Research lab on 3D bioprinting of Zhejiang University

OverviewThe Research Lab on 3D Bioprinting of Zhejiang University focuses on developing innovative 3D bioprinting equipment and technology for healthcare and biomedical applications, since founded in 2017. To further enhance the international collaboration, a joint international research lab on 3D bioprinting of Zhejiang University and University of Oxford was set up. The lab is based on the State Key Laboratory of Fluid Power and Mechatronic Systems and the Oxford Centre for Tissue Engineering and Bioprocessing. The aim of the lab is to establish a world class research and development platform on 3D bioprinting. The lab has extensive and close collaborations with University of Oxford, University College London and multidisciplinary partners of Zhejiang University.

Strengths, weaknesses, and applications of computational axial lithography in tissue engineering

Recently,Kelly and colleagues[1],inspired by computed tomography(CT),report a“volumetric additive manufacturing”technology via a computed axial lithography(CAL)approach.A related US patent application[2]has also been filed.The cumulative light exposure solidifies the material in the target area,while the other area remains uncured,resulting in only specific points in the designed 3D objects being printed.This technology significantly improves the capability of the digital light processing(DLP)technique.Meanwhile,the lithography approach based on a similar algorithm was already proposed by Xiang Wu in a patent(application No.PCT/CN2016/080097)in 2016[3].

Biofabrication of aligned structures that guide cell orientation and applications in tissue engineering

The organized alignment of cells in various tissues plays a significant role in the maintenance of specific functions.To induce such an alignment,ideal scaffolds should simulate the characteristics and morphologies of natural tissues.Aligned structures that guide cell orientation are used to facilitate tissue regeneration and repair.We here review how various aligned structures are fabricated,including aligned electrospun nanofibers,aligned porous or channeled structures,micropatterns and combinations thereof,and their application in nerve,skeletal muscle,tendon,and tubular dentin regeneration.The future use of aligned structures in tissue engineering is also discussed.

Gelatin-Based Metamaterial Hydrogel Films with High Conformality for Ultra-Soft Tissue Monitoring

Implantable hydrogel-based bioelectronics(IHB)can precisely monitor human health and diagnose diseases.However,achieving biodegradability,biocompatibility,and high conformality with soft tissues poses significant challenges for IHB.Gelatin is the most suitable candidate for IHB since it is a collagen hydrolysate and a substantial part of the extracellular matrix found naturally in most tissues.This study used 3D printing ultrafine fiber networks with metamaterial design to embed into ultra-low elastic modulus hydrogel to create a novel gelatin-based conductive film(GCF)with mechanical programmability.The regulation of GCF nearly covers soft tissue mechanics,an elastic modulus from 20 to 420 kPa,and a Poisson’s ratio from-0.25 to 0.52.The negative Poisson’s ratio promotes conformality with soft tissues to improve the efficiency of biological interfaces.The GCF can monitor heartbeat signals and respiratory rate by determining cardiac deformation due to its high conformability.Notably,the gelatin characteristics of the biodegradable GCF enable the sensor to monitor and support tissue restoration.The GCF metamaterial design offers a unique idea for bioelectronics to develop implantable sensors that integrate monitoring and tissue repair and a customized method for endowing implanted sensors to be highly conformal with soft tissues.

A general Boolean semantic modelling approach for complex and intelligent industrial systems in the framework of DES

Discrete event system(DES)models promote system engineering,including system design,verification,and assessment.The advancement in manufacturing technology has endowed us to fabricate complex industrial systems.Consequently,the adoption of advanced modeling methodologies adept at handling complexity and scalability is imperative.Moreover,industrial systems are no longer quiescent,thus the intelligent operations of the systems should be dynamically specified in the model.In this paper,the composition of the subsystem behaviors is studied to generate the complexity and scalability of the global system model,and a Boolean semantic specifying algorithm is proposed for generating dynamic intelligent operations in the model.In traditional modeling approaches,the change or addition of specifications always necessitates the complete resubmission of the system model,a resource-consuming and error-prone process.Compared with traditional approaches,our approach has three remarkable advantages:(i)an established Boolean semantic can be fitful for all kinds of systems;(ii)there is no need to resubmit the system model whenever there is a change or addition of the operations;(iii)multiple specifying tasks can be easily achieved by continuously adding a new semantic.Thus,this general modeling approach has wide potential for future complex and intelligent industrial systems.

