Bio-Manufacturing Research Center at Tsinghua University

Overview and research infrastructure As one of the leading laboratories in the interdisciplinary field of additive manufacturing and bio-3D printing,the Bio-Manufacturing Center at Tsinghua University is highly dedicated to conducting cutting-edge research in the emerging field of bio-manufacturing.The latter is comprised of research involving biomaterials,living cells,proteins,and/or other biological compounds as basic building blocks to fabricate biomimetic structures,in vitro functional biological models and/or cellular systems with application to tissue engineering,regenerative medicine,disease pathogenesis,drug screening,and tissue/organ-on-a-chip.

完全胸腔镜下解剖性肺段切除术治疗早期肺癌的体会

背景与目的肺段切除较肺叶切除能够更多地保留健康肺组织,但其在早期肺癌根治性方面仍存在争议。本研究分析35例完全胸腔镜下解剖性肺段切除术临床病理资料并复习文献,探讨胸腔镜下肺段切除术在早期肺癌治疗中面临的问题。方法回顾北京大学第三医院2013年5月-2017年7月单一手术组35例完全胸腔镜下肺段切除术患者的临床病理资料,观察术中及术后并发症等安全性指标及淋巴结清扫数目、转移情况,并将术后病理类型与术前影像类型比对分析。35例肺段切除术中男性11例,女性24例,平均年龄57.7岁。病灶位于右肺上叶者8例,右肺下叶者8例,左肺上叶者13例,左肺下叶者6例。计算机断层扫描(computed tomography,CT)影像学肿瘤最大径平均12.7 mm,肺门及纵隔淋巴结最大直径均小于10 mm,以磨玻璃成为主者23例,以实性成分为主者12例。结果 35例均顺利完成电视辅助胸腔镜手术(video-assisted thoracic surgery,VATS)解剖性肺段切除术,平均手术时间为153 min,出血量为51 m L。术后漏气10例,均未超过3天。健侧肺不张1例,乳糜胸1例。平均住院时间为6.1天。出院后30天内门诊复查未发生其他院外手术相关并发症。病理为转移瘤者2例,良性肺病8例,原发肺癌25例。25例原发肺癌中浸润性肺腺癌14例[CT以肺磨玻璃影(ground-glass opacity,GGO)为主者7例],微小浸润腺癌4例(GGO为主者3例),原位腺癌6例(CT均为纯GGO),肺鳞癌1例(CT以实性成分为主)。25例肺癌平均切除淋巴结7.2枚,所有淋巴结无癌转移。结论 VATS解剖性肺段切除术技术上安全可靠,其在肺癌治疗中适应症需严格掌握,其优势仍需前瞻性随机对照实验来证实。

Engineering organoid microfluidic system for biomedical and health engineering:A review

In recent years,organoid technology,i.e.,in vitro three-dimensional(3D)tissue culture,has attracted increasing attention in biomedical engineering.Organoids are cell complexes induced by differentiation of stem cells or organ-progenitor cells in vitro using 3D culture technology.They can replicate the key structural and functional characteristics of the target organs in vivo.With the opening up of this new field of health engineering,there is a need for engineering-system approaches to the production,control,and quantitative analysis of organoids and their microenvironment.Traditional organoid technology has limitations,including lack of physical and chemical microenvironment control,high heterogeneity,complex manual operation,imperfect nutritional supply system,and lack of feasible online analytical technology for the organoids.The introduction of microfluidic chip technology into organoids has overcome many of these limitations and greatly expanded the scope of applications.Engineering organoid microfluidic system has become an interdisciplinary field in biomedical and health engineering.In this review,we summarize the development and culture system of organoids,discuss how microfluidic technology has been used to solve the main technical challenges in organoid research and development,and point out new opportunities and prospects for applications of organoid microfluidic system in drug development and screening,food safety,precision medicine,and other biomedical and health engineering fields.

Raltitrexed as a synergistic hyperthermia chemotherapy drug screened in patient-derived colorectal cancer organoids

Objective:Organoids have recently been used as in vitro models to screen chemotherapy drugs in combination with hyperthermia treatment in colorectal cancer.Our research aimed to establish a library of patient-derived colorectal cancer organoids to evaluate synergism between chemotherapy drugs and hyperthermia;validate an index of the hyperthermia chemotherapy sensitization enhancement ratio(HCSER)to identify the chemotherapeutics most enhanced by hyperthermia;and recommend chemotherapy drugs for hyperthermic intraperitoneal treatment.Methods:Organoids were grown from cells extracted from colorectal cancer patient samples or colorectal cancer cell lines.Cells from both sources were encapsulated in 3 D Matrigel droplets,which were formulated in microfluidics and phase-transferred into identical cell-laden Matrigel microspheres.The microspheres were seeded in 96-well plates,with each well containing a single microsphere that developed into an organoid after 7 days.The organoids were used to evaluate the efficacy of chemotherapy drugs at both 37℃ as a control and 43℃ for 90 min to examine hyperthermia synergism.Cell viability was counted with 10%CCK8.Results:We successfully established a library of colorectal cancer organoids from 22 patient parental tumors.We examined the hyperthermia synergism of 7 commonly used hyperthermic intraperitoneal chemotherapy drugs.In 11 of the 22 patient organoids,raltitrexed had significant hyperthermia synergism,which was indexed as the highest HCSER score within each patient group.Conclusions:Our results primarily demonstrated the use of patient-derived colorectal cancer organoids as in vitro models to evaluate hyperthermia synergistic chemotherapeutics.We found that hyperthermia enhanced the effect of raltitrexed the most among the common anti-colorectal cancer drugs.

