Wei Sun

Drexel University, Philadelphia, Pennsylvania, United States

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Publications (90)110.82 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Advances in micro-electro-mechanical systems (MEMS) have led to an increased fabrication of micro-channels. Microfabrication techniques are utilized to develop microfluidic channels for continuous nutrition supply to cells inside a micro-environment. The ability of cells to build tissues and maintain tissue-specific functions depends on the interaction between cells and the extracellular matrix (ECM). SU-8 is a popular photosensitive epoxy-based polymer in MEMS. The patterning of bare SU-8 alone does not provide the appropriate ECM necessary to develop microsystems for biological applications. Manipulating the chemical composition of SU-8 will enhance the biological compatibility, giving the fabricated constructs the appropriate ECM needed to promote a functional tissue array. This article investigates three frequently used surface treatment techniques: (1) plasma treatment, (2) chemical reaction, and (3) deposition treatment to determine which surface treatment is the most beneficial for enhancing the biological properties of SU-8. The investigations presented in this article demonstrated that the plasma, gelatin, and sulfuric acid treatments have a potential to enhance SU-8's surface for biological application. Of course each treatment has their advantages and disadvantages (application dependent). Cell proliferation was studied with the use of the dye Almar Blue, and a micro-plate reader. After 14 days, cell proliferation to plasma treated surfaces was statistically significantly enhanced (p < 0.00001), compared to untreated surfaces. The plasma treated surface is suggested to be the better of the three treatments for biological enhancement followed by gelatin and sulfuric acid treatments, respectively. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2014.
    Journal of Biomedical Materials Research Part B Applied Biomaterials 06/2014; · 2.31 Impact Factor
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    ABSTRACT: The re-creation of the tumor microenvironment including tumor-stromal interactions, cell-cell adhesion and cellular signaling is essential in cancer-related studies. Traditional two-dimensional (2D) cell culture and animal models have been proven to be valid in some areas of explaining cancerous cell behavior and interpreting hypotheses of possible mechanisms. However, a well-defined three-dimensional (3D) in vitro cancer model, which mimics tumor structures found in vivo and allows cell-cell and cell-matrix interactions, has gained strong interest for a wide variety of diagnostic and therapeutic applications. This communication attempts to provide a representative overview of applying 3D in vitro biological model systems for cancer related studies. The review compares and comments on the differences in using 2D models, animal models and 3D in vitro models for cancer research. Recent technologies to construct and develop 3D in vitro cancer models are summarized in aspects of modeling design, fabrication technique and potential application to biology, pathogenesis study and drug testing. With the help of advanced engineering techniques, the development of a novel complex 3D in vitro cancer model system will provide a better opportunity to understand crucial cancer mechanisms and to develop new clinical therapies.
    Biofabrication 04/2014; 6(2):022001. · 3.71 Impact Factor
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    ABSTRACT: Advances in three-dimensional (3D) printing have enabled the direct assembly of cells and extracellular matrix materials to form in vitro cellular models for 3D biology, the study of disease pathogenesis and new drug discovery. In this study, we report a method of 3D printing for Hela cells and gelatin/alginate/fibrinogen hydrogels to construct in vitro cervical tumor models. Cell proliferation, matrix metalloproteinase (MMP) protein expression and chemoresistance were measured in the printed 3D cervical tumor models and compared with conventional 2D planar culture models. Over 90% cell viability was observed using the defined printing process. Comparisons of 3D and 2D results revealed that Hela cells showed a higher proliferation rate in the printed 3D environment and tended to form cellular spheroids, but formed monolayer cell sheets in 2D culture. Hela cells in 3D printed models also showed higher MMP protein expression and higher chemoresistance than those in 2D culture. These new biological characteristics from the printed 3D tumor models in vitro as well as the novel 3D cell printing technology may help the evolution of 3D cancer study.
