Balancing the customization and standardization:exploration and layout surrounding the regulation of the growing field of 3D-printed medical devices in China

Medical devices are instruments and other tools that act on the human body to aid clinical diagnosis and disease treatment,playing an indispensable role in modern medicine.Nowadays,the increasing demand for personalized medical devices poses a significant challenge to traditional manufacturing methods.The emerging manufacturing technology of three-dimensional(3D)printing as an alternative has shown exciting applications in the medical field and is an ideal method for manufacturing such personalized medical devices with complex structures.However,the application of this new technology has also brought new risks to medical devices,making 3D-printed devices face severe challenges due to insufficient regulation and the lack of standards to provide guidance to the industry.This review aims to summarize the current regulatory landscape and existing research on the standardization of 3D-printed medical devices in China,and provide ideas to address these challenges.We focus on the aspects concerned by the regulatory authorities in 3D-printed medical devices,highlighting the quality system of such devices,and discuss the guidelines that manufacturers should follow,as well as the current limitations and the feasible path of regulation and standardization work based on this perspective.The key points of the whole process quality control,performance evaluation methods and the concept of whole life cycle management of 3D-printed medical devices are emphasized.Furthermore,the significance of regulation and standardization is pointed out.Finally,aspects worthy of attention and future perspectives in this field are discussed.

Corrosion Prevention of the Generator Stator Hollow Copper Conductor and Water Quality Adjustment of Its Internal Cooling Water

On the basis of expounding the corrosion mechanism of the stator hollow copper conductor in the water-cooling generator, methods of preventing corrosion of the stator hollow copper conductor in the wa-ter-cooling generator through adjusting water quality of its cooling water have been proposed. For internal water cooling systems which are airtight, the corrosion of the hollow copper conductor can be prevented through keeping foreign oxygen and carbon dioxide from entering the system, and the amount of oxygen in the internal water can be lowered by blowing high purity nitrogen. For systems not airtight, the corrosion of the hollow copper conductor can be inhibited through lowering the amount of oxygen to some extent by sealing and increasing pH value by processing part of cooling water with bypass small flow sodium-type mix-bed.

EUV-dependence of Venusian dayside ionopause altitude:VEX and PVO observations

The Venusian dayside ionosphere, similar to other planetary ionospheres, is produced primarily by ionization of its neutral upper atmosphere due to solar extreme ultraviolet (EUV) radiation. It has become clear that the expansion of the ionosphere may be strongly controlled by the EUV level, as exhibited in data collected by the Pioneer Venus Orbiter (PVO) during one solar cycle (1978 1992). However, the EUV-dependence of the Venusian dayside ionopause altitude, which defines the outer boundary of the ionosphere, remains obscure because the PVO crossed the dayside ionopause only during the solar maximum;its periapsis lifted too high during the solar minimum. Recently, during the period 2006 2014, which included the longest and quietest solar minimum of the past several decades, Venus Express (VEX) provided measurements of the photoelectron boundary (PEB) over the northern high-latitude region. Since the photoelectron boundary is closely related to the ionopause, we have an opportunity to analyze the EUV effect on the dayside ionopause by combining PVO and VEX observations. We have evaluated and then reduced the orbit bias effect in data from both PVO and VEX, and then used the results to derive a relationship between solar EUV level and the dayside ionopause altitude. We find that the dayside ionopause altitude increases as the solar EUV level increases, which is consistent with theoretical expectations.

Evaluation of the effectiveness of alginate-based hydrogels in preventing peritoneal adhesions

Infertility and intestinal blockage are just two examples of the postoperative consequences that can arise from peritoneal damage,which can also result in severe peritoneal fibrosis and peritoneal adhesions.Peritoneal adhesions are still not effectively treated,and both pharmaceutical therapy and biomaterial barriers have only had modest preventative effects.In this work,we looked into the effectiveness of in-place injectable sodium alginate hydrogel for peritoneal adhesion prevention.The findings demonstrated that sodium alginate hydrogel promoted human peritoneal mesothelial cell proliferation and migration,prevented peritoneal fibrosis by suppressing the production of transforming growth factor-β1,and,most importantly,promoted mesothelium self-repair.These findings imply that this brand-new sodium alginate hydrogel is a good candidate material for peritoneal adhesion prevention.

Preclinical testing of immunotoxicity for animal-derived dermal materials

Animal derived materials have been widely used in biomedical products owing to their good biocompatibility and appropriate mechanical properties.It is crucial to evaluate the immunotoxicity of such materials in preclinical testing to prevent severe immune responses in patients.In this study,a pipeline of immunotoxicity tests was established to evaluate animal-derived materials before de-cellularization and final products.This pipeline contains a serial of animal tests on BALB/c mice and an in vitro quantification test for a-Gal antigen.It is wellrecognized that the interaction between materials and patients profoundly alters immune responses,thus,a comprehensive dataset including body weight,immune organ coefficient,histopathology,peripheral hematology,serum immunoglobulin level,spleen lymphocyte proliferation rate,and their subpopulation was created and analyzed using the SPSS tool.These results clearly suggested that the de-cellularized materials possessed better biocompatibility,in addition,the a-Gal antigen content was effectively decreased by 96.0%after decellularization.Thus,this study confirmed that this multi-step enzymatic de-cellularization treatment is a potent method to reduce the immunotoxicity of animal-derived biomaterials.Moreover,the experimental pipeline will likely be transferable to other biomedical materials and products.

