Liisa T. Kuhn, Ph.D.Associate Professor of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development
- Education & Training
- Clinical Interests
- Committees & Organizations
- Research Opportunities
- Lab Rotations
Welcome to the Kuhn Biomaterials Lab at the University of Connecticut Health Center (UConn Health). Our laboratory works at the interface of materials science and medicine. We use biological and engineering techniques to investigate bone regeneration after delivery of growth factors and stem cells from biomaterial scaffolds. We also study nanoparticle delivery of chemotherapy using calcium phosphate-based biomaterials that may one day be used to minimize painful and debilitating side effects of anti-cancer therapies.
Dr. Kuhn's research spans fundamental studies to translational research. She has an expertise in drug delivery and conducting in vitro and in vivo studies that she gained while working in industry and at UConn Health. The Kuhn Lab's mission is to use biomaterial technologies to develop better treatments for damaged or diseased tissue, particularly in the elderly.
Dr. Kuhn is a tenured Associate Professor in the Reconstructive Sciences Department, School of Dental Medicine. She is also core faculty in the Biomedical Engineering Department at the University of Connecticut-Storrs. She received her undergraduate degree in Mechanical Engineering at Duke University and worked at General Dynamics in San Diego, CA before completing her MS and PhD in Materials Engineering at the University of California Santa Barbara. Dr. Kuhn held postdoctoral positions at Case Western University and Harvard Medical School/Boston Children’s Hospital, conducting biomineralization studies and orthopedic research. She joined the faculty at UConn Health after co-founding and selling a start-up company in Boston, MA that developed bone graft substitutes.
The Connecticut Technology Council recognized Dr. Kuhn's entrepreneurial efforts with the Women of Innovation award in 2009. Her cutting edge research in orthopedic biomaterials and drug delivery systems has been supported by federal (NIH), state (Connecticut) and private funding sources (e.g. Komen Foundation, Coulter Foundation). She is currently funded by the NIH National Institute of Dental and Craniofacial Research (NIDCR) for her work in growth factor releasing biomaterials for bone regeneration in the elderly. Her publications span several scientific areas and reflect her range of interests and specialities including: bone regeneration, physical and chemical characterization of bone mineral, anti-cancer drug delivery, nanoparticles, mechanics of materials, immunological adjuvants, cell culture plate coatings for stem cell expansion and guided differentiation of pluripotent stem cells. She serves on the editorial boards of several biomaterials, tissue engineering and stem cell journals and reviews manuscripts for many different scientific journals. She is a regular grants reviewer for the National Institutes of Health (NIH) and has served for many years as a reviewer for private, state-based and European funding agencies.
An active member of the Society for Biomaterials (SFB) since 1997, Dr. Kuhn has a long record of service to the Society. She has been very active in the programmatic activity of the Society For Biomaterials by serving as the 2002 Annual Meeting Program Chair; Treasurer and Chair of the Orthopedic SIG (1999, 2001); Vice-Chair and Chair of the Drug Delivery SIG (2005, 2006, 2007); and she organized several symposia (in 2005, 2006, 2010, 2012, and 2013), a workshop on regulatory pathways (2009). She has reviewed abstracts nearly every year and has moderated many sessions. Dr. Kuhn was the SFB Book Reviewer for the Biomaterials Forum (the Society's new magazine) for 9 years (2002-2011). In 2011 she became the Executive Editor of the Biomaterials Forum. She has experience with the governance of the Society through her service as a member of the Educational and Professional Development Committee (2003), the Membership Committee (2005), the Awards Committee (2007 and 2009), and the SFB Council (2011-present).
Medical product standards are a critical component of the regulatory approval pathway and Dr. Kuhn has been directly involved in writing new medical product standards through the American Society of Testing and Materials International (ASTM). Standards accelerate and positively impact healthcare because standards are used by the Food and Drug Administration to facilitate regulatory decisions. For her distinguished service and exceptional contributions to medical product standards writing, Dr. Kuhn been recognized by ASTM with the organization's top three awards, including, in 2014, the Award of Merit with an accompanying honorary title of Fellow.
|B.S.||Duke University||Mechanical Engineering|
|M.S.||University of California||Materials Engineering|
|Ph.D.||University of California||Materials Engineering|
|Postdoctoral||Case Western Reserve University||Biomineralization|
|Name of Award/Honor||Awarding Organization|
|Women of Innovation Award, Academic Innovation and Leadership Category||Connecticut Technology Council|
|Patrick Laing Award for Outstanding and Meritorious Service||American Society of Testing and Materials (ASTM)|
Dr. Kuhn (PhD) conducts preclinical testing of promising dental and orthopedic technologies that can improve bone regeneration.