    Biofabrication 04/2014; 6(3):035001. · 3.71 Impact Factor
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    ABSTRACT: Three-dimensional tissue platforms are rapidly becoming the method of choice for quantification of the heterogeneity of cell populations for many diagnostic and drug therapy applications. Microfluidic sensors and the integration of sensors with microfluidic systems are often described as miniature versions of their macro-scale counterparts. This technology presents unique advantages for handling costly and difficult-to-obtain samples and reagents as a typical system requires between 100 nL to 10 µL of working fluid. The fabrication of a fully functional cell-based biosensor utilizes both biological patterning and microfabrication techniques. A digital micro-mirror (photolithographic) system is initiated to construct the tissue platform while a cell printer is used to precisely embed the cells within the construct. Tissue construct developed with these technologies will provide an early diagnostic of a drug's potential use. A three-dimensional interconnected microfluidic environment has the potential to eliminate the limitations of the traditional mainstays of two-dimensional investigations. This paper illustrates an economical and an innovative approach of fabricating a three-dimensional cell-laden microfluidic chip for detecting drug metabolism.
    Biofabrication 04/2014; 6(2):025008. · 3.71 Impact Factor
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    ABSTRACT: An engineered three-dimensional scaffold with hierarchical porosity and multiple niche microenvironments is produced using a combined multi-nozzle deposition-freeze casting technique. In this paper we present a process to fabricate a scaffold with improved interconnectivity and hierarchical porosity. The scaffold is produced using a two-stage manufacturing process which superimposes a printed porous alginate (Alg) network and a directionally frozen ceramic-polymer matrix. The combination of two processes, multi-nozzle deposition and freeze casting, provides engineering control of the microenvironment of the scaffolds over several length scales; including the addition of lateral porosity and the ratio of polymer to ceramic microstructures. The printed polymer scaffold is submerged in a ceramic-polymer slurry and subsequently, both structures are directionally frozen (freeze cast), superimposing and patterning both microenvironments into a single hierarchical architecture. An optional additional sintering step removes the organic material and densifies the ceramic phase to produce a well-defined network of open pores and a homogenous cell wall material composition. The techniques presented in this contribution address processing challenges, such as structure definition, reproducibility and fine adjustments of unique length scales, which one typically encounters when fabricating topological channels between longitudinal and transverse porous networks.
    Biofabrication 01/2014; 6(1):015007. · 3.71 Impact Factor
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    ABSTRACT: Recent development in bioprinting technology enables the fabrication of complex, precisely controlled cell-encapsulated tissue constructs. Bioprinted tissue constructs have potential in both therapeutic applications and nontherapeutic applications such as drug discovery and screening, disease modelling and basic biological studies such as in vitro tissue modelling. The mechanical properties of bioprinted in vitro tissue models play an important role in mimicking in vivo the mechanochemical microenvironment. In this study, we have constructed three-dimensional in vitro soft tissue models with varying structure and porosity based on the 3D cell-assembly technique. Gelatin/alginate hybrid materials were used as the matrix material and cells were embedded. The mechanical properties of these models were assessed via compression tests at various culture times, and applicability of three material constitutive models was examined for fitting the experimental data. An assessment of cell bioactivity in these models was also carried out. The results show that the mechanical properties can be improved through structure design, and the compression modulus and strength decrease with respect to time during the first week of culture. In addition, the experimental data fit well with the Ogden model and experiential function. These results provide a foundation to further study the mechanical properties, structural and combined effects in the design and the fabrication of in vitro soft tissue models.
    Biofabrication 12/2013; 5(4):045010. · 3.71 Impact Factor
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    ABSTRACT: Fifteen years ago, the field of cell and organ printing began with a few research groups looking to take newly developed direct-write tools and apply them to living cells. Initial experiments demonstrated cell viability and functionality post-deposition. Recently, research has begun in earnest to create three-dimensional cellular constructs that mimic both the heterogeneous structure and function of natural tissue. Several companies are now marketing cell printers, expanding access to a wider group of scientists and accelerating the pace of development. This article describes the past decade and a half of research by showing examples of some of the most sophisticated work, comparing the approaches and tools used in the field, and predicting the products that will arrive in the not too distant future.
