熟料粒度对骨粉/磷酸钙生物骨水泥结构与性能的影响

采用新方法首次将动物骨中的鱼骨引入到磷酸三钙和磷酸氢钙等原料体系中通过高温烧结制备磷酸钙基生物骨水泥（CPC）,以柠檬酸和柠檬酸钠的缓冲液为固化液、按一定的液固比制备固化试样,通过扫描电子显微分析（SEM）和力学性能测试等方法,研究了熟料粒度对其固化试样结构与抗压强度的影响.结果表明：制备过程中骨水泥粉末的粒度对其固化试样的微观结构及其抗压强度有着较为显著的影响,通过调整骨水泥粉末的粒度可达到优化其固化试样的微观结构和改善其力学性能的目的.     

骨胶与表氯醇接枝共聚物的合成及应用性能

研究骨胶与表氯醇的接枝共聚反应。接枝共聚产物在1402cm-1(C—O—C伸缩振动)处的红外光谱验证了接枝共聚反应的发生。探讨了水胶比、碱用量、碱解温度、反应时间等因素对接枝共聚产物的影响。当水胶比为1:1,NaOH用量为胶液量的3%,碱解温度为60℃,表氯醇用量为胶液量的1%,接枝共聚温度为50℃时,合成胶粘剂的初粘力为100%,凝固点为-5℃,与工业骨胶相比,剪切强度大,其应用范围更广,应用性能得到较大的改善。     

Evaluation of apatite-coated chitosan microspheres for bone regeneration

The apatite-coated chitosan microspheres were fabricated by incubating chitosan in five times simulated body fluid. The apatite deposited on the microspheres was similar to natural bone mineral, as demonstrated by scanning electron microscopy, X-ray diffraction spectra and Fourier transformed-infrared spectroscopy analyses. Rat bone marrow-derived mesenchymal stem cells （BMSCs） were seeded on apatite- coated microspheres to investigate the effect of this scaffold on cell proliferation and differentiation. BMSCs seeded on uncoated microspheres were served as a control. In vivo experiment was evaluated by transplanting the microspheres loaded with or without BMSCs in 5-mm cranial defects of Wistar rats. Bone regeneration was investigated via micro-CT and histological analysis. It was found that apatite-coated chitosan microspheres could significantly promote the proliferation and alkaline phosphatase activity of BMSCs compared with uncoated microspheres. Histological slices and Micro-CT images at 8 weeks revealed much better regeneration of bone in the apatite-coated microspheres loaded with BMSCs than the control. In addition, the defect filled with pure microspheres induced little new bone formation. Our findings suggest that the apatite-coated chitosan microspheres scaffold is a promising carrier of stem cells for cranial bone tissue engineering.     

骨髓成骨细胞在碱热处理的磷灰石涂层钛表面的分化增殖研究

为了研究骨髓基质细胞转化的成骨细胞在碱热处理的涂层磷灰石钛表面的分化增殖，将钛片经过碱热处理后，浸泡于与类似体液的环境进行表面磷灰石涂层。应用骨髓成骨细胞作为实验工具，观察体外细胞在处理的涂层钛片上的生长，碱性磷酸酶以及降钙素的分泌。在早期，有磷灰石涂层的钛片成骨细胞黏附高于对照组；在晚期，两组之间没有明显差异；成骨细胞分化的标志——碱性磷酸酶活性和降钙素的表达，磷灰石涂层组都明显高于对照组。研究表明：碱热处理的磷灰石涂层钛能够促进成骨细胞黏附，有利于细胞向成骨分化。     

基于兼容性网格分割的骨骼参数计算

为了解决骨骼参数难以测量的问题,提出一种利用网格分割结果计算参数的方法.首先对骨骼网格模型在提取少量特征点的基础上进行语义分割;然后将分割得到的模板借助基于Laplacian变形的非刚性配准,指导同类骨骼模型实现快速兼容性分割;最后结合网格分割结果及特征点计算出骨骼的主要形态参数.实验结果表明,该方法仅需少量的用户交互就能获得较好的测量效果,结合模板的策略也支持大批量骨骼模型的参数测定.     