Sustainable and untethered soft robots created using printable and recyclable ferromagnetic fibers

Integrated printing of magnetic soft robots with complex structures using recyclable materials to achieve sustainability of the soft robots remains a persistent challenge.Here,we propose a kind of ferromagnetic fibers that can be used to print soft robots with complex structures.These ferromagnetic fibers are recyclable and can make soft robots sustainable.The ferromagnetic fibers based on thermoplastic polyurethane(TPU)/NdFeB hybrid particles are extruded by an extruder.We use a desktop three-dimensional(3D)printer to demonstrate the feasibility of printing two-dimensional(2D)and complex 3D soft robots.These printed soft robots can be recycled and reprinted into new robots once their tasks are completed.Moreover,these robots show almost no difference in actuation capability compared to prior versions and have new functions.Successful applications include lifting,grasping,and moving objects,and these functions can be operated untethered wirelessly.In addition,the locomotion of the magnetic soft robot in a human stomach model shows the prospect of medical applications.Overall,these fully recyclable ferromagnetic fibers pave the way for printing and reprinting sustainable soft robots while also effectively reducing e-waste and robotics waste materials,which is important for resource conservation and environmental protection.

Rapid fabrication of modular 3D paper-basedmicrofluidic chips using projection-based 3D printing

Paper-based microchips have different advantages,such as better biocompatibility,simple production,and easy handling,making them promising candidates for clinical diagnosis and other fields.This study describes amethod developed to fabricate modular three-dimensional(3D)paper-based microfluidic chips based on projection-based 3D printing(PBP)technology.A series of two-dimensional(2D)paper-based microfluidic modules was designed and fabricated.After evaluating the effect of exposure time on the accuracy of the flow channel,the resolution of this channel was experimentally analyzed.Furthermore,several 3D paper-based microfluidic chips were assembled based on the 2D ones using different methods,with good channel connectivity.Scaffold-based 2D and hydrogel-based 3D cell culture systems based on 3D paper-based microfluidic chips were verified to be feasible.Furthermore,by combining extrusion 3D bioprinting technology and the proposed 3D paper-based microfluidic chips,multiorgan microfluidic chips were established by directly printing 3D hydrogel structures on 3D paperbased microfluidic chips,confirming that the prepared modular 3D paper-based microfluidic chip is potentially applicable in various biomedical applications.

MAPOD Analysis in Eddy Current Testing of Flaws Considering Multiple Response Signals and Multiple Flaw Parameters

The reliability of the eddy current testing (ECT) in flaw detection is quantitatively evaluated by theprobability of detection (POD). Precise and efficient modeling of POD gives direction for the implement of ECTon sites to avoid false or missing flaw detection. Traditional POD analysis focuses on single uncertain factor orsingle response signal with limited credibility in engineering. This paper considers multiple response signals andmultiple flaw parameters to perform POD. The flaw length, the flaw depth, the coil impedance, and the magneticflux density are comprehensively studied under various lift-off distances. A finite element model (FEM) of ECT isestablished and verified with experiments to obtain sufficient simulation data for discrete POD modeling. Thecontinuous POD function is then fitted based on the discrete values to show the superiority of integrating multiplefactors. A comparison with conventional POD analysis further demonstrates the higher reliability of ECT flawdetection considering multiple flaw parameters and multiple response signals, especially for small flaws.

Development of 3D bioprinting:From printing methods to biomedical applications

Biomanufacturing of tissues/organs in vitro is our big dream,driven by two needs:organ transplantation and accurate tissue models.Over the last decades,3D bioprinting has been widely applied in the construction of many tissues/organs such as skins,vessels,hearts,etc.,which can not only lay a foundation for the grand goal of organ replacement,but also be served as in vitro models committed to pharmacokinetics,drug screening and so on.As organs are so complicated,many bioprinting methods are exploited to figure out the challenges of different applications.So the question is how to choose the suitable bioprinting method?Herein,we systematically review the evolution,process and classification of 3D bioprinting with an emphasis on the fundamental printing principles and commercialized bioprinters.We summarize and classify extrusion-based,dropletbased,and photocuring-based bioprinting methods and give some advices for applications.Among them,coaxial and multi-material bioprinting are highlighted and basic principles of designing bioinks are also discussed.

Bioprinting of novel 3D tumor array chip for drug screening

Biomedical field has been seeking a feasible standard drug screening system consisting of 3D tumor model array for drug researching due to providing sufficient samples and simulating actual in vivo tumor growth situation,which is still a challenge to rapidly and uniformly establish though.Here,we propose a novel drug screening system,namely 3D tumor array chip with“layer cake”structure,for drug screening.Accurate gelatin methacryloyl hydrogel droplets(~0.1μL)containing tumor cells can be automatically deposited on demand with electrohydrodynamic 3D printing.Transparent conductive membrane is introduced as a chip basement for preventing charges accumulation during fabricating and convenient observing during screening.Culturing chambers formed by stainless steel and silicon interlayer is convenient to be assembled and recycled.As this chip is compatible with the existing 96-well culturing plate,the drug screening protocols could keep the same as convention.Important properties of this chip,namely printing stability,customizability,accuracy,microenvironment,tumor functionalization,are detailly examined.As a demonstration,it is applied for screening of epirubicin and paclitaxel with breast tumor cells to confirm the compatibility of the proposed screening system with the traditional screening methods.We believe this chip will potentially play a significant role in drug evaluation in the future.