    MRS Bulletin 10/2013; 38(10):834-843. · 5.07 Impact Factor
  • Robert Chang, Jae Nam, Wei Sun
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    ABSTRACT: A novel targeted application of tissue engineering is the development of an in vitro 3D tissue model for drug screening and toxicology. This paper discusses the modeling, design, and freeform fabrication of 3D cell-embedded tissue constructs for creating a pharmacokinetic model. This is achieved using a combinatorial setup involving a CAD-driven automated syringe-based, layered direct cell writing process in conjunction with soft lithographic micro-patterning techniques. This enables the rational design of a microscale in vitro device housing a bioprinted 3D tissue construct (or micro-organ) that biomimics the cell’s physiological microenvironment for enhanced functionality. This paper specifically addresses issues related to the development and implementation of a unique direct cell writing process for biofabrication of 3D cell-encapsulated hydrogel-based tissue constructs with defined patterns, the direct integration onto a microfluidic device, and the perfusion of the 3D tissue constructs for pharmacokinetic study. Micron-sized features enables the achievement of large hydrodynamic shear forces on our tissue constructs while preserving predictable laminar flow regimes. It has been demonstrated in literature that these shear stresses serve as mechanical stimuli which cells mechanotransduce to influence drug response. The motivation for the design and modeling of the bioprinted flow pattern is to predict, tune, and optimize the metabolic drug response of 3D bio-printed liver tissue to hydrodynamic perturbations under varying experimental flow conditions and structural flow patterns.
    Computer-Aided Design and Applications 08/2013; 5(1):363-370.
  • Biofabrication: Micro- and Nano-fabrication, Printing, Patterning and Assemblies, First edited by Gabor Forgacs, Wei Sun, 04/2013: chapter 9: pages 167-182; Elsevier., ISBN: 978-1-4557-2852-7
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    ABSTRACT: In the field of tissue engineering, regenerative medicine, and life sciences, the topological biochemical cues regulate cell attachment and alignment within the construct. In a native biological system, these cues are inherent. However, most of the biological materials utilized in the fabrication of tissue construct do not possess the appropriate cues required to develop an architecture to support the cell attachment and growth of a functional tissue Therefore the ability to manipulate structural and biochemical cues plays an important role in biofabrication process, and it is a key element to evaluate a engineered cellular model. Plasma surface functionalization and biologics printing have been investigated and validated as two effective techniques to guide cell functions by creating microenvironments. The objective of this work is to develop a novel dual functional platform for freeform microplasma surface patterning and biologics printing process as well as to study the underlying process science and the process induced cellular functions. The microplasma jet system was assembled by two parts. The upper part is a plastic NPT connector surrounding an extending high voltage copper electrode. The lower part is a dielectric Pasteur pipette connected with a capillary micro-scale nozzle tip. The lower part is interchangeable and the diameter of the tip ranges from 50 μm to 1 mm. With up to 20 kV output capability, a high-voltage power supply was connected to the copper electrode through the NPT connector which also served as gas inlet. A high-voltage probe linked to an oscilloscope is used to monitor the real time voltage. The whole microplasma jet system was set up on automation platform, which allows X-Y-Z motion control and switch control. This integrated system operates at atmospheric pressured environment. All tissue constructs could be fabricated at room temperature without the use of a mask. Clear polystyrene microplates were used as plasma treatment substrates. After O2-He mixed microplasma treatment, 7F2 mouse osteoblastic cells were cultured in the microplates for cell biology studies. We demonstrated the capability of our dual functional platform by applying microplasma in the polystyrene wells and control group (without any treatment) in other wells of the same microplate substrate. The results show that the microplasma treatment changed the surface properties and improved cell attachment. This dual functional freeform system allows for surface patterning and printing of cells, proteins, growth factors, etc. to fabricate three-dimensional tissue constructs.
