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Cellular Interactions with Biomaterials
 


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ONGOING RESEARCH 


Dr. Douglas Hamilton discusses his research on video ...
Watch as Dr. Douglas Hamilton discusses his drive to improve wound repair and regeneration in connective tissues with bio materials and how he hopes to see his research impact patients with non-closing wounds in the future.
                                                            Cick on You Tube to watch!    


Research in our laboratory is focused on the molecular biology underlying wound repair and regeneration in connective tissues including bone, skin and the periodontium.

Our research goals are to:

1.  Assess the molecular factors involved in degeneration and regeneration of skin,
     bone and gingival connective tissues.
2.  Enhance wound repair around/with bio (active) materials
3.  Design of new topographical and chemical features to enhance integration of
     biomaterials.

We are investigating the above areas through:

A) Design of model systems to assess that factors that govern cellular interactions with bio-active materials.

Since the experiments by Harrison (1911) and Weiss (1945), it has been long recognized that mammalian cells are sensitive to the composition of their microenvironment. Surface chemistry and topography have been observed to influence many cellular processes such as adhesion, spreading, morphology, cytoskeletal organization, proliferation, migration, and gene expression. As methods of material fabrication and characterization have evolved, it has become possible to identify the limits of cell sensing and how topographical and chemical cues can influence tissue integration around implanted materials, as well as in vitro tissue development. We are developing new model systems, in conjunction with Dr. Silvia Mittler to evaluate cell response to biomaterial surface characteristics, using state of the art microscopy and proteomic techniques.

B) Design of novel bioactive materials to enhance dermal fibroblast function and extracellular matrix production

Chronic wounds represent a significant burden to health care across world and one of the most devastating complications of diabetes is the occurrence of ulcers and chronic wounds.  Approximately 15% of 2.3 million Canadians who live with diabetes today will develop a non-healing foot ulcer in their lifetime.  A non-healing foot ulcer results in amputations of limb and an estimated 1500 Ontarians with diabetes had a limb amputated in 2008. Non-healing wounds are characterized by increased inflammation, a loss of extracellular matrix (ECM, support scaffold in normal skin) and dermal fibroblasts (which make the ECM). As a result the wounds do not contract and remain open, causing patients considerable pain, disability and putting them at risk for systemic infection. In collaboration with Dr. Jianjun Guan, we have developed an artificial scaffold containing proteins required for normal skin repair. The purpose of these scaffolds is to essentially create an artificial extracellular matrix that would normally be present as wounds repair, but is absent in non-healing wounds. 

C) In vitro and in vivo evaluation of biomaterials and cellular response.

To date, the development of biomaterials has often been driven on an empirical basis, rather than on advances made in the understanding of cell and tissue biology/pathophysiology. Our philosophy on biomaterials development is to use biological data from in vitro and in vivo models to re-design materials that will further promote desired cell behaviour, and advantageous gene and protein expression. Through characterization of the material chemistry and topography, as well as the cellular response, materials can be furthered adapted where applicable, through the incorporation of biologically active molecules on the surfaces. We are developing a rigorous screening system for gene and protein changes in newly implanted, as well as end stage failure biomaterials. Furthermore, such an approach could be used to identify gene changes in pathologies prior to the onset of implant or biomaterial failure. 

D) Use of transgenic mice and proteomic/genomic techniques to assess the role of proteins in biomaterial integration and wound repair.

In vitro analyses of the effects of topographical and chemical cues on mammalian cell behaviours have correlated relatively well with in vivo observations. Exactly how substratum topography regulates bone and connective tissue formation at the molecular level remains unknown. Does short-term protein activation and translation influence long-term tissue development? Our approach to address these questions involves the use of gene knockout mice and cell lines in collaboration with as well as state of the art proteomics and genomic techniques. Such an approach could lead to the identification of novel diagnostic markers and therapeutic targets that can be applied to other bone and connective tissue diseases. 

