THE WALDMAN LAB
Institute for Biomedical Engineering, Science and Technology (Ryerson University and St. Michael's Hospital)
Department of Chemical Engineering (Ryerson University)
Cartilage Tissue Engineering
Cartilage is a dense, load-bearing connective tissue found in many parts of the body. In joints, articular cartilage serves to not only to transmit the compressive joint loads to the underlying subchondral bone but, also to provide a low-friction interface between the contacting cartilage surfaces of the joint. Alternatively, the elastic cartilage of the outer ear is a flexible tissue that amplifies and directs sound to the auditory canal. A major clinical problem is that once cartilage is damaged, either by trauma or disease, tissue function can be permanently affected as cartilage generally has a limited capacity for repair in adults. As the few surgical techniques available to repair or reconstruct cartilage have not proven to be entirely successful, efforts have focused on tissue engineering methods to create suitable tissue for implantation.
Our research group focuses on the engineering of functional cartilage constructs suitable for joint resurfacing, spine repair, ear and tracheal reconstruction through the use of bioreactors and mechanical stimuli to guide tissue growth as well as the development of patient-specific constructs that can be tailored to anatomy of the implantation site.
Dr. Waldman named Lady David Fellow at the Technion (Israel)
Dr. Waldman is the Lady Davis Visiting Professor at the Technion (Israel) during his sabbatical leave (2019-2020).
The NSERC has approved the program "CREATE: Industry-ready talent for Canadian MedTech" for 6 years; a joint initiative between Ryerson University and McGill University.
Awarded CIHR Grant: "Controlling glucose metabolism to develop superior tissue engineered cartilage"
The CIHR has approved the project "Controlling glucose metabolism to develop superior tissue engineered cartilage" for 5 years. Applicants: Drs. Waldman (Ryerson-SMH), Bardana (KGH), Kandel (MSH), and Pang (Queens).
Stefan Balko successfully defends MASc
Congratulations to Stefan who successfully defended his MASc.
Omar Sudebar successfully defends MASc
Congratulations to Omar who successfully defended his MASc.
Olena Bojchuk successfully defends MASc
Congratulations to Olena who successfully defended her MASc.
Imran Sheik successfully defends MASc
Congratulations to Imran who successfully defended his MASc.
Dr. Waldman nominated Fellow of International Orthopaedic Research (FIOR)
Dr. Waldman nominated Fellow of International Orthopaedic Research (FIOR) by the International Combined Orthopaedic Research Socieities (iCORS) at their first meeting held in Xian, China. Furhter details of iCORS and their College of Fellows can be found at: http://i-cors.org/
Awarded PSI Grant: "Development of human engineered cartilage suitable for joint resurfacing"
The PSI Foundation has approved the project "Development of human engineered cartilage suitable for joint resurfacing" for 2 years. Applicants: Drs. Bardana (KGH), Waldman (Ryerson-SMH), and Pang (Queens).
Loraine Chiu receives CIHR PDF Award
Congratulations to Loariane who was just awarded a CIHR PDF Award for 2 years.
Joanna Weber successfully defends PhD
Congratulations to Joanna who successfully defended her PhD.
Awarded NSERC Discovery Grant: "Cartilage Mechanobiology"
NSERC has approved the Discovery Grant project "Cartilage Mechanobiology" for the next five (5) years.
Bethany Hughes successfully defends MASc
Congratulations to Bethany who successfully defended her MASc.
Kristina Collavino successfully defends MASc
Congratulations to Kristina who successfully defended her MASc.