    ASME/ISCIE 2012 International Symposium on Flexible Automation; 06/2012
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    ABSTRACT: Micro-Electro-Mechanical Systems (MEMS) technologies have been very attractive and demonstrate the potential for many applications in the field of tissue engineering, regenerative medicine, and life sciences. These fields bring together the multidisciplinary field of engineering and integrated sciences to fabricate three-dimensional models that aides the exploration, generation or regeneration of organic tissues and organs. Presently, monolayer cell cultures are frequently used to investigate potential anti-cancer agents. The issues at hand are that these models give very little in terms of feedback on the effects of the microenvironment on chemotherapeutic and the heterogeneity of the tumor. Three-dimensional tumor and cancer models that mimic the actual disease are developed for in vitro investigations. These models create an environment that enables diseases to have an enhanced evaluation (compared to two dimensional) and eliminate the limitations of the traditional mainstays of cancer research. Three-dimensional Cancer models are economic, allow for biological characterizations. Cancer models are developed from investigations of the actual disease; computer tomography (CT) and magnetic resonance imaging (MRI) allow for biomodeling of the disease’s environmental conditions.Unlike many traditional microfabrication techniques, the Digitial Micro-mirror Microfabrication (DMM) System eliminates the need for mask by incorporating a dynamic mask-less fabrication technique. The DMM is specifically designed for the developments of biologically inspired devices, whether it’s a multicellular spheroid, hollow fiber, or multicellular layer (MCL) models; the DMM has the potential to utilize its dynamic micro mirrors to build the tissue model according to its desired design and characteristics. Each model is specifically designed to mimic the in vivo conditions of the tissue of interest.
    ASME/ISCIE 2012 International Symposium on Flexible Automation; 06/2012
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    ABSTRACT: The objective of this work is to produce a 3-dimensional scaffold with hierarchical porosity produced with automated manufacturing control. In this paper we present a two-step manufacturing process: solid freeform fabrication (SFF) of a polymer scaffold, followed by freeze casting, a directional solidification technique, of composite slurry. This combination allows for the production of composite scaffolds with well defined, gradient porosity in two directions. Transverse porosity is created by immersing a printed alginate scaffold in a chitosan (CS)-hydroxyapatite (HA) slurry which is freeze cast to produce a scaffold with highly aligned porosity in the longitudinal direction. The combination of these two processes, printing and freeze casting, provides engineering control over chemical, structural and mechanical cues of the interconnected microenvironment within the scaffolds over several length scales, including features like overall porosity, pore size and shape as well as the choice of material and for example the ratio of polymer to ceramic within the highly porous composite material. Thus, the material’s structure and architecture can be custom-designed by the fabrication processes to regulate diffusion throughout the scaffold as well as to potentially direct cell proliferation and migration.
    ASME/ISCIE 2012 International Symposium on Flexible Automation; 06/2012
  • Qudus Hamid, Wei Sun
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    ABSTRACT: The present invention relates to an integrated Assisting Cooling (AC) device, system and method for use with PED devices, allowing use of biopolymers having higher melting points in the fabrication of 3D scaffolds. The AC device cools the filament as it is extruding from ...
    Ref. No: U.S. Patent Application 13/243,226., Year: 09/2011
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    ABSTRACT: An atmospheric pressure non-thermal microplasma jet (Ø 50 μm) was developed for localized functionalization of various substrates, including polymers, to allow maskless freeform cell printing. The applied microplasma jet power ranged from 0.1 to 0.2 W without causing any damage to the polyethylene substrate. The surface characterization results demonstrate that the microplasma treatment locally changes the surface roughness and the concentration of oxygen-containing functional groups on the polyethylene surface. The biological characterization confirms that the osteoblast cells attach and survive on the plasma activated line while untreated surfaces show almost no attachment and viability.
