Titanium alloys have emerged as the primary material for orthopedic implants, particularly with the advent of 3D-printing technology that has revolutionized the fabrication of complex, biomimetic porous structures. However, the potential release of wear particles poses a critical safety concern, and due to the relatively short clinical history of these novel implants, in vivo data evaluating their safety profile is still limited. Herein, this study established a single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) method to quantify low-concentration Ti-containing nanoparticles (Ti-NPs) and total Ti in peri-implant tissues, blood, and major organs of rabbits at 1, 2, 3, and 4 months following implantation. A split-body design was utilized to compare HA-coated and uncoated 3D-printed Ti-6Al-4V implants. The results showed that Ti-containing nanoparticles (Ti-NPs) were detected across all peri-implant tissues, blood, and major organs, with the majority being nanosized (< 100 nm). In the peri-implant tissues, the Ti-NPs exhibited smaller sizes and lower concentrations in the HA-coated group compared to the uncoated group, demonstrating the protective barrier effect of the coating. Furthermore, the release profile showed that ionic titanium was the dominant species (Ti-NPs < 10%), with a distinct systemic distribution pattern. Specifically, by the fourth month, total Ti concentrations in organs decreased sharply due to excretion, whereas Ti-NPs conversely accumulated, with the spleen identified as the primary reservoir. Overall, this work provides important evidence and offers useful guidance for the safety evaluation of 3D-printed implants.

Cardiovascular diseases have become one of the major threats to human health. There is an urgent clinical need for small-diameter vascular grafts to achieve long-term implantation in the body. In previous studies, some progress has been made, but the prognosis is still poor. Heparin (HEP) is an anticoagulant that is widely applied in the clinical field and commonly used for anticoagulation modification of biomaterials. However, there is an important problem: HEP has almost no direct inhibitory effect on platelet adhesion, which may become one of the potential dangers after graft implantation. In recent years, it has been found that calcification is also a key factor affecting the long-term patency of small-diameter vascular grafts, which is often ignored. Therefore, in this study, based on HEP, procyanidin (PC) was introduced to modify the thermoplastic polyurethane (TPU) grafts fabricated by electrospinning to enhance the anticoagulation and anticalcification properties simultaneously. To verify the effects of drug modification on the material, the physical and chemical characterization, biocompatibility experiments and effectiveness tests of this vascular graft were conducted. The results indicated that the HEP-PC grafts could not only inhibit the excessive proliferation of human umbilical artery smooth muscle cells to some extent but also have excellent hemocompatibility. Particularly, in vivo experiments showed that this graft also achieved dual anticoagulation and delayed the calcification after implantation. These results suggested that HEP-PC-modified TPU might be a promising candidate for inhibiting intimal hyperplasia and anticalcification of small-diameter grafts.

Injectable sodium hyaluronate (NaHA) is extensively utilized in aesthetic medicine as a dermal hydrating agent. However, there are few standardized, human-relevant preclinical methods that can reliably evaluate the moisturizing performance of those products. Existing animal and simplified cell-based models show restricted physiological relevance and insufficient sensitivity. To address this gap, we established a depot-mimicking reconstructed human full-thickness skin (RhFS) platform incorporating an inclusion-based intradermal delivery strategy. Instead of conventional mixing, this strategy mimics the clinical 'depot effect' of intradermal injection, allowing for the simultaneous assessment of cellular responses and tissue-level hydration dynamics. It forms a localized NaHA depot within the dermal compartment of RhFS and preserves spatial hydration gradients, which are lost when NaHA is mixed homogenously. The platform integrates physicochemical characterization of polymer-bound water states with cellular and tissue-level functional readouts. By quantifying key biomarkers, including CD44, aquaporin-3 (AQP3) and natural moisturizing factors (NMFs), our results demonstrate that the inclusion-based delivery strategy significantly outperforms conventional mixing approaches in activating epidermal hydration pathways. Crucially, this platform effectively distinguished the moisturizing efficacy of multiple commercial NaHA formulas, thereby revealing a structure-activity relationship between water-binding states and biological outcomes. Overall, this study presents a reproducible, mechanism-informed and human-relevant framework for preclinical performance evaluation of NaHA-based injectable biomaterials and provides a sensitive alternative to conventional animal-based approaches.

A method for determining volatile organic compounds (VOCs) emitted from medical molecular sieve oxygen concentrators was developed using thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). The oxygen concentrator gas was sampled at a flow rate of 0.5 L/min through a branched sampling system onto Tenax GR/carbopack B adsorption tubes. The adsorbed compounds were desorbed and introduced using a programmed temperature vaporization inlet system, followed by chromatographic separation on an SH-I-624Sil MS column. Four VOCs (BHT-Q, PTBP, BHT-quinol, and EHB) were detected in the medical oxygen concentrator using this method. Calibration curves for these compounds exhibited excellent linearity (R2>0.99) within the range of 3~100 ng. With a sampling volume of 20 L, the detection limit of the four VOCs ranged from 0.003 9 to 0.022 2 μg/m3. Spike recovery rates for the four VOCs were between 95% and 115%, with relative standard deviations (RSDs) below 5% (n=6). The method is simple, rapid, highly sensitive, and accurate, making it suitable for VOCs detection in medical molecular sieve oxygen concentrators.

