Learn About the Santerre Biomedical Polymer Lab for Tissue Engineering and Drug Delivery

Institute of Biomaterials and Biomedical Engineering

University of Toronto

 

Cardiovascular Disease & Regenerative Medicine

The Santerre group in collaboration with fellow biomaterials, biomechanics and engineering scientists are exploring the application of tissue engineering principles for the development of cardiovascular tissue that has mechanical, cellular and physiological properties comparable to that of native healthy tissue.

New Biomaterials for Tissue Engineering

Design of new polyurethane biomaterials for tissue engineering applications.

Polymeric Drug Delivery Strategies

Use of polymer-based delivery platforms for controlled release of drug.

Biomaterial/Blood/Protein Interactions

Understanding protein interactions with surfaces to guide new biomaterial design.

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Dental Materials with Enhanced Stability

Synthesizing new dental resin polymers to minimize degradation at the filling site and reduce the risk of secondary caries.

Orthopaedic Regeneration and Repair

Collaborative work in the Santerre Lab focuses on regeneration of the annulus fibrosis using electrospun scaffolds and dynamic culture techniques.

Drive to Commercialization

At the Santerre Lab, focus is placed on innovation with a drive to commercialize. A spin-off biomedical polymer company, Interface Biologics Inc., started in the lab over a decade ago.

Cardiovascular Disease & Regenerative Medicine

Cardiovascular disease (CVD) accounts for 32% of deaths in Canada, costing the economy ~$18 billion/year. While new drugs and innovative biomedical devices have played a significant role in improving the quality of life for patients suffering from CVD, they have not been successful in improving the morbidity or mortality rates. Tissue engineering has emerged as a promising solution to replace the various components of the cardiovascular system (blood vessels, heart valves and cardiac muscle). The Santerre group in collaboration with fellow biomaterials, biomechanics and engineering scientists are exploring the application of tissue engineering principles for the development of cardiovascular tissue that has mechanical, cellular and physiological properties comparable to that of native healthy tissue. To achieve the latter objective, extensive research has been dedicated to exploring and manipulating the scaffold chemistries, cell sources and culture environments (biochemical, mechanical and electrical cues).

Vascular Tissue Engineering

The Santerre laboratory has extensively investigated vascular tissue engineering and the use of polyurethane (PU)-based polymeric scaffolds for the replacement of diseased small-diameter blood vessels. Using stem/progenitor cells and three-dimensional PU scaffolds, the lab focuses on studying the role of physiologically-relevant mechanical and biomechanical (white blood cells) stimuli in modulating cell function and vascular tissue regeneration with the ultimate goal of generating a functional small-diameter blood vessel.

Cardiac Tissue Engineering

We are also extending our research and tissue engineering knowledge to develop functional cardiac tissue. The lack of oxygen and nutrient supply to the cardiomyocytes following a myocardial infarction results in extensive cell death and myocardium damage. The Santerre group aims to use stem/progenitor cells with PU-based scaffolds (electrospun, porogen-leached) in combination with biochemical, mechanical and electrical stimuli to generate a vascularized myocardium with appropriate contractile functionality. Our interests also lies in the use of PU-based nanoparticles in combination with the engineered patches, as a vehicle for the delivery of drugs/bioactive agents (e.g. growth factors) to the cardiac tissue.

Valve Tissue Engineering

The generation of viable heart valve tissue using tissue engineering represents a novel strategy to overcome the limitations of traditional valve replacements. The Santerre group is specifically focused on the development of PU-based polymeric scaffolds that support the synthesis and organization of cell and extracellular matrix with target compositional, organizational, and mechanical properties. Our interests also involve the study of biochemical and biomechanical conditions that promote valvular tissue generation.

 

New Biomaterials for Tissue Engineering

Polyurethanes have become a popular material in biomedical engineering due to their versatile segmented block co-polymeric structure and associated flexible biocompatibility and biodegradation characteristics. The Santerre laboratory has thoroughly investigated biodegradation mechanisms of synthetic polyurethanes and focused on developing new polyurethane biomaterials that modulate immune cell (e.g. monocyte/macrophage) activation to support favourable cell-material/cell-cell interactions for new tissue regeneration. One example of the novel polyurethanes developed by the Santerre laboratory is a degradable polar hydrophobic ionic (D-PHI) polyurethane. D-PHI has been shown to have good biocompatibility, controlled biodegradation rate and tunable mechanical properties. Furthermore, D-PHI has been demonstrated to stimulate low-inflammatory phenotype of immune cells and promote functional marker expression of both vascular smooth muscle cells and endothelial cells, suggesting its great potential in engineering mature vascular tissues as well as other soft tissue engineering applications.

Relevant Publications:

Battiston, Kyle G., Rosalind S. Labow, and J. Paul Santerre. 2012. “Protein Binding Mediation of Biomaterial-Dependent Monocyte Activation on a Degradable Polar Hydrophobic Ionic Polyurethane.” Biomaterials 33(33):8316–28.