Simona Perrotti (MASc Candidate: 2021-present)
Lea Zila (MASc Candidate: 2021-present)
Loriane Chiu (Research Associate: 2018-present)
Roberto Tarantino (PhD Candidate: 2018-present)
Aisha Momin (MASc Candidate: 2019-2021)
Arianna Soave (MASc Candidate: 2017-2020)
Andjela Bajic (MASc Candidate: 2018-2019)
Julia Sofia Kolacz (Visiting Student, Charité University: 2018)
Stefan Balko (MASc Candidate: 2016-2018)
Omar Sudebar (MASc Candidate: 2015-2018)
Olena Bojchuk (MASc Candidate: 2015-2018)
Michael Mercer (Undergraduate Researcher: 2018)
Joanna Weber (Post Doctoral Fellow: 2016-2017)
Loriane Chiu (Post Doctoral Fellow: 2014-2017)
Imran Sheikh (MASc Candidate: 2014-2017)
Warren Tang (Research Technician: 2012-2017)
Manuela Boos (Visiting Student, ETH: 2017)
Kayla Soon (Undergraduate Researcher: 2017)
Hannah Le (High School Student, ROPE Program: 2017)
Roberto Tarantino (Undergraduate Researcher: 2015-2016)
Kristina Collavino (MASc Candidate: 2014-2016)
Bethany Hughes (MASc Candidate: 2014-2016)
Kimia Raahemifar (High School Student, ROPE Program: 2016)
Joanna Weber (PhD Candidate: 2011-2015)
Nabila Abraham (Undergraduate Researcher: 2015)
Omar Sudebar (Undergraduate Researcher: 2015)
Olena Bojchuk (Undergraduate Researcher: 2015)
Roman Perez (Post Doctoral Fellow: 2013-2014)
James Hayami (PhD Candidate: 2009-2014)
Ainhoa Ugarteche (High School Student, ROPE Program: 2014)
Anand Lakhani (Undergraduate Researcher: 2013)
Juares Bianco (Post Doctoral Fellow: 2012-2013)
Kristina Collavino (Undergraduate Researcher: 2012-2013)
Renata Rosa (Post Doctoral Fellow: 2011-2013)
Justin Morton (MASc Candidate: 2011-2013)
Julie Leising (Undergraduate Researcher: 2012)
Kathryn Thomas (Undergraduate Researcher: 2011-2012)
Elizabeth Delve (Undergraduate Researcher: 2011-2012)
Jillian Brenner (MASc Candidate: 2009-2012)
Steve Devlin (MASc Candidate: 2007-2012)
Jake Kaupp (PhD Candidate: 2007-2012)
Kathleen Matrin (Undergraduate Researcher: 2010-2011)
Jackie Fan (Lab Technician: 2009-2011)
Jennifer Bow (MASc Candidate: 2008-2011)
Yimu Zhao (MASc Candidate: 2008-2011)
Denver Surrao (PhD Candidate: 2007-2011)
Nabeil Alazzam (Undergraduate Researcher: 2009-2010)
Gavin Chu (Undergraduate Researcher: 2009-2010)
Jenna Usprech (MASc Candidate: 2008-2010)
Emily Brander (Undergraduate Researcher: 2009)
Jon Brunneti (Undergraduate Researcher: 2009)
Stephanie Fisher (Undergraduate Researcher: 2008-2009)
Kelsea Fitzpatrick (Undergraduate Researcher: 2008-2009)
Aaron McGregor (MASc Candidate: 2007-2009)
James Hayami (Lab Technician: 2007-2009)
Jackie Fan (MASc Candidate: 2006-2009)
Brent Lievers (PhD Candidate: 2004-2009)
Kate Colizza (Undergraduate Researcher: 2008)
Caleb Werner (Undergraduate Researcher: 2007-2008)
Gavin LeNobel (Undergraduate Researcher: 2007-2008)
Stephen Faust (Undergraduate Researcher: 2007-2008)
Nikki Apostolakis (Undergraduate Researcher: 2007-2008)
Stephen Gauthier (Undergraduate Researcher: 2007-2008)
Alexis Pietak (Post Doctoral Fellow: 2006-2007)
Andrew Engbretson (Undergraduate Researcher: 2006-2007)
Aaron McGregor (Undergraduate Researcher: 2006-2007)
Fiona Rask (Undergraduate Researcher: 2006-2007)
Shael Martin (Undergraduate Researcher: 2006)
Patrick MacGillivray (Undergraduate Researcher: 2005-2006)
Venhiah Tjong (Undergraduate Researcher: 2005-2006)
Matt Rossiter (Undergraduate Researcher: 2005-2006)
Megan MacCloud (Undergraduate Researcher: 2005-2006)
Ben Thorek (Undergraduate Researcher: 2005-2006)
James Hayami (MASc Candidate: 2004-2006)
Felix Yuen (MASc Candidate: 2004-2006)
Jake Kaupp (MASc Candidate: 2004-2006)
Jocelyn Suits (MASc Candidate: 2004-2006)
Laura Williams (Undergraduate Researcher: 2004-2005)
David Walmsley (Undergraduate Researcher: 2004-2005)
Yasmine Usmani (Undergraduate Researcher: 2004-2005)
Jackie Lian (Undergraduate Researcher: 2004-2005)
Julia O'Keefe (Undergraduate Researcher: 2004)
Through a combination of non-invasive imaging, 3D modelling, and rapid prototyping we are developing patient-specific tissue engineered cartilage grafts which match the anatomy of the defect site for joint resurfacing.
External Ear Reconstruction
Anatomically shaped cartilaginous ear constructs developed for patients suffering from microtia or cancer.
We use mechanical stimulation as a method to enhance the growth and properties of our engineered tissues. In addition, we investigate specific pathways in which cells sense and respond to mechanical stimuli.
