Publications
The complete publication list can be found at Google Scholar
Optimization of Printability of Bioinks with Multi-Response Optimization (MRO) and Artificial Neural Networks (ANN)
In bioprinting, printing resolution and structural stability depend closely on the bioinks’ rheological properties such as zero shear viscosity, storage modulus, thixotropic recovery, viscoelasticity, and gelation point. Thus, understanding the material-rheology-printability relationships is crucial for multi-material bioinks. This study adopted a design of experiment (DoE) with response surface methodology using a central composite design to systematically investigate the rheological and printability parameters of bio-inks formed through combinations of sodium alginate, gelatin, and a nano-clay reinforcing agent (laponite) for enhanced storage modulus and cellular attachment. The material composition for the optimal printability was determined by the multi-response optimization method. Furthermore, this study incorporated machine learning techniques to generalize the effects of various rheological properties on printability and extrusion pressure. Multi-objective optimization was employed to statistically optimize solution properties based on the two opposing parameters: printed structure conformity and minimum extrusion pressure. The optimized bioinks demonstrated high-fidelity printing performance: less than 5% deformation from the computer-aided-design (CAD) models at low extrusion pressures below 30 Kpa for maintaining good cell viability. Resampling data from the DoE-fitted model equations facilitated the generation of extensive datasets for training artificial neural network (ANN) models. This process resulted in a robust machine learning model capable of accurately predicting bioink printability with a maximum 6.3% mean absolute error (MAE) solely based on the rheological properties. In summary, the DoE-based data sampling, MRO optimization, and ML modeling approach enabled the development of a robust bioink formulation method applicable to creating bioinks with extreme properties. The study underscores the crucial role of data-driven modelling and optimization approaches in extrusion-based bioprinting for tissue engineering applications.
Teaming Engineering Students with Medical Students-Interdisciplinary Learning for Biomedical Innovation
This paper presents the implementation of the first-semester course and the corresponding preliminary research results. The educational objective of this course is to equip students with skills for problem exploration and project establishment in the field of healthcare. The knowledge acquisition was evaluated based on the grades of homework and quizzes. The critical thinking and research competency were evaluated by the research reports and the final proposals. The technical communication ability was evaluated by the oral presentations. In addition, we conducted a pre-semester survey and a post-semester survey to evaluate students’ self-efficacy. Gains in self-efficacy were measured by aggregating five items asking students to indicate how much this course increases their confidence in the following areas: (1) background research, (2) innovation, (3) teamwork, (4) communication, and (5) career interest. This paper presents the preliminary data about the learning outcomes of this interdisciplinary course for biomedical innovation.
Near-field electrospinning polycaprolactone microfibers to mimic arteriole-capillary–venule structure
This paper presents the near-field electrospinning (ES) technique to fabricate a branched microfiber structure that mimics the morphology of capillaries. Polycaprolactone solution was electrospun onto a sloped collector that resulted in morphological and geometric variation of the fibers. With proper control over the solution viscosity and the electrospinning voltage, a single fiber was scattered into a branched fiber network and then converged back to a single fiber on the collector. The obtained fibers have a diameter of less than 100 microns at the two ends with coiled and branched fibers of less than 10 microns that mimics the arteriole-capillary-venule structure.
Effects of Solution Viscosity on Poly (l-Lactic Acid) Porous Microtubes Fabricated by Core–Sheath Electrospinning
This paper presents a process based on core–sheath electrospinning to fabricate poly(L-lactic acid) (PLLA) microtubes with nanopores on the tube wall. The morphology of the microtubes mimics human fenestrated capillary vessels. This study investigates the effects of the viscosities of the core and the sheath solutions on the microtube outer diameter and the nanopore size. The core solution shows a dominating influence on the microtube diameter. At the same core solution viscosity level, the microtube diameter is negatively correlated to the core-to-sheath viscosity ratio. The pore size is positively correlated to the microtube diameter.
Biomimetic strategies for fabricating musculoskeletal tissue scaffolds: a review
This paper reviews recent progress in fabrication strategy of biomimetic scaffolds for musculoskeletal tissue engineering from three key aspects: bioinspired materials, biomimetic structures, and biofabrication techniques. The emerging hybrid biofabrication technologies that enable rapid manufacturing of 3D composite constructs with complex features will be a promising pathway toward highly efficient bench-to-bedside translation. Future biomimetic scaffolds should possess modulated functions in response to the dynamic physiological and mechanical environments. This is the prerequisite of future development of reliable, flexible, and cost-effective alternatives to achieve long-term regeneration and good clinical outcomes.