    Applied Physics Letters 09/2011; 99(11):111502-111502-3. · 3.52 Impact Factor
  • Plasma Processes and Polymers 02/2011; 8(3):256 - 267. · 3.73 Impact Factor
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    ABSTRACT: In their normal in vivo matrix milieu, tissues assume complex well-organized 3D architectures. Therefore, a primary aim in the tissue engineering design process is to fabricate an optimal analog of the in vivo scenario, in which the precise configuration and composition of cells and bioactive matrix components can establish the well-defined biomimetic microenvironments that promote cell-cell and cell-matrix interactions. With the advent and refinements in microfabricated systems which can present physical and chemical cues to cells in a controllable and reproducible fashion unrealizable with conventional tissue culture, high-fidelity, high-throughput in vitro models are achieved. The convergence of solid freeform fabrication (SFF) technologies, namely microprinting, along with microfabrication techniques, a 3D microprinted micro-organ, can serve as an in vitro platform for cell culture, drug screening, or to elicit further biological insights. This chapter firstly details the principles, methods, and applications that undergird the fabrication process development and adaptation of microfluidic devices for the creation of a drug screening model. This model involves the combinatorial setup of an automated syringe-based, layered direct cell writing microprinting process with soft lithographic micropatterning techniques to fabricate a microscale in vitro device housing a chamber of microprinted 3D micro-organ that biomimics the cell's natural microenvironment for enhanced performance and functionality. In order to assess the structural formability and biological feasibility of such a micro-organ, 3D cell-encapsulated hydrogel-based tissue constructs are microprinted reproducibly in defined design patterns and biologically characterized for both viability and cell-specific function. Another key facet of the in vivo microenvironment that is recapitulated with the in vitro system is the necessary dynamic perfusion of the 3D microscale liver analog with cells probed for their collective drug metabolic function and suitability as a drug metabolism model.
    Methods in molecular biology (Clifton, N.J.) 01/2011; 671:219-38. · 1.29 Impact Factor
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    ABSTRACT: In their normal in vivo matrix milieu, tissues assume complex well-organized three-dimensional architectures. Therefore, the primary aim in the tissue engineering design process is to fabricate an optimal analog of the in vivo scenario. This challenge can be addressed by applying emerging layered biofabrication approaches in which the precise configuration and composition of cells and bioactive matrix components can recapitulate the well-defined three-dimensional biomimetic microenvironments that promote cell-cell and cell-matrix interactions. Furthermore, the advent of and refinements in microfabricated systems can present physical and chemical cues to cells in a controllable and reproducible fashion unmatched with conventional cultures, resulting in the precise construction of engineered biomimetic microenvironments on the cellular length scale in geometries that are readily parallelized for high throughput in vitro models. As such, the convergence of layered solid freeform fabrication (SFF) technologies along with microfabrication techniques enables the creation of a three-dimensional micro-organ device to serve as an in vitro platform for cell culture, drug screening or to elicit further biological insights, particularly for NASA's interest in a flight-suitable high-fidelity microscale platform to study drug metabolism in space and planetary environments. The proposed model in this paper involves the combinatorial setup of an automated syringe-based, layered direct cell writing bioprinting process with micro-patterning techniques to fabricate a microscale in vitro device housing a chamber of bioprinted three-dimensional liver cell-encapsulated hydrogel-based tissue constructs in defined design patterns that biomimic the cell's natural microenvironment for enhanced biological functionality. In order to assess the structural formability and biological feasibility of such a micro-organ, reproducibly fabricated tissue constructs were biologically characterized for liver cell-specific function. Another key facet of the in vivo microenvironment that was recapitulated with the in vitro system included the necessary dynamic perfusion of the three-dimensional microscale liver analog with cells probed for their collective drug metabolic function and suitability as a drug metabolism model. This paper details the principles and methods that undergird the direct cell writing biofabrication process development and adaptation of microfluidic devices for the creation of a drug screening model, thereby establishing a novel drug metabolism study platform for NASA's interest to adopt a microfluidic microanalytical device with an embedded three-dimensional microscale liver tissue analog to assess drug pharmacokinetic profiles in planetary environments.