Cartilaginous tubes lined with a respiratory epithelium for trachea repair and/or reconstruction.
Anatomically shaped cartilage grafts for nasal-septal repair and/or reconstruction.
Intervertebral Disc Repair
Injectable biological scaffolds for disc repair and regeneration.
Wrinkling non-spherical particles and its application in cell attachment promotion.
Li M, Joung D, Hughes B, Waldman SD, Kozinski JA, Hwang DK (2016)
Scientific Reports 6:30463.
Surface wrinkled particles are ubiquitous in nature and present in different sizes and shapes, such as plant pollens and peppercorn seeds. These natural wrinkles provide the particles with advanced functions to survive and thrive in nature. In this work, by combining flow lithography and plasma treatment, we have developed a simple method that can rapidly create wrinkled non-spherical particles, mimicking the surface textures in nature. Due to the oxygen inhibition in flow lithography, the non-spherical particles synthesized in a microfluidic channel are covered by a partially cured polymer (PCP) layer. When exposed to plasma treatment, this PCP layer rapidly buckles, forming surface-wrinkled particles. We designed and fabricated various particles with desired shapes and sizes. The surfaces of these shapes were tuned to created wrinkle morphologies by controlling UV exposure time and the washing process. We further demonstrated that wrinkles on the particles significantly promoted cell attachment without any chemical modification, potentially providing a new route for cell attachment for various biomedical applications.
Chondrocyte generation of cartilage-like tissue following photoencapsulation in methacrylated polysaccharide solution blends.
Hayami JWS, Waldman SD, Amsden BG (2016)
Macromolecular Bioscience 16(7):1083-1095.
Chondrocyte-seeded, photo-cross-linked hydrogels prepared from solutions containing 50% mass fractions of methacrylated glycol chitosan or methacrylated hyaluronic acid (MHA) with methacrylated chondroitin sulfate (MCS) are cultured in vitro under static conditions over 35 d to assess their suitability for load-bearing soft tissue repair. The photo-cross-linked hydrogels have initial equilibrium moduli between 100 and 300 kPa, but only the MHAMCS hydrogels retain an approximately constant modulus (264 ± 5 kPa) throughout the culture period. Visually, the seeded chondrocytes in the MHAMCS hydrogels are well distributed with an apparent constant viability in culture. Multicellular aggregates are surrounded by cartilaginous matrix, which contain aggrecan and collagen II. Thus, co-cross-linked MCS and MHA hydrogels may be suited for use in an articular cartilage or nucleus pulposus repair applications.
Stochastic resonance is a method to improve the biosynthetic response of chondrocytes to mechanical stimulation.
Weber JF, Waldman SD (2016)
Journal of Orthopaedic Research 34(2):231-239.
Cellular mechanosensitivity is an important factor during the mechanical stimulation of tissue engineered cartilage. While the application of mechanical stimuli improves tissue growth and properties, chondrocytes also rapidly desensitize under prolonged loading thereby limiting its effectiveness. One potential method to mitigate load-induced desensitization is by superimposing noise on the loading waveforms ("stochastic resonance"). Thus, the purpose of this study was to investigate the effects of stochastic resonance on chondrocyte matrix metabolism. Chondrocyte-seeded agarose gels were subjected to dynamic compressive loading, with or without, superimposed vibrations of different amplitudes and frequency bandwidths. Changes in matrix biosynthesis were determined by radioisotope incorporation and subsequent effects on intracellular calcium signaling were evaluated by confocal microscopy. Although dependent on the duration of loading, superimposed vibrations improved cellular sensitivity to mechanical loading by further increasing matrix synthesis between 20-60%. Stochastic resonance also appeared to limit load-induced desensitization by maintaining sensitivity under desensitized loading conditions. While superimposed vibrations had little effect on the magnitude of intracellular calcium signaling, recovery of mechanosensitivity after stimulation was achieved at a faster rate suggesting that less time may be required between successive loading applications. Thus, stochastic resonance appears to be a valuable tool during the mechanical stimulation of cartilage constructs, even when suboptimal stimulation conditions are used.
Microarchitecture for a three-dimensional wrinkled surface platform.
Li M1, Hakimi N, Perez R, Waldman S, Kozinski JA, Hwang DK (2015)
Advanced Materials 27(11):1880-1886.
Partial polymerization during photolithography is precisely controlled to obtain a partially cured (PCP) layer on the formed 3D microstructures. Upon plasma treatment, a 3D surface with morphologically tunable and spatially controllable wrinkles is obtained. The fabrication process is characterized and its ability to make various wrinkled microstructures is demonstrated. Experiments show cells can sense 3D wrinkled microstructures, attach, and bridge between them.
