Seeram Ramakrishna, Ph.D.
Director, Center for Nanofibers & Nanotechnology, National University of Singapore
Biomaterials: Future Perspectives
From the perspective of thousands of years of history, the role of biomaterials in healthcare and wellbeing of humans is at best accidental. However, since 1970s with the introduction of national regulatory frameworks for medical devices, the biomaterials field evolved and reinforced with strong science and engineering understandings. The biomaterials field also flourished on the backdrop of growing need for better medical devices and medical treatments, and sustained investments in research and development. It is estimated that the world market size for medical devices is ~300 billion dollars and for biomaterials it is ~30 billion dollars. Healthcare is now one of the fastest growing sectors worldwide. Legions of scientists, engineers, and clinicians worldwide are attempting to design and develop newer medical treatments involving tissue engineering, regenerative medicine, nanotech enabled drug delivery, and stem cells. They are also engineering ex-vivo tissues and disease models to evaluate therapeutic drugs, biomolecules, and medical treatments. Engineered nanoparticles and nanofiber scaffolds have emerged as important class of biomaterials as many see them as necessary in creating suitable biomimetic micro-environment for engineering and regeneration of various tissues, expansion & differentiation of stem cells, site specific controlled delivery of biomolecules & drugs, and faster & accurate diagnostics. This lecture will capture the progress made thus far in pre-clinical and clinical studies. Further this lecture will discuss the way forward for translation of bench side research into the bed side practice. This lecture also seeks to identify newer opportunities for biomaterials beyond the medical devices.
Lalitha Subramanian, Ph.D.
Chief Scientific Officer & VP, Services at Scienomics, USA
Nanoscale Simulations – Tackling Form and Formulation Challenges in Drug Development and Drug Delivery
Lalitha Subramanian, Dora Spyriouni, Andreas Bick, Sabine Schweizer, and Xenophon Krokidis Scienomics
The discovery of a compound which is potent in activity against a target is a major milestone in Pharmaceutical and Biotech industry. However, a potent compound is only effective as a therapeutic agent when it can be administered such that the optimal quantity is transported to the site of action at an optimal rate. The active pharmaceutical ingredient (API) has to be tested for its physicochemical properties before the appropriate dosage form and formulation can be designed. Some of the commonly evaluated parameters are crystal forms and polymorphs, solubility, dissolution behavior, stability, partition coefficient, water sorption behavior, surface properties, particle size and shape, etc. Pharmaceutical development teams face the challenge of quickly and efficiently determining a number of properties with small quantities of the expensive candidate compounds. Recently the trend has been to screen these properties as early as possible and often the candidate compounds are not available in sufficient quantities. Increasingly, these teams are leveraging nanoscale simulations similar to those employed by drug discovery teams for several decades. Nanoscale simulations are used to predict the behavior using very little experimental data and only if this is promising further experiments are done. Another aspect where nanoscale simulations are being used in drug development and drug delivery is to get insights into the behavior of the system so that process failures can be remediated and formulation performance can be improved. Thus, the predictive screening and the in-depth understanding leads to experimental efficiency resulting in far-reaching business impacts.
With specific examples, this talk will focus on the different types of nanoscale simulations used to predict properties of the API in excipients and also provide insight into system behavior as a function of shelf life, temperature, mechanical stress, etc.
Jeff Perry, Ph.D.
Assistant Professor, University of California, Riverside
Combined Crystallography and SAXS Methods for Studying Macromolecular Complexes
Recent developments in small angle X-ray scattering (SAXS) are rapidly providing new insights into protein interactions, complexes and conformational states in solution, allowing for detailed biophysical quantification of samples of interest1. Initial analyses provide a judgment of sample quality, revealing the potential presence of aggregation, the overall extent of folding or disorder, the radius of gyration, maximum particle dimensions and oligomerization state. Structural characterizations may include ab initio approaches from SAXS data alone, or enhance structural solutions when combined with previously determined crystal/NMR domains. This combination can provide definitions of architectures, spatial organizations of the protein domains within a complex, including those not yet determined by crystallography or NMR, as well as defining key conformational states. Advantageously, SAXS is not generally constrained by macromolecule size, and rapid collection of data in a 96-well plate format provides methods to screen sample conditions. Such screens include co-factors, substrates, differing protein or nucleotide partners or small molecule inhibitors, to more fully characterize the variations within assembly states and key conformational changes. These analyses are also useful for screening constructs and conditions that are most likely to promote crystal growth. Moreover, these high throughput structural determinations can be leveraged to define how polymorphisms affect assembly formations and activities. Also, SAXS-based technologies may be potentially used for novel structure-based screening, for compounds inducing shape changes or associations/diassociations. This is addition to defining architectural characterizations of complexes and interactions for systems biology-based research, and distinctions in assemblies and interactions in comparative genomics. Thus, SAXS combined with crystallography/NMR and computation provides a unique set of tools that should be considered as being part of one’s repertoire of biophysical analyses, when conducting characterizations of protein and other macromolecular interactions.
1 Perry JJ & Tainer JA. Developing advanced X-ray scattering methods combined with crystallography and computation. Methods. 2013 Mar;59(3):363-71.