基于TW3-C RUS法的骨龄评估方法研究

经典TW3-C RUS (Tanner and Whitehouse 3-Chinese RUS)法将手骨的关键骨骺区域严格划分为9个等级,未充分考虑骨骺发育的连续性,导致骨龄评估存在一定误差。针对该问题,本文提出一种基于TW3-C RUS法的改进骨龄评估方法。采用阈值法的思想,动态选择网络模型输出的前N个等级概率值,并将前N个概率值作为权值计算手骨的加权得分,降低由于手骨单一等级判定引起的误差。针对网络模型冗余问题,采用跨阶段局部网络(cross stage partial network, CSP-Net)轻量化深度残差网络(residual network 50,Resnext50)。实验表明,改进后的方法对男性骨龄评估的平均绝对误差(mean absolute error,MAE)为0.421 4岁,女性MAE为0.412 8岁,相比于经典TW3-C RUS法,骨龄评估准确率有明显提升。轻量化后的网络模型参数量为46.28 MB,相比Resnext50网络模型有明显降低。     

Versatile Hypoxic Extracellular Vesicles Laden in an Injectable and Bioactive Hydrogel for Accelerated Bone Regeneration

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have emerged as an appealing alternative to cell therapy in regenerative medicine. Unlike bone marrow MSCs (BMSCs) cultured in vitro with normoxia, bone marrow in vivo is exposed to a hypoxic environment. To date, it remains unclear whether hypoxia preconditioning can improve the function of BMSC-derived EVs and be more conducive to bone repair. Herein, it is found that hypoxia preconditioned BMSCs secrete more biglycan (Bgn)-rich EVs via proteomics analysis, and these hypoxic EVs (Hypo-EVs) significantly promote osteoblast proliferation, migration, differentiation, and mineralization by activating the phosphatidylinositide 3-kinase/protein kinase B pathway. Subsequently, an injectable bioactive hydrogel composed of poly(ethylene glycol)/polypeptide copolymers is developed to improve the stability and retention of Hypo-EVs in vivo. The Hypo-EVs-laden hydrogel shows continuous liberation of Hypo-EVs for 3 weeks and substantially accelerates bone regeneration in 5-mm rat cranial defects. Finally, it is confirmed that Bgn in EVs is a pivotal protein regulating osteoblast differentiation and mineralization and exerts its effects through paracrine mechanisms. Therefore, this study shows that hypoxia stimulation is an effective approach to optimize the therapeutic effects of BMSC-derived EVs and that injectable hydrogel-based EVs delivery is a promising strategy for tissue regeneration.     

Self-Mineralizing Dnazyme Hydrogel as a Multifaceted Bone Microenvironment Amendment for Promoting Osteogenesis in Osteoporosis

The accumulation of reactive oxygen species (ROS) and minimal osteogenic raw material in the osteoporotic bone microenvironment greatly inhibits the activity of osteoblasts. Herein, it is originally proposed to construct a biomatrix multifaceted bone microenvironment amendment -Mineralized zippered G4-Hemin DNAzyme hydrogel (MDH)-to improve osteoporotic osteogenic capacity and promote high-quality bone defect repair. The programmed design of the rolling circle amplified DNA hydrogel synthesis system allows the introduction of massive amounts of zippered G4-Hemin DNAzyme in MDH. The zippered G4-Hemin DNAzyme highly mimics the tight catalytic configuration of horseradish peroxidase and exerts excellent enzyme-like activity with considerable ROS molecule scavenging ability. In addition, the DNA amplification by-product pyrophosphate is ingeniously employed as a sufficient phosphorus source, thus constituting an autonomous mineralization system for waste reuse through the introduction of pyrophosphate hydrolase and calcium ions, which deposits in MDH as an osteogenic raw material and addresses the challenge of DNA hydrogel bio-application stability. The remarkable in vitro and in vivo outcomes demonstrate that MDH can effectively improve the oxidative stress status of osteoblasts, restore the balance of mitochondrial membrane potential, and reduce apoptosis, ultimately demonstrating superior osteogenic capacity.     

Simulation of Cortical and Cancellous Bone to Accelerate Tissue Regeneration

Different tissues have complex anisotropic structures to support biological functions. Mimicking these complex structures in vitro remains a challenge in biomaterials designs. Here, inspired by different types of silk nanofibers, a composite materials strategy is pursued toward this challenge. A combination of fabrication methods is utilized to achieve separate control of amorphous and beta-sheet rich silk nanofibers in the same solution. Aqueous solutions containing two types of silk nanofibers are simultaneously treated with an electric field and with ethylene glycol diglycidyl ether (EGDE). Under these conditions, the beta-sheet rich silk nanofibers in the mixture responded to the electric field while the amorphous nanofibers are active in the crosslinking process with the EGDE. As a result, cryogels with anisotropic structures are prepared, including mimics for cortical- and cancellous-like bone biomaterials as a complex osteoinductive niche. In vitro studies revealed that mechanical cues of the cryogels induced osteodifferentiation of stem cells while the anisotropy inside the cryogels influenced immune reactions of macrophages. These bioactive cryogels also stimulated improved bone regeneration in vivo through modulation of inflammation, angiogenesis and osteogenesis responses, suggesting an effective strategy to develop bioactive matrices with complex anisotropic structures beneficial to tissue regeneration.