3D printing of calcium phosphate bioceramic with tailored biodegradation rate for skull bone tissue reconstruction

The bone regenerative scaffold with the tailored degradation rate matching with the growth rate of the new bone is essential for adolescent bone repair.To satisfy these requirement,we proposed bone tissue scaffolds with controlled degradation rate using osteoinductive materials(Ca-P bioceramics),which is expected to present a controllable biodegradation rate for patients who need bone regeneration.Physicochemical properties,porosity,compressive strength and degradation properties of the scaffolds were studied.3D printed Ca-P scaffold(3DS),gas foaming Ca-P scaffold(FS)and autogenous bone(AB)were used in vivo for personalized beagle skull defect repair.Histological results indicated that the 3DS was highly vascularized and well combined with surrounding tissues.FS showed obvious newly formed bone tissues.AB showed the best repair effect,but it was found that AB scaffolds were partially absorbed and degraded.This study indicated that the 3D printed Ca-P bioceramics with tailored biodegradation rate is a promising candidate for personalized skull bone tissue reconstruction.

Laser direct writing of Ga_(2)O_(3)/liquid metal-based flexible humidity sensors

Flexible and wearable humidity sensors play a vital role in daily point-of-care diagnosis and noncontact human-machine interactions.However,achieving a facile and high-speed fabrication approach to realizing flexible humidity sensors remains a challenge.In this work,a wearable capacitive-type Ga_(2)O_(3)/liquid metal-based humidity sensor is demonstrated by a one-step laser direct writing technique.Owing to the photothermal effect of laser,the Ga_(2)O_(3)-wrapped liquid metal particles can be selectively sintered and converted from insulative to conductive traces with a resistivity of 0.19Ω·cm,while the untreated regions serve as active sensing layers in response to moisture changes.Under 95%relative humidity,the humidity sensor displays a highly stable performance along with rapid response and recover time.Utilizing these superior properties,the Ga_(2)O_(3)/liquid metal-based humidity sensor is able to monitor human respiration rate,as well as skin moisture of the palm under different physiological states for healthcare monitoring.

Keep Healthcare Workers Safe:Application of Teleoperated Robot in Isolation Ward for COVID‑19 Prevention and Control

At the time of writing,the coronavirus disease(COVID-19)has affected 212 countries and territories across the globe.According to the world health organization(WHO),a total number of 4,735,622 confirmed cases,including 316,289 deaths was reported[1].In the fight against COVID-19,nurses,doctors,and other healthcare workers are in the front line of the battle bearing the higher risk of infection[2].The International Council of Nurses(ICN)gathered further information to suggest that more than 90,000 healthcare workers have been infected worldwide[3].Personal protective equipment(PPE)shortage is one of the key factors increasing the infection risk for the medical staffs.Therefore,finding alternative ways to lower the infection risk has become an urgent problem to be solved.

Light-Weight Design Method for Force-Performance-Structure of Complex Structural Part Based Co-operative Optimization

A light?weight design method of integrated structural topology and size co?optimization for the force?performance?structure of complex structural parts is presented in this paper. Firstly, the supporting function of a complex structural part is built to map the force transmission, where the force exerted areas and constraints are considered as connecting structure and the structural configuration, to determine the part performance as well as the force routines. Then the connecting structure design model, aiming to optimize the static and dynamic performances on connection configuration, is developed, and the optimum design of the characteristic parameters is carried out by means of the collaborative optimization method, namely, the integrated structural topology optimization and size optimization. In this design model, the objective is to maximize the connecting stiffness. Based on the relationship between the force and the structural configuration of a part, the optimal force transmission routine that can meet the performance requirements is obtained using the structural topology optimization technology. Accordingly, the light?weight design of conceptual configuration for complex parts under multi?objective and multi?condition can be realized. Finally, based on the proposed collaborative optimization design method, the optimal performance and optimal structure of the complex parts with light weight are realized, and the reasonable structural unit configuration and size charac?teristic parameters are obtained. A bed structure of gantry?type machining center is designed by using the proposed light?weight structure design method in this paper, as an illustrative example. The bed after the design optimization is lighter 8% than original one, and the rail deformation is reduced by 5%. Moreover, the lightweight design of the bed is achieved with enhanced performance to show the effectiveness of the proposed method.