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MEMBERS OF THE HAMILTON LAB
 

Please direct research position and other inquiries to:

Dr. Douglas W. Hamilton
Department of Dentistry
Schulich School of Medicine & Dentistry at Western University
London, Ontario, CANADA N6A 5C1
Phone   519.661.2111 x81594              Fax 519.850.2459
Email     Douglas.Hamilton@schulich.uwo.ca
 

 

 

Douglas W. Hamilton, PhD Principal Investigator

 

Shawna Kim
MSc Candidate

 

John Walker
MSc Candidate
Anatomy & Cell Biology

   

Project: Role of profibrotic extracellular matrix signals
in the development of
Gingival Hyperplasia.

 

Project: Role of Galectin-3 in wound healing

         
   

Kendal Creber
MSc Candidate
Biomedical Engineering

 

Sarah Michelsons
MSc Candidate
Anatomy & Cell Biology

 

Kathleen Martin
DDS Candidate

 

Project: Design and validation of biomaterials to enhance human periodontal ligament fibroblast plasticity and
tissue regeneration.

 

Project: Modulation of extracellular matrix
production in gingival fibroblast by cytokines
and biomaterials

 

Project: Development of novel polymer membranes for applications in guided tissue regeneration.

         
   

 

 

Cick on 'You Tube' to

hear Daniel Pepe!   

Joel Keshwah
DDS Candidate

 

Daniel Pepe
MD Student

 

 

 

Project: Regulation of osteoclast and osteoblast physiology by substratum topography.

 

Project:  Influence of galectin-3 and thrombospondin-1 in the regulation of non-specific inflammation in chronic skin wounds.

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Alumni  

Paul Prowse
Defended MSc

Alvin Choi - DDS Candidate
Summer Student

Richard Miron
Defended MSc

Project: Design of novel biomaterials to enhance craniofacial reconstruction
and bone remodeling.
Project: Gingival fibroblast matrix gene expression
and dental implant
substratum topography.
Project: Influence of titanium and Emdogain on osseoin-
tegration in vitro and in vivo.

 

   

Christine J. Oates
Defended MSc

Eric Bellis Undergraduate Student

Melanie Wong
NSERC USRA  

Project: Influence of focal adhesion kinase on fibroblast physiology on substratum topography. Project: Comparison of osteoblast and fibroblast
response to periostin.   
Project: Role of GTPases in osteoblast commitment and terminal differentiation.

 

   

Sarah Prescott
Work Study Student

Weiyan Wen
Research Technician  

Chris Elliott
Defended PhD 

Project: Expression of matricellular proteins in
human chronic skin wounds.
  Project:  Regulation and function of periostin in collagenous tissues.
     

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PUBLICATIONS:  


S Kim, L Jackson, T Daley, M Darling, M Reider and DW Hamilton. Nifedipine Induces Periostin Expression in Gingival Tissue Through Canonical Transforming Growth Factor Beta Signalling. J Dental Research. 92(11):1022-8, 2013. PubMed

Costa DO, Prowse PD, Chrones T, Sims SM, Hamilton DW, Rizkalla AS, Dixon SJ. The differential regulation of osteoblast and osteoclast activity by surface topography of hydroxyapatite coatings. Biomaterials. 34(30):7215-26, 2013. PubMed

Chau E, Daley T, Darling MR, Hamilton D. The expression and immunohistochemical localization of periostin in odontogenic tumors of mixed epithelial/mesenchymal origin. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Aug;116(2):214-20. doi: 10.1016/j.oooo.2013.05.008.

Prowse PD, Elliott CG, Hutter J, Hamilton DW. Inhibition of Rac and ROCK Signalling Influence Osteoblast Adhesion, Differentiation and Mineralization on Titanium Topographies. PLoS One. 2013;8(3):e58898. doi: 10.1371/journal.pone.0058898. Epub 2013 Mar 7.  PubMed

Ertorer E, Vasefi F, Keshwah J, Najiminaini M, Halfpap C, Langbein U, Carson JJ, Hamilton DW, Mittler S. Large area periodic, systematically changing, multishape nanostructures by laser interference lithography and cell response to these topographies. J Biomed Opt. 2013 Mar;18(3):035002. doi: 10.1117/1.JBO.18.3.035002. PMID: 23460125. PubMed