Injectable fillers for plastic surgery are widely used in the field of aesthetic plastic surgery, and their safety and effectiveness are of vital importance. To ensure the safety and effectiveness of the products, it is indispensable to conduct scientific, rigorous, comprehensive and standardized preclinical physicochemical evaluations. According to the raw materials, injectable fillers for plastic surgery can be classified into sodium hyaluronate type, collagen type and polyester type, etc. The evaluation items and indicators for different materials vary. Preclinical physicochemical evaluations not only include general physicochemical project evaluation, such as the content of active ingredients, pH value, osmotic pressure, total heavy metal content, trace elements, etc., but also need to carry out corresponding evaluation items according to the particularity of different materials, such as the crosslinking degree of sodium hyaluronate gel, the collagen content of collagen products and the copolymerization rate of polyester products. This article not only briefly introduces the test methods of some general evaluation items, but also provides detailed introductions to some evaluation items that have no mature methods or have room for improvement in existing methods, aiming to provide references for the research and development and quality control of injectable fillers for plastic surgery, and help improve the safety and effectiveness of injectable fillers for plastic surgery.

As representatives of the third generation of biomedical materials, hydrogels exhibit revolutionary potential in tissue engineering, precision drug delivery, and smart medical devices due to their ability to construct bionic microenvironments. However, the clinical translation of hydrogels is still limited by multidimensional challenges, including biocompatibility, scalable production, and regulatory complexity. This paper systematically reviews the design innovations, functionalization strategies, and translational bottlenecks of hydrogel materials, integrates the latest technological trends, such as 4D printing and AI-driven design, and proposes a collaborative optimization pathway encompassing materials, technology, clinical applications, and policy. By introducing local Chinese innovation cases and monitoring scientific advancements, this study offers solutions that possess both academic significance and practical guidance for the clinical translation of hydrogels.

As a new type of high-risk packaging container, prefilled syringes are more widely used, and concerns regarding their effectiveness, stability and safety in clinical use have become prominent increasingly. However, the leachable substances from prefilled syringes may cause harm to humans in different degrees. Therefore, this paper reviews the research progress of leachable substances in prefilled syringes, which is not only of great significance for the quality control of prefilled syringe products, but also contributes to the healthy development of the industry.

With the development of the economy and technological progress,more and more animal-derived mesh products are being utilized in the medical field for tissue and organ repair and replacement.Owing to the complexity of their structure and production process,these animal-derived meshes still face several challenges in practical applications,such as insufficient mechanical strength,rapid degradation rates,and the detection of harmful leachable substances.Among these challenges,the production process is a key factor affecting product quality.This paper reviews the key aspects of the production process and quality control for animal-derived meshes in China,offering new insights for the quality control and regulatory oversight of such products.

Immunotoxicity evaluation has been crucial in preclinical testing for implantable animal-derived biomaterials due to their prolonged contact with the human body, which requires stringent safety assessments. By creating experimental models with varying levels of immunotoxicity, this study reveals the decisive role of decellularization treatment in diminishing the immunogenicity of materials, thus ensuring clinical safety. Employing cutting-edge differential gene expression analysis, the research not only accurately quantifies gene expression alterations in immune responses but also, through pathway enrichment analysis, identifies gene networks associated with oncogenesis. This offers novel insights into the mechanisms of immune responses following biomaterial implantation. Additionally, the study highlights the importance of developing highly sensitive immunotoxicity testing methods and validates the efficacy of high-throughput sequencing and bioinformatics tools in assessing biomaterial safety, providing robust scientific support for future preclinical evaluations.

建立医疗器械标准化工作档案有助于提高档案管理工作的整体质量和效率,并推进考核评估工作.文章从医疗器械标准化技术委员会标准化工作档案的管理现状出发,结合档案管理要求和标委会考核评估细则,提出标准化工作档案归纳分类和归档范围的建议,建立医疗器械标准化工作档案的归档指南,为标委会档案管理提供参考.