Trends on physical understanding of bioink printability

Recently, 3D bioprinting is developed as an emerging approach, increasingly applied to materials for healthcare;while, the precise placement of cells and materials, and the shape fidelity of forming constructs is of great importance for successful application of 3D bioprinting. Research efforts have been made to develop new bioinks as "raw materials" with better biocompatibility and biofunctionality, but the printability of bioinks is largely ignored and still needs to be carefully examined to enable robotic bioprinting. This article aims to introduce a recent published review (Appl. Phys. Rev. 2018, 5, 041304) on the evaluation of bioink printability by Huang's research group from University of Florida. Huang et al. comprehensively reviewed the bioink printability based on the physical point of view during inkjet printing, laser printing, and microextrusion, and a series of self-consistent time scales and dimensi on less quantities were utilized to physically understand and evaluate bioink printability. This article would be helpful to know the trends on physical understanding of bioink printability.

Analysis of Gas-Solid Flow Characteristics in a Spouted Fluidized Bed Dryer by Means of Computational Particle Fluid Dynamics

In order to grasp the particle flow characteristics and energy consumption of industrial fluidized spouted beds,we conduct numerical simulations on the basis of a Computational Particle Fluid Dynamics(CPFD)approach.In particular,the traction model of Wen-Yu-Ergun is used and different inlet conditions are considered.Using a low-speed fluidizing gas,the flow state of the particles is better and the amount of particles accumulated at the bottom of the bed wall becomes smaller.For the same air intake,the energy loss of a circular nozzle is larger than that of a square nozzle.

Experimental Research on A New Type of Floating Breakwater for Wave-Absorbing and Energy-Capturing

To avoid the damage caused by big wind and wave in cage culture, and to solve the problem of energy supply faced by automatic breeding equipment, a new type of floating breakwater, named as Savonius double buoy breakwater(SDBB), is proposed in the paper. The floating breakwater is composed of HDPE cylindrical double buoys and horizontal axis Savonius rotors, and has the functions of wave-absorbing and energy-capturing. Based on the linear wave theory and energy conservation law, the Fourier Transform was applied to separate the two-dimensional wave frequency domain, and the energy captured by the rotors and absorbed by the floating breakwater were calculated.Experiments were conducted in a two-dimensional wave-making flume, and the transmitted waves at different wave heights and periods, the tension of mooring lines, and the rotational torque exerted on the Savonius rotor were measured. A series of performance comparison tests were also performed on the new floating breakwater and the traditional double-floating breakwater. Results show that the new floating breakwater is better than the traditional one in terms of reducing wave transmittance, and the combination of the floating breakwater with Savonius rotors can provide for marine aquaculture equipments with green power supply to a certain degree of self-sufficiency.

Why choose 3D bioprinting? Part I: a brief introduction of 3D bioprinting for the beginners

Graphic abstract Concept of 3D bioprinting 3D printing,also called additive manufacturing,is a layerby-layer manufacturing method,and it has been implemented in a wide variety of areas.3D printing could be treated as the reverse process of potato cutting,automatically assembling the chips or slicing into a potato[1].When this simple idea is met with biomedical engineering,3D bioprinting is born.

The construction of in vitro tumormodels based on 3D bioprinting

Cancer is characterized by a high fatality rate,complex molecular mechanism,and costly therapies.The microenvironment of a tumor consists of multiple biochemical cues and the interaction between tumor cells,stromal cells,and extracellular matrix plays a key role in tumor initiation,development,angiogenesis,invasion and metastasis.To better understand the biological features of tumor and reveal the critical factors of therapeutic treatments against cancer,it is of great significance to build in vitro tumor models that could recapitulate the stages of tumor progression and mimic tumor behaviors in vivo for efficient and patient-specific drug screening and biological studies.Since conventional tissue engineering methods of constructing tumor models always fail to simulate the later stages of tumor development due to the lack of ability to build complex structures and angiogenesis potential,three-dimensional(3D)bioprinting techniques have gradually found its applications in tumor microenvironment modeling with accurate composition and well-organized spatial distribution of tumor-related cells and extracellular components in the past decades.The capabilities of building tumor models with a large range of scale,complex structures,multiple biomaterials and vascular network with high resolution and throughput make 3D bioprinting become a versatile platform in bio-manufacturing aswell as inmedical research.In this review,wewill focus on 3D bioprinting strategies,design of bioinks,current 3D bioprinted tumor models in vitro classified with their structures and propose future perspectives.

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.