Core–sheath wet electrospinning of nanoporous polycaprolactone microtubes to mimic fenestrated capillaries
Rapid fabrication of artificial capillary vessels (<10 µm) is challenging. In this study, a novel electrospinning approach is developed to fabricate nanoporous polycaprolactone microtubes as potential functional capillaries. The results show that ambient environment parameters and solution properties affect the pore formation and tube morphology. Porous microbeads, helical fibers, and microtubes were fabricated under different processing conditions. The optimal tubular structure is obtained with consistent viscosities between the core and the sheath solutions. The biomimetic nanoporous microtubes hold great potential for vascularization in tissue engineering.
Polyvinylchloride coated with silver nanoparticles and zinc oxide nanowires for antimicrobial applications
Catheter-associated urinary tract infection is among the most common types of infections in the United States. In this study, silver nanoparticles were covalently-bonded on polyvinylchloride (PVC) film, and zinc oxide nanowires with a radiating acicular structure were then self-assembled on the composite surface. The composite film reduced the attachment of Staphylococcus aureus by nearly two orders of magnitude in 24 h. The integration of silver nanoparticles and zinc oxide nanowires holds potential for antimicrobial applications.
Laser engineered net shaping of antimicrobial and biocompatible titanium-silver alloys
Post-surgery infection is one of the main causes of orthopedic implant failure. This paper presents a powder-feed 3D printing strategy for fabrication of silver (Ag) incorporated titanium (Ti) alloys as an antimicrobial solution for orthopedic implants. Alloys with various Ag concentration, ranging from 0.5% to 2% by weight, were fabricated through laser engineered net shaping (LENS) process. Results showed that LENS fabricated Ti-Ag alloys had a marginally higher microhardness and a lower ductility compared to pure Ti. Within only 3 h, Ti-Ag alloys significantly reduced the bacterial attachment of both gram-positive and gram-negative strains by one to four orders of magnitudes. These alloys also demonstrated excellent in-vitro biocompatibility to human osteosarcoma cells.
Integration of silver nanoparticles and microcurrent for water filtration
This paper proposed a novel strategy which integrates AgNP-impregnated membranes with low intensity electrofiltration technology. Polysulfone membranes incorporated with AgNPs or polyaniline nanofibers were fabricated by wet phase-inversion method. The membranes were connected to the cathode of a low intensity direct current source to form an electric field which facilitated electrophoretic force to direct aqueous ions. Without the presence of AgNPs, the low intensity electric activation alone did not exert a significant effect on membrane filtration efficacy or biofilm resistance. However, the combined effect of AgNP and electric activation resulted in a substantial biofilm reduction against both gram-positive and gram-negative bacterial strains over 24 h. The mass spectrometry and X-ray photoelectron spectroscopy showed that the cathodization preserved the metallic state of AgNPs for long period, and thus led to a superior performance than passive AgNP membranes. The integration of AgNP and electrofiltration extended the duration of biofouling resistance and minimized the silver leaching.
The effects of collector geometry on the internal structure of the 3D nanofiber scaffold fabricated by divergent electrospinning
This paper presented an innovative divergence electrospinning strategy to fabricate 3D polycaprolactone (PCL) scaffolds comprised of uniaxially aligned nanofibers. The effects of collector geometry on the nanofiber structure were characterized by polynomial regression analysis. The length-to-width ratio and inclination angle of the collector were found to be critical to nanofiber distribution within the 3D scaffold. The nanofiber orientation was consistent with the direction of electric field vectors between the two bevels of the collector. After a continuous culturing for 7 days, fibroblast cells were uniaxially organized within the 3D scaffolds, closely resembling the fibrous structure in musculoskeletal tissues. This study provided a novel approach to biomimetic native tissue microstructures and showed a great potential as a future fabrication additive manufacturing platform for tissue engineering.
Hybrid fabrication of biomimetic meniscus scaffold by 3D printing and parallel electrospinning
This paper presents a novel meniscus tissue scaffold fabricated by a hybrid additive manufacturing technology to closely resemble the natural topology of the extracellular matrix. A skeletal scaffold was 3D printed and a layer of random or aligned polycaprolactone and collagen nanofibers were embedded between two frames. A compression test was performed to study the mechanical properties of the system. Human osteosarcoma cells were cultured in the scaffold for 7 days to evaluate the effect of scaffold microstructure on cell growth. With reinforced nanofibers, the hybrid scaffold showed superior compression strength compared to 3D printed scaffold without nanofibers. The hybrid scaffold induced the cells to organize into an aligned structure. The study shows the potential of hybrid bio fabrication process to be developed as a scalable platform for biomimetic scaffolds with patterned fibrous microstructure.