目的:建立高效液相色谱法(High Performance Liquid Chromatography,HPLC)鉴别检测贻贝黏蛋白(Mussel Adhesive Protein,MAP)的方法.方法:采用Agilent Zobax SB 300A C8(4.6×250mm,5μm)色谱柱,流动相为0.1％三氟乙酸水溶液(A)和含0.1％三氟乙酸乙腈溶液(B)梯度洗脱,检测波长280nm,洗脱温度25?C,流量为0.9mL/min.进样量20μL.考察方法的系统适用性、线性、精密度、检测限及定量限.结果:贻贝黏蛋白供试样品与对照品的HPLC图谱一致.贻贝黏蛋白在0.01～9.79mg/mL范围内峰面积与其浓度呈良好的线性关系(r=1),峰面积及保留时间RSD均小于5％,最低定量限(LOQ)为0.03mg/mL,最低检出限(LOD)为0.01mg/mL.结论:该方法专属性强,稳定性好,简单易用,适用贻贝黏蛋白的检测.

目的 探讨新型"瓣中瓣"技术——经导管瓣中瓣对治疗"二次瓣膜病变"患者的有效性.方法 以人体真实血流流量波形为基准,构建体外循环流动系统,采用粒子图像测速技术对人工心脏瓣膜下游血管内流场进行重构,在获取运动学信息的基础上引入时间平均壁面剪切应力、震荡剪切指数、相对停留时间等动力学参数,对经导管瓣中瓣以及经导管瓣膜的性能进行评估.结果 分析心脏收缩早期、收缩峰值期、收缩晚期以及舒张早期四个特征状态,在流量较大时,经导管瓣中瓣会因诱发返流而导致一定程度的流动不稳定,但其性能总体上与经导管瓣膜相同,可在宽流量范围内正常使用.结论 本文建立了一套有效的瓣膜下游流场动力学参数瓣膜性能体外评估体系,可对新型经导管瓣中瓣结构的适用性提供实验依据.

Fluorometholone (FMT) is a frequently prescribed drug for the alleviation of dry eye. However, due to low aqueous solubility, it has been routinely used as an ophthalmic suspension, which is characterized by low bioavailability, inconvenience of administration, and difficulty in delivering accurate dose. Furthermore, the opaque appearance of the ophthalmic suspension is not desirable for optical purpose. In the present study, a transparent FMT nanoformulation (FMT-CD NPs) was fabricated by the cyclodextrin (CD) nanoparticle technology without organic solvents. It was demonstrated that FMT was encapsulated in an amorphous form, which was associated with increased release rate and enhanced corneal penetration efficiency. The biocompatibility of FMT-CD NPs was confirmed by the Live/Dead assay, CCK-8 assay and the wound healing assay. Most importantly, FMT-CD NPs alleviated dry eye signs more efficiently than the commercial eye drop, with one-fifth the dosage of FMT in the latter. Collectively, our study provides a promising FMT formulation for improved management of dry eye while reducing drug related side effects.

对用于医用增材制造的国产Ti6Al4V/Ti6Al4V ELI粉末的特性进行评价和质量控制研究,以期为我国医用增材制造行业提供数据参考.采用经过验证的或者现行标准中的测试方法对Ti6Al4V/Ti6Al4V ELI粉末的化学成分、粒度分布、振实密度、松装密度、流动性等性能进行测试.结果表明:研究所用的国产Ti6Al4V/Ti6Al4VELI粉末粉末粒径分布较窄,能满足对能量的均匀吸收.化学成分满足GB/T3620.1-2016和GB/T 13810-2017中的相应要求,用于SLM工艺时的粉末松装密度均不小于2.2 g/cm3、振实密度均不小于2.5g/cm3、流动性均不大于50 s/50 g.用于EBM工艺时的粉末松装密度均不小于2.3 g/cm3、振实密度均不小于2.5 g/cm3、流动性均不大于30 s/50 g.

目的 随着之前植入外科人工生物心脏瓣膜患者瓣膜毁损的病例增加,介入瓣膜瓣中瓣越来越多地被用于临床.由于其临床应用时间不长,目前没有长期临床数据可以参考,故实验采用体外加速方法,对一种介入瓣膜瓣中瓣耐久性能进行测试及评价.方法 将23 mm、27 mm、29 mrm 3个规格(牛心包材质)介入瓣膜作为瓣中瓣分别安装在23 mm、27 mm、29 mm对应规格外科生物心脏瓣膜中,通过预扩达到相同的内径后进行体外加速疲劳耐久性能测试,每5000万次对其脉动流性能进行测试.2.0亿次疲劳测试后,对瓣叶进行热力学分析、双光子共聚焦显微镜下观察瓣叶胶原纤维结构.结果 经过2.0亿次耐久性能测试,介入瓣膜瓣中瓣平均跨瓣压差无显著变化[23 mm:1.92～1.98 kPa(14.4～14.9 mmHg);27 mm:0.92～1.64 kPa(6.9～12.3 mmHg);29 mm:0.72～1.02 kPa(5.4～7.4 mmHg)],有效瓣口面积基本一致(23 mm:1.45～1.66 cm2;27 mm:1.88～ 2.17 cm2;29 mm:2.24～2.54 cm2),反流百分比减小(23mm:7.2％～3.3 ％;27 mm:14.9％～3.3 ％;29 mm:14.7％～3.9％),脉动流性能满足YY/T 1449.3-2016标准的要求,具有良好的脉动流性能.瓣叶材料的热力学变性温度降低,从(105.4±0.9)℃变为(98.1±0.5)℃(P＜0.05).瓣叶材料中胶原纤维形状发生变化,由疲劳测试前卷曲的立体结构变为疲劳测试后波浪形线状结构.结论 经过模拟临床使用5年(2.0亿次)体外疲劳测试后,虽然介入瓣膜瓣中瓣瓣叶材料发生蠕变,胶原蛋白纤维结构发生变化,热变性温度降低,但瓣膜整体仍具有良好的流体力学性能.