Multilineage co-culture of adipose-derived stem cells for tissue engineering
Zhao Y, Waldman SD, Flynn LE (2015)
Journal of Tissue Engineering and Regenerative Medicine 9(7):826-837.
Stem cell interactions through paracrine cell signalling can regulate a range of cell responses, including metabolic activity, proliferation and differentiation. Moving towards the development of optimized tissue-engineering strategies with adipose-derived stem cells (ASCs), the focus of this study was on developing indirect co-culture models to study the effects of mature adipocytes, chondrocytes and osteoblasts on bovine ASC multilineage differentiation. For each lineage, ASC differentiation was characterized by histology, gene expression and protein expression, in the absence of key inductive differentiation factors for the ASCs. Co-culture with each of the mature cell populations was shown to successfully induce or enhance lineage-specific differentiation of the ASCs. In general, a more homogeneous but lower-level differentiation response was observed in co-culture as compared to stimulating the bovine ASCs with inductive differentiation media. To explore the role of the Wnt canonical and non-canonical signalling pathways within the model systems, the effects of the Wnt inhibitors WIF-1 and DKK-1 on multilineage differentiation in co-culture were assessed. The data indicated that Wnt signalling may play a role in mediating ASC differentiation in co-culture with the mature cell populations.
Photo-cross-linked methacrylated polysaccharide solution blends with high chondrocyte viability, minimal swelling, and moduli similar to load bearing soft tissues.
Hayami JWS, Waldman SD, Amsden BG (2015)
European Polymer Journal 72:687-690.
Photo-cross-linked hydrogels produced from solution blends of methacrylated glycol chitosan (MGC), hyaluronic acid (MHA) and chondroitin sulfate (MCS) were examined for their potential use as load bearing soft tissue (LBST) repair constructs. The effect of the degree of prepolymer methacrylation (X, Y or Z; based on a repeating dimer unit) on the final hydrogel properties was investigated using solutions of 6% w/v for MGC (6%MGC-X, where X = 12%, 26% or 58%) and MHA (6%MHA-Y, where Y = 14%, 42% or 96%) and 20% w/v for MCS (20%MCS-Z, where Z = 16%, 26% or 45%). The goal was to adjust the cross-link density to produce hydrogels with moduli greater than 100 kPa to be suitable for load bearing applications while also minimizing swelling after cross-linking (±10% change in volume), and maintaining high viability and high metabolic activity of the encapsulated chondrocytes. These objectives were achieved by cross-linking solution blends of either the 6%MGC-12 or 6%MHA-42 with the 20%MCS-45 prepolymer at 50% mass fraction (5050 MGC12MCS45 and 5050 MHA42MCS45). Chondrocyte viability within blended hydrogels were greater than 70% after 24 h of culture, but metabolic activity was highest in the MHA based hydrogels (single component and blended) over a 35 day culture period. Overall, the high initial modulus, low swelling and enhanced metabolic activity of the encapsulated chondrocytes within the 5050 MHA42MCS45 hydrogels suggests they may be suitable for use in a reparative load bearing soft tissue construct.
Post Doctoral Research Associate
We are seeking an enthusiastic, self-motivated researcher who has just recently completed their PhD program (ideally within the past 2 years). Qualified candidates should hold a Ph.D. in biomedical engineering, chemical engineering, cell biology, biochemistry or a related field with relevance to tissue engineering. The desired skills include: cell culture, biochemistry, molecular biology and biomechanics. In addition, the ability to write and present research results, and assist in the development of future granting proposals are strongly sought. The position is available immediately for a one-year contract which is renewable depending on the performance of the candidate and the current funding situation.
Interested individuals should send a current curriculum vita, a brief statement of research interests, and the names and contact information of at least two references to Dr. Stephen Waldman.
Graduate Students (PhD and Masters)
We are always seeking enthusiastic, self-motivated graduate students at either the Masters or PhD level. Qualified candidates should have a background in biomedical engineering, chemical engineering, cell biology, biochemistry or a related field with relevance to tissue engineering. Interested individuals should send a current curriculum vita and a brief statement of research interests to Dr. Stephen Waldman.
Ryerson University has an employment equity program, welcomes diversity in the workplace and encourages applications for all qualified candidates including women, aboriginal peoples, persons with disabilities, and racial minorities.
Dr. Waldman's Office:
Department of Chemical Engineering
Faculty of Engineering & Architectural Science
Kerr Hall South, KHS 241N
Toronto, Ontario, Canada M5B 2K3
416.979.5000 x 4200
Li Ka Shing Knowledge Institute
7W2 - 209 Victoria St.
St. Michael's Hospital
30 Bond Street
Toronto, Ontario, Canada M5B 1W8