Biomaterials Day 2014 Agenda
Faculty Presentation Abstracts
Title: Accelerated Medical Innovation
Name: Jeffrey Karp
Abstract: This talk will explore state of the art technologies that are currently being developed in theKarpLab at the Brigham and Women’s Hospital, Harvard Medical School, to tackle some ofthe most challenging medical problems. Namely, minimally invasive sealing of tissues andwounds, achieving long term local drug delivery for treatment of diseases suchas rheumatoid arthritis and brain cancer, and engineered stem cell therapy for treatment ofdiseases such as multiple sclerosis and prostate cancer. Many of the technologies developedin the Karplab harness lessons from nature for inspiration, as evolution is truly the bestproblem solver (creatures used for inspiration include geckos, spider webs, jellyfish,porcupine quills, snails, and spiny headed worms). Some of the technologies that will bedescribed are rapidly advancing to the clinic (www.geckobiomedical.com) and some arealready on the market (www.skintifique.com).
Title: Biopolymer Conjugates For Production of Responsive Biomaterials
Name: Kristi L. Kiick
Abstract: Macromolecular structures that are capable of selectively and efficientlyengaging cellular targets offer important approaches for mediating biologicalevents and in the development of hybrid materials. We have employed acombination of biosynthetic tools, bioconjugation strategies, and biomimeticassembly in the design of multiple types of biopolymer-conjugate-basedmaterials. In one specific area, PEG-biopolymer conjugates have been used inthe formation of hydrogels by covalent click-based chemistries that are selectively degradable underpathological conditions. Interactions of various cells with these materials can be modulated on the basis ofmechanical and chemical cues. Most recently, we have developed resilin-based hydrogels with controlledproperties useful for cardiovascular and vocal fold therapies. These materials can be designed withmicrostructural heterogeneity as well as into nanoparticles that could be useful in a variety of drugdelivery approaches.
Title: Bioplastics vs. Traditional Packaging Plastics
Name: Stephen A. Miller
Abstract: Expanded worldwide efforts have identified plant-based buildingblocks for the synthesis of polymers that readily degrade in naturalenvironments. The Miller Research Group has developed novel methods forsynthesizing linear thermoplastic polymers from a variety of biogenicfeedstocks, including sugars, triglycerides, lignin, and C1 feedstocks obtainedfrom trees. First, this presentation will describe our efforts toward the directpolymerization of C1 feedstocks to polyglycolic acid (PGA) and relatedmaterials. Second, this presentation will show how vanillin, ferulic acid, andother bio-based aromatics can be used for the synthesis of thermally robustpolyesters. These novel thermoplastics will be discussed in the context ofreplacing traditional, fossil fuel-based plastics. Central to commercialization isthe symbiosis between academic innovation and a recent start-up company,U.S. Bioplastics (http://usbioplastics.com)
Title: Biomaterials and Type 1 Diabetes
Name: Clive Wasserfall
Abstract: Type 1 diabetes (T1D) is an autoimmune disease. This statement is based on decades of research in mouse and man that has revealed that the hallmark insulin deficiency in T1D is the result of an immune mediated destruction of the cells that produce insulin. Exogenous insulin replacement is the only current treatment for this disease and is critical for survival. While the introduction of insulin turned T1D from a fatal diagnosis into a chronic managed disorder, long term complications including kidney, heart and nervous system disorders remain.In terms of the natural history of T1D there is a long prodrome period during which the autoimmune attack begins and after some variable period of time a point is reached where blood glucose is no longer maintained and the diagnosis is made based on blood glucose levels. Insulin therapy is instituted and may be adjusted overmany years, with complications managed medically or surgically as necessary. So there is opportunity to intervene at any of these periods along the course of this disease, including from the biomaterials point of view. Our own experience with biomaterials is largely with the design of a vaccine to prevent T1D using PLGA microparticles and hydrogel matrices. To that end we used as adjuvants CpG and hemoglobin:haptoglobin (Hb:Hp) complexes delivered in a hydrogel along with microparticles (MP) containing denatured insulin (25.8mg insulin/mg MP, 5mg MP/injection). Five groups of NOD females (n=10 each starting at 8 weeks of age) were treated by subcutaneous injection of; 1) empty hydrogel/empty MP, 2) soluble CpG/Hb:Hp and insulin without matrix, 3) CpG/Hb:Hp in the hydrogel along with insulin MP (3 injections two weeks apart), 4)CpG/Hb:Hp with insulin MP with additional two injections 3 weeks apart and 5) a no treatment control. Blood glucose (BG) levels were monitored once per week from10 weeks of age until study endpoint at 28 weeks of age. Diabetes was defined as BG > 250mg/dL on two consecutive days. The no treatment, empty gel/ empty MP and soluble CpG/Hb:Hp/insulin groups all had 10-20% diabetes free survival at end point. While the 3 injection and 5 injection group with the full adjuvant and insulin matrix were at 50 and 80% diabetes free survival respectively. (p<0.0114, Kaplan Meier). In conclusion this is an example of a biomaterials approach to this disease. We deliberately designed this around material already approved for use in humans to get us closer to the clinic, but other materials are and will become available with additional research. We are actively pursuing interdiction of T1D using these approaches.
Title: Putting Nanomaterials to Work for Biomedical Research
Name: Younan Xia
Abstract: Nanomaterials are finding widespread use in the diagnosis and treatment of various diseases. Inthis talk, I will focus on gold nanocages, a novel class of nanomaterials with hollow interiors andporous walls that can be prepared in relatively large quantities using a remarkably simpleprocedure based on the galvanic replacement reaction between silver nanocubes and chloroauricacid in an aqueous solution. By controlling their size and/or wall thickness, the optical scatteringand absorption peaks of gold nanocages can be easily and precisely tuned to any wavelength inthe near-infrared region (for example, 700-900 nm, the transparent window of soft tissues)Additionally, their compact sizes, large absorption cross sections (almost five orders ofmagnitude greater than thhose of conventional organic dyes), and inertness in biological systemsall make them particularly intriguing for biomedical applications. I will present some of the mostrecent advances in the use of gold nanocages for a broad range of theranostic applications,including their use as tracers for tracking by multi-photon luminescence, as contrast agents forphotoacoustic and mutimodal imaging, and as radioactive probes for both imaging and therapy.In addition, gold nanocages can selectively target cancerous or diseased tissue followed byactivation as photothermal agents for the selective destruction of those targeted cells. Finally,gold nanocages can serve as drug delivery vehicles for controlled and localized release inresponse to external stimuli such as NIR radiation or high-intensity focused ultrasound.