The therapeutic benefits of transplanting mesenchymal stem cells (MSCs) to the injury site of traumatic optic neuropathy (TON) represents a crucial, yet unresolved question, the answer to which may facilitate development of innovative therapies for TON, a frustrating disease with no effective treatment. Herein, we address this issue by showing that MSC transplantation to the injury site is able to promote optic nerve regeneration in terms of retinal ganglion cell survival and axon regeneration using MSC@MS, implantable patches assembled with MSCs and gelatin/silk fibroin composite microspheres, which integrate 3D culture and trypsin-free harvesting, and can increase in vivo retention of transplanted MSCs. In contrast, conventional bolus injection of MSC suspension is not potent enough to produce significant benefits. We also show MSCs in MSC@MS demonstrate superior gene expression profiles over monolayer culture after IGF-1 stimulation. In future study, microspheres in MSC@MS can further be harnessed to deliver therapeutic cargoes that boost the potency of MSCs or treat TON synergistically with MSCs, making MSC@MS a versatile platform to develop tailored MSC-based therapies for TON. (c) 2021 Elsevier Ltd. All rights reserved.

随着生物技术的发展,近年来出现了通过覆盖钙结合位点的牛心包处理技术,并以此为瓣叶材料制备出干性生物瓣膜.由于干性生物瓣膜临床应用时间短,尚缺少长期耐久性数据.本研究采用体外加速方法,对一种干性生物瓣膜耐久性能进行测试及评价.选取23和32 mm这两个规格干性生物瓣膜进行体外耐久性能测试.通过瓣膜脉动流实验、瓣叶热力学分析和显微镜下胶原纤维观察,对其耐久性能进行评价.经过2亿次循环(模拟临床使用5年),干性生物瓣膜流体力学性能无明显变化,其中23 mm规格干性生物瓣膜平均跨瓣压差有所升高,但仍处于同规格生物瓣膜较低水平;32 mm规格干性生物瓣膜平均跨瓣压差几乎没有变化.有效瓣口面积基本一致,返流百分比无明显变化,说明干性生物瓣膜未发生明显的狭窄和返流,能量损失无明显变化,说明瓣膜的效能无明显降低.瓣叶材料的热力学变性温度由96.6℃降至91.2℃;在双光子共聚焦显微镜下观察,同样测试条件下亮度变暗,但胶原纤维形状未发生变化,仍是卷曲的立体结构,说明胶原纤维含量降低,化学键部分丢失,与热变性温度表现一致.干性生物瓣膜耐久性能实验后,微观结构发生一定变化,但仍具有良好的流体力学性能.

介绍可降解血管支架不溶性微粒的危害及来源,列举可降解血管支架不溶性微粒的评价方法,并分析可降解血管支架的不溶性微粒评价的发展趋势.

目的:研究经导管瓣膜镍钛合金支架动态疲劳中镍离子释放及其潜在体外细胞毒性,为该类创新医疗器械产品的临床前安全性评价提供参考,为推动医疗器械创新发展提供技术支撑.方法:以经导管瓣膜镍钛合金支架为研究对象,利用脉动疲劳试验模拟支架临床植入10年的情况(4亿次疲劳测试),研究其动态疲劳过程中镍离子的释放情况,并利用细胞模型评估所释放镍离子的潜在毒性效应.结果:随着镍钛合金支架疲劳试验时间的增加,测试溶液中镍离子浓度增大,测试液中镍离子最大浓度为0.075 mg·L-1.利用不同浓度梯度的镍离子溶液对L929细胞进行细胞毒性试验,当离子浓度为小于等于6.25 mg·L-1时,无体外细胞毒性,当镍离子浓度大于等于12.5 mg·L-1时,有潜在的细胞毒性.结论:经4亿次动态疲劳测试后(模拟临床使用10年)经导管瓣膜支架中镍离子的释放量低于安全限值,无体外细胞毒性.