Ghrebi S, Hamilton DW, Douglas Waterfield J, Brunette DM. The effect of surface topography on cell shape and early ERK1/2 signaling in macrophages; linkage with FAK and Src.  J Biomed Mater Res A. 2013 Feb 20. doi: 10.1002/jbm.a.34509. Epub ahead of print

Elliott CG, Kim SS, Hamilton DW. Functional significance of periostin in excisional skin repair: is the devil in the detail?  Cell Adh Migr. 2012 Jul-Aug;6(4):319-26. Epub 2012 Jul. PubMed

X. Guo, C.G. Elliott, Z. Li, Y. Xu,  D.W. Hamilton, J. Guan. Creating 3D angiogenic growth factor gradients in fibrous constructs to guide fast angiogenesis. Biomacromolecules. 2012 Oct 8;13(10):3262-71. Epub 2012 Sep PubMed

C.G. Elliott, J. Wang, X. Guo, S.W. Xu, M. Eastwood, J. Guan, A. Leask, S.J. Conway, D.W. Hamilton. Periostin modulates myofibroblast differentiation during full-thickness cutaneous wound repair. J Cell Sci. 125(Pt 1):121-32, 2012. Pub Med

C.G. Elliott, D.W. Hamilton. Deconstructing fibrosis research: do pro-fibrotic signals point the way for chronic dermal wound regeneration? J Cell Commun Signal, 2011. PubMed

D.W. Hamilton, C.J. Oates, A. Hasanzadeh, S.M. Mittler. Migration of Periodontal Ligament Fibroblasts on Nanometric Topographical Patterns: Influence of Filopodia and Focal Adhesions on Contact Guidance. PLoS ONE, 5(12):e15129, 2010. PubMed

W. Wen, E. Chau, L. Jackson, T. Daley and D.W. Hamilton. TGF beta 1 and FAK Regulate Periostin Expression in PDLFibroblasts. Journal of Dental Research, 89(12):1439-43, 2010. PubMed

K. Thompson, D.W. Hamilton and A. Leask. ALK5 Inhibition Blocks TGFbeta-induced CCN2 Expression in Gingival Fibroblasts. Journal of Dental Research, 89(12):1450-4, 2010. PubMed

H.M. Zhou, J. Wang, C. Elliott, W. Wen, D.W. Hamilton and S.J. Conway. Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formation. Journal of Cell Communication and Signaling, 4(2):99-107, 2010. PubMed

SM.Z. Khaled, R.J. Miron, D.W. Hamilton, P.A. Charpentier and A.S. Rizkalla. Reinforcement  of Resin Based Cement with Titania Nanotubes. Dental Materials, 262:169-178, 2010. Pub Med  

R. Miron, C.J. Oates, A. Molenberg, M. Dard and D. W. Hamilton. The effect of enamel matrix   proteins on the spreading, proliferation and differentiation of osteoblasts cultured on titanium surfaces. Biomaterials, 31(3): 449-60, 2010. Pub Med   

D.W. Hamiton, C. Oakley, N.A.F. Jaeger and D.M. Brunette.  Directional Change Produced by Perpendicularly-Oriented Microgrooves is Microtubule-Dependent for Fibroblasts and Epithelium. Cell Motility and the Cytoskeleton, 66(5):260-71, 2009.

M. Schuler, D.W. Hamilton, T.P. Kunzler, C. M. Sprecher, M. de Wild, D.M. Brunette, M. Textor and S. Tosatti. Response of osteoblasts outgrown from rat calvarial bone chips to non-fouling KRSR and FHRRIKA-peptide rough modified titanium surfaces. In press, Journal of Biomedical Materials Research Part B, Applied Biomaterials, 2009.

L. Jackson-Boeters, W. Wen and D.W. Hamilton. Periostin localizes to cells in normal skin, but is associated with the extracellular matrix during wound repairJournal of Cell Communication and Signaling, 2009. 3(2):125-133, 2009 PubMed

D.W. Hamilton. Functional Role of Periostin Expression in Development and Wound Repair: Implications for Connective Tissue Disease. Journal of Cellular Communication and Signaling, 2(1-2):9-17, 2008. PubMed

E. Kokubu, D.W. Hamilton, T. Inoue and D.M. Brunette. Modulation of Human Gingival Fibroblast Adhesion, Morphology, tyrosine phosphorylation, and ERK 1/2 localization on Polished, Grooved and SLA Substratum Topographies. Journal of Biomedical Materials Research Part A, 2008.