​Hybrid Additive Microfabrication Scaffold Incorporated with Highly Aligned Nanofibers for Musculoskeletal Tissues
The skeleton of the scaffold was 3D printed by fused deposition modeling, and a layer of random or aligned polycaprolactone nanofibers were embedded between two frames. A parametric study was performed to investigate the effects of process parameters on nanofiber morphology. The tip-to-collector distance showed a positive correlation with the fiber alignment, and the electrospinning time showed a negative correlation with the fiber density. With reinforced nanofibers, the hybrid scaffold demonstrated superior compression strength compared to conventional 3D-printed scaffold. The hybrid scaffold with aligned nanofibers led to higher cell attachment and proliferation rates, and a directional cell organization. In addition, there was a nonlinear relationship between the fiber diameter/density and the cell actin-filament density.
Anti-biofilm AgNP-polyaniline-polysulfone composite membrane activated by low intensity direct/alternating current
This study developed and evaluated a conductive ultrafiltration membrane activated by electric current for biofilm control. The polysulfone(PSF)-based membrane was incorporated with polyaniline (PANI) and silver nanoparticles (AgNPs) as the electrical conductivity enhancer and the antimicrobial agent, respectively. Compared to the bare PSF membrane, the AgNP-PANI-PSF membrane showed lower porosity but higher surface hydrophilicity. The membranes were connected to power sources providing either direct current (DC) or alternating current (AC) at an intensity level of 60 μA. The AgNP-PANI-PSF membrane activated by electric current (DC and AC) effectively prevented bacterial colonization by six orders of magnitude, and limited the silver leaching under 0.1 mg L−1 after 24 hour tests. The AC activation maximized the anti-biofilm efficacy of the AgNPs, and the DC activation minimized the silver loss from the membrane. This study indicated that the electrically-activated AgNP-PANI-PSF membrane can be further developed as an alternative solution for membrane fouling control.
Tunable 3D nanofiber architecture of polycaprolactone by divergence electrospinning for potential tissue engineering applications
This study focuses on an innovative electrospinning strategy that adopts a symmetrically divergent electric field to induce rapid self-assembly of aligned polycaprolactone (PCL) nanofibers into a centimeter-scale architecture. PCL/collagen (type I) nanofiber scaffolds with different density gradients were incorporated in sodium alginate hydrogels. Human fibroblasts were seeded onto the scaffolds and cultured for 7 days. Our studies showed that the inclination angle of the collector had significant effects on nanofiber attributes, including the mean diameter, density gradient, and alignment gradient. By altering the geometry of the conductive areas on the collecting bevels, polyhedral and cylindrical scaffolds composed of aligned fibers were directly fabricated. By using a four-bevel collector, the nanofibers formed a matrix of microgrids. The scaffolds provided biophysical stimuli to facilitate cell adhesion, proliferation, and morphogenesis.
Engineering the hard–soft tissue interface with random-to-aligned nanofiber scaffolds
Regeneration of the tendon/ligament-to-bone interface is critical to provide functional graft integration after injury. The objective of this study is to recreate the tendon-to-bone interface using a gradient scaffold which is fabricated by a one-station electrospinning process. Two cell phenotypes were grown on a poly-ε-caprolactone nanofiber scaffold which possesses a gradual transition from random to aligned nanofiber patterns. Osteosarcoma and fibroblast cells were seeded on the random and aligned sections of scaffolds, respectively. A random-to-aligned cocultured tissue interface which mimicked the native transition in composition of enthesis was created after 96 h culturing. The results showed that the microstructure gradient influenced the cell morphology, tissue topology, and promoted enthesis formation. This study demonstrates a heterogeneous nanofiber scaffold strategy for interfacial tissue regeneration. It provides a potential solution for mimicking transitional interface between distinct tissues.
Antibacterial efficacy and cytotoxicity of low intensity direct current activated silver–titanium implant system prototype
This study investigates the in vitro antibacterial efficacy and cytotoxicity of a low intensity direct current (LIDC)-activated silver–titanium implant system prototype designed for localized generation and delivery of silver ions at the implantation site. First, the antibacterial efficacy of the system was assessed against methicillin-resistant Staphylococcus aureus (MRSA) over 48 h at current levels of 3 and 6 µA in Mueller–Hinton broth. The cytotoxicity of the system was then evaluated over 48 h in two phases using an in vitro model with in which the activated electrodes were suspended in growth medium in a cell-seeded tissue culture plate. In phase-1, the system was tested on human osteosarcoma (MG-63) cell line and compared to titanium controls. In phase-2, the cytotoxicity characteristics were validated with normal human diploid osteoblast cells. The LIDC-activated system demonstrated high antimicrobial efficacy against MRSA, but was also toxic to human cells immediately surrounding the electrodes. The statistical analysis showed that the cytotoxicity was a result of the presence of silver, and the electric activation did not make it worse.