Cheung, Jane W. C., Devika Jain, Christopher a G. McCulloch, and J. Paul Santerre. 2015. “Pro-Angiogenic Character of Endothelial Cells and Gingival Fibroblasts Cocultures in Perfused Degradable Polyurethane Scaffolds.” Tissue engineering. Part A 21:1–13.

McBane, Joanne E., Loren a Matheson, Soroor Sharifpoor, J. Paul Santerre, and Rosalind S. Labow. 2009. “Effect of Polyurethane Chemistry and Protein Coating on Monocyte Differentiation towards a Wound Healing Phenotype Macrophage.” Biomaterials 30(29):5497–5504.

McBane, Joanne E., Soroor Sharifpoor, Kuihua Cai, Rosalind S. Labow, and J. Paul Santerre. 2011. “Biodegradation and in Vivo Biocompatibility of a Degradable, Polar/hydrophobic/ionic Polyurethane for Tissue Engineering Applications.” Biomaterials 32(26):6034–44.

Drug Delivery

For many years, research in the Santerre Lab has investigated the use of polymers for drug delivery strategies. The antibiotic ciprofloxacin has been  incorporated into polyurethane polymer chains for use as an implant material with a release of antibiotic proportional to the extent of infection at the implant site.  This latter work contributed to the formation of a start up company, Interface Biologics Inc.  and conception of new antimicrobial resin monomers for dental composites. More recent work involves blending a ciprofloxacin-based polymer with polyurethane to form electrospun anti-infective gingival tissue engineering scaffolds.

Another line of research in the Santerre group is focused in the development of different drug delivery system (DDS) for their application as non-stent-based local drug delivery with the use of drug-coated balloons (DCBs) in the treatment of restenosis. DCB consists of a standard balloon catheter coated with antiproliferative drug and a nanocarrier which should be delivered during the period of balloon inflation. The current commercial nanocarriers generated by the field present some limitations (including poor vascular wall tissue penetration of drugs during balloon inflation and diffusivity).The Santerre Lab in collaboration with the Interface Biological Inc. are trying to overcome the limitations of the current carriers  by the development of new biodegradable self-assembled nanocarries based on the versatility of the polyurethane chemistry. The variety of hard and soft segments could allow one to obtain a variety of colloidal systems that match the requirements for their blood contacting  applications.

Relevant Publications:

Woo, G. L., M. W. Mittelman, and J. P. Santerre. 2000. “Synthesis and Characterization of a Novel Biodegradable Antimicrobial Polymer.” Biomaterials 21(12):1235–46.

Woo, G. L. Y. et al. 2002. “Biological Characterization of a Novel Biodegradable Antimicrobial Polymer Synthesized with Fluoroquinolones.” Journal of biomedical materials research 59(1):35–45.

Luisa Lopez-Donaire, M. and J. Paul Santerre. 2014. “Surface Modifying Oligomers Used to Functionalize Polymeric Surfaces: Consideration of Blood Contact Applications.” Journal of Applied Polymer Science.

Protein and Blood Interactions

One of the first events that occurs following the implantation of biomaterials is adsorption of proteins from protein-rich bodily fluids (e.g. blood, interstitial fluid) that translates the biomaterial surface into a new biological substrate that will guide subsequent cellular and tissue interactions. Protein adsorption plays an important role in regulating blood biocompatibility, immune cell activation, stem cell differentiation, and other cellular activities. The Santerre laboratory is interested in the study of protein-biomaterial interactions, particularly in the context of blood biocompatibility and immune cell activation. Understanding how biomaterial properties (e.g. surface chemistry, roughness, surface energy) regulate protein interactions in a manner that can reduce pro-inflammatory immune cell activation or minimize platelet adhesion allows for intelligent design of new biomaterials with properties desirable for different applications.

Relevant Publications:

Battiston KG, Labow RS, Santerre JP. Protein binding mediation of biomaterial-dependent monocyte activation on a degradable polar hydrophobic ionic polyurethane. Biomaterias 2012;33(33):8316-28.

Blit PH, McClung WG, Brash JL, Woodhouse KA, Santerre JP. Platelet inhibition and endothelial cell adhesion on elastin-like polypeptide surface modified materials. Biomaterials 2011;32(25):5790-800.

Massa TM, Yang ML, Ho JY, Brash JL, Santerre JP. Fibrinogen surface distribution correlates to platelet adhesion pattern on fluorinated surface-modified polyetherurethane. Biomaterials 2005;26(35):7367-76.

Jahangir R, McCloskey C, McClung WG, Labow RS, Santerre JP. The influence of protein adsorption and surface modifying macromolecules on the hydrolytic degradation of a poly(ether-urethane) by cholesterol esterase. Biomaterials 2003;24(1):121-30.

Dental Materials

Resin composite is the most widely used dental restorative material due to its superior esthetics and ease of handling. However, despite the extensive use resin composites have a limited longevity in the oral cavity, which has been attributed in-part to material degradation by salivary enzymes and bacteria, compromised adhesion by clinical factors, fracture, polymerization shrinkage, and secondary caries.

