促进体内颅骨骨缺损模型中的新骨形成。MoTiC MXene 水凝胶促进神经发生因子神经生长因子(NGF)和脑源性神经营养因子(BDNF)的表达,并促进新生神经元标志物 Tuj-1 和感觉神经元标志物 5-羟色胺(5-HT)以及成骨途径蛋白 runt 相关转录因子 2(Runx2)、骨钙素(OCN)、SMAD 家族成员 4(SMAD4)和骨形态发生蛋白 2(BMP2)在骨缺损修复过程中的表达。MoTiC MXene 水凝胶促进成骨和神经发生,从而扩展了其在骨缺损重建中的生物医学应用。

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