基于3D氧化石墨烯纳米支架培养脐源性MSC调节关节微环境对肾虚血瘀型膝OA软骨修复机制研究

The knee osteoarthritis (OA) is mainly in the middle and old age, and the kidney deficiency and blood stasis type is common.In the early stage,we constructed the KOA musculoskeletal model of kidney deficiency and blood stasis. We found the nonlinear characteristics of the stress distribution in the knee "tendon" and "bone",and I have identified the characteristics of the damping of the mechanical microenvironment steady state of cartilage repair.In this project, we useed biomechanics test and reverse engineering technology to construct the graphene oxide nanoscale scaffolds through analyzing stress nonlinear characteristics of the "tendon" and "bone"and the characteristics of the damping of the mechanical microenvironment steady state.To evaluate 3D graphene oxide nanoscale scaffold for the cultivation of umbilical cord derived MSC regulating the joint microenvironment.We loaded the 3D graphene oxide nanoscale scaffold rich with umbilical MSC into animal modelsthath which suffering fromkidney deficiency and blood stasis type KOA, and evaluated the degree of cartilage repairing by biochemical, pathological, gene expression and gait analysis.Combining with biology coupled wave theory and demonstration of the steady state of mechanical microenvironment,it proved that the characteristics of 3D graphene oxide nanoscale scaffold for the cultivation of umbilical cord derived MSC regulating the joint microenvironment,and clarified the dynamic equilibrium characteristics of the 3D graphene oxide nanoscale scaffold for the cultivation of umbilical MSC in the regulation of the joint microenvironment,revealed the cartilage repairing mechanism of 3D graphene oxide nanoscale scaffold for the cultivation of umbilical cord derived MSC to regulate the joint microenvironment.It provides quantitative diagnostic evidence and qualitative treatment for clinical diagnosis and treatment of kidney deficiency and blood stasis type KOA.

膝骨性关节炎（OA）以中老年为主，肾虚血瘀型多见。前期研究构建了肾虚血瘀型膝OA肌骨模型，发现了膝部"筋""骨"应力分布非线性特征，明确了软骨修复力学微环境稳态阻尼特点。本项目通过"筋""骨"应力非线性特征和关节微环境稳态软骨阻尼特点，采用生物力学测试、逆向工程技术构建仿真模型并评价3D氧化石墨烯纳米支架培养脐源性MSC调节关节微环境。采用肾虚血瘀型膝OA动物模型，把富含脐源性MSC的3D氧化石墨烯纳米支架加载于动物模型，运用生化、病理、基因表达、步态分析评价软骨修复程度。结合生物耦合理论，对力学微环境稳态进行论证，证明3D氧化石墨烯纳米支架培养脐源性MSC调节关节微环境特点，阐明3D氧化石墨烯纳米支架培养脐源性MSC调节关节微环境动态平衡特征，揭示3D氧化石墨烯纳米支架培养脐源性MSC调节关节微环境对软骨修复机制，为临床诊治肾虚血瘀型膝OA贡献定量诊断证据和定性治疗思路。

膝骨关节炎（OA）以中老年为主，肾虚血瘀型多见。前期研究构建了肾虚血瘀型膝OA肌骨模型，发现了膝部"筋""骨"应力分布非线性特征，明确了软骨修复力学微环境稳态阻尼特点。.本项目运用来自前期研究所获取的肾虚血瘀型膝OA膝部"筋""骨"应力非线性特征：胫骨应力特征、大腿肌群应力特征、小腿肌群应力特征、关节软骨表面应力特征，构建肾虚血瘀型膝OA仿真模型评价3D氧化石墨烯纳米支架材料。采用经典的Hulth 造模法建立膝骨关节炎模型，去卵巢法建立肾虚模型，肾上腺皮质激素和肾上腺素法建立血瘀模型,复合而成肾虚血瘀型骨性关节炎动物模型。把仿生实体模型膝 OA 力学微环境稳态软骨阻尼的非线性参数经过换算后干预数据加载于肾虚血瘀型膝 OA 动物模型，加载干预数据后，分别进行滑动坡度；接触面积；润滑液体对3D氧化石墨烯纳米支架培养脐源性MSC调节关节微环境影响软骨阻尼特性实验。运用生化指标、病理切片、基因表达、步态分析评价软骨修复程度和验证软骨阻尼。结合生物耦合理论，对力学微环境稳态进行论证，证明了3D氧化石墨烯纳米支架培养脐源性MSC调节关节微环境特点，阐明了3D氧化石墨烯纳米支架培养脐源性MSC调节关节微环境动态平衡特征，揭示了3D氧化石墨烯纳米支架培养脐源性MSC调节关节微环境对软骨修复机制，为临床诊治肾虚血瘀型膝OA贡献定量诊断证据和定性治疗思路。