基于潮位校正的中国潮间带遥感监测及变化

潮间带位于海洋和陆地的过渡地带,在生物多样性保护、社会经济发展以及全球环境变化等方面具有重要价值.由于潮汐的动态性,潮间带的卫星遥感监测存在很大挑战,迄今为止还没有完整的全国滨海潮间带的相应数据.本文综合遥感与地理信息系统方法,利用1995和2015年覆盖全国滨海的156景LandsatTM/OLI卫星影像,反演了中国滨海潮间带的时空分布,并基于高分辨率影像,目视解译了潮间带开发的土地利用类型.在此基础上分析了中国潮间带变化的时空特征和潮间带变化的驱动力因素.结果表明:(1)2015年中国潮间带总面积约为14070 km^2,其中潮间带分布面积最多的为福建省(18%),其次是辽宁省(15%)、山东省(14%)、江苏省(12%)和广东省(11%);面积最小的是海南省(2%).(2)1995～2015年全国潮间带面积净减少了1375km^2,减少约8.9%.全国不同省市潮间带面积表现了增加与减少不同的趋势,其中潮间带面积减少最多的是浙江省,面积减少为1189km^2;江苏省潮间带面积由1995年的全国第1缩减为第4.而福建省潮间带增加最多,达453km^2.(3)潮间带被开发利用的趋势持续增强. 1995年中国沿海潮间带被开发占用的面积为3490 km^2,到2015年达到4581 km^2.潮间带开发利用类型由农业用海为主(41.8%)转变为围海养殖;城镇建设占用比例也达13%.同时围垦中(在建/未知用途)的潮间带面积持续增长,由1995年的18.1%增长为29%.(4)人为和自然两种因素叠加的"挤压效应"造成了我国潮间带面积的减少.经济发展和滨海生态环境保护的矛盾依然表现突出.

Key considerations on the development of biodegradable biomaterials for clinical translation of medical devices:With cartilage repair products as an example

With the interdisciplinary convergence of biology,medicine and materials science,both research and clinical translation of biomaterials are progressing at a rapid pace.However,there is still a huge gap between applied basic research on biomaterials and their translational products-medical devices,where two significantly different perspectives and mindsets often work independently and non-synergistically,which in turn significantly increases financial costs and research effort.Although this gap is well-known and often criticized in the biopharmaceutical industry,it is gradually widening.In this article,we critically examine the developmental pipeline of biodegradable biomaterials and biomaterial-based medical device products.Then based on clinical needs,market analysis,and relevant regulations,some ideas are proposed to integrate the two different mindsets to guide applied basic research and translation of biomaterial-based products,from the material and technical perspectives.Cartilage repair substitutes are discussed here as an example.Hopefully,this will lay a strong foundation for biomaterial research and clinical translation,while reducing the amount of extra research effort and funding required due to the dissonance between innovative basic research and commercialization pipeline.

Quantification of rhBMP2 in bioactive bone materials

Bone morphogenetic protein(BMP),belongs to transforming growth factor-b(TGF-b)superfamily except BMP-1.Implanting BMP into muscular tissues induces ectopic bone formation at the site of implantation,which provides opportunity for the treatment of bone defects.Recombinant human BMP-2(rhBMP-2)has been used clinically,but the lack of standard methods for quantifying rhBMP-2 biological activity greatly hindered the progress of commercialization.In this article,we describe an in vitro rhBMP-2 quantification method,as well as the data analyzation pipeline through logistic regression in RStudio.Previous studies indicated that alkaline phosphatase(ALP)activity of C2C12 cells was significantly increased when exposed to rhBMP-2,and showed dose-dependent effects in a certain concentration range of rhBMP-2.Thus,we chose to quantify ALP activity as an indicator of rhBMP-2 bioactivity in vitro.A sigmoid relationship between the ALP activity and concentration of rhBMP-2 was discovered.However,there are tons of regression models for such a non-linear relationship.It has always been a major concern for researchers to choose a proper model that not only fit data accurately,but also have parameters representing practical meanings.Therefore,to fit our rhBMP-2 quantification data,we applied two logistic regression models,three-parameter log-logistic model and four-parameter log-logistic model.The four-parameter log-logistic model(adj-R2>0.98)fits better than three-parameter log-logistic model(adj-R2>0.75)for the sigmoid curves.Overall,our results indicate rhBMP-2 quantification in vitro can be accomplished by detecting ALP activity and fitting four-parameter log-logistic model.Furthermore,we also provide a highly adaptable R script for any additional logistic models.