    Biofabrication 11/2010; 2(4):045004. · 3.71 Impact Factor
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    ABSTRACT: As the field of Tissue Engineering advances to its ultimate goal of engineering a fully functional organ, there’s an increase need for enabling technologies and integrated system. Important roles in scaffold guided tissue engineering are the fabrication of extra-cellular matrices (ECM) that have the capabilities to maintain cell growth, cell attachment, and ability to form new tissues. Three-dimensional scaffolds often address multiple mechanical, biological and geometrical design constraints. With advances of technologies in the recent decades, Computer Aided Tissue Engineering (CATE) has much development in solid freeform fabrication (SFF) process, which includes but not limited to the fabrication of tissue scaffolds with precision control. Drexel University patented Precision Extrusion Deposition (PED) device uses computer aided motion and extrusion to precisely fabricate the internal and external architecture, porosity, pore size, and interconnectivity within the scaffold. The high printing resolution, precision, and controllability of the PED allows for closer mimicry of tissues and organs. Literatures have shown that some cells prefer scaffolds built from stiff material; stiff materials typically have a high melting point. Biopolymers with high melting points are difficult to manipulate to fabricate 3D scaffold. With the use of the PED and an integrated Assisting Cooling (AC) device; high melting points of biopolymer should no longer limit the fabrication of 3D scaffold. The AC device is mounted at the nozzle of the PED where the heat from the material delivery chamber of the PED has no influence on the AC fluid temperature. The AC has four cooling points, located north, south, east, and west; this allows for cooling in each direction of motion on a XY plane. AC uses but not limited to nitrogen, compressed air, and water to cool polymer filaments as it is extruded from the PED and builds scaffolds. Scaffolds fabricated from high melting point polymers that use this new integrated component to the PED should illustrate good mechanical properties, structural integrity, and precision of pore sizes and interconnectivity.
    ASME 2010 Conference on Smart Materials, Adaptive Structures and Intelligent Systems; 09/2010
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    ABSTRACT: One of the major challenges in scaffold guided regenerative therapies is identifying the essential cues such as mechanical forces that induce cellular responses to form functional tissue. Developing multi-scale modelling methods would facilitate in predicting responses of encapsulated cells for controlling and maintaining the cell phenotype in an engineered tissue construct, when mechanical loads are applied. The objective of this study is to develop a 3D multi-scale numerical model for analyzing the stresses and deformations of the cell when the tissue construct is subjected to macro-scale mechanical loads and to predict load-induced cell damage. Specifically, this methodology characterizes the macro-scale structural behavior of the scaffold, and quantifies 3D stresses and deformations of the cells at the micro-scale and at a cellular level, wherein individual cell components are incorporated. Assuming that cells have inherent ability to sustain a critical load without damage, a damage criterion is established and a stochastic simulation is employed to predict the percentage cell viability within the tissue constructs. Bio-printed cell-alginate tissue constructs were tested with 1%, 5% and 10% compression strain applied and the cell viability were characterized experimentally as 23.2+/-16.8%, 9.0+/-5.4% and 4.6+/-2.1%. Using the developed method, the corresponding micro-environments of the cells were analyzed, the mean critical compressive strain was determined as 0.5%, and the cell viability was predicted as 26.6+/-7.0, 13.3+/-4.5, and 10.1+/-2.8. The predicted results capture the trend of the damage observed from the experimental study.
    Journal of biomechanics 04/2010; 43(6):1031-8. · 2.66 Impact Factor
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    ABSTRACT: A combined effect of protein coating and plasma modification on the quality of the osteoblast-scaffold interaction was investigated. Three-dimensional polycaprolactone (PCL) scaffolds were manufactured by the precision extrusion deposition (PED) system. The structural, physical, chemical and biological cues were introduced to the surface through providing 3D structure, coating with adhesive protein fibronectin and modifying the surface with oxygen-based plasma. The changes in the surface properties of PCL after those modifications were examined by contact angle goniometry, surface energy calculation, surface chemistry analysis (XPS) and surface topography measurements (AFM). The effects of modification techniques on osteoblast short-term and long-term functions were examined by cell adhesion, proliferation assays and differentiation markers, namely alkaline phosphatase activity (ALP) and osteocalcin secretion. The results suggested that the physical and chemical cues introduced by plasma modification might be sufficient for improved cell adhesion, but for accelerated osteoblast differentiation the synergetic effects of structural, physical, chemical and biological cues should be introduced to the PCL surface.
    Biofabrication 03/2010; 2(1):014109. · 3.71 Impact Factor

Publication Stats

1k Citations
110.82 Total Impact Points

Institutions

  • 2000–2014
    • Drexel University
      • • Department of Mechanical Engineering and Mechanics
      • • Department of Computer Science
      Philadelphia, Pennsylvania, United States
  • 2012–2013
    • Tsinghua University
      • Department of Mechanical Engineering
      Peping, Beijing, China
  • 2010
    • The College of New Jersey
      • Department of Mechanical Engineering
      New York City, NY, United States