Dr. Liisa Kuhn trains the next generation of scientists by advising undergraduate, graduate and postdoctoral trainees and giving lectures in her own courses and others. She developed and taught the UConn biomedical engineering core course called BME 4710/5700 Biomaterials and Tissue Engineering for eight years. In 2014 she created a new, follow-on course that is a combined undergrad/grad course and taught every spring: Controlling Stem Cells With Biomaterials, listed as BME 4985-003/BME 6086-004.
Course Description: In this course participants will learn how to design biomaterials that actively control stem cells to achieve tissue regeneration. Biological and biomaterials principles will be taught with a focus on cell/extracellular matrix interactions during embryonic development and wound healing. Biomaterial and biomechanical techniques to influence the attachment, proliferation and differentiation of stem cells on a biomaterial scaffold will be studied including: chemical and physical modifications of biomaterials, use of natural tissues as scaffolds and bioreactor culture.
Dr. Kuhn also serves as Faculty facilitator for D400-720 Critical Thinking in Dentistry and Correlated Dental Problem Solving. It is a two semester course.
Mentoring and Outreach Lectures 2005 & 2006 Lecturer. Capital Community College. Discoveries in Modern Medicine at Capital Community College, Hartford, CT. Course Director: M. Mednieks. Bridges to Baccalaureate outreach program to underrepresented minorities in science. Fall semester.
2009 “A Day in the Life of a Research Scientist” Career Panel Speaker, Connecticut DigiGirlZ program for minority high school students. Microsoft Corporation. March 27, 2009.
“Women in Science and Engineering”, Keynote speaker, Annual Banquet of Women in Math, Science and Engineering, University of Connecticut Storrs Campus, CT. April 15, 2009.
“A Career in Biomedical Science and Engineering” Panelist for Career Paths in the Sciences, organized by the Women in Math, Science and Engineering (WiMSE). University of Connecticut Storrs Campus, CT. November 30, 2009.
2010 “Making the Transition from Industry to Academia” Panelist at the annual retreat of the Skeletal, Craniofacial and Oral Biology, Biomedical Sciences Graduate program. UConn-Avery Point, CT. June 12, 2010.
2011 “University Partnerships using the NIH SBIR Small Business Grants Program”, Panelist at the Connecticut Innovations Regional NIH SBIR workshop. UConn-Health Center, Farmington, CT. October 20, 2011.
|Name & Description||Category||Role||Type||Scope||Start Year||End Year|
|Editor, Biomaterials Forum Society For Biomaterials||Professional/Scientific Organization||Editor||External||National||2011|
|General Interest Vice-Chair of the Main Committee F04 Medical and Surgical Materials and Devices, American Society of Testing and Materials (ASTM)||Professional/Scientific Organization||Vice Chair||External||National||2004||2012|
|NIH CSR Study Section Member (NIAMS, SBIR/STTR), Ad hoc member - present.||Study Section||Member||External||National||2003|
|Overall Meeting Program Chair, 28th Annual Meeting of the Society for Biomaterials||Professional/Scientific Organization||Chair||External||National||2002||2002|
The Kuhn lab's research mission is to bring regenerative and anti-cancer biomaterials technologies closer to patient use through pre-clinical testing and research.
Bone morphogenetic protein-2 (BMP-2) is now used clinically in patients to enhance bone regeneration during spinal fusion, fracture healing and dental bone implant procedures. While BMP-2 has been demonstrated to significantly enhance bone repair, the complication profile, likely related to the supraphysiologic dose of BMP-2 delivered in its current formulation, has lead to safety concerns and has limited its clinical use. Reported complications include early inflammatory reaction and osteolysis, ectopic bone formation sometimes leading to compression of neural elements, seroma formation and a possible increase in the risk of malignancy. Thus, there is a need to refine the delivery and improve the efficacy of BMP-2 so that it can be delivered in lower doses with less risk of complications. The Kuhn lab is addressing the BMP-2 problem by developing a better delivery system. We are designing and testing polyelectrolyte multi-layer coated scaffolds to achieve controlled delivery of BMP-2 in conjunction with other growth factors to regenerate bone for dental and orthopedic applications.
Many older adults have a compromised ability to repair fractures or replace lost bone. It has been suggested that a decrease in numbers of osteogenic progenitor cells in elderly patients contributes to the decrease in skeletal bone formation and rate of fracture repair observed with aging and in osteoporotic patients. Further, mesenchymal stem cells in post-menopausal women have a lower growth rate and are deficient in their ability to differentiate along the osteogenic lineage. The problem of reduced bone formation in the aging mammalian body remains unsolved. While the biology of aging is complex, strategies that improve the number and function of osteoprogenitor cells in elderly patients is likely to contribute to increased bone formation; thus that is our research focus.