Sphingolipid profiles and their relationship with inflammatory factors in asthmatic patients of different sexes

Background:Asthma is a heterogeneous disease with distinct prevalence and manifestation between sexes.This study was to identify sex-specific features of asthma via metabolomic analysis of sphingolipids.Methods:Forty-two asthma patients(27 women and 15 men)admitted to the Peking University Third Hospital from January 2015 to December 2015 were enrolled.Peripheral venous blood was collected for metabolomic analysis by targeted liquid chromatography-mass spectrometry.Sex hormones(estradiol,progesterone,testosterone,and androstenedione)and multiple inflammatory factors(periostin,leptin,IgE,IL-4,IL-5,IL-10,IL-13,IL-17A,and IFN-γ)were also assessed.The eosinophil percentage in induced sputum was also detected.All these data were applied to comparative analysis between sexes.Results:Testosterone was negatively related to periostin(ρ=-0.420,P=0.009)and IL-5(ρ=-0.540,P=0.012),while estradiol was positively related to the blood eosinophil percentage(ρ=0.384,P=0.025).Among the eighteen species of sphingolipids detected in the 42 patients,five ceramide(Cer)species(Cer16:0,Cer:20:0,Cer22:0,Cer24:0,and Cer26:0)and one sphingomyelin(SM)species(SM38:0)were significantly higher in male than in female patients.Further investigation found that the correlation between Cer20:0 and IL-5 was positive in males(ρ=0.943,P=0.005)but negative in females(ρ=-0.561,P=0.030).Conclusions:Testosterone was negatively correlated with eosinophil inflammatory factors,but estradiol was positively correlated.Male asthma patients had higher ceramide and sphingomyelin levels than female patients.Different sexes had opposite correlations with ceramide and IL-5,respectively,suggesting that therapeutic strategies targeting ceramide should be different between sexes.

Capacity Configuration of Energy Storage Systems for Echelon Utilization Based on Accelerated Life Test in Microgrids

Retired power battery construction energy storage systems(ESSs)for echelon utilization can not only extend the remaining capacity value of the battery,and decrease environmental pollution,but also reduce the initial cost of energy storage systems.In this paper,an ESS constructed of retired power batteries for echelon utilization in microgrids(MGs)is considered.Firstly,considering the influence of different discharge depths on the battery life cycle,the correlation equation between the state of charge(SOC)and the state of health(SOH)is established.Secondly,the accelerated life test method,based on the inverse power law coefficient equation,is proposed,and it is used to evaluate the reliability of the ESS.Finally,according to the SOC characteristics,the dynamic security margin of the ESS is established.The life cycle cost,supply-demand balance and ESS balanced control are comprehensively considered,and the location and capacity of energy storage in MGs are determined.It is simulated using the IEEE-RTS 24 node system;the results show that the investment cost of the ESS is reduced and the operational life is prolonged.

CNS Organoid Surpasses Cell-Laden Microgel Assembly to Promote Spinal Cord Injury Repair

The choice of therapeutic agents remains an unsolved issue in the repair of spinal cord injury.In this work,various agents and configurations were investigated and compared for their performance in promoting nerve regeneration,including bead assembly and bulk gel of collagen and Matrigel,under acellular and cell-laden conditions,and cerebral organoid(CO)as the in vitro preorganized agent.First,in Matrigel-based agents and the CO transplantations,the recipient animal gained more axon regeneration and the higher Basso,Beattie,and Bresnahan(BBB)scoring than the grafted collagen gels.Second,new nerves more uniformly infiltrated into the transplants in bead form assembly than the molded chunks.Third,the materials loaded the neural progenitor cells(NPCs)or the CO implantation groups received more regenerated nerve fibers than their acellular counterparts,suggesting the necessity to transplant exogenous cells for large trauma(e.g.,a 5 mm long spinal cord transect).In addition,the activated microglial cells might benefit from neural regeneration after receiving CO transplantation in the recipient animals.The organoid augmentation may suggest that in vitro maturation of a microtissue complex is necessary before transplantation and proposes organoids as the premium therapeutic agents for nerve regeneration.

Extracellular scaffold design for ultra-soft microtissue engineering

Soft and ultra-soft extracellular scaffolds constitute a major fraction of most human internal organs,except for the skeletal system.Modelling these organs in vitro requires a comprehensive understanding of their native scaffolding materials and proper engineering approaches to manufacture tissue architectures with microscale precision.This review focuses on the properties of soft and ultra-soft scaffolds,including their interactions with cells,mechanical properties(e.g.viscoelasticity),and existing microtissue engineering techniques.It also summarises challenges presented by the conflict between the properties of the materials demanded by cell behaviours and the capacities of engineering techniques.It proposes that leveraging the engineering ability of soft and ultra-soft scaffolds will promote therapeutic advances and regenerative medicine.