Research

Research Areas

• Orthopedic and cardiovascular biomaterials
• Drug Delivery
• Tissue engineering
• Biodegradable materials

The research areas at the AIMS lab include biomaterial constructs for both orthopedic and cardiovascular applications of tissue engineering and drug delivery. We are investigating cell interactions in cocultures and in a variety of polymeric scaffolds to develop biodegradable tissue engineering scaffolds for bone regeneration and angiogenesis in large bone defects. Tissue engineering approaches are also being employed to develop an in vivo coronary artery occlusion model as well as to improve treatment for aortic aneurysms. In the area of drug delivery, we are investigating the use of self-assembled monolayers to attach drug molecules to the surfaces of metal stents used in coronary arteries and other implants.

Rena Bizios, PhD
rena.bizios@utsa.edu
210-458-6646

*More information coming soon*

Joo Ong, PhD, Director UTSA/UTHSCSA Joint Graduate Program

The research interest of our laboratory is developing functional hybrid biomaterial solution for implantology, regenerative medicine and specific diseases by means of surface modification, tissue engineering and nanotechnology. Our research lies at the interfaces of fundamental material science, biology and clinical applications at the macro-, micro- and nano- scale level, where basic understanding of biology inspires the development of functional hybrid biomaterials for medical applications. We believe quality work depends on idea, passion and persistence. The students and postdoc fellows who join our group will have opportunities to learn from and work with engineers, biologists and clinicians.

Tissue engineering

Tissue engineering consists of four categories: scaffold, drug release, cell and signals. In our lab, we focus on optimization of scaffold design and fabrication to mimic the in vivo natural environment, to aid and induce tissue regeneration. In our lab, bioceramics, polymer and composite scaffolds with different composition, geometry structure and shapes are fabricated using different techniques, and their effect on bone cell and bone tissue have been evaluated. Currently our research is in the field of controlled biodegradable rate of scaffolds with porous covered polymeric microsphere, thereby achieving a controlled release rate of growth factor and drugs within antibacterial effect. In addition, we are interested in applying the developing biomaterials for specific diseases such as bony birth defects and cancer therapy.

Surface Engineering

Surface engineering focuses on implant surface chemistry, texture and mechanical properties to improve performance of dental and orthopedic implant devices. In clinical, osseointegration, which is defined as the direct bone-implant contact, is critical for initial fixation and long-term success of endosseous dental and orthopedic implants. In our lab, the implant surface chemistry, texture and mechanical properties have been modified via chemical treatment and ion beam sputtering within antibacterial effect. The enhancement of osseointegraion has been evidenced by in vitro cell culture and in vivo animal study.

Functional Hybrid Biomaterials Lab

The research interest of our laboratory is developing functional hybrid biomaterial solution for implantology, regenerative medicine and specific diseases by means of surface modification, tissue engineering and nanotechnology. Our research lies at the interfaces of fundamental material science, biology and clinical applications at the macro-, micro- and nano- scale level, where basic understanding of biology inspires the development of functional hybrid biomaterials for medical applications. We believe quality work depends on idea, passion and persistence. The students and postdoc fellows who join our group will have opportunities to learn from and work with engineers, biologists and clinicians.

Tissue Engineering

Tissue engineering consists of four categories: scaffold, drug release, cell and signals. In our lab, we focus on optimization of scaffold design and fabrication to mimic the in vivo natural environment, to aid and induce tissue regeneration. In our lab, bioceramics, polymer and composite scaffolds with different composition, geometry structure and shapes are fabricated using different techniques, and their effect on bone cell and bone tissue have been evaluated. Currently our research is in the field of controlled biodegradable rate of scaffolds with porous covered polymeric microsphere, thereby achieving a controlled release rate of growth factor and drugs within antibacterial effect. In addition, we are interested in applying the developing biomaterials for specific diseases such as bony birth defects and cancer therapy.

Surface Engineering

Surface engineering focuses on implant surface chemistry, texture and mechanical properties to improve performance of dental and orthopedic implant devices. In clinical, osseointegration, which is defined as the direct bone-implant contact, is critical for initial fixation and long-term success of endosseous dental and orthopedic implants. In our lab, the implant surface chemistry, texture and mechanical properties have been modified via chemical treatment and ion beam sputtering within antibacterial effect. The enhancement of osseointegraion has been evidenced by in vitro cell culture and in vivo animal study

Liang Tang, Ph.D.
Associate Professor
liang.tang@utsa.edu
210.458.6557

This research laboratory has great interests in nanomaterials and nanomedicine to advance point-of-care diagnosis and personalized therapy in cardiovascular and cancer research.