M. Nematollahi, D.W. Hamilton and D.M. Brunette. Hexagonal Micron Scale Pillars Influence Epithelial Cell Adhesion, Morphology, Migration and Cytoskeletal Organization. Journal of Biomedical Materials Research Part A, 2008.

D.W. Hamilton, B. Chehroudi and D.M. Brunette. Comparative response of epithelial cells and osteoblasts to microfabricated tapered pit topographies in vitro and in vivo. Biomaterials, 28(14):2281-2293, 2007. PubMed

T.M. Maul, D.W. Hamilton, A. Nieponice and D.A Vorp. A novel experimental system for the extended application of cyclic hydrostatic pressure to cell culture. Journal of Biomechanical Engineering, 129(1):110-6, 2007. PubMed

D.W. Hamilton and D.M. Brunette. The effect of substratum topography on osteoblast adhesion mediated signal transduction and phosphorylation. Biomaterials, 28(10): 1806-1809, 2007. PubMed

D.W. Hamilton, K.S. Wong and D. M. Brunette. Microfabricated Discontinuous Edge Surface Topographies Influence Osteoblast Adhesion, Migration, Cytoskeletal Organization, Proliferation and Enhance Matrix and Mineral Deposition in vitro. Calcified Tissue International, 78(5):314-25, 2006. PubMed

M. Schuler, G.Rh. Owen, D.W. Hamilton, M. Wieland, D.M. Brunette, M. Textor and S. Tosatti. Biomimetic Modification of Titanium Dental Implant Model Surfaces Using the RGDSP-Peptide Sequence: A Preliminary Study for a Cell-Selective Surface. Biomaterials, 27(21):4003-4015, 2006. PubMed

D.W. Hamilton, M. Riehle, W. Monaghan, and A.S.G. Curtis. Chondrocyte Aggregation on Micrometric Surface Topography: A time-lapse study. Tissue Engineering, 12(1), p189-199, 2006.  PubMed

D.W. Hamilton, S. Ghrebi, H. Kim, B. Chehroudi and D. M. Brunette. Surface Topography and Cell Behaviour. The Encyclopedia of Biomaterials and Biomedical Engineering. Published online 28/11/2005. Editors, Gary Bowlin and Gary Wnek. Marcel Dekker, New York, P1-11.

D.M. Brunette, D.W. Hamilton, B. Chehroudi and J.D. Waterfield. Update on improving the bio-implant interface by controlling cell behaviour using surface topography. International Congress Series, 1284C, p229-238, 2005. LinkedOut

D.W. Hamilton and D.M. Brunette. Gap Guidance of Fibroblasts and Epithelial cells by Discontinuous Surface Topography. Experimental Cell Research, vol 309(2), p429-437, 2005. PubMed

D.W. Hamilton, M. Riehle, R. Rappuoli, W. Monaghan, R. Barbucci and A.S.G. Curtis. The response of primary articular chondrocytes to micrometric topography and sulphated hyaluronic acid based matrices. Cell Biology International, vol 29(8), p605-615, 2005. PubMed

D.W. Hamilton, M. Riehle, W. Monaghan and A.S.G. Curtis. Chondrocyte passage number: Influence on adhesion, migration, cytoskeletal organization and phenotype in response to nano- and micro-metric topography. Cell Biology International, vol 29(6), p408-421, 2005. PubMed

D.W. Hamilton and D.A. Vorp. Tissue Engineering, Blood Vessel. In the Encyclopedia of Biomaterials and Biomedical Engineering. Published online 08/31/04, print, 06/30/2004. Editors, Gary Bowlin and Gary Wnek. Marcel Dekker, New York. p1491-1499.