Fibroblast growth factor-2 (FGF-2) regulates the proliferation and differentiation of many cell types, including osteoblasts, and is stored in the extracellular matrix. In mice, FGF receptor 2 loss of function results in progressive osteopenia and decreased bone formation rates, suggesting a role for FGF-2 in maintaining bone mass, especially with aging. Several studies by our co-investigator Dr. Hurley at our institute and others have shown that FGF-2 is a potent stimulator of preosteoblast replication. FGF-2 and platelet-derived growth factor (PDGF) were observed to be the only growth factors that increased mineralized nodule formation in calvarial osteoblasts from aged rats, and FGF-2 was twice as potent as PDGF. Whereas chronic exposure to FGF-2 can also stimulate osteoclast formation, and increase bone resorption, intermittent FGF-2 treatment stimulates bone formation in vitro and in vivo. FGF-2 has great potential to increase the activity and function of osteoprogenitor cells in elderly patients and thus we are developing biomaterial scaffolds that can delivery it locally, in combination with BMP-2 to stimulate more rapid bone healing.
FGF-2 and BMP-2 have synergistic bone enhancing effects resulting in increased bone volume as a function of dose in ectopic sites and in rat calvaria parietal bones, but the combination has been primarily testing in young animals, not old. Our current research thus studies effects of these two factors in old animals. Too much FGF-2 has been shown to reduce the amount of in vivo bone formation with BMP-2 because it can maintain cells in an undifferentiated state too long thus dose optimization is mandatory. FGF-2 enhances BMP-2 stimulated bone formation and may be the solution for reducing the dose and complications associated with BMP-2 use.
We have a major research effort investigating polyelectrolyte multi-layer (PEM) technology applied to bone substitute materials to enable sequential delivery of FGF-2 and BMP-2. The PEM technology is a thin film deposition technique that forms nanoreservoirs for drug delivery and antimicrobial protection. Bioactive proteins can be directly integrated into PEM coatings in the absence of covalent bonding and thus keep secondary structures close to their native form. The growth factors are released through cell-based PEM degradation, rather than by the undesirable non-cell initiated polymer hydrolysis which leads to burst release and may degrade the growth factor or initiate inflammation. Our work, and that of others, indicates that sequential delivery of FGF-2 followed by BMP-2, rather than co-delivery of FGF-2/BMP-2, produces the maximal osteogenic effect. Our work in this area is currently funded by the NIH NIDCR and has been presented at the Society For Biomaterials and Orthopedic Research Society annual meetings.
Recent publications in this area include:
LF Charles, JL Woodman, D Ueno, G Gronowicz, MM Hurley, LT Kuhn*. Effects of Low Dose FGF-2 and BMP-2 on Healing of Calvarial Defects in Old Mice. Exp Gerontol, 2015; 64: 62-69. http://dx.doi.org/10.1016/j.exger.2015.02.006.
L Kuhn*, G Ou, L Charles, M Hurley, C Rodner and G Gronowicz, Fibroblast growth factor-2 and Bone Morphogenetic Protein-2 Have a Synergistic Stimulatory Effect on Bone Formation in Cell Cultures from Aging Mouse and Human Bone, J Gerontol A Biol Sci Med Sci. 2013 Oct;68(10):1170-80. doi: 10.1093/gerona/glt018.
L Xiao, D Ueno, S Catros, L Charles, L Kuhn, MM Hurley. Exported 18-kDa Isoform of Fibroblast Growth Factor-2 Improved Bone Regeneration in Critical Size Mice Calvarial Defects. Endocrinology, 2014 Mar;155(3):965-74. doi: 10.1210/en.2013-1919.
If you are interested in learning about biomaterials and preclinical testing, please contact Dr. Liisa Kuhn for research opportunities.
There are no paid openings available in the Kuhn lab at this time, but volunteer positions are available.
Accepting Lab Rotation Students: Summer '19, Fall '19, Spring '20
Implant Guided Bone Growth Mediated by Local Delivery of Osteogenic Agents
The long term goal of this research is to develop dental implant guided bone augmentation procedures for the reconstruction of the resorbed alveolar ridge of the mandible. This work is done in collaboration with clinicians Dr. Martin Freilich and Dr. David Shafer, and biologists Dr. Gloria Gronowicz and Dr. Marja Hurley. Our goals are to deliver locally acting osteogenic agents from bioactive implant surfaces or scaffolds to guide new supracrestal alveolar bone formation at resorbed sites. Towards this end, we have recently developed novel study models utilizing both miniaturized and full sized titanium implant components to deliver osteogenic agents or stabilize scaffolds for guiding the growth of a new layer of intramembraneous bone. We are now focussed on developing biomaterial scaffolds capable of the release of multiple growth factors that can orchestrate the homing and recruitment of host progenitor cells to achieve bone regeneration in the elderly.