1. Nanomaterial and nanopattern assembly

Nanoparticles provide a particularly useful platform, demonstrating unique properties with potentially wide-ranging applications in medicine, biology, energy, and electronics. The unique properties and utility of this nanomaterial arise from a variety of attributes, including the similar size of nanoparticles and biomolecules such as proteins and polynucleic acids. Additionally, nanoparticles can be fashioned with a wide range of metal and semiconductor core materials that enable useful properties such as surface plasmon resonance and magnetic behavior. Here, gold and magnetic nanoparticles are at the center of attention. We strive to develop new class of nanocomposites with size- and geometry-dependent properties. For example, we fabricated an Fe3O4 magnetic nanoparticle coated with gold nanoshell to enable both optical and magnetic properties in the single nanostructure. Further manipulation of these nanomaterials for self assembly with a desired nanopattern onto solid substrates opens up a new paradigm for advanced 2D and 3D architecture at nanoscale. The specifically engineered nanostructures result in enhanced properties not available in individual nanomaterial. Compared to commonly used patterning techniques such as photolithography, E-beam lithography, the orderly assembly is cost-effective, highly controllable, and easy scale up. We are performing a systematic study and simulation modeling to precisely control the nanopattern to fashion a tunable plasmonic feature. Current efforts are focused on novel applications of the assembly pattern in biosensing, solar cell, and bioreactor.

2. High throughput, multiplexed nano-biochip

Gold nanorods (GNRs) are utilized as a label-free platform for protein and DNA detections. The optical transduction by GNR is based upon the phenomenon of localized surface plasmon resonance (LSPR), which arises from light induced collective oscillations of surface electrons in a conduction band. The extremely intense and highly localized electromagnetic fields caused by LSPR make it highly sensitive to changes in the local refractive index. These changes are exhibited in a shift of peak wavelength in extinction and scattering spectra in proportional to target binding on the nanorod surface. This unique optical property is the basis of their biosensing utility in a label free approach. Compared to conventional methods, LSPR assay eliminates detection tags such as fluorescent, enzymatic, and radioactive agents. Unlike fluorophore, plasmonic nanoparticles do not photobleach or blink. As such, gold nanorods have been widely used in immunoassays, cellular imaging, and surface-enhanced spectroscopies. Here, we aim to develop a high-throughput, multiplexed GNR biochip to deliver point-of-care testing of cardiac and tumor biomarkers in physiological samples. Surface modification of the GNRs for biofunctionalization is widely explored. Application of magnetic nanoparticles on the LSPR sensitivity enhancement is demonstrated. The nanosensor is then fully integrated with microfluidics, which can perform a complex series of biochemical manipulations – everything from filtration to amplification, purification, and separation – and then detect multiple target analytes with high sensitivity, specificity, and dynamic range.

3. Multifunctional nanoparticles as theranostic platform in drug/gene delivery

Nanoparticles can be used as effective carriers for DNA, RNA, or proteins, protecting these materials from degradation and transporting them across the cell-membrane barrier. ‘‘Safe’’ delivery of these biomolecules provides access to gene therapy as well as protein-based therapeutic approaches. We are taking multidisciplinary approach combining nanotechnology, biomolecular engineering, surface chemistry, and cellular engineering to investigate nanomaterial-tissue interaction. A key goal of delivery systems is to discharge their payloads specifically at the diseased tissue. Nanoparticle provides an attractive way for active targeting as it relies on specific recognition of the ligands that are over-expressed on tumor cells by the nanoparticle bound receptors. Additionally, magnetic nanoparticles provide an interesting route for targeted delivery. Insight into the new nanocomposites and nanopattern assembly will benefit designing multifunctional nanomaterial as a theranostic agent. We emphasize remote and active control of drug and siRNA co-delivery for effective cancer treatment. Further addition of magnetic core to the multifunctional nanoparticle allows a diagnostic capability to track the tumor size and assess the therapeutic efficacy in situ. The gold nanorod's excellent light absorption at tunable wavelength to generate localized heat can provide additional photothermal therapy if needed.

Director: Jing Yong Ye, Ph. D.

Group Members:

• Post Doctoral Fellow:
  • Bailin Zhang
• Post Doctoral Fellow:
  • He (River) Huang
• Ph.D. Students:
  • Ralph Peterson
  • Gilbert Bustamante
  • Steven Solis
  • Juan Manuel Tamez Vela
• M.S. Students:
  • Anthony Botting
  • Adnon Plumber
  • Jonathan Scudder
  • Denny Nguyen
  • Makawat Jangjai
  • I-Te Lee
• Undergrad Students:
  • Andy Morales
  • Casey Whitney

Research Projects:

Biophotonics has emerged in recent years as a key research field that leads to many revolutionary advances in biomedical science and clinical applications. It offers unique ways to image, analyze, and manipulate various biological systems (biomolecules, cells, and tissues) with great precision and accuracy. Especially, the possibilities of convergence with nanotechnology, allow biophotonics to address some of the most challenging problems. The primary focus of our research group is to develop cutting-edge ultrasensitive and ultrafast laser-based technologies and methodologies to address critical issues at the frontiers of biomedical science and technology. Our research activities embrace a wide range of areas in biomedical optics and nanobiotechnology, including photoacoustic imaging, label-free bioassays with photonic crystal structures, in vivo fiber-optic biosensing and imaging, multiphoton scanning microscopy, in vivo two-photon flow cytometry, femtosecond laser interactions with nanoparticle-targeted cells and tissues, adaptive optical aberration correction in confocal microscopy, and single-molecule fluorescence imaging and spectroscopy.

1. Photoacoustic imaging with a unique patented optoacoustic sensor

We have been working on the development of the next-generation functional photoacoustic imaging technology by taking advantage of our patented optoacoustic sensor. This new imaging technology may open up a wide range of applications in biomedical and life science research fields. One of the applications is to obtain in vivo images of 3D morphology of melanoma and its surrounding microvasculature with significantly improved sensitivity and resolution. It will provide rich information not only about the size and depth of melanoma but also on tumor growth and metastasis by noninvasive in vivo imaging of angiogenesis changes with time for a long period. If the advantages of the new imaging technology can be validated through this project, other applications such as for prostate or bladder cancer imaging may be explored in future by combining with endoscopy techniques.

2. Label-free bioassays with a patented photonic crystal biosensor

Specific interactions of biological molecules with various ligands, biopolymers, and membranes, such as protein:protein, protein:lipid, protein:DNA and protein:membrane binding, provide a chemical foundation for all cellular processes. The study of these biomolecular affinities and binding kinetics is of great importance for biomedical research and pharmaceutical applications. Although the surface plasmon resonance (SPR)-based analytical technique is currently being widely used, it has serious limitations to obtain accurate kinetic analysis due to mass-transport problems and to measure small analyte molecules. We are developing a new detection mechanism and constructing a photonic crystal-based analytical system to overcome these drawbacks. We hold a patent on this novel photonic crystal biosensor that allows label-free, real-time biomolecular binding assays and cell analysis for drug discovery and cancer research.

3. Real-time, in vivo optical biosensing of a multifunctional nano-device for drug delivery

Laser-induced fluorescence detection has gained wide application in the fields of biology and medicine. However, quantitative analysis of fluorescent markers in internal tumors is difficult due to strong tissue scattering and absorption. We have demonstrated for the first time a two-photon optical fiber fluorescence (TPOFF) probe, where femtosecond laser pulses were delivered through an optical fiber for nonlinear excitation and the emitted fluorescence was collected back through the same fiber. This new detection scheme enables in vivo fluorescence measurements on a localized region while bypassing the highly scattering surrounding tissue.

We observed a trade-off between the excitation and collection efficiencies for the TPOFF probe using conventional single-mode fibers (SMF) or multimode fibers (MMF). We have patented a technique, which utilizes a double-clad photonic crystal fiber (DCPCF) that ultimately solves this trade-off problem. In addition, we further demonstrate that fluorescence lifetime and fluorescence correlation spectroscopy can be obtained using this TPOFF probe. We have applied this novel technique for real-time quantification of a dendrimer-based multifunctional nano-device for targeted drug delivery in tumors of live mice.

4. Laser-induced optical breakdown in dendrimer nanoparticle targeted cancer cells

The primary goal of this project is to develop a general approach to molecular imaging and therapy in which a dendrimer nanoparticle composite (DNC) is transduced by a femtosecond laser into a microbubble easily detectable with high-frequency ultrasound. Nonlinear absorption of an ultrafast light pulse, with high peak intensity but negligible pulse energy, can disrupt the material via laser-induced optical breakdown (LIOB), simultaneously emitting an acoustic shock wave and generating a microbubble. We demonstrated that the size and lifetime of the LIOB-generated microbubbles in a tissue mimicking gelatin phantom can be controlled with different laser parameters. In addition, we performed LIOB in single cells and found that LIOB can be controlled to operate within two distinct regimes. In the nondestructive regime, a single, short-lived bubble can be generated within a cell, without affecting its viability. In the destructive regime, the induced photodisruption can kill a targeted cell. To generate and monitor this range of bioeffects in real time, we have developed a system integrating an ultrafast laser source with an acoustic microscope.

Dendrimer nanoparticle composites (DNCs) are nearly monodisperse, hybrid nanoparticles containing very small and uniformly dispersed inorganic domains topologically trapped in an organic matrix. They are stable, with precise size, variable inorganic content, and a well-defined, bio-friendly surface. In addition, various moieties can be attached covalently to target them to specific cell receptors of desired cell types. By trapping metallic domains, such as silver, we observed that the DNC can significantly reduce the LIOB threshold due to local field enhancement by the nano-domain of the silver content in the DNC. DNC-enhanced LIOB has been conducted in cancer cells on a single-cell basis. Localized cell killing has been confirmed.

5. Development of a compact dual-clad fiber scanning multiphoton microscope

Despite the fact that laser scanning confocal microscopy (LSCM) has been used as an important tool for high-resolution 3D imaging, its bulky configuration, high cost, and small field of view have limited its applications. To overcome these drawbacks, we have developed a compact double-clad fiber-scanning multiphoton microscope (DCF-SMM), which is based on a unique scanning mechanism fundamentally different from a conventional LSCM. In the DCF-SMM, beam-scanning is achieved by directly scanning an optical fiber probe, which uses a gradient-index (GRIN) lens to focus a femtosecond laser beam on a sample for two-photon excitation and to collect fluorescence back through the same fiber probe (Fig.3a). The fluorescence signal collected back through the GRIN lens forms a large spot at the fiber tip because of the chromatic aberrations of the GRIN lens (Fig.3b), which results in very inefficient fluorescence detection if a conventional fiber is used. However, this problem can be completely overcome by our double-clad photonic crystal fiber (DCPCF). We expect that successful development of the DCF-SMM will lead to the next-generation scanning multiphoton microscope that has an extremely simple structure and a number of unique features, such as high flexibility, arbitrarily large scan range, aberration-free imaging, and low cost. We have an issued patent resulted from this work and have been working with a a leading company in endomicroscopy to commercialize this technology.

6. In vivo two-photon flow cytometry

With a nearly 40-year track record of being the most accurate and well–defined technology for measuring properties of single cells, flow cytometry might appear to be commonplace and mature. However, one major limitation in conventional flow cytometry is that hydrodynamic forces are required to align single cells in a laminar flow, which prevents this technology from being used for in vivo detection. We recently demonstrated a novel flow cytometer, which realized single-cell detection with two-photon excitation using a femtosecond near-infrared laser, and relaxed the requirements on the fluid flow.

We used this system to non-invasively investigate the circulation dynamics in live animals of breast cancer cells with different metastatic potentials, showing for the first time that different populations of circulating cells can be quantified simultaneously in the vasculature of a single live mouse. We also monitored a population of labeled, circulating red blood cells for more than two weeks, demonstrating that this technique can also quantify the dynamics of abundant cells in the vascular system for prolonged periods of time. Our data represent the first in vivo applications of multichannel flow cytometry utilizing two-photon excitation, which will greatly enhance our capability to study circulating cells in cancer and other disease processes.

Publications:

86 Peer Reviewed Articles
2 Book chapters
12 Patents
150 Conference Presentations

To prospective students:

Highly motivated students are welcome to work on a wide range of exciting research projects in our lab. If interested, please contact Dr. Ye to inquire the possibilities.

Faculty specializing in Sustainable Energy and Petroleum Engineering include:

• Abelardo Ramirez-Hernandez, Ph.D.
• Esteban E. Ureña-Benavides, Ph.D.
• Gary Jacobs, Ph.D.
• Shrihari Sankarasubramanian, Ph.D.

Faculty specializing in Materials Engineering include:

• Gary Jacobs, Ph.D.
• Esteban E. Ureña-Benavides, Ph.D.
• Abelardo Ramirez-Hernandez, Ph.D.
• Nehal Abu-Lail, Ph.D.
• Gabriela Romero, Ph.D.
• Liang Tang, Ph.D.
• Shrihari Sankarasubramanian, Ph.D.

Faculty specializing in Environmental Engineering include:

• Nehal Abu-Lail, Ph.D.
• Esteban E. Ureña-Benavides, Ph.D.
• Gary Jacobs, Ph.D.
• Shrihari Sankarasubramanian, Ph.D.

Faculty specializing in Environmental Engineering include:

• Gabriela Romero, Ph.D.
• Nehal Abu-Lail, Ph.D.
• Amina Qutub, Ph.D.
• Liang Tang, Ph.D.
• Eric Brey, Ph.D.