The modern day restorative resin chemistries have an inherent vulnerability with respect to degradation in the oral cavity. The Santerre laboratory is interested in developing new monomers for dental restorative applications with chemistries that will improve longevity of resin composites. Two approaches are currently being investigated: biostable monomers that could resist degradation by human derived esterases and probiotic monomers that will provide antimicrobial function upon degradation in order to resist bacterial biofilm formation on the restorative material. In addition to new chemistry synthesis, the Santerre laboratory is also interested in understanding the biological factors (such as potent enzyme complexes) that are involved in the biochemical breakdown of traditional polymeric material in the oral cavity and lastly understanding the interaction of bacteria with the biodegradation products released from resin composites.

Relevant Publications:

Cai K, Delaviz Y, Banh M, Guo Y, Santerre JP. Biodegradation of composite resin with ester linkages: identifying human salivary enzyme activity with a potential role in the esterolytic process. Dent Mater 2014; 30(8): 848-860.

Khalichi P, Singh J, Cvitkovitch DG, Santerre JP. The influence of triethylene glycol derived from dental composite resins on the regulation of Streptococcus mutans gene expression. Biomaterials 2009;30(4):452–9.

Finer Y, Jaffer F, Santerre JP. Mutual influence of cholesterol esterase and pseudocholinesterase on the biodegradation of dental composites. Biomaterials 2004;25(10):1787–93.

Lin BA, Jaffer F, Duff MD, Tang Y, Santerre JP. Identifying enzyme activities within human saliva which are relevant to dental resin composite biodegradation. Biomaterials 2005;26(20):4259–64.

 

Orthopaedic Repair and Regeneration

The Santerre lab has established a program in the area of musculoskeletal research collaboration with Professor Robert Pilliar in Dentistry and IBBME, clinical teams at Mount Sinai Hospital (Drs. Rita Kandel and Marc Grynpas) and Sunnybrook (Drs. Cari Whyne and Jeff Fiakov).  Projects include a substitute tissue engineered spinal disc, where our group has contributed to the development the annulus fibrosus scaffold with a patented degradable electrospun polyurethane fibre with a unique fibronectin adhesive surface modifying additive.

Working with Robert Pilliar and Marc Grynpas we have developed a novel bone composite made up of degradable calcium polyphosphate (CPP) and an in-situ curing degradable polymer carbonate resin interfacing with a natural bio-adhesive molecule.  This technology is currently in the process of being patented and preliminary in vivo studies undertaken.

Research with Cari Whyne and JeffFiakov at Sunnybrook hospital has resulted in the development of a novel degradable composite called Bone Tape.  Using Robert Pilliar’s porous CPP and a degradable vinyl resin formulation we have conceived a material that could provide bonding of cranio-facial defects by applying the tape rather than traditional metal plates and screws.  Deformities of the face and skull (craniomaxillofacial, CMF) can result from high impact trauma, congenital malformations or tumours, leading to functional disabilities and physical disfigurement. Like a shattered vase, the fractured CMF skeleton requires alignment and stabilization of multiple pieces for successful reconstruction.  Bone tape has been conceived to address these changes and IP has been filed and the material evaluated in vivo and is currently being developed for commercial translation.

Relevant Publications:

Iu J., Santerre JP, Kandel RA, Inner and outer annulus fribosus cells exhibit differentiated phenotypes and yield changes in extracellular matrix composition in vitro on a polycarbonate urethane scaffold, Tissue Engineering Part A20(23-24):3176-88, (2014).

Nosikova YS, Santerre JP, Grynpas M, Gibson G, Kandel RA, Characterization of the annulus fibrosus-vertebral bone interface: identification of new structural features, Journal of Anatomy, 221(6) 577-589 (2012).

The Drive to Commercialization

The deliberate linking of science for the benefit of everyday life and the realization that industry and the creation of industry is part of the equation must be a fundamental and integrated strategy of any thriving research program today. The Santerre lab believes that conducting fundamental research can lead to a commercializable idea, and that students have the ability to take these ideas and turn them into products that can improve healthcare in Canada and worldwide, either by working with industry partners or through entrepreneurship, where students can lead new start-ups that not only generate valuable healthcare products, but also produce job opportunities for new graduates.

The Santerre lab is ideally positioned to achieve these goals within Toronto’s Discovery District (www.torontodiscoverydistrict.ca), featuring world-class research facilities, hospitals, and MaRS, which aims to commercialize publicly funded medical research, creating successful businesses from Canada’s scientific discoveries and innovations. Dr. Santerre is the author on >60 patents (38 awarded). More importantly, these patentable ideas have been used to generate new start-ups, such as Interface Biologics Inc., a new company that emerged from research conducted in Paul Santerre’s lab, which developed within the ecosystem provided by MaRS and the University of Toronto, and currently employs 20 people.

For students or post-docs interested in a career in entrepreneurship, numerous resources are provided by MaRS, the University of Toronto, and other facilities, including MaRS Entrepreneurship 101 (www.marsdd.com/entrepreneurship-101/) and the numerous campus-linked accelerators (CLAs) whose goal is to help students realize the commercial potential of their ideas (www.entrepreneurs.utoronto.ca).