D.W. Hamilton, T.M. Maul and D.A. Vorp. Characterization of the response of Bone Marrow Derived Progenitor Cells to Cyclic Strain: Implications for Vascular Tissue Engineering Applications. Tissue Engineering, vol 10(3/4), p361-369, 2004. PubMed

M. Riehle, D. Ferris, D. Hamilton and A. Curtis. Cell Behaviour in Tubes. Exp Biol. Online vol 3:2, p1-15, 1998. LinkedOut

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RESEARCH FUNDING 

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NEWS 

 

Congratulations to Christopher Elliott for successfully defending his PhD Thesis!
Supervisors: Doug Hamilton / Andrew Leask [2013 Aug]
Thesis Title:  Evaluation of Matricellular Proteins as Potential Therapeutics for the Treatment of Human Chronic Skin Wounds

Funding Awarded - ITI (International Team for Implantology) Foundation
Dr. Doug Hamilton / Dr. Walter Siqueira - $102,000 for one year [2012 Jan]
Title: Acquired Enamel Matrix Protein Titanium Pellicle: Development of Biomimetic Surfaces to Improve Dental Implant Integration 

Funding Awarded - CIHR
The Hamilton laboratory has received 3 years funding from the CIHR to investigate novel treatments for the closure of chronic skin wounds.  [2011 Sep]
Title: Matricellular Protein Biomimetic Scaffolds to Enhance Skin Regeneration 

Funding Awarded - Early Researcher Award
Dr. Hamilton was recently awarded an Ontario Ministry of Research and Innovation Early Researcher award for his research investigating surface treatments to enhance metal implant integration with bone. [2011 Aug]
Title: Surface treatments to enhance metal implant integration

Congratulations to Paul Prowse for successfully defending his Master's Thesis
Supervisor: Doug Hamilton / Co-supervisor: Amin Rizkalla [2011 Nov]
Thesis Title: Role of Rac1 and RhoA-ROCK Signaling on Osteoblast Differentiation on Smooth and Rough Titanium Topographies.

Canadian Association of Dental Research (CADR) Student award
Shawna Kim (MSc Candidate) won second place in the Canadian Association of Dental Research Student awards in the senior science category. She will present an oral presentation on her findings at the 2012 AADR/CADR Conference in Tampa, Florida [2011 Sep]

Implant Research Group Young Investigator Award Competition
Paul Prowse (PhD Candidate) won 2nd place at the 2011 Annual Meeting of the International Association for Dental Research in San Diego [2011 March]
Title: Regulation of Osteoblast Differentiation on Smooth and Rough Titanium by Rac1 GTPase.

Dentist Clinicial Scientist (DCS) Program - Acceptance for 2012
Shawna Kim (MSc Candidate) was accepted into the 2012 DCS Program.  The DCS program is a joint degree program (DDS/MSc or DDS/PhD) geared towards students who are interested in dental research or academic dentistry. Students accepted into the DCS program complete all requirements of dental related courses with the MSc or PhD program prior to entering the DDS class [2011 May]

Funding Awarded - NSERC
Dr. Hamilton's application to the National Sciences & Engineering Research Council's Discovery Grants Competition was approved. This latest grant will provide $32,000 in funding per year for the next 5 years. [2009]

Funding Awarded - CFI
The Hamilton Lab was successful in their application to the Canadian Foundation for Innovation (CFI) with an awarded grant of $406,000.
Title: Centre for the Study of Biomaterials and Tissue Regeneration.

Alexander Graham Bell Canada Graduate Scholarship
Congratulations to Ricky Miron on the receipt of a 1 year Alexander Graham Bell Canada Graduate Scholarship from the National Sciences and Engineering Research Council of Canada! [2009]

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CONTACT INFORMATION:
 

Please direct research position and other inquiries to:

Dr. Douglas W. Hamilton
Department of Dentistry
Schulich School of Medicine & Dentistry at Western University
London, Ontario, CANADA  N6A 5C1
Tel: 519.661.2111 x81594     Fax: 519.850.2459
Email: Douglas.Hamilton@schulich.uwo.ca

Dr. Douglas W. Hamilton, Principal Investigator                                        

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