Cellular and Tissue Engineering

Cellular and tissue engineering applies the principles and methods of life sciences, physical sciences and engineering principles to understand physiological and pathological systems and to restore, maintain, improve or create cells and tissues for therapeutic applications. This area of study has been used as a tool to study virtually all of the physiological systems of the body as well as pathologies and has resulted in both clinically used and experimental therapies. True biological tissue substitutes would be ideal for any patient who has lost tissue or tissue function, including cancer patients.

For example, Jaw bone repair for oral cancer patients following intense treatments has always presented a challenge. Professor Mikos, however, is developing new bioengineering techniques to create artificial bone, to stimulate bone regeneration and use for bone repair. In this approach, synthetic biodegradable polymers are used as supportive scaffolds for cells, as conduits for guided tissue growth, as specific substrates for targeted cell adhesion, or as stimulants for a desired cellular response. 

This group has pioneered the use of CAD/CAM and polymer chemistry fabrication technologies for the production of synthetic biomimetic materials that exhibit the mechanical responsiveness and biochemical processing capabilities of living cells and tissues. In this work, Dr. Mikos collaborates with Drs. Michael Miller and Alan Yasko at the MD Anderson Cancer Center.

In other labs, such as the Athanasiou lab, tissue engineering based solutions to musculoskeletal disorders are being developed. Following trauma or pathologic affliction cartilage is unable to heal itself in a way that would allow it to function properly under its strenuous and biomechanically difficult environment. Their approach entails the use of biodegradable scaffolds designed to incorporate suitable bioactive agents and signals to regenerate cartilage.

Bioengineering at Rice University, in close partnership with the oral and maxillofacial departments of the Texas Medical Center, is poised to address effectively the debilitating problems related to cartilage damage in joints. On cardiac fronts, the West and Mikos laboratories have developed biodegradable hydrogels that can be injected after interventional cardiovascular procedures to repave and heal injured arteries and prevent arterial restenosis. Several other tissue engineering challenges continue to be addressed by collaborations between Rice researchers and faculty in the Texas Medical Center.

Computational Bioengineering

Computational Bioengineering takes a mathematical approach to understanding biological and biomedical problems. The objectives are to develop accurate quantitative models and to formulate new scientific paradigms to view and understand complex systems in biology. The precise three-dimensional structure of large biological molecules, including dynamic changes in structure, provides the foundation for understanding molecular mechanisms of many fatal diseases.

Computational bioengineering efforts at Rice are at the forefront of novel biological discoveries in the areas of cancer, influenza and drug side effects, among others. Researchers at Rice and M.D. Anderson are developing computational models to predict protein structures and protein interactions and are using this knowledge to guide the rational design of cancer inhibiting drugs. The lab of Rice Professor Jianpeng Ma is employing a novel combined computational and experimental approach to develop new agents for fighting a number of fatal diseases. A major target is human fatty acid synthase (FAS), which has recently ascended to the forefront as one of the most promising diagnostic and therapeutic targets for both prostate and breast cancer.

In collaboration with Dr. Florante A. Quiochio at Baylor and Dr. William Bornmann at UT MD Anderson, active chemical compounds have been identified and organically synthesized that displayed pharmacological activities in cell-based assays. Another major target is the influenza virus. Through the study of X-ray structures of influenza hemagglutinin, the Ma's lab has identified agents that can efficiently block the challenges of several influenza strains.  A similar approach is also being applied to developing inhibitors against Ebola viruses.

On a different front, a recent discovery in the lab of Professor Ariel Fernandez may drastically change the outlook of new drugs by alleviating the problem of side effects.  The lab has discovered a wrapping technology among proteins that may lead to the design of inhibitors that wrap packing effects as a means of achieving high selectivity and avoiding off-target associations that cause undesirable side effects. 

The wrapping technology at work
Left: Lead compound to be modified in order to achieve highly selective inhibition of ABL, a target in leukemia therapy. The arrow represents the wrapping effect induced by modifying the lead compound. The packing defect in green) is a vulnerable sticky bond.	Right: Aligned structures of alternative targets revealing the uniqueness of the packing defect (the crankshaft region is only present in ABL). Thus, targeting this defect ensures high selectivity.

Molecular Imaging

The aims of Molecular Imaging research focus on the development of new methodology for clinical image acquisition and processing, with the goal of establishing new procedures for diagnosis of disease and therapeutic monitoring.  In the last decade, enormous progress has been made to understand the molecular events that accompany carcinogenesis.  The identification of unique molecular markers of cancer has led to the development of new molecular cancer therapies, such as chemoprevention, chemo-radiation, gene therapy, and immunotherapeutics. 

Moving toward a molecular characterization of cancer has important clinical benefits, including (1) earlier cancer detection, (2) the ability to predict the risk of precancerous lesion progression, (3) real time margin detection in the operating room, (4) the ability to rationally select molecular therapy and (5) the capacity to monitor response to a therapy in real time at a molecular level.  Bioengineers at Rice are working to integrate advances in functional genomics of cancer, advances in nanobiotechnology and advances in computing, fiber optics and semiconductor technology to develop low-cost, portable, real-time imaging systems to image the molecular profile of cancers and their precursors.

Research in the labs of Drs. Richards-Kortum and Drezek has resulted in novel and portable fiber optic systems to measure tissue reflectance and fluorescence spectra over the UV-Vis-NIR spectral regions in near real time.  In collaboration with the UT MD Anderson Cancer Center, Rice faculty are carrying out clinical trials to test the ability of fluorescence and reflectance spectroscopy to detect cervical pre-cancer and early ovarian cancer.  Trials of more than 2,000 women have been carried out and have shown that fluorescence spectroscopy measures the increase in metabolic activity of precancerous epithelial cells, as well as the potential of these cells to invade the supporting stroma.

Nanobiotechnology

Nanobiotechnology is a highly interdisciplinary and rapidly advancing area of scientific and technological research that aims at understanding the basic principles of biological functional units. Researchers apply the tools and processes of nano/microfabrication in a biological context to build extremely small elements at nano-scale for studying biosystems. Nanobiotechnology research at Rice is making significant strides in areas of cancer detection and imaging as well as in other fronts. Research in the labs of Professors West, Drezek and Richards-Kortum is leading to the development of molecular-specific, optically interrogatable contrast agents that will dramatically expand the range of molecular changes which can be profiled using optical imaging. For example, Professors Drezek and West have developed unique emissive nanoparticles consisting of a gold nanoparticle tethered to a quantum dot via a peptide linker. 

QD-peptide-AuNPs complex	Peptide Cleavage	Photoluminescence

The peptide sequence measuring only a few nanometers holds the gold close enough to quench the quantum dot luminescence. Promising results have been obtained using a peptide tether that is cleaved by the enzyme collagenase. Luminescence of the quantum dots is reduced by more than 70 percent when attached to the gold particles, and they remained dark until the nanostructures are exposed to collagenase; after which luminescence steadily returns. These experiments lay the groundwork for developing a series of quantum dots contrast agents, each with a unique NIR optical signature, to an index of linker peptides.  In the area of imaging, novel microfabrication techniques are being employed in Dr. Richards-Kortum lab to create miniature, battery powered confocal microscopes.  Low cost CMOS image sensors and powerful DSP algorithms can be used to create handheld microscopes for inexpensive screening for early cancers and to guide